Patent Publication Number: US-2023136787-A1

Title: Compositions and methods for silencing vegf-a expression

Description:
RELATED APPLICATIONS 
     This application claims priority to U.S. provisional application No. 62/972,519, filed on Feb. 10, 2020, U.S. provisional application No. 63/055,627, filed on Jul. 23, 2020, and U.S. provisional application No. 63/140,714, filed on Jan. 22, 2021. The entire contents of the foregoing applications are hereby incorporated herein by reference. 
    
    
     SEQUENCE LISTING 
     The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Feb. 4, 2021, is named A2038-7236WO_SL.txt and is 1,327,255 bytes in size. 
     FIELD OF THE DISCLOSURE 
     The disclosure relates to the specific inhibition of the expression of the VEGF-A. 
     BACKGROUND 
     Vascular eye diseases are the leading cause of vision loss in today&#39;s aging population, including exudative age-related macular degeneration (exudative AMD), retinal vein occlusion (RVO), retinopathy of prematurity (ROP), diabetic retinopathy (DR), and diabetic macular edema (DME). Several of these ocular disorders are associated with pathological angiogenesis. The release of vascular endothelial growth factors (VEGFs) contributes to increased vascular permeability and inappropriate new vessel growth in the eye. New treatments for angiogenic ocular disorders are needed. 
     SUMMARY 
     The present disclosure describes methods and iRNA compositions for modulating the expression of VEGF-A. In certain embodiments, expression of VEGF-A is reduced or inhibited using a VEGF-A-specific iRNA. Such inhibition can be useful in treating disorders related to VEGF-A expression, such as ocular disorders (e.g., age-related macular degeneration (AMD), macular edema following retinal vein occlusion (MEfRVO) or central retinal vein occlusion (CVO), retinopathy of prematurity (ROP), diabetic macular edema (DME), and diabetic retinopathy (DR)). 
     Accordingly, described herein are compositions and methods that effect the RNA-induced silencing complex (RISC)-mediated cleavage of RNA transcripts of VEGF-A, such as in a cell or in a subject (e.g., in a mammal, such as a human subject). Also described are compositions and methods for treating a disorder related to expression of VEGF-A, such as an angiogenic ocular disorder (e.g., AMD, RVO, MEfRVO, CVO, ROP, DME, mCNV, and DR)). 
     The iRNAs (e.g., dsRNAs) included in the compositions featured herein include an RNA strand (the antisense strand) having a region, e.g., a region that is 30 nucleotides or less, generally 19-24 nucleotides in length, that is substantially complementary to at least part of an mRNA transcript of VEGF-A (e.g., a human VEGF-A) (also referred to herein as a “VEGF-A-specific iRNA”). In some embodiments, the VEGF-A mRNA transcript is a human VEGF-A mRNA transcript, e.g., SEQ ID NO: 1 herein. 
     In some embodiments, the iRNA (e.g., dsRNA) described herein comprises an antisense strand having a region that is substantially complementary to a region of a human VEGF-A mRNA. In some embodiments, the human VEGF-A mRNA has the sequence NM_001171623.1 (SEQ ID NO: 1). The sequence of NM_001171623.1 is also herein incorporated by reference in its entirety. The reverse complement of SEQ ID NO: 1 is provided as SEQ ID NO: 2 herein. 
     In some aspects, the present disclosure provides a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of vascular endothelial growth factor A (VEGF-A), wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region, wherein the sense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of a coding strand of human VEGF-A and the antisense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of the corresponding portion of a non-coding strand of human VEGF-A such that the sense strand is complementary to the at least 15 contiguous nucleotides in the antisense strand. 
     In some aspects, the present disclosure provides a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of VEGF-A, wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region, wherein the antisense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of nucleotide sequence of SEQ ID NO: 2 such that the sense strand is complementary to the at least 15 contiguous nucleotides in the antisense strand. 
     In some aspects, the present disclosure provides a human cell or tissue comprising a reduced level of VEGF-A mRNA or a level of VEGF-A protein as compared to an otherwise similar untreated cell or tissue, wherein optionally the cell or tissue is not genetically engineered (e.g., wherein the cell or tissue comprises one or more naturally arising mutations, e.g., VEGF-A), wherein optionally the level is reduced by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the human cell or tissue is a retinal pigment epithelium (RPE), a retinal tissue, an astrocyte, a pericyte, a Müller cell, a ganglion cell, an endothelial cell, a photoreceptor cell, a retinal blood vessel (e.g., including endothelial cells and vascular smooth muscle cells), or choroid tissue, e.g., a choroid vessel. 
     The present disclosure also provides, in some aspects, a cell containing the dsRNA agent described herein. 
     In another aspect, provided herein is a human ocular cell, e.g., (an RPE cell, a retinal cell, an astrocyte, a pericyte, a Müller cell, a ganglion cell, an endothelial cell, or a photoreceptor cell) comprising a reduced level of VEGF-A mRNA or a level of VEGF-A protein as compared to an otherwise similar untreated cell. In some embodiments, the level is reduced by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. 
     In some aspects, the present disclosure also provides a pharmaceutical composition for inhibiting expression of a gene encoding VEGF-A, comprising a dsRNA agent described herein. 
     The present disclosure also provides, in some aspects, a method of inhibiting expression of VEGF-A in a cell, the method comprising: 
     (a) contacting the cell with the dsRNA agent described herein, or a pharmaceutical composition described herein; and 
     (b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of VEGF-A, thereby inhibiting expression of the VEGF-A in the cell. 
     The present disclosure also provides, in some aspects, a method of inhibiting expression of VEGF-A in a cell, the method comprising: 
     (a) contacting the cell with the dsRNA agent described herein, or a pharmaceutical composition described herein; and 
     (b) maintaining the cell produced in step (a) for a time sufficient to reduce levels of VEGF-A mRNA, VEGF-A protein, or both of VEGF-A mRNA and protein, thereby inhibiting expression of the VEGF-A in the cell. 
     The present disclosure also provides, in some aspects, a method of inhibiting expression of VEGF-A in an ocular cell or tissue, the method comprising: 
     (a) contacting the cell or tissue with a dsRNA agent that binds VEGF-A; and 
     (b) maintaining the cell or tissue produced in step (a) for a time sufficient to reduce levels of VEGF-A mRNA, VEGF-A protein, or both of VEGF-A mRNA and protein, thereby inhibiting expression of VEGF-A in the cell or tissue. 
     The present disclosure also provides, in some aspects, a method of treating a subject diagnosed with VEGF-A-associated disorder comprising administering to the subject a therapeutically effective amount of the dsRNA agent described herein or a pharmaceutical composition described herein, thereby treating the disorder. 
     In any of the aspects herein, e.g., the compositions and methods above, any of the embodiments herein (e.g., below) may apply. 
     In some embodiments, the coding strand of human VEGF-A has the sequence of SEQ ID NO: 1. In some embodiments, the non-coding strand of human VEGF-A has the sequence of SEQ ID NO: 2. 
     In some embodiments, the sense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, or 1, 2, or 3 mismatches, of the corresponding portion of the nucleotide sequence of SEQ ID NO: 1. 
     In some embodiments, the dsRNA agent comprises a sense strand and an antisense strand, wherein the antisense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of nucleotide sequence of SEQ ID NO: 2 such that the sense strand is complementary to the at least 17 contiguous nucleotides in the antisense strand. In some embodiments, the sense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides, with 0, or 1, 2, or 3 mismatches, of the corresponding portion of the nucleotide sequence of SEQ ID NO: 1. 
     In some embodiments, the dsRNA agent comprises a sense strand and an antisense strand, wherein the antisense strand comprises a nucleotide sequence comprising at least 19 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of nucleotide sequence of SEQ ID NO: 2 such that the sense strand is complementary to the at least 19 contiguous nucleotides in the antisense strand. In some embodiments, the sense strand comprises a nucleotide sequence comprising at least 19 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of the corresponding portion of the nucleotide sequence of SEQ ID NO: 1. 
     In some embodiments, the dsRNA agent comprises a sense strand and an antisense strand, wherein the antisense strand comprises a nucleotide sequence comprising at least 21 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of nucleotide sequence of SEQ ID NO: 2 such that the sense strand is complementary to the at least 21 contiguous nucleotides in the antisense strand. In some embodiments, the sense strand comprises a nucleotide sequence comprising at least 21 contiguous nucleotides, with 0, or 1, 2, or 3 mismatches, of the corresponding portion of the nucleotide sequence of SEQ ID NO: 1. 
     In some embodiments, the portion of the sense strand is a portion within nucleotides 1855-1875, 1858-1878, 2178-2198, 2181-2201, 2944-2964, 2946-2966, 2952-2972, 3361-3381, or 3362-3382 of SEQ ID NO: 1. In some embodiments, the portion of the sense strand is a portion corresponding to SEQ ID NO: 4200, 4201, 4202, 4203, 4204, 4205, 4206, 4207, 4208, 4209, 4210, or 4211. 
     In some embodiments, the portion of the sense strand is a portion within a sense strand in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. 
     In some embodiments, the portion of the antisense strand is a portion within an antisense strand in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. 
     In some embodiments, the antisense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from one of the antisense sequences listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. In some embodiments, the sense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from a sense sequence listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B that corresponds to the antisense sequence. 
     In some embodiments, the antisense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from one of the antisense sequences listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. In some embodiments, the sense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from a sense sequence listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B that corresponds to the antisense sequence. 
     In some embodiments, the antisense strand comprises a nucleotide sequence comprising at least 19 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from one of the antisense sequences listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. In some embodiments, the sense strand comprises a nucleotide sequence comprising at least 19 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from a sense sequence listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A 8B, 10A, 10B, 12, 13, 14, 18A and 18B that corresponds to the antisense sequence. 
     In some embodiments, the antisense strand comprises a nucleotide sequence comprising at least 21 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from one of the antisense sequences listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. In some embodiments, the sense strand comprises a nucleotide sequence comprising at least 21 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from a sense sequence listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A 8B, 10A, 10B, 12, 13, 14, 18A and 18B that corresponds to the antisense sequence. 
     In some embodiments, the sense strand of the dsRNA agent is at least 23 nucleotides in length, e.g., 23-30 nucleotides in length. 
     In some embodiments, the portion of the sense strand is a portion within a sense strand from a duplex chosen from AD-1020574 (CGACAGAACAGUCCUUAAUCA (SEQ ID NO: 4200)), AD-901094 (CAGAACAGUCCUUAAUCCAGA (SEQ ID NO: 4201)), AD-1020575 (CAGAACAGUCCUUAAUCCAGA (SEQ ID NO: 4202)), AD-901100 (AACAGUGCUAAUGUUAUUGGA (SEQ ID NO: 4203)), AD-901101 (AGUGCUAAUGUUAUUGGUGUA (SEQ ID NO: 4204)), AD-901113 (GAGAAAGUGUUUUAUAUACGA (SEQ ID NO: 4205)), AD-901123 (AAAAUAGACAUUGCUAUUCUA (SEQ ID NO: 4206)), AD-901124 (AAAUAGACAUUGCUAUUCUGA (SEQ ID NO: 4207)), AD-901158 (GAAAGUGUUUUAUAUACGGUA (SEQ ID NO: 4208)), AD-901159 (GUUUUAUAUACGGUACUUAUA (SEQ ID NO: 4209)), AD-1020573 (AGUGCUAATGTUAUUGGUGUA (SEQ ID NO: 4210)), or AD-1023143 (AAAAUAGACATUGCUAUUCUA (SEQ ID NO: 4211)). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 2A, 3A, 4A, or Table 18A. 
     In some embodiments, the portion of the sense strand is a sense strand chosen from the sense strands of AD-1020574 (CGACAGAACAGUCCUUAAUCA (SEQ ID NO: 4200)), AD-901094 (CAGAACAGUCCUUAAUCCAGA (SEQ ID NO: 4201)), AD-1020575 (CAGAACAGUCCUUAAUCCAGA (SEQ ID NO: 4202)), AD-901100 (AACAGUGCUAAUGUUAUUGGA (SEQ ID NO: 4203)), AD-901101 (AGUGCUAAUGUUAUUGGUGUA (SEQ ID NO: 4204)), AD-901113 (GAGAAAGUGUUUUAUAUACGA (SEQ ID NO: 4205)), AD-901123 (AAAAUAGACAUUGCUAUUCUA (SEQ ID NO: 4206)), AD-901124 (AAAUAGACAUUGCUAUUCUGA (SEQ ID NO: 4207)), AD-901158 (GAAAGUGUUUUAUAUACGGUA (SEQ ID NO: 4208)), AD-901159 (GUUUUAUAUACGGUACUUAUA (SEQ ID NO: 4209)), AD-1020573 (AGUGCUAATGTUAUUGGUGUA (SEQ ID NO: 4210)), or AD-1023143 (AAAAUAGACATUGCUAUUCUA (SEQ ID NO: 4211)). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 2A, 3A, 4A, or Table 18A. 
     In some embodiments, the portion of the sense strand is a portion within a sense strand from a duplex chosen from AD-953374 (SEQ ID NO: 813), AD-953504 (SEQ ID NO: 1297), AD-953481 (SEQ ID NO: 1298), AD-953351 (SEQ ID NO: 800), AD-901356 (SEQ ID NO: 261), AD-953344 (SEQ ID NO: 787), AD-901355 (SEQ ID NO: 262), AD-953410 (SEQ ID NO: 845), AD-953363 (SEQ ID NO: 779), AD-953411 (SEQ ID NO: 844), AD-953350 (SEQ ID NO: 784), or AD-953375 (SEQ ID NO: 790). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 2A, 3A, 4A, or Table 18A. 
     In some embodiments, the portion of the sense strand is a sense strand chosen from the sense strands of AD-953374 (SEQ ID NO: 813), AD-953504 (SEQ ID NO: 1297), AD-953481 (SEQ ID NO: 1298), AD-953351 (SEQ ID NO: 800), AD-901356 (SEQ ID NO: 261), AD-953344 (SEQ ID NO: 787), AD-901355 (SEQ ID NO: 262), AD-953410 (SEQ ID NO: 845), AD-953363 (SEQ ID NO: 779), AD-953411 (SEQ ID NO: 844), AD-953350 (SEQ ID NO: 784), or AD-953375 (SEQ ID NO: 790). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 2A, 3A, 4A, or Table 18A. 
     In some embodiments, the portion of the antisense strand is a portion within an antisense strand from a duplex chosen from AD-1020574 (UGAUUAAGGACUGUUCUGUCGAU (SEQ ID NO: 4212)), AD-901094 (UCUGGAUUAAGGACUGUUCUGUC (SEQ ID NO: 4213)), AD-1020575 (UCUGGATUAAGGACUGUUCUGUC (SEQ ID NO: 4214)), AD-901100 (UCCAAUAACAUUAGCACUGUUAA (SEQ ID NO: 4215)), AD-901101 (UACACCAAUAACAUUAGCACUGU (SEQ ID NO: 4216)), AD-901113 (UCGUAUAUAAAACACUUUCUCUU (SEQ ID NO: 4217)), AD-901123 (UAGAAUAGCAAUGUCUAUUUUAU (SEQ ID NO: 4218)), AD-901124 (UCAGAAUAGCAAUGUCUAUUUUA (SEQ ID NO: 4219)), AD-901158 (UACCGUAUAUAAAACACUUUCUC (SEQ ID NO: 4220)), AD-901159 (UAUAAGUACCGUAUAUAAAACAC (SEQ ID NO: 4221)), AD-1020573 (UACACCAAUAACATUAGCACUGU (SEQ ID NO: 4222)), or AD-1023143 (UAGAAUAGCAATGTCTAUUUUAU (SEQ ID NO: 4223)). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 2A, 3A, 4A, or Table 18A. 
     In some embodiments, the portion of the antisense strand is an antisense strand chosen from the antisense strands of AD-1020574 (UGAUUAAGGACUGUUCUGUCGAU (SEQ ID NO: 4212)), AD-901094 (UCUGGAUUAAGGACUGUUCUGUC (SEQ ID NO: 4213)), AD-1020575 (UCUGGATUAAGGACUGUUCUGUC (SEQ ID NO: 4214)), AD-901100 (UCCAAUAACAUUAGCACUGUUAA (SEQ ID NO: 4215)), AD-901101 (UACACCAAUAACAUUAGCACUGU (SEQ ID NO: 4216)), AD-901113 (UCGUAUAUAAAACACUUUCUCUU (SEQ ID NO: 4217)), AD-901123 (UAGAAUAGCAAUGUCUAUUUUAU (SEQ ID NO: 4218)), AD-901124 (UCAGAAUAGCAAUGUCUAUUUUA (SEQ ID NO: 4219)), AD-901158 (UACCGUAUAUAAAACACUUUCUC (SEQ ID NO: 4220)), AD-901159 (UAUAAGUACCGUAUAUAAAACAC (SEQ ID NO: 4221)), AD-1020573 (UACACCAAUAACATUAGCACUGU (SEQ ID NO: 4222)), or AD-1023143 (UAGAAUAGCAATGTCTAUUUUAU (SEQ ID NO: 4223)). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 2A, 3A, 4A, or Table 18A. 
     In some embodiments, the portion of the antisense strand is a portion within an antisense strand from a duplex chosen from AD-953374 (SEQ ID NO: 943), AD-953504 (SEQ ID NO: 1427), AD-953481 (SEQ ID NO: 1428), AD-953351 (SEQ ID NO: 930), AD-901356 (SEQ ID NO: 390), AD-953344 (SEQ ID NO: 917), AD-901355 (SEQ ID NO: 391), AD-953410 (SEQ ID NO: 975), AD-953363 (SEQ ID NO: 909), AD-953411 (SEQ ID NO: 974), AD-953350 (SEQ ID NO: 914), or AD-953375 (SEQ ID NO: 920). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 2A, 3A, 4A, or Table 18A. 
     In some embodiments, the portion of the antisense strand is an antisense strand chosen from the antisense strands of AD-953374 (SEQ ID NO: 943), AD-953504 (SEQ ID NO: 1427), AD-953481 (SEQ ID NO: 1428), AD-953351 (SEQ ID NO: 930), AD-901356 (SEQ ID NO: 390), AD-953344 (SEQ ID NO: 917), AD-901355 (SEQ ID NO: 391), AD-953410 (SEQ ID NO: 975), AD-953363 (SEQ ID NO: 909), AD-953411 (SEQ ID NO: 974), AD-953350 (SEQ ID NO: 914), or AD-953375 (SEQ ID NO: 920). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 2A, 3A, 4A, or Table 18A. 
     In some embodiments, the sense strand and the antisense strand of the dsRNA agent comprise nucleotide sequences of the paired sense strand and antisense strand of a duplex selected from AD-1020574 (SEQ ID NO: 4200 and 4212), AD-901094 (SEQ ID NO: 4201 and 4213), AD-1020575 (SEQ ID NO: 4202 and 4214), AD-901100 (SEQ ID NO: 4203 and 4215), AD-901101 (SEQ ID NO: 4204 and 4216), AD-901113 (SEQ ID NO: 4205 and 4217), AD-901123 (SEQ ID NO: 4206 and 4218), AD-901124 (SEQ ID NO: 4207 and 4219), AD-901158 (SEQ ID NO: 4208 and 4220), AD-901159 (SEQ ID NO: 4209 and 4221), AD-1020573 (SEQ ID NO: 4210 and 4222), or AD-1023143 (SEQ ID NO: 4211 and 4223). In some embodiments, the sense strand and antisense strand comprises the corresponding chemically modified sense sequence and antisense sequence provided in Tables 2A, 3A, 4A, or Table 18A. 
     In some embodiments, the sense strand and the antisense strand of the dsRNA agent comprise nucleotide sequences of the paired sense strand and antisense strand of a duplex selected from AD-953374 (SEQ ID NO: 813 and 943), AD-953504 (SEQ ID NO: 1297 and 1427), AD-953481 (SEQ ID NO: 1298 and 1428), AD-953351 (SEQ ID NO: 800 and 930), AD-901356 (SEQ ID NO: 261 and 390), AD-953344 (SEQ ID NO: 787 and 917), AD-901355 (SEQ ID NO: 262 and 391), AD-953410 (SEQ ID NO: 845 and 975), AD-953363 (SEQ ID NO: 779 and 909), AD-953411 (SEQ ID NO: 844 and 974), AD-953350 (SEQ ID NO: 784 and 914), or AD-953375 (SEQ ID NO: 790 and 920). In some embodiments, the sense strand and antisense strand comprises the corresponding chemically modified sense sequence and antisense sequence provided in Tables 2A, 3A, 4A, or Table 18A. 
     In some embodiments, at least one of the sense strand and the antisense strand is conjugated to one or more lipophilic moieties. In some embodiments, the lipophilic moiety is conjugated to one or more positions in the double stranded region of the dsRNA agent. In some embodiments, the lipophilic moiety is conjugated via a linker or carrier. In some embodiments, lipophilicity of the lipophilic moiety, measured by log Kow, exceeds 0. In some embodiments, In some embodiments, the hydrophobicity of the double-stranded RNAi agent, measured by the unbound fraction in a plasma protein binding assay of the double-stranded RNAi agent, exceeds 0.2. In some embodiments, the plasma protein binding assay is an electrophoretic mobility shift assay using human serum albumin protein. 
     In some embodiments, the dsRNA agent comprises at least one modified nucleotide. In some embodiments, no more than five of the sense strand nucleotides and not more than five of the nucleotides of the antisense strand are unmodified nucleotides. In some embodiments, all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand comprise a modification. 
     In some embodiments, at least one of the modified nucleotides is selected from the group consisting of a deoxy-nucleotide, a 3′-terminal deoxy-thymine (dT) nucleotide, a 2′-O-methyl modified nucleotide, a 2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an unlocked nucleotide, a conformationally restricted nucleotide, a constrained ethyl nucleotide, an abasic nucleotide, a 2′-amino-modified nucleotide, a 2′-O-allyl-modified nucleotide, 2′-C-alkyl-modified nucleotide, a 2′-methoxyethyl modified nucleotide, a 2′-O-alkyl-modified nucleotide, a morpholino nucleotide, a phosphoramidate, a non-natural base comprising nucleotide, a tetrahydropyran modified nucleotide, a 1,5-anhydrohexitol modified nucleotide, a cyclohexenyl modified nucleotide, a nucleotide comprising a phosphorothioate group, a nucleotide comprising a methylphosphonate group, a nucleotide comprising a 5′-phosphate, a nucleotide comprising a 5′-phosphate mimic, a glycol modified nucleotide, and a 2-O—(N-methylacetamide) modified nucleotide; and combinations thereof. In some embodiments, no more than five of the sense strand nucleotides and not more than five of the nucleotides of the antisense strand include modifications other than 2′-O-methyl modified nucleotide, a 2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, unlocked nucleic acids (UNA) or glycerol nucleic acid (GNA). 
     In some embodiments, the dsRNA comprises a non-nucleotide spacer (wherein optionally the non-nucleotide spacer comprises a C3-C6 alkyl) between two of the contiguous nucleotides of the sense strand or between two of the contiguous nucleotides of the antisense strand. 
     In some embodiments, each strand is no more than 30 nucleotides in length. In some embodiments, at least one strand comprises a 3′ overhang of at least 1 nucleotide. In some embodiments, at least one strand comprises a 3′ overhang of at least 2 nucleotides. In some embodiments, at least one strand comprises a 3′ overhang of 2 nucleotides. 
     In some embodiments, the double stranded region is 15-30 nucleotide pairs in length. In some embodiments, the double stranded region is 17-23 nucleotide pairs in length. In some embodiments, the double stranded region is 17-25 nucleotide pairs in length. In some embodiments, the double stranded region is 23-27 nucleotide pairs in length. In some embodiments, the double stranded region is 19-21 nucleotide pairs in length. In some embodiments, the double stranded region is 21-23 nucleotide pairs in length. In some embodiments, each strand has 19-30 nucleotides. In some embodiments, each strand has 19-23 nucleotides. In some embodiments, each strand has 21-23 nucleotides. 
     In some embodiments, the agent comprises at least one phosphorothioate or methylphosphonate internucleotide linkage. In some embodiments, the phosphorothioate or methylphosphonate internucleotide linkage is at the 3′-terminus of one strand. In some embodiments, the strand is the antisense strand. In some embodiments, the strand is the sense strand. 
     In some embodiments, the phosphorothioate or methylphosphonate internucleotide linkage is at the 5′-terminus of one strand. In some embodiments, the strand is the antisense strand. In some embodiments, the strand is the sense strand. 
     In some embodiments, each of the 5′- and 3′-terminus of one strand comprises a phosphorothioate or methylphosphonate internucleotide linkage. In some embodiments, the strand is the antisense strand. 
     In some embodiments, the base pair at the 1 position of the 5′-end of the antisense strand of the duplex is an AU base pair. 
     In some embodiments, the sense strand has a total of 21 nucleotides and the antisense strand has a total of 23 nucleotides. 
     In some embodiments, one or more lipophilic moieties are conjugated to one or more internal positions on at least one strand. In some embodiments, the one or more lipophilic moieties are conjugated to one or more internal positions on at least one strand via a linker or carrier. 
     In some embodiments, the internal positions include all positions except the terminal two positions from each end of the at least one strand. In some embodiments, the internal positions include all positions except the terminal three positions from each end of the at least one strand. In some embodiments, the internal positions exclude a cleavage site region of the sense strand. In some embodiments, the internal positions include all positions except positions 9-12, counting from the 5′-end of the sense strand. In some embodiments, the internal positions include all positions except positions 11-13, counting from the 3′-end of the sense strand. In some embodiments, the internal positions exclude a cleavage site region of the antisense strand. In some embodiments, the internal positions include all positions except positions 12-14, counting from the 5′-end of the antisense strand. In some embodiments, the internal positions include all positions except positions 11-13 on the sense strand, counting from the 3′-end, and positions 12-14 on the antisense strand, counting from the 5′-end. 
     In some embodiments, the one or more lipophilic moieties are conjugated to one or more of the internal positions selected from the group consisting of positions 4-8 and 13-18 on the sense strand, and positions 6-10 and 15-18 on the antisense strand, counting from the 5′end of each strand. In some embodiments, the one or more lipophilic moieties are conjugated to one or more of the internal positions selected from the group consisting of positions 5, 6, 7, 15, and 17 on the sense strand, and positions 15 and 17 on the antisense strand, counting from the 5′-end of each strand. 
     In some embodiments, the positions in the double stranded region exclude a cleavage site region of the sense strand. 
     In some embodiments, the sense strand is 21 nucleotides in length, the antisense strand is 23 nucleotides in length, and the lipophilic moiety is conjugated to position 21, position 20, position 15, position 1, position 7, position 6, or position 2 of the sense strand or position 16 of the antisense strand. In some embodiments, the lipophilic moiety is conjugated to position 21, position 20, position 15, position 1, or position 7 of the sense strand. In some embodiments, the lipophilic moiety is conjugated to position 21, position 20, or position 15 of the sense strand. In some embodiments, the lipophilic moiety is conjugated to position 20 or position 15 of the sense strand. In some embodiments, the lipophilic moiety is conjugated to position 16 of the antisense strand. In some embodiments, the lipophilic moiety is conjugated to position 6, counting from the 5′-end of the sense strand. 
     In some embodiments, the lipophilic moiety is an aliphatic, alicyclic, or polyalicyclic compound. In some embodiments, the lipophilic moiety is selected from the group consisting of lipid, cholesterol, retinoic acid, cholic acid, adamantane acetic acid, 1-pyrene butyric acid, dihydrotestosterone, 1,3-bis-O(hexadecyl)glycerol, geranyloxyhexyanol, hexadecylglycerol, borneol, menthol, 1,3-propanediol, heptadecyl group, palmitic acid, myristic acid, O3-(oleoyl)lithocholic acid, O3-(oleoyl)cholenic acid, dimethoxytrityl, or phenoxazine. In some embodiments, the lipophilic moiety contains a saturated or unsaturated C4-C30 hydrocarbon chain, and an optional functional group selected from the group consisting of hydroxyl, amine, carboxylic acid, sulfonate, phosphate, thiol, azide, and alkyne. In some embodiments, the lipophilic moiety contains a saturated or unsaturated C6-C18 hydrocarbon chain. In some embodiments, the lipophilic moiety contains a saturated or unsaturated C16 hydrocarbon chain. 
     In some embodiments, the lipophilic moiety is conjugated via a carrier that replaces one or more nucleotide(s) in the internal position(s) or the double stranded region. In some embodiments, the carrier is a cyclic group selected from the group consisting of pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, [1,3]dioxolanyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, quinoxalinyl, pyridazinonyl, tetrahydrofuranyl, and decalinyl; or is an acyclic moiety based on a serinol backbone or a diethanolamine backbone. 
     In some embodiments, the lipophilic moiety is conjugated to the double-stranded iRNA agent via a linker containing an ether, thioether, urea, carbonate, amine, amide, maleimide-thioether, disulfide, phosphodiester, sulfonamide linkage, a product of a click reaction, or carbamate. 
     In some embodiments, the lipophilic moiety is conjugated to a nucleobase, sugar moiety, or internucleosidic linkage. 
     In some embodiments, the lipophilic moiety or targeting ligand is conjugated via a bio-cleavable linker selected from the group consisting of DNA, RNA, disulfide, amide, functionalized monosaccharides or oligosaccharides of galactosamine, glucosamine, glucose, galactose, mannose, and combinations thereof. 
     In some embodiments, the 3′ end of the sense strand is protected via an end cap which is a cyclic group having an amine, said cyclic group being selected from the group consisting of pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, [1,3]dioxolanyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, quinoxalinyl, pyridazinonyl, tetrahydrofuranyl, and decalinyl. 
     In some embodiments, the dsRNA agent further comprises a targeting ligand, e.g., a ligand that targets an ocular tissue or a liver tissue. In some embodiments, the ocular tissue is a retinal pigment epithelium (RPE) or choroid tissue, e.g., a choroid vessel. 
     In some embodiments, the ligand is conjugated to the sense strand. In some embodiments, the ligand is conjugated to the 3′ end or the 5′ end of the sense strand. In some embodiments, the ligand is conjugated to the 3′ end of the sense strand. 
     In some embodiments, the ligand comprises N-acetylgalactosamine (GalNAc). In some embodiments, the targeting ligand comprises one or more GalNAc conjugates or one or more GalNAc derivatives. In some embodiments, the ligand is one or more GalNAc conjugates or one or more GalNAc derivatives are attached through a monovalent linker, or a bivalent, trivalent, or tetravalent branched linker. In some embodiments, the ligand is 
     
       
         
         
             
             
         
       
     
     In some embodiments, the dsRNA agent is conjugated to the ligand as shown in the following schematic 
     
       
         
         
             
             
         
       
     
     wherein X is O or S. In some embodiments, the X is O. 
     In some embodiments, the dsRNA agent further comprises a terminal, chiral modification occurring at the first internucleotide linkage at the 3′ end of the antisense strand, having the linkage phosphorus atom in Sp configuration, a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, and a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the sense strand, having the linkage phosphorus atom in either Rp configuration or Sp configuration. 
     In some embodiments, the dsRNA agent further comprises a terminal, chiral modification occurring at the first and second internucleotide linkages at the 3′ end of the antisense strand, having the linkage phosphorus atom in Sp configuration, a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, and a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the sense strand, having the linkage phosphorus atom in either Rp or Sp configuration. 
     In some embodiments, the dsRNA agent further comprises a terminal, chiral modification occurring at the first, second and third internucleotide linkages at the 3′ end of the antisense strand, having the linkage phosphorus atom in Sp configuration, a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, and a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the sense strand, having the linkage phosphorus atom in either Rp or Sp configuration. 
     In some embodiments, the dsRNA agent further comprises a terminal, chiral modification occurring at the first, and second internucleotide linkages at the 3′ end of the antisense strand, having the linkage phosphorus atom in Sp configuration, a terminal, chiral modification occurring at the third internucleotide linkages at the 3′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, and a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the sense strand, having the linkage phosphorus atom in either Rp or Sp configuration. 
     In some embodiments, the dsRNA agent further comprises a terminal, chiral modification occurring at the first, and second internucleotide linkages at the 3′ end of the antisense strand, having the linkage phosphorus atom in Sp configuration, a terminal, chiral modification occurring at the first, and second internucleotide linkages at the 5′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, and a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the sense strand, having the linkage phosphorus atom in either Rp or Sp configuration. 
     In some embodiments, the dsRNA agent further comprises a phosphate or phosphate mimic at the 5′-end of the antisense strand. In some embodiments, the phosphate mimic is a 5′-vinyl phosphonate (VP). 
     In some embodiments, a cell described herein, e.g., a human cell, was produced by a process comprising contacting a human cell with the dsRNA agent described herein. 
     In some embodiments, a pharmaceutical composition described herein comprises the dsRNA agent and a lipid formulation. 
     In some embodiments (e.g., embodiments of the methods described herein), the cell is within a subject. In some embodiments, the subject is a human. In some embodiments, the level of VEGF-A mRNA is inhibited by at least 50%. In some embodiments, the level of VEGF-A protein is inhibited by at least 50%. In some embodiments, the expression of VEGF-A is inhibited by at least 50%. In some embodiments, inhibiting expression of VEGF-A decreases the VEGF-A protein level in a biological sample (e.g., an aqueous ocular fluid sample) from the subject by at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%. In some embodiments, inhibiting expression of VEGF-A gene decreases the VEGF-A mRNA level in a biological sample (e.g., an aqueous ocular fluid sample) from the subject by at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%. 
     In some embodiments, the subject has been diagnosed with a VEGF-A-associated disorder. In some embodiments, the subject meets at least one diagnostic criterion for a VEGF-A-associated disorder. In some embodiments, the VEGF-A associated disorder is wet age-related macular degeneration (wet AMD), diabetic retinopathy (DR), diabetic macular edema (DME), retinal vein occlusion (RVO), macular edema following retinal vein occlusion (MEfRVO), retinopathy of prematurity (ROP), or myopic choroidal neovascularization (mCNV). In some embodiments, the VEGF-A associated disorder is macular edema, e.g., diabetic macular edema. 
     In some embodiments, the ocular cell or tissue is RPE, a retinal cell, an astrocyte, a pericyte, a Müller cell, a ganglion cell, an endothelial cell, a photoreceptor cell, a retinal blood vessel (e.g., including endothelial cells and vascular smooth muscle cells), or choroid tissue, e.g., a choroid vessel. 
     In some embodiments, the VEGF-A-associated disorder is an angiogenic ocular disorder. In some embodiments, the angiogenic ocular disorder is caused by or associated with the growth or proliferation of blood vessels. In some embodiments, the angiogenic ocular disorder is caused by or associated with ocular neovascularization. In some embodiments, the angiogenic ocular disorder is AMD, DR, DME, RVO, MEfRVO, ROP, or mCNV. 
     In some embodiments, treating comprises amelioration of at least one sign or symptom of the disorder. In some embodiments, the at least one sign or symptom includes a measure of one or more of angiogenesis, choroidal neovascularization, ocular inflammation, visual acuity, or presence, level, or activity of VEGF-A (e.g., VEGF-A gene, VEGF-A mRNA, or VEGF-A protein). 
     In some embodiments, a level of the VEGF-A that is higher than a reference level is indicative that the subject has an angiogenic ocular disorder. In some embodiments, treating comprises prevention of progression of the disorder. In some embodiments, the treating comprises one or more of (a) inhibiting angiogenesis; (b) inhibiting or reducing the expression or activity of VEGF-A; (c) inhibiting choroidal neovascularization; (d) inhibiting growth of new blood vessels in the choriocapillaris; (e) reducing retinal thickness; (f) increasing visual acuity; or (g) reducing intraocular inflammation. 
     In some embodiments, the treating results in at least a 30% mean reduction from baseline of VEGF-A mRNA in the retina, RPE, a retinal blood vessel (e.g., including endothelial cells and vascular smooth muscle cells), or choroid tissue, e.g., a choroid vessel. In some embodiments, the treating results in at least a 60% mean reduction from baseline of VEGF-A mRNA in the retina, RPE, a retinal blood vessel (e.g., including endothelial cells and vascular smooth muscle cells), or choroid tissue, e.g., a choroid vessel. In some embodiments, the treating results in at least a 90% mean reduction from baseline of VEGF-A mRNA in the retina, RPE, a retinal blood vessel (e.g., including endothelial cells and vascular smooth muscle cells), or choroid tissue, e.g., a choroid vessel. 
     In some embodiments, after treatment the subject experiences at least an 8-week duration of knockdown following a single dose of dsRNA as assessed by VEGF-A protein in the retina. In some embodiments, treating results in at least a 12-week duration of knockdown following a single dose of dsRNA as assessed by VEGF-A protein in the retina. In some embodiments, treating results in at least a 16-week duration of knockdown following a single dose of dsRNA as assessed by VEGF-A protein in the retina. 
     In some embodiments, the subject is human. 
     In some embodiments, the dsRNA agent is administered at a dose of about 0.01 mg/kg to about 50 mg/kg. 
     In some embodiments, the dsRNA agent is administered to the subject intraocularly. In some embodiments, the intraocular administration comprises intravitreal administration, e.g., intravitreal injection; transscleral administration, e.g., transscleral injection; subconjunctival administration, e.g., subconjunctival injection; retrobulbar administration, e.g., retrobulbar injection; intracameral administration, e.g., intracameral injection, or subretinal administration, e.g., subretinal injection. 
     In some embodiments, the dsRNA agent is administered to the subject intravenously. In some embodiments, the dsRNA agent is administered to the subject topically. 
     In some embodiments, a method described herein further comprises measuring a level of VEGF-A (e.g., VEGF-A gene, VEGF-A mRNA, or VEGF-A protein) in the subject. In some embodiments, measuring the level of VEGF-A in the subject comprises measuring the level of VEGF-A protein in a biological sample from the subject (e.g., an aqueous ocular fluid sample). In some embodiments, a method described herein further comprises performing a blood test, an imaging test, or an aqueous ocular fluid biopsy (e.g., an aqueous humor tap). 
     In some embodiments, a method described herein further measuring level of VEGF-A (e.g., VEGF-A gene, VEGF-A mRNA, or VEGF-A protein) in the subject is performed prior to treatment with the dsRNA agent or the pharmaceutical composition. In some embodiments, upon determination that a subject has a level of VEGF-A that is greater than a reference level, the dsRNA agent or the pharmaceutical composition is administered to the subject. In some embodiments, measuring level of VEGF-A in the subject is performed after treatment with the dsRNA agent or the pharmaceutical composition. 
     In some embodiments, a method described herein further comprises treating the subject with a therapy suitable for treatment or prevention of a VEGF-A-associated disorder, e.g., wherein the therapy comprises photodynamic therapy, photocoagulation therapy, or vitrectomy. In some embodiments, a method described herein further comprises administering to the subject an additional agent suitable for treatment or prevention of a VEGF-A-associated disorder. In some embodiments, the additional agent comprises a steroid, a non-steroidal anti-inflammatory agent, or an anti-VEGF-A agent. 
     In some embodiments, the anti-VEGF-A agent comprises a fusion protein or an anti-VEGF-A antibody or antigen-binding fragment thereof (e.g., an anti-VEGF-A antibody molecule). 
     All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. 
     The details of various embodiments of the disclosure are set forth in the description below. Other features, objects, and advantages of the disclosure will be apparent from the description and the drawings, and from the claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1 A  depicts the sequences and chemistry of the exemplary VEGF-A siRNAs including AD-64228 (SEQ ID NO: 4162 and 4163), AD-953374 (SEQ ID NO: 553 and 683), AD-953504 (SEQ ID NO: 1037 and 1167), AD-953336 (SEQ ID NO: 518 and 648), AD-953337 (SEQ ID NO: 522 and 652), AD-901376 (SEQ ID NO: 4157 and 131), AD-953364 (SEQ ID NO: 567 and 697).  FIG.  1 B  depicts the sequences and chemistry of the exemplary VEGF-A siRNAs including AD-953340 (SEQ ID NO: 517 and 647), AD-953351 (SEQ ID NO: 540 and 670), AD-953342 (SEQ ID NO: 523 and 653), AD-953308 (SEQ ID NO: 579 and 709), AD-953344 (SEQ ID NO: 527 and 657), AD-953339 (SEQ ID NO: 528 and 658), and AD-953363 (SEQ ID NO: 519 and 649). For each siRNA, “F” is the “2′-fluoro” modification, OMe is a methoxy group, GNA refers to a glycol nucleic acid, “DNA” refers to a DNA base, 2-C16 refers to the targeting ligand, and PS refers to the phosphorothioate linkage. 
         FIG.  2    is a graph depicting the percent VEGF-A message remaining normalized to PBS in mice on day 14 post-treatment with the exemplary duplexes indicated on the X-axis (from left to right: PBS control, naïve control, AAV positive control (AD-64228), AD-901376.2, AD-953308.2, AD-953336.2, AD-953337.2, AD-953339.2, AD-953340.2, AD-953342.2, AD-953344.2, AD-953351.2, AD-953363.2, AD-953364.2, AD-953374.2, AD-953504.2). 
         FIG.  3 A  depicts the sequences and chemistry of the exemplary VEGF-A siRNAs including AD-901349 (SEQ ID NO: 4156 and 130), AD-953481 (SEQ ID NO: 1038 and 1168), AD-901356 (SEQ ID NO: 3 and 132), AD-901355 (SEQ ID NO: 4 and 133), AD-953365 (SEQ ID NO: 552 and 682), AD-953410 (SEQ ID NO: 585 and 715), AD-953411 (SEQ ID NO: 584 and 714).  FIG.  3 B  depicts the sequences and chemistry of the exemplary VEGF-A siRNAs including AD-953338 (SEQ ID NO: 520 and 650), AD-953350 (SEQ ID NO: 524 and 654), AD-953375 (SEQ ID NO: 530 and 660), AD-953341 (SEQ ID NO: 532 and 662), AD-953370 (SEQ ID NO: 533 and 663), AD-953386 (SEQ ID NO: 541 and 671), AD-64958 (SEQ ID NO: 5003 and 5004). For each siRNA, “F” is the “2′-fluoro” modification, OMe is a methoxy group, GNA refers to a glycol nucleic acid, 2-C16 refers to the targeting ligand, and PS refers to the phosphorothioate linkage. 
         FIG.  4    is a graph depicting the percent VEGF-A message remaining normalized to PBS in mice on day 14 post-treatment with the exemplary duplexes indicated on the X-axis (from left to right: PBS control, naïve control, AD-901349.1, AD-953481.1, AD-901356.1, AD-901355.1, AD-953365.1, AD-953410.1, AD-953411.1, AD-953338.1, AD-953350.1, AD-953375.1, AD-953341.1, AD-953370.1, AD-953386.1, and AD-64958 (ELF8 TTR control). 
         FIG.  5 A  depicts the sequences and chemistry of the exemplary VEGF-A siRNAs including AD-1397050 (SEQ ID NO: 5005 and 3936), AD-1397051 (SEQ ID NO: 5006 and 3918), AD-1397052 (SEQ ID NO: 10 and 3957), AD-1397053 (SEQ ID NO: 5007 and 3924), AD-1397054 (SEQ ID NO: 5008 and 2640), AD-1397055 (SEQ ID NO: 5009 and 2775).  FIG.  5 B  depicts the sequences and chemistry of the exemplary VEGF-A siRNAs including AD-1397056 (SEQ ID NO: 5010 and 2776), AD-1397058 (SEQ ID NO: 5011 and 3953), AD-1397059 (SEQ ID NO: 5012 and 3889), AD-1397060 (SEQ ID NO: 5013 and 3902), AD-1397061 (SEQ ID NO: 5014 and 3932), and AD-1397062 (SEQ ID NO: 5015 and 3944).  FIG.  5 C  depicts the sequences and chemistry of the exemplary VEGF-A siRNAs including AD-1397064 (SEQ ID NO: 5016 and 3938), AD-1397065 (SEQ ID NO: 5017 and 3965), AD-1397066 (SEQ ID NO: 5018 and 3962), AD-1397067 (SEQ ID NO: 5019 and 3971), AD-1397068 (SEQ ID NO: 1044 and 3901), AD-1397069 (SEQ ID NO: 5020 and 3928), and AD-64958 (SEQ ID NO: 5003 and 5004). For each siRNA, “F” is the “2′-fluoro” modification, OMe is a methoxy group, GNA refers to a glycol nucleic acid, “(A2p)” refers to adenosine 2′-phosphate, “(C2p)” refers to cytosine 2′-phosphate, “(U2p)” refers to uracil 2′-phosphate, “DNA” refers to a DNA base, 2-C16 refers to the targeting ligand, and PS refers to the phosphorothioate linkage. 
         FIG.  6    is a graph depicting the percent VEGF-A message remaining normalized to PBS in mice on day 14 post-treatment with the exemplary duplexes indicated on the X-axis (from left to right: PBS control, naïve control, AD-1397050.2, AD-1397051.2, AD-1397052.2, AD-1397053.2, AD-1397054.2, AD-1397055.2, AD-1397056.2, AD-1397058.2, AD-1397059.2, AD-1397060.2, AD-1397061.2, AD-1397062.2, AD-1397064.2, AD-1397065.2, AD-1397066.2, AD-1397067.2, AD-1397068.2, AD-1397069.2, and AD-64958.100. 
     
    
    
     DETAILED DESCRIPTION 
     iRNA directs the sequence-specific degradation of mRNA through a process known as RNA interference (RNAi). Described herein are iRNAs and methods of using them for modulating (e.g., inhibiting) the expression of VEGF-A. Also provided are compositions and methods for treatment of disorders related to VEGF-A expression, such as an angiogenic ocular disorder (e.g., wet age-related macular degeneration (wet AMD), diabetic retinopathy (DR), diabetic macular edema (DME), retinal vein occlusion (RVO), macular edema following retinal vein occlusion (MEfRVO), retinopathy of prematurity (ROP), or myopic choroidal neovascularization (mCNV)). 
     Human VEGF-A is a dimeric glycoprotein of approximately 40 kDa and is a potent endothelial cell mitogen with a role in proliferation, migration, and tube formation leading to angiogenic growth of new blood vessels. VEGF-A is typically expressed and secreted by a variety of tissues including the retinal pigmented epithelium (RPE), retinal tissues, astrocytes, Müller cells, photoreceptor cells, endothelial cells (e.g., vascular endothelial cells), retinal blood vessels (e.g., including endothelial cells and vascular smooth muscle cells), choroid tissue, e.g., a choroid vessel, and ganglion cells. Several angiogenic ocular disorders are associated with pathological angiogenesis, including wet AMD, DR, DME, RVO, MEfRVO, ROP, and mCNV. Without wishing to be bound by theory, VEGF-A may exacerbate the pathogenesis of angiogenic ocular disorders, e.g., by increasing vascular permeability and promoting neovascularization. 
     The following description discloses how to make and use compositions containing iRNAs to modulate (e.g., inhibit) the expression of VEGF-A, as well as compositions and methods for treating disorders related to expression of VEGF-A. 
     In some aspects, pharmaceutical compositions containing VEGF-A iRNA and a pharmaceutically acceptable carrier, methods of using the compositions to inhibit expression of VEGF-A, and methods of using the pharmaceutical compositions to treat disorders related to expression of VEGF-A (e.g., angiogenic ocular disorders) are featured herein. 
     I. Definitions 
     For convenience, the meaning of certain terms and phrases used in the specification, examples, and appended claims, are provided below. If there is an apparent discrepancy between the usage of a term in other parts of this specification and its definition provided in this section, the definition in this section shall prevail. 
     The term “about” when referring to a number or a numerical range means that the number or numerical range referred to is an approximation within experimental variability (or within statistical experimental error), and thus the number or numerical range may vary from, for example, between 1% and 15% of the stated number or numerical range. 
     The term “at least” prior to a number or series of numbers is understood to include the number adjacent to the term “at least”, and all subsequent numbers or integers that could logically be included, as clear from context. For example, the number of nucleotides in a nucleic acid molecule must be an integer. For example, “at least 17 nucleotides of a 20-nucleotide nucleic acid molecule” means that 17, 18, 19, or 20 nucleotides have the indicated property. When at least is present before a series of numbers or a range, it is understood that “at least” can modify each of the numbers in the series or range. 
     As used herein, “no more than” or “less than” is understood as the value adjacent to the phrase and logical lower values or integers, as logical from context, to zero. For example, a duplex with mismatches to a target site of “no more than 2 nucleotides” has a 2, 1, or 0 mismatches. When “no more than” is present before a series of numbers or a range, it is understood that “no more than” can modify each of the numbers in the series or range. 
     As used herein, “up to” as in “up to 10” is understood as up to and including 10, i.e., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. 
     Ranges provided herein are understood to include all individual integer values and all subranges within the ranges. 
     The terms “activate,” “enhance,” “up-regulate the expression of,” “increase the expression of,” and the like, in so far as they refer to a VEGF-A gene, herein refer to the at least partial activation of the expression of a VEGF-A gene, as manifested by an increase in the amount of VEGF-A mRNA, which may be isolated from or detected in a first cell or group of cells in which a VEGF-A gene is transcribed and which has or have been treated such that the expression of a VEGF-A gene is increased, as compared to a second cell or group of cells substantially identical to the first cell or group of cells but which has or have not been so treated (control cells). 
     In some embodiments, expression of a VEGF-A gene is activated by at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by administration of an iRNA as described herein. In some embodiments, a VEGF-A gene is activated by at least about 60%, 70%, or 80% by administration of an iRNA featured in the disclosure. In some embodiments, expression of a VEGF-A gene is activated by at least about 85%, 90%, or 95% or more by administration of an iRNA as described herein. In some embodiments, the VEGF-A gene expression is increased by at least 1-fold, at least 2-fold, at least 5-fold, at least 10-fold, at least 50-fold, at least 100-fold, at least 500-fold, at least 1000-fold or more in cells treated with an iRNA as described herein compared to the expression in an untreated cell. Activation of expression by small dsRNAs is described, for example, in Li et al., 2006  Proc. Natl. Acad. Sci. U.S.A.  103:17337-42, and in US2007/0111963 and US2005/226848, each of which is incorporated herein by reference. 
     The terms “silence,” “inhibit expression of,” “down-regulate expression of,” “suppress expression of,” and the like, in so far as they refer to VEGF-A, herein refer to the at least partial suppression of the expression of VEGF-A, as assessed, e.g., based on VEGF-A mRNA expression, VEGF-A protein expression, or another parameter functionally linked to VEGF-A expression. For example, inhibition of VEGF-A expression may be manifested by a reduction of the amount of VEGF-A mRNA which may be isolated from or detected in a first cell or group of cells in which VEGF-A is transcribed and which has or have been treated such that the expression of VEGF-A is inhibited, as compared to a control. The control may be a second cell or group of cells substantially identical to the first cell or group of cells, except that the second cell or group of cells have not been so treated (control cells). The degree of inhibition is usually expressed as a percentage of a control level, e.g., 
     
       
         
           
             
               
                 
                   ( 
                   
                     mRNA 
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                     in 
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                     control 
                     ⁢ 
                         
                     cells 
                   
                   ) 
                 
                 - 
                 
                   ( 
                   
                     mRNA 
                     ⁢ 
                         
                     in 
                     ⁢ 
                         
                     treated 
                     ⁢ 
                         
                     cells 
                   
                   ) 
                 
               
               
                 ( 
                 
                   mRNA 
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                   in 
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                   control 
                   ⁢ 
                       
                   cells 
                 
                 ) 
               
             
             ⁢ 
             •100 
             ⁢ 
             % 
           
         
       
     
     Alternatively, the degree of inhibition may be given in terms of a reduction of a parameter that is functionally linked to VEGF-A expression, e.g., the amount of protein encoded by a VEGF-A gene. The reduction of a parameter functionally linked to VEGF-A expression may similarly be expressed as a percentage of a control level. In principle, VEGF-A silencing may be determined in any cell expressing VEGF-A, either constitutively or by genomic engineering, and by any appropriate assay. 
     For example, in certain instances, expression of VEGF-A is suppressed by at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by administration of an iRNA disclosed herein. In some embodiments, VEGF-A is suppressed by at least about 60%, 65%, 70%, 75%, or 80% by administration of an iRNA disclosed herein. In some embodiments, VEGF-A is suppressed by at least about 85%, 90%, 95%, 98%, 99%, or more by administration of an iRNA as described herein. 
     The term “antisense strand” or “guide strand” refers to the strand of an iRNA, e.g., a dsRNA, which includes a region that is substantially complementary to a target sequence. 
     As used herein, the term “region of complementarity” refers to the region on the antisense strand that is substantially complementary to a sequence, for example a target sequence, as defined herein. Where the region of complementarity is not fully complementary to the target sequence, the mismatches may be in the internal or terminal regions of the molecule. In some embodiments, the region of complementarity comprises 0, 1, or 2 mismatches. 
     The term “sense strand” or “passenger strand” as used herein, refers to the strand of an iRNA that includes a region that is substantially complementary to a region of the antisense strand as that term is defined herein. 
     The terms “blunt” or “blunt ended” as used herein in reference to a dsRNA mean that there are no unpaired nucleotides or nucleotide analogs at a given terminal end of a dsRNA, i.e., no nucleotide overhang. One or both ends of a dsRNA can be blunt. Where both ends of a dsRNA are blunt, the dsRNA is said to be blunt ended. To be clear, a “blunt ended” dsRNA is a dsRNA that is blunt at both ends, i.e., no nucleotide overhang at either end of the molecule. Most often such a molecule will be double-stranded over its entire length. 
     As used herein, and unless otherwise indicated, the term “complementary,” when used to describe a first nucleotide sequence in relation to a second nucleotide sequence, refers to the ability of an oligonucleotide or polynucleotide comprising the first nucleotide sequence to hybridize and form a duplex structure under certain conditions with an oligonucleotide or polynucleotide comprising the second nucleotide sequence, as will be understood by the skilled person. Such conditions can, for example, be stringent conditions, where stringent conditions may include: 400 mM NaCl, 40 mM PIPES pH 6.4, 1 mM EDTA, 50° C. or 70° C. for 12-16 hours followed by washing. Other conditions, such as physiologically relevant conditions as may be encountered inside an organism, can apply. The skilled person will be able to determine the set of conditions most appropriate for a test of complementarity of two sequences in accordance with the ultimate application of the hybridized nucleotides. 
     Complementary sequences within an iRNA, e.g., within a dsRNA as described herein, include base-pairing of the oligonucleotide or polynucleotide comprising a first nucleotide sequence to an oligonucleotide or polynucleotide comprising a second nucleotide sequence over the entire length of one or both nucleotide sequences. Such sequences can be referred to as “fully complementary” with respect to each other herein. However, where a first sequence is referred to as “substantially complementary” with respect to a second sequence herein, the two sequences can be fully complementary, or they may form one or more, but generally not more than 5, 4, 3 or 2 mismatched base pairs upon hybridization for a duplex up to 30 base pairs, while retaining the ability to hybridize under the conditions most relevant to their ultimate application, e.g., inhibition of gene expression via a RISC pathway. However, where two oligonucleotides are designed to form, upon hybridization, one or more single stranded overhangs, such overhangs shall not be regarded as mismatches with regard to the determination of complementarity. For example, a dsRNA comprising one oligonucleotide 21 nucleotides in length and another oligonucleotide 23 nucleotides in length, wherein the longer oligonucleotide comprises a sequence of 21 nucleotides that is fully complementary to the shorter oligonucleotide, may yet be referred to as “fully complementary” for the purposes described herein. 
     Complementary sequences, as used herein, may also include, or be formed entirely from, non-Watson-Crick base pairs and/or base pairs formed from non-natural and modified nucleotides, in as far as the above requirements with respect to their ability to hybridize are fulfilled. Such non-Watson-Crick base pairs includes, but are not limited to, G:U Wobble or Hoogstein base pairing. 
     The terms “complementary,” “fully complementary” and “substantially complementary” herein may be used with respect to the base matching between the sense strand and the antisense strand of a dsRNA, or between the antisense strand of an iRNA agent and a target sequence, as will be understood from the context of their use. 
     As used herein, a polynucleotide that is “substantially complementary to at least part of” a messenger RNA (mRNA) refers to a polynucleotide that is substantially complementary to a contiguous portion of the mRNA of interest (e.g., an mRNA encoding a VEGF-A protein). For example, a polynucleotide is complementary to at least a part of a VEGF-A mRNA if the sequence is substantially complementary to a non-interrupted portion of an mRNA encoding VEGF-A. The term “complementarity” refers to the capacity for pairing between nucleobases of a first nucleic acid and a second nucleic acid. 
     As used herein, the term “region of complementarity” refers to the region of one nucleotide sequence agent that is substantially complementary to another sequence, e.g., the region of a sense sequence and corresponding antisense sequence of a dsRNA, or the antisense strand of an iRNA and a target sequence, e.g., a VEGF-A nucleotide sequence, as defined herein. Where the region of complementarity is not fully complementary to the target sequence, the mismatches can be in the internal or terminal regions of the antisense strand of the iRNA. Generally, the most tolerated mismatches are in the terminal regions, e.g., within 5, 4, 3, or 2 nucleotides of the 5′- or 3′-terminus of the iRNA agent. 
     “Contacting,” as used herein, includes directly contacting a cell, as well as indirectly contacting a cell. For example, a cell within a subject may be contacted when a composition comprising an iRNA is administered (e.g., intraocularly, topically, or intravenously) to the subject. 
     “Introducing into a cell,” when referring to an iRNA, means facilitating or effecting uptake or absorption into the cell. Absorption or uptake of an iRNA can occur through unaided diffusive or active cellular processes, or by auxiliary agents or devices. The meaning of this term is not limited to cells in vitro; an iRNA may also be “introduced into a cell,” wherein the cell is part of a living organism. In such an instance, introduction into the cell will include the delivery to the organism. For example, for in vivo delivery, iRNA can be injected into a tissue site or administered systemically. In vivo delivery can also be by a β-glucan delivery system, such as those described in U.S. Pat. Nos. 5,032,401 and 5,607,677, and U.S. Publication No. 2005/0281781, which are hereby incorporated by reference in their entirety. In vitro introduction into a cell includes methods known in the art such as electroporation and lipofection. Further approaches are described herein below or known in the art. As used herein, a “disorder related to VEGF-A expression,” a “disease related to VEGF-A expression,” a “pathological process related to VEGF-A expression,” “a VEGF-A-associated disorder,” “a VEGF-A-associated disease,” or the like includes any condition, disorder, or disease in which VEGF-A expression is altered (e.g., decreased or increased relative to a reference level, e.g., a level characteristic of a non-diseased subject). In some embodiments, VEGF-A expression is decreased. In some embodiments, VEGF-A expression is increased. In some embodiments, the decrease or increase in VEGF-A expression is detectable in a tissue sample from the subject (e.g., in an aqueous ocular fluid sample). The decrease or increase may be assessed relative the level observed in the same individual prior to the development of the disorder or relative to other individual(s) who do not have the disorder. The decrease or increase may be limited to a particular organ, tissue, or region of the body (e.g., the eye). VEGF-A-associated disorders include, but are not limited to, angiogenic ocular disorders. 
     The term “angiogenic ocular disorder,” as used herein, means any disease of the eye that is caused by or associated with the growth or proliferation of blood vessels or by blood vessel leakage. Non-limiting examples of angiogenic ocular disorders that are treatable using methods provided herein include age-related macular degeneration (e.g., wet AMD, exudative AMD, etc.), retinal vein occlusion (RVO), central retinal vein occlusion (CRVO; e.g., macular edema following RVO (MEfRVO)), branch retinal vein occlusion (BRVO), retinopathy of prematurity (ROP), diabetic macular edema (DME), choroidal neovascularization (CNV; e.g., myopic CNV), iris neovascularization, neovascular glaucoma, post-surgical fibrosis in glaucoma, proliferative retinopathy, proliferative vitreoretinopathy (PVR), optic disc neovascularization, corneal neovascularization, retinal neovascularization, vitreal neovascularization, pannus, pterygium, vascular retinopathy, von Hippel-Lindau disease, histoplasmosis, and diabetic retinopathies. 
     The term “double-stranded RNA,” “dsRNA,” or “siRNA” as used herein, refers to an iRNA that includes an RNA molecule or complex of molecules having a hybridized duplex region that comprises two anti-parallel and substantially complementary nucleic acid strands, which will be referred to as having “sense” and “antisense” orientations with respect to a target RNA. The duplex region can be of any length that permits specific degradation of a desired target RNA, e.g., through a RISC pathway, but will typically range from 9 to 36 base pairs in length, e.g., 15-30 base pairs in length. Considering a duplex between 9 and 36 base pairs, the duplex can be any length in this range, for example, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 and any sub-range therein between, including, but not limited to 15-30 base pairs, 15-26 base pairs, 15-23 base pairs, 15-22 base pairs, 15-21 base pairs, 15-20 base pairs, 15-19 base pairs, 15-18 base pairs, 15-17 base pairs, 18-30 base pairs, 18-26 base pairs, 18-23 base pairs, 18-22 base pairs, 18-21 base pairs, 18-20 base pairs, 19-30 base pairs, 19-26 base pairs, 19-23 base pairs, 19-22 base pairs, 19-21 base pairs, 19-20 base pairs, 20-30 base pairs, 20-26 base pairs, 20-25 base pairs, 20-24 base pairs, 20-23 base pairs, 20-22 base pairs, 20-21 base pairs, 21-30 base pairs, 21-26 base pairs, 21-25 base pairs, 21-24 base pairs, 21-23 base pairs, or 21-22 base pairs. dsRNAs generated in the cell by processing with Dicer and similar enzymes are generally in the range of 19-22 base pairs in length. One strand of the duplex region of a dsDNA comprises a sequence that is substantially complementary to a region of a target RNA. The two strands forming the duplex structure can be from a single RNA molecule having at least one self-complementary region, or can be formed from two or more separate RNA molecules. Where the duplex region is formed from two strands of a single molecule, the molecule can have a duplex region separated by a single stranded chain of nucleotides (herein referred to as a “hairpin loop”) between the 3′-end of one strand and the 5′-end of the respective other strand forming the duplex structure. The hairpin loop can comprise at least one unpaired nucleotide; in some embodiments the hairpin loop can comprise at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 20, at least 23 or more unpaired nucleotides. Where the two substantially complementary strands of a dsRNA are comprised by separate RNA molecules, those molecules need not, but can be covalently connected. In some embodiments, the two strands are connected covalently by means other than a hairpin loop, and the connecting structure is a linker. 
     In some embodiments, the iRNA agent may be a “single-stranded siRNA” that is introduced into a cell or organism to inhibit a target mRNA. In some embodiments, single-stranded RNAi agents can bind to the RISC endonuclease Argonaute 2, which then cleaves the target mRNA. The single-stranded siRNAs are generally 15-30 nucleotides and are optionally chemically modified. The design and testing of single-stranded siRNAs are described in U.S. Pat. No. 8,101,348 and in Lima et al., (2012)  Cell  150: 883-894, the entire contents of each of which are hereby incorporated herein by reference. Any of the antisense nucleotide sequences described herein (e.g., sequences provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B) may be used as a single-stranded siRNA as described herein and optionally as chemically modified, e.g., as described herein, e.g., by the methods described in Lima et al., (2012)  Cell  150:883-894. 
     In some embodiments, an RNA interference agent includes a single stranded RNA that interacts with a target RNA sequence to direct the cleavage of the target RNA. Without wishing to be bound by theory, long double stranded RNA introduced into cells is broken down into siRNA by a Type III endonuclease known as Dicer (Sharp et al.,  Genes Dev.  2001, 15:485). Dicer, a ribonuclease-III-like enzyme, processes the dsRNA into 19-23 base pair short interfering RNAs with characteristic two base 3′ overhangs (Bernstein, et al., (2001)  Nature  409:363). The siRNAs are then incorporated into an RNA-induced silencing complex (RISC) where one or more helicases unwind the siRNA duplex, enabling the complementary antisense strand to guide target recognition (Nykanen, et al., (2001)  Cell  107:309). Upon binding to the appropriate target mRNA, one or more endonucleases within the RISC cleaves the target to induce silencing (Elbashir, et al., (2001)  Genes Dev.  15:188). Thus, in some embodiments, the disclosure relates to a single stranded RNA that promotes the formation of a RISC complex to effect silencing of the target gene. 
     “G,” “C,” “A,” “T” and “U” each generally stand for a nucleotide that contains guanine, cytosine, adenine, thymidine and uracil as a base, respectively. However, it will be understood that the terms “deoxyribonucleotide,” “ribonucleotide,” or “nucleotide” can also refer to a modified nucleotide, as further detailed below, or a surrogate replacement moiety. The skilled person is well aware that guanine, cytosine, adenine, and uracil may be replaced by other moieties without substantially altering the base pairing properties of an oligonucleotide comprising a nucleotide bearing such replacement moiety. For example, without limitation, a nucleotide comprising inosine as its base may base pair with nucleotides containing adenine, cytosine, or uracil. Hence, nucleotides containing uracil, guanine, or adenine may be replaced in the nucleotide sequences of dsRNA featured in the disclosure by a nucleotide containing, for example, inosine. In another example, adenine and cytosine anywhere in the oligonucleotide can be replaced with guanine and uracil, respectively to form G-U Wobble base pairing with the target mRNA. Sequences containing such replacement moieties are suitable for the compositions and methods featured in the disclosure. 
     As used herein, the term “iRNA,” “RNAi”, “iRNA agent,” or “RNAi agent” or “RNAi molecule” refers to an agent that contains RNA as that term is defined herein, and which mediates the targeted cleavage of an RNA transcript, e.g., via an RNA-induced silencing complex (RISC) pathway. In some embodiments, an iRNA as described herein effects inhibition of VEGF-A expression, e.g., in a cell or mammal. Inhibition of VEGF-A expression may be assessed based on a reduction in the level of VEGF-A mRNA or a reduction in the level of the VEGF-A protein. 
     The term “linker” or “linking group” means an organic moiety that connects two parts of a compound, e.g., covalently attaches two parts of a compound. 
     The term “lipophile” or “lipophilic moiety” broadly refers to any compound or chemical moiety having an affinity for lipids. One way to characterize the lipophilicity of the lipophilic moiety is by the octanol-water partition coefficient, log K ow , where K ow  is the ratio of a chemical&#39;s concentration in the octanol-phase to its concentration in the aqueous phase of a two-phase system at equilibrium. The octanol-water partition coefficient is a laboratory-measured property of a substance. However, it may also be predicted by using coefficients attributed to the structural components of a chemical which are calculated using first-principle or empirical methods (see, for example, Tetko et al.,  J. Chem. Inf. Comput. Sci.  41:1407-21 (2001), which is incorporated herein by reference in its entirety). It provides a thermodynamic measure of the tendency of the substance to prefer a non-aqueous or oily milieu rather than water (i.e. its hydrophilic/lipophilic balance). In principle, a chemical substance is lipophilic in character when its log K ow  exceeds 0. Typically, the lipophilic moiety possesses a log K ow  exceeding 1, exceeding 1.5, exceeding 2, exceeding 3, exceeding 4, exceeding 5, or exceeding 10. For instance, the log K ow  of 6-amino hexanol, for instance, is predicted to be approximately 0.7. Using the same method, the log K ow  of cholesteryl N-(hexan-6-ol) carbamate is predicted to be 10.7. 
     The lipophilicity of a molecule can change with respect to the functional group it carries. For instance, adding a hydroxyl group or amine group to the end of a lipophilic moiety can increase or decrease the partition coefficient (e.g., log K ow ) value of the lipophilic moiety. 
     Alternatively, the hydrophobicity of the double-stranded RNAi agent, conjugated to one or more lipophilic moieties, can be measured by its protein binding characteristics. For instance, in certain embodiments, the unbound fraction in the plasma protein binding assay of the double-stranded RNAi agent could be determined to positively correlate to the relative hydrophobicity of the double-stranded RNAi agent, which could then positively correlate to the silencing activity of the double-stranded RNAi agent. 
     In some embodiments, the plasma protein binding assay determined is an electrophoretic mobility shift assay (EMSA) using human serum albumin protein. An exemplary protocol of this binding assay is illustrated in detail in, e.g., PCT/US2019/031170. The hydrophobicity of the double-stranded RNAi agent, measured by fraction of unbound siRNA in the binding assay, exceeds 0.15, exceeds 0.2, exceeds 0.25, exceeds 0.3, exceeds 0.35, exceeds 0.4, exceeds 0.45, or exceeds 0.5 for an enhanced in vivo delivery of siRNA. 
     Accordingly, conjugating the lipophilic moieties to the internal position(s) of the double-stranded RNAi agent provides optimal hydrophobicity for the enhanced in vivo delivery of siRNA. 
     The term “lipid nanoparticle” or “LNP” is a vesicle comprising a lipid layer encapsulating a pharmaceutically active molecule, such as a nucleic acid molecule, e.g., a RNAi agent or a plasmid from which a RNAi agent is transcribed. LNPs are described in, for example, U.S. Pat. Nos. 6,858,225, 6,815,432, 8,158,601, and 8,058,069, the entire contents of which are hereby incorporated herein by reference. 
     As used herein, the term “modulate the expression of,” refers to an at least partial “inhibition” or partial “activation” of a gene (e.g., VEGF-A gene) expression in a cell treated with an iRNA composition as described herein compared to the expression of the corresponding gene in a control cell. A control cell includes an untreated cell, or a cell treated with a non-targeting control iRNA. 
     The skilled artisan will recognize that the term “RNA molecule” or “ribonucleic acid molecule” encompasses not only RNA molecules as expressed or found in nature, but also analogs and derivatives of RNA comprising one or more ribonucleotide/ribonucleoside analogs or derivatives as described herein or as known in the art. Strictly speaking, a “ribonucleoside” includes a nucleoside base and a ribose sugar, and a “ribonucleotide” is a ribonucleoside with one, two or three phosphate moieties or analogs thereof (e.g., phosphorothioate). However, the terms “ribonucleoside” and “ribonucleotide” can be considered to be equivalent as used herein. The RNA can be modified in the nucleobase structure, in the ribose structure, or in the ribose-phosphate backbone structure, e.g., as described herein below. However, the molecules comprising ribonucleoside analogs or derivatives must retain the ability to form a duplex. As non-limiting examples, an RNA molecule can also include at least one modified ribonucleoside including but not limited to a 2′-O-methyl modified nucleoside, a nucleoside comprising a 5′ phosphorothioate group, a terminal nucleoside linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group, a locked nucleoside, an abasic nucleoside, an acyclic nucleoside, a glycol nucleotide, a 2′-deoxy-2′-fluoro modified nucleoside, a 2′-amino-modified nucleoside, 2′-alkyl-modified nucleoside, morpholino nucleoside, a phosphoramidate or a non-natural base comprising nucleoside, or any combination thereof. Alternatively, or in combination, an RNA molecule can comprise at least two modified ribonucleosides, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 15, at least 20 or more, up to the entire length of the dsRNA molecule. The modifications need not be the same for each of such a plurality of modified ribonucleosides in an RNA molecule. In some embodiments, modified RNAs contemplated for use in methods and compositions described herein are peptide nucleic acids (PNAs) that have the ability to form the required duplex structure and that permit or mediate the specific degradation of a target RNA, e.g., via a RISC pathway. For clarity, it is understood that the term “iRNA” does not encompass a naturally occurring double stranded DNA molecule or a 100% deoxynucleoside-containing DNA molecule. 
     In some aspects, a modified ribonucleoside includes a deoxyribonucleoside. In such an instance, an iRNA agent can comprise one or more deoxynucleosides, including, for example, a deoxynucleoside overhang(s), or one or more deoxynucleosides within the double stranded portion of a dsRNA. In certain embodiments, the RNA molecule comprises a percentage of deoxyribonucleosides of at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95% or higher (but not 100%) deoxyribonucleosides, e.g., in one or both strands. 
     As used herein, the term “nucleotide overhang” refers to at least one unpaired nucleotide that protrudes from the duplex structure of an iRNA, e.g., a dsRNA. For example, when a 3′-end of one strand of a dsRNA extends beyond the 5′-end of the other strand, or vice versa, there is a nucleotide overhang. A dsRNA can comprise an overhang of at least one nucleotide; alternatively, the overhang can comprise at least two nucleotides, at least three nucleotides, at least four nucleotides, or at least five nucleotides or more. A nucleotide overhang can comprise or consist of a nucleotide/nucleoside analog, including a deoxynucleotide/nucleoside. The overhang(s) may be on the sense strand, the antisense strand or any combination thereof. Furthermore, the nucleotide(s) of an overhang can be present on the 5′ end, 3′ end or both ends of either an antisense or sense strand of a dsRNA. 
     In some embodiments, the antisense strand of a dsRNA has a 1-10 nucleotide overhang at the 3′ end and/or the 5′ end. In some embodiments, the sense strand of a dsRNA has a 1-10 nucleotide overhang at the 3′ end and/or the 5′ end. In some embodiments, one or more of the nucleotides in the overhang is replaced with a nucleoside thiophosphate. 
     As used herein, a “pharmaceutical composition” comprises a pharmacologically effective amount of a therapeutic agent (e.g., an iRNA) and a pharmaceutically acceptable carrier. As used herein, “pharmacologically effective amount,” “therapeutically effective amount” or simply “effective amount” refers to that amount of an agent (e.g., iRNA) effective to produce the intended pharmacological, therapeutic or preventive result. For example, in a method of treating a disorder related to VEGF-A expression (e.g., an angiogenic ocular disorder), an effective amount includes an amount effective to reduce one or more symptoms associated with the disorder (e.g., an amount effective to (a) inhibit angiogenesis; (b) inhibit or reduces the expression or activity of VEGF-A; (c) inhibit choroidal neovascularization; (d) inhibit growth of new blood vessels in the choriocapillaris; (e) reduce retinal thickness; (f) increase visual acuity; or (g) reduce intraocular inflammation) or an amount effective to reduce the risk of developing conditions associated with the disorder. For example, if a given clinical treatment is considered effective when there is at least a 10% reduction in a measurable parameter associated with a disease or disorder, a therapeutically effective amount of a drug for the treatment of that disease or disorder is the amount necessary to obtain at least a 10% reduction in that parameter. For example, a therapeutically effective amount of an iRNA targeting VEGF-A can reduce a level of VEGF-A mRNA or a level of VEGF-A protein by any measurable amount, e.g., by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. 
     The term “pharmaceutically acceptable carrier” refers to a carrier for administration of a therapeutic agent. Such carriers include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol, and combinations thereof. The term specifically excludes cell culture medium. For drugs administered orally, pharmaceutically acceptable carriers include, but are not limited to pharmaceutically acceptable excipients such as inert diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservatives. Suitable inert diluents include sodium and calcium carbonate, sodium and calcium phosphate, and lactose, while corn starch and alginic acid are suitable disintegrating agents. Binding agents may include starch and gelatin, while the lubricating agent, if present, will generally be magnesium stearate, stearic acid or talc. If desired, the tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate, to delay absorption in the gastrointestinal tract. Agents included in drug formulations are described further herein below. 
     As used herein, the term “SNALP” refers to a stable nucleic acid-lipid particle. A SNALP represents a vesicle of lipids coating a reduced aqueous interior comprising a nucleic acid such as an iRNA or a plasmid from which an iRNA is transcribed. SNALPs are described, e.g., in U.S. Patent Application Publication Nos. 2006/0240093, 2007/0135372, and in International Application No. WO 2009/082817. These applications are incorporated herein by reference in their entirety. In some embodiments, the SNALP is a SPLP. As used herein, the term “SPLP” refers to a nucleic acid-lipid particle comprising plasmid DNA encapsulated within a lipid vesicle. 
     As used herein, the term “strand comprising a sequence” refers to an oligonucleotide comprising a chain of nucleotides that is described by the sequence referred to using the standard nucleotide nomenclature. 
     As used herein, a “subject” to be treated according to the methods described herein, includes a human or non-human animal, e.g., a mammal. The mammal may be, for example, a rodent (e.g., a rat or mouse) or a primate (e.g., a monkey). In some embodiments, the subject is a human. 
     A “subject in need thereof” includes a subject having, suspected of having, or at risk of developing a disorder related to VEGF-A expression, e.g., overexpression (e.g., an angiogenic ocular disorder). In some embodiments, the subject has, or is suspected of having, a disorder related to VEGF-A expression or overexpression. In some embodiments, the subject is at risk of developing a disorder related to VEGF-A expression or overexpression. 
     As used herein, “target sequence” refers to a contiguous portion of the nucleotide sequence of an mRNA molecule formed during the transcription of a gene, e.g., VEGF-A, including mRNA that is a product of RNA processing of a primary transcription product. The target portion of the sequence will be at least long enough to serve as a substrate for iRNA-directed cleavage at or near that portion. For example, the target sequence will generally be from 9-36 nucleotides in length, e.g., 15-30 nucleotides in length, including all sub-ranges therebetween. As non-limiting examples, the target sequence can be from 15-30 nucleotides, 15-26 nucleotides, 15-23 nucleotides, 15-22 nucleotides, 15-21 nucleotides, 15-20 nucleotides, 15-19 nucleotides, 15-18 nucleotides, 15-17 nucleotides, 18-30 nucleotides, 18-26 nucleotides, 18-23 nucleotides, 18-22 nucleotides, 18-21 nucleotides, 18-20 nucleotides, 19-30 nucleotides, 19-26 nucleotides, 19-23 nucleotides, 19-22 nucleotides, 19-21 nucleotides, 19-20 nucleotides, 20-30 nucleotides, 20-26 nucleotides, 20-25 nucleotides, 20-24 nucleotides, 20-23 nucleotides, 20-22 nucleotides, 20-21 nucleotides, 21-30 nucleotides, 21-26 nucleotides, 21-25 nucleotides, 21-24 nucleotides, 21-23 nucleotides, or 21-22 nucleotides. 
     As used herein, the phrases “therapeutically effective amount” and “prophylactically effective amount” and the like refer to an amount that provides a therapeutic benefit in the treatment, prevention, or management of any disorder or pathological process related to VEGF-A expression (e.g., an angiogenic ocular disorder). The specific amount that is therapeutically effective may vary depending on factors known in the art, such as, for example, the type of disorder or pathological process, the patient&#39;s history and age, the stage of the disorder or pathological process, and the administration of other therapies. 
     In the context of the present disclosure, the terms “treat,” “treatment,” and the like mean to prevent, delay, relieve or alleviate at least one symptom associated with a disorder related to VEGF-A expression, or to slow or reverse the progression or anticipated progression of such a disorder. For example, the methods featured herein, when employed to treat an angiogenic ocular disorder, may serve to reduce or prevent one or more symptoms of the angiogenic ocular disorder, as described herein, or to reduce the risk or severity of associated conditions. Thus, unless the context clearly indicates otherwise, the terms “treat,” “treatment,” and the like are intended to encompass prophylaxis, e.g., prevention of disorders and/or symptoms of disorders related to VEGF-A expression. Treatment can also mean prolonging survival as compared to expected survival in the absence of treatment. 
     By “lower” in the context of a disease marker or symptom is meant any decrease, e.g., a statistically or clinically significant decrease in such level. The decrease can be, for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%. The decrease can be down to a level accepted as within the range of normal for an individual without such disorder. 
     As used herein, “VEGF-A” refers to “vascular endothelial growth factor A” the corresponding mRNA (“VEGF-A mRNA”), or the corresponding protein (“VEGF-A protein”). The sequence of a human VEGF-A mRNA transcript can be found at SEQ ID NO: 1. 
     II. iRNA Agents 
     Described herein are iRNA agents that modulate (e.g., inhibit) the expression of VEGF-A. 
     In some embodiments, the iRNA agent activates the expression of VEGF-A in a cell or mammal. 
     In some embodiments, the iRNA agent includes double-stranded ribonucleic acid (dsRNA) molecules for inhibiting the expression of VEGF-A in a cell or in a subject (e.g., in a mammal, e.g., in a human), where the dsRNA includes an antisense strand having a region of complementarity which is complementary to at least a part of an mRNA formed in the expression of VEGF-A, and where the region of complementarity is 30 nucleotides or less in length, generally 19-24 nucleotides in length, and where the dsRNA, upon contact with a cell expressing VEGF-A, inhibits the expression of VEGF-A, e.g., by at least 10%, 20%, 30%, 40%, or 50%. 
     The modulation (e.g., inhibition) of expression of VEGF-A can be assayed by, for example, a PCR or branched DNA (bDNA)-based method, or by a protein-based method, such as by Western blot. Expression of VEGF-A in cell culture, such as in COS cells, ARPE-19 cells, hTERT RPE-1 cells, HeLa cells, primary hepatocytes, HepG2 cells, primary cultured cells or in a biological sample from a subject can be assayed by measuring VEGF-A mRNA levels, such as by bDNA or TaqMan assay, or by measuring protein levels, such as by immunofluorescence analysis, using, for example, Western Blotting or flow cytometric techniques. 
     A dsRNA typically includes two RNA strands that are sufficiently complementary to hybridize to form a duplex structure under conditions in which the dsRNA will be used. One strand of a dsRNA (the antisense strand) typically includes a region of complementarity that is substantially complementary, and generally fully complementary, to a target sequence, derived from the sequence of an mRNA formed during the expression of VEGF-A. The other strand (the sense strand) typically includes a region that is complementary to the antisense strand, such that the two strands hybridize and form a duplex structure when combined under suitable conditions. Generally, the duplex structure is between 15 and 30 inclusive, more generally between 18 and 25 inclusive, yet more generally between 19 and 24 inclusive, and most generally between 19 and 21 base pairs in length, inclusive. Similarly, the region of complementarity to the target sequence is between 15 and 30 inclusive, more generally between 18 and 25 inclusive, yet more generally between 19 and 24 inclusive, and most generally between 19 and 21 nucleotides in length, inclusive. 
     In some embodiments, the dsRNA is between 15 and 20 nucleotides in length, inclusive, and in other embodiments, the dsRNA is between 25 and 30 nucleotides in length, inclusive. As the ordinarily skilled person will recognize, the targeted region of an RNA targeted for cleavage will most often be part of a larger RNA molecule, often an mRNA molecule. Where relevant, a “part” of an mRNA target is a contiguous sequence of an mRNA target of sufficient length to be a substrate for RNAi-directed cleavage (i.e., cleavage through a RISC pathway). dsRNAs having duplexes as short as 9 base pairs can, under some circumstances, mediate RNAi-directed RNA cleavage. Most often a target will be at least 15 nucleotides in length, e.g., 15-30 nucleotides in length. 
     One of skill in the art will also recognize that the duplex region is a primary functional portion of a dsRNA, e.g., a duplex region of 9 to 36, e.g., 15-30 base pairs. Thus, in some embodiments, to the extent that it becomes processed to a functional duplex of e.g., 15-30 base pairs that targets a desired RNA for cleavage, an RNA molecule or complex of RNA molecules having a duplex region greater than 30 base pairs is a dsRNA. Thus, an ordinarily skilled artisan will recognize that in some embodiments, then, an miRNA is a dsRNA. In some embodiments, a dsRNA is not a naturally occurring miRNA. In some embodiments, an iRNA agent useful to target VEGF-A expression is not generated in the target cell by cleavage of a larger dsRNA. 
     A dsRNA as described herein may further include one or more single-stranded nucleotide overhangs. The dsRNA can be synthesized by standard methods known in the art as further discussed below, e.g., by use of an automated DNA synthesizer, such as are commercially available from, for example, Biosearch, Applied Biosystems, Inc. 
     In some embodiments, VEGF-A is a human VEGF-A. 
     In specific embodiments, the dsRNA comprises a sense strand that comprises or consists of a sense sequence selected from the sense sequences provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B and an antisense strand that comprises or consists of an antisense sequence selected from the antisense sequences provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B. 
     In some aspects, a dsRNA will include at least sense and antisense nucleotide sequences, whereby the sense strand is selected from the sequences provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B and the corresponding antisense strand is selected from the sequences provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B. 
     In these aspects, one of the two sequences is complementary to the other of the two sequences, with one of the sequences being substantially complementary to a sequence of an mRNA generated by the expression of VEGF-A. As such, a dsRNA will include two oligonucleotides, where one oligonucleotide is described as the sense strand, and the second oligonucleotide is described as the corresponding antisense strand. As described elsewhere herein and as known in the art, the complementary sequences of a dsRNA can also be contained as self-complementary regions of a single nucleic acid molecule, as opposed to being on separate oligonucleotides. 
     The skilled person is well aware that dsRNAs having a duplex structure of between 20 and 23, but specifically 21, base pairs have been hailed as particularly effective in inducing RNA interference (Elbashir et al.,  EMBO  2001, 20:6877-6888). However, others have found that shorter or longer RNA duplex structures can be effective as well. 
     In the embodiments described above, by virtue of the nature of the oligonucleotide sequences provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B, dsRNAs described herein can include at least one strand of a length of minimally 19 nucleotides. It can be reasonably expected that shorter duplexes having one of the sequences of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B minus only a few nucleotides on one or both ends will be similarly effective as compared to the dsRNAs described above. 
     In some embodiments, the dsRNA has a partial sequence of at least 15, 16, 17, 18, 19, 20, or more contiguous nucleotides from one of the sequences of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B. 
     In some embodiments, the dsRNA has an antisense sequence that comprises at least 15, 16, 17, 18, or 19 contiguous nucleotides of an antisense sequence provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B and a sense sequence that comprises at least 15, 16, 17, 18, or 19 contiguous nucleotides of a corresponding sense sequence provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B. 
     In some embodiments, the dsRNA comprises an antisense sequence that comprises at least 15, 16, 17, 18, 19, 20, 21, 22, or 23 contiguous nucleotides of an antisense sequence provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B and a sense sequence that comprises at least 15, 16, 17, 18, 19, 20, or 21 contiguous nucleotides of a corresponding sense sequence provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B. 
     In some such embodiments, the dsRNA, although it comprises only a portion of the sequences provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B is equally effective in inhibiting a level of VEGF-A expression as is a dsRNA that comprises the full-length sequences provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A or 18B. In some embodiments, the dsRNA differs in its inhibition of a level of expression of VEGF-A by not more than 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50% inhibition compared with a dsRNA comprising the full sequence disclosed herein. 
     The iRNAs of Tables 5A and 5B were designed based on rat VEGF-A sequence. Without wishing to be bound by theory, VEGF-A sequence is conserved sufficiently between species such that certain iRNAs designed based on a rodent sequence have activity against a primate VEGF-A. Working Example 2 herein gives evidence of iRNAs designed based on a rodent sequence having activity against cynomolgus monkey VEGF-A. 
     Consequently, in some embodiments, an iRNA of Table 5A or Table 5B decreases VEGF-A protein or VEGF-A mRNA levels in a cell. In some embodiments, the cell is a rodent cell (e.g., a rat cell), or a primate cell (e.g., a cynomolgus monkey cell or a human cell). In some embodiments, VEGF-A protein or VEGF-F mRNA levels are reduced by at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%. In some embodiments, the iRNA of Table 5A or 5B that inhibits VEGF-A in a human cell has less than 5, 4, 3, 2, or 1 mismatches to the corresponding portion of human VEGF-A. In some embodiments, the iRNA of Table 5A or 5B that inhibits VEGF-A in a human cell has no mismatches to the corresponding portion of human VEGF-A. 
     iRNAs designed based on rodent sequences can have utility, e.g., for inhibiting VEGF-A in human cells, e.g., for therapeutic purposes, or for inhibiting VEGF-A in rodent cells, e.g., for research characterizing VEGF-A in a rodent model. 
     In some embodiments, an iRNA described herein comprises an antisense strand comprising at least 15 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of nucleotide sequence of SEQ ID NO: 2. In some embodiments, an iRNA described herein comprises a sense strand comprising at least 15 contiguous nucleotides, with 0, or 1, 2, or 3 mismatches, of the corresponding portion of the nucleotide sequence of SEQ ID NO: 1. 
     A human VEGF-A mRNA may have the sequence of SEQ ID NO: 1 provided herein.  Homo sapiens  vascular endothelial growth factor A (VEGFA), transcript variant 1, mRNA 
     
       
         
           
               
            
               
                 (SEQ ID NO: 1) 
               
               
                 TCGCGGAGGCTTGGGGCAGCCGGGTAGCTCGGAGGTCGTGGCGCTGGGGG 
               
               
                   
               
               
                 CTAGCACCAGCGCTCTGTCGGGAGGCGCAGCGGTTAGGTGGACCGGTCAG 
               
               
                   
               
               
                 CGGACTCACCGGCCAGGGCGCTCGGTGCTGGAATTTGATATTCATTGATC 
               
               
                   
               
               
                 CGGGTTTTATCCCTCTTCTTTTTTCTTAAACATTTTTTTTTAAAACTGTA 
               
               
                   
               
               
                 TTGTTTCTCGTTTTAATTTATTTTTGCTTGCCATTCCCCACTTGAATCGG 
               
               
                   
               
               
                 GCCGACGGCTTGGGGAGATTGCTCTACTTCCCCAAATCACTGTGGATTTT 
               
               
                   
               
               
                 GGAAACCAGCAGAAAGAGGAAAGAGGTAGCAAGAGCTCCAGAGAGAAGTC 
               
               
                   
               
               
                 GAGGAAGAGAGAGACGGGGTCAGAGAGAGCGCGCGGGCGTGCGAGCAGCG 
               
               
                   
               
               
                 AAAGCGACAGGGGCAAAGTGAGTGACCTGCTTTTGGGGGTGACCGCCGGA 
               
               
                   
               
               
                 GCGCGGCGTGAGCCCTCCCCCTTGGGATCCCGCAGCTGACCAGTCGCGCT 
               
               
                   
               
               
                 GACGGACAGACAGACAGACACCGCCCCCAGCCCCAGCTACCACCTCCTCC 
               
               
                   
               
               
                 CCGGCCGGCGGCGGACAGTGGACGCGGCGGCGAGCCGCGGGCAGGGGCCG 
               
               
                   
               
               
                 GAGCCCGCGCCCGGAGGCGGGGTGGAGGGGGTCGGGGCTCGCGGCGTCGC 
               
               
                   
               
               
                 ACTGAAACTTTTCGTCCAACTTCTGGGCTGTTCTCGCTTCGGAGGAGCCG 
               
               
                   
               
               
                 TGGTCCGCGCGGGGGAAGCCGAGCCGAGCGGAGCCGCGAGAAGTGCTAGC 
               
               
                   
               
               
                 TCGGGCCGGGAGGAGCCGCAGCCGGAGGAGGGGGAGGAGGAAGAAGAGAA 
               
               
                   
               
               
                 GGAAGAGGAGAGGGGGCCGCAGTGGCGACTCGGCGCTCGGAAGCCGGGCT 
               
               
                   
               
               
                 CATGGACGGGTGAGGCGGCGGTGTGCGCAGACAGTGCTCCAGCCGCGCGC 
               
               
                   
               
               
                 GCTCCCCAGGCCCTGGCCCGGGCCTCGGGCCGGGGAGGAAGAGTAGCTCG 
               
               
                   
               
               
                 CCGAGGCGCCGAGGAGAGCGGGCCGCCCCACAGCCCGAGCCGGAGAGGGA 
               
               
                   
               
               
                 GCGCGAGCCGCGCCGGCCCCGGTCGGGCCTCCGAAACCATGAACTTTCTG 
               
               
                   
               
               
                 CTGTCTTGGGTGCATTGGAGCCTTGCCTTGCTGCTCTACCTCCACCATGC 
               
               
                   
               
               
                 CAAGTGGTCCCAGGCTGCACCCATGGCAGAAGGAGGAGGGCAGAATCATC 
               
               
                   
               
               
                 ACGAAGTGGTGAAGTTCATGGATGTCTATCAGCGCAGCTACTGCCATCCA 
               
               
                   
               
               
                 ATCGAGACCCTGGTGGACATCTTCCAGGAGTACCCTGATGAGATCGAGTA 
               
               
                   
               
               
                 CATCTTCAAGCCATCCTGTGTGCCCCTGATGCGATGCGGGGGCTGCTGCA 
               
               
                   
               
               
                 ATGACGAGGGCCTGGAGTGTGTGCCCACTGAGGAGTCCAACATCACCATG 
               
               
                   
               
               
                 CAGATTATGCGGATCAAACCTCACCAAGGCCAGCACATAGGAGAGATGAG 
               
               
                   
               
               
                 CTTCCTACAGCACAACAAATGTGAATGCAGACCAAAGAAAGATAGAGCAA 
               
               
                   
               
               
                 GACAAGAAAAAAAATCAGTTCGAGGAAAGGGAAAGGGGCAAAAACGAAAG 
               
               
                   
               
               
                 CGCAAGAAATCCCGGTATAAGTCCTGGAGCGTGTACGTTGGTGCCCGCTG 
               
               
                   
               
               
                 CTGTCTAATGCCCTGGAGCCTCCCTGGCCCCCATCCCTGTGGGCCTTGCT 
               
               
                   
               
               
                 CAGAGCGGAGAAAGCATTTGTTTGTACAAGATCCGCAGACGTGTAAATGT 
               
               
                   
               
               
                 TCCTGCAAAAACACAGACTCGCGTTGCAAGGCGAGGCAGCTTGAGTTAAA 
               
               
                   
               
               
                 CGAACGTACTTGCAGATGTGACAAGCCGAGGCGGTGAGCCGGGCAGGAGG 
               
               
                   
               
               
                 AAGGAGCCTCCCTCAGGGTTTCGGGAACCAGATCTCTCACCAGGAAAGAC 
               
               
                   
               
               
                 TGATACAGAACGATCGATACAGAAACCACGCTGCCGCCACCACACCATCA 
               
               
                   
               
               
                 CCATCGACAGAACAGTCCTTAATCCAGAAACCTGAAATGAAGGAAGAGGA 
               
               
                   
               
               
                 GACTCTGCGCAGAGCACTTTGGGTCCGGAGGGCGAGACTCCGGCGGAAGC 
               
               
                   
               
               
                 ATTCCCGGGCGGGTGACCCAGCACGGTCCCTCTTGGAATTGGATTCGCCA 
               
               
                   
               
               
                 TTTTATTTTTCTTGCTGCTAAATCACCGAGCCCGGAAGATTAGAGAGTTT 
               
               
                   
               
               
                 TATTTCTGGGATTCCTGTAGACACACCCACCCACATACATACATTTATAT 
               
               
                   
               
               
                 ATATATATATTATATATATATAAAAATAAATATCTCTATTTTATATATAT 
               
               
                   
               
               
                 AAAATATATATATTCTTTTTTTAAATTAACAGTGCTAATGTTATTGGTGT 
               
               
                   
               
               
                 CTTCACTGGATGTATTTGACTGCTGTGGACTTGAGTTGGGAGGGGAATGT 
               
               
                   
               
               
                 TCCCACTCAGATCCTGACAGGGAAGAGGAGGAGATGAGAGACTCTGGCAT 
               
               
                   
               
               
                 GATCTTTTTTTTGTCCCACTTGGTGGGGCCAGGGTCCTCTCCCCTGCCCA 
               
               
                   
               
               
                 GGAATGTGGAAGGCCAGGGCATGGGGGCAAATATGACCCAGTTTTGGGAA 
               
               
                   
               
               
                 CACCGACAAACCCAGCCCTGGCGCTGAGCCTCTCTACCCCAGGTCAGACG 
               
               
                   
               
               
                 GACAGAAAGACAGATCACAGGTACAGGGATGAGGACACCGGCTCTGACCA 
               
               
                   
               
               
                 GGAGTTTGGGGAGCTTCAGGACATTGCTGTGCTTTGGGGATTCCCTCCAC 
               
               
                   
               
               
                 ATGCTGCACGCGCATCTCGCCCCCAGGGGCACTGCCTGGAAGATTCAGGA 
               
               
                   
               
               
                 GCCTGGGCGGCCTTCGCTTACTCTCACCTGCTTCTGAGTTGCCCAGGAGA 
               
               
                   
               
               
                 CCACTGGCAGATGTCCCGGCGAAGAGAAGAGACACATTGTTGGAAGAAGC 
               
               
                   
               
               
                 AGCCCATGACAGCTCCCCTTCCTGGGACTCGCCCTCATCCTCTTCCTGCT 
               
               
                   
               
               
                 CCCCTTCCTGGGGTGCAGCCTAAAAGGACCTATGTCCTCACACCATTGAA 
               
               
                   
               
               
                 ACCACTAGTTCTGTCCCCCCAGGAGACCTGGTTGTGTGTGTGTGAGTGGT 
               
               
                   
               
               
                 TGACCTTCCTCCATCCCCTGGTCCTTCCCTTCCCTTCCCGAGGCACAGAG 
               
               
                   
               
               
                 AGACAGGGCAGGATCCACGTGCCCATTGTGGAGGCAGAGAAAAGAGAAAG 
               
               
                   
               
               
                 TGTTTTATATACGGTACTTATTTAATATCCCTTTTTAATTAGAAATTAAA 
               
               
                   
               
               
                 ACAGTTAATTTAATTAAAGAGTAGGGTTTTTTTTCAGTATTCTTGGTTAA 
               
               
                   
               
               
                 TATTTAATTTCAACTATTTATGAGATGTATCTTTTGCTCTCTCTTGCTCT 
               
               
                   
               
               
                 CTTATTTGTACCGGTTTTTGTATATAAAATTCATGTTTCCAATCTCTCTC 
               
               
                   
               
               
                 TCCCTGATCGGTGACAGTCACTAGCTTATCTTGAACAGATATTTAATTTT 
               
               
                   
               
               
                 GCTAACACTCAGCTCTGCCCTCCCCGATCCCCTGGCTCCCCAGCACACAT 
               
               
                   
               
               
                 TCCTTTGAAATAAGGTTTCAATATACATCTACATACTATATATATATTTG 
               
               
                   
               
               
                 GCAACTTGTATTTGTGTGTATATATATATATATATGTTTATGTATATATG 
               
               
                   
               
               
                 TGATTCTGATAAAATAGACATTGCTATTCTGTTTTTTATATGTAAAAACA 
               
               
                   
               
               
                 AAACAAGAAAAAATAGAGAATTCTACATACTAAATCTCTCTCCTTTTTTA 
               
               
                   
               
               
                 ATTTTAATATTTGTTATCATTTATTTATTGGTGCTACTGTTTATCCGTAA 
               
               
                   
               
               
                 TAATTGTGGGGAAAAGATATTAACATCACGTCTTTGTCTCTAGTGCAGTT 
               
               
                   
               
               
                 TTTCGAGATATTCCGTAGTACATATTTATTTTTAAACAACGACAAAGAAA 
               
               
                   
               
               
                 TACAGATATATCTTAAAAAAAAAAAAGCATTTTGTATTAAAGAATTTAAT 
               
               
                   
               
               
                 TCTGATCTCAAAAAAAAAAAAAAAAAA  
               
            
           
         
       
     
     The reverse complement of SEQ ID NO: 1 is provided as SEQ ID NO: 2 herein: 
     
       
         
           
               
            
               
                 (SEQ ID NO: 2) 
               
               
                 TTTTTTTTTTTTTTTTTTGAGATCAGAATTAAATTCTTTAATACAAAATG 
               
               
                   
               
               
                 CTTTTTTTTTTTTAAGATATATCTGTATTTCTTTGTCGTTGTTTAAAAAT 
               
               
                   
               
               
                 AAATATGTACTACGGAATATCTCGAAAAACTGCACTAGAGACAAAGACGT 
               
               
                   
               
               
                 GATGTTAATATCTTTTCCCCACAATTATTACGGATAAACAGTAGCACCAA 
               
               
                   
               
               
                 TAAATAAATGATAACAAATATTAAAATTAAAAAAGGAGAGAGATTTAGTA 
               
               
                   
               
               
                 TGTAGAATTCTCTATTTTTTCTTGTTTTGTTTTTACATATAAAAAACAGA 
               
               
                   
               
               
                 ATAGCAATGTCTATTTTATCAGAATCACATATATACATAAACATATATAT 
               
               
                   
               
               
                 ATATATATACACACAAATACAAGTTGCCAAATATATATATAGTATGTAGA 
               
               
                   
               
               
                 TGTATATTGAAACCTTATTTCAAAGGAATGTGTGCTGGGGAGCCAGGGGA 
               
               
                   
               
               
                 TCGGGGAGGGCAGAGCTGAGTGTTAGCAAAATTAAATATCTGTTCAAGAT 
               
               
                   
               
               
                 AAGCTAGTGACTGTCACCGATCAGGGAGAGAGAGATTGGAAACATGAATT 
               
               
                   
               
               
                 TTATATACAAAAACCGGTACAAATAAGAGAGCAAGAGAGAGCAAAAGATA 
               
               
                   
               
               
                 CATCTCATAAATAGTTGAAATTAAATATTAACCAAGAATACTGAAAAAAA 
               
               
                   
               
               
                 ACCCTACTCTTTAATTAAATTAACTGTTTTAATTTCTAATTAAAAAGGGA 
               
               
                   
               
               
                 TATTAAATAAGTACCGTATATAAAACACTTTCTCTTTTCTCTGCCTCCAC 
               
               
                   
               
               
                 AATGGGCACGTGGATCCTGCCCTGTCTCTCTGTGCCTCGGGAAGGGAAGG 
               
               
                   
               
               
                 GAAGGACCAGGGGATGGAGGAAGGTCAACCACTCACACACACACAACCAG 
               
               
                   
               
               
                 GTCTCCTGGGGGGACAGAACTAGTGGTTTCAATGGTGTGAGGACATAGGT 
               
               
                   
               
               
                 CCTTTTAGGCTGCACCCCAGGAAGGGGAGCAGGAAGAGGATGAGGGCGAG 
               
               
                   
               
               
                 TCCCAGGAAGGGGAGCTGTCATGGGCTGCTTCTTCCAACAATGTGTCTCT 
               
               
                   
               
               
                 TCTCTTCGCCGGGACATCTGCCAGTGGTCTCCTGGGCAACTCAGAAGCAG 
               
               
                   
               
               
                 GTGAGAGTAAGCGAAGGCCGCCCAGGCTCCTGAATCTTCCAGGCAGTGCC 
               
               
                   
               
               
                 CCTGGGGGCGAGATGCGCGTGCAGCATGTGGAGGGAATCCCCAAAGCACA 
               
               
                   
               
               
                 GCAATGTCCTGAAGCTCCCCAAACTCCTGGTCAGAGCCGGTGTCCTCATC 
               
               
                   
               
               
                 CCTGTACCTGTGATCTGTCTTTCTGTCCGTCTGACCTGGGGTAGAGAGGC 
               
               
                   
               
               
                 TCAGCGCCAGGGCTGGGTTTGTCGGTGTTCCCAAAACTGGGTCATATTTG 
               
               
                   
               
               
                 CCCCCATGCCCTGGCCTTGCACATTCCTGGGCAGGGGAGAGGACCCTGGC 
               
               
                   
               
               
                 CCCACCAAGTGGGACAAAAAAAAGATCATGCCAGAGTCTCTCATCTCCTC 
               
               
                   
               
               
                 CTCTTCCCTGTCAGGATCTGAGTGGGAACATTCCCCTCCCAACTCAAGTC 
               
               
                   
               
               
                 CACAGCAGTCAAATACATCCAGTGAAGACACCAATAACATTAGCACTGTT 
               
               
                   
               
               
                 AATTTAAAAAAAGAATATATATATTTTATATATATAAAATAGAGATATTT 
               
               
                   
               
               
                 ATTTTTATATATATATAATATATATATATATAAATGTATGTATGTGGGTG 
               
               
                   
               
               
                 GGTGTGTCTACAGGAATCCCAGAAATAAAACTCTCTAATCTTCCGGGCTC 
               
               
                   
               
               
                 GGTGATTTAGCAGCAAGAAAAATAAAATGGCGAATCCAATTCCAAGAGGG 
               
               
                   
               
               
                 ACCGTGCTGGGTCACCCGCCCGGGAATGCTTCCGCCGGAGTCTCGCCCTC 
               
               
                   
               
               
                 CGGACCCAAAGTGCTCTGCGCAGAGTCTCCTCTTCCTTCATTTCAGGTTT 
               
               
                   
               
               
                 CTGGATTAAGGACTGTTCTGTCGATGGTGATGGTGTGGTGGCGGCAGCGT 
               
               
                   
               
               
                 GGTTTCTGTATCGATCGTTCTGTATCAGTCTTTCCTGGTGAGAGATCTGG 
               
               
                   
               
               
                 TTCCCGAAACCCTGAGGGAGGCTCCTTCCTCCTGCCCGGCTCACCGCCTC 
               
               
                   
               
               
                 GGCTTGTCACATCTGCAAGTACGTTCGTTTAACTCAAGCTGCCTCGCCTT 
               
               
                   
               
               
                 GCAACGCGAGTCTGTGTTTTTGCAGGAACATTTACACGTCTGCGGATCTT 
               
               
                   
               
               
                 GTACAAACAAATGCTTTCTCCGCTCTGAGCAAGGCCCACAGGGATGGGGG 
               
               
                   
               
               
                 CCAGGGAGGCTCCAGGGCATTAGACAGCAGCGGGCACCAACGTACACGCT 
               
               
                   
               
               
                 CCAGGACTTATACCGGGATTTCTTGCGCTTTCGTTTTTGCCCCTTTCCCT 
               
               
                   
               
               
                 TTCCTCGAACTGATTTTTTTTCTTGTCTTGCTCTATCTTTCTTTGGTCTG 
               
               
                   
               
               
                 CATTCACATTTGTTGTGCTGTAGGAAGCTCATCTCTCCTATGTGCTGGCC 
               
               
                   
               
               
                 TTGGTGAGGTTTGATCCGCATAATCTGCATGGTGATGTTGGACTCCTCAG 
               
               
                   
               
               
                 TGGGCACACACTCCAGGCCCTCGTCATTGCAGCAGCCCCCGCATCGCATC 
               
               
                   
               
               
                 AGGGGCACACAGGATGGCTTGAAGATGTACTCGATCTCATCAGGGTACTC 
               
               
                   
               
               
                 CTGGAAGATGTCCACCAGGGTCTCGATTGGATGGCAGTAGCTGCGCTGAT 
               
               
                   
               
               
                 AGACATCCATGAACTTCACCACTTCGTGATGATTCTGCCCTCCTCCTTCT 
               
               
                   
               
               
                 GCCATGGGTGCAGCCTGGGACCACTTGGCATGGTGGAGGTAGAGCAGCAA 
               
               
                   
               
               
                 GGCAAGGCTCCAATGCACCCAAGACAGCAGAAAGTTCATGGTTTCGGAGG 
               
               
                   
               
               
                 CCCGACCGGGGCCGGCGCGGCTCGCGCTCCCTCTCCGGCTCGGGCTGTGG 
               
               
                   
               
               
                 GGCGGCCCGCTCTCCTCGGCGCCTCGGCGAGCTACTCTTCCTCCCCGGCC 
               
               
                   
               
               
                 CGAGGCCCGGGCCAGGGCCTGGGGAGCGCGCGCGGCTGGAGCACTGTCTG 
               
               
                   
               
               
                 CGCACACCGCCGCCTCACCCGTCCATGAGCCCGGCTTCCGAGCGCCGAGT 
               
               
                   
               
               
                 CGCCACTGCGGCCCCCTCTCCTCTTCCTTCTCTTCTTCCTCCTCCCCCTC 
               
               
                   
               
               
                 CTCCGGCTGCGGCTCCTCCCGGCCCGAGCTAGCACTTCTCGCGGCTCCGC 
               
               
                   
               
               
                 TCGGCTCGGCTTCCCCCGCGCGGACCACGGCTCCTCCGAAGCGAGAACAG 
               
               
                   
               
               
                 CCCAGAAGTTGGACGAAAAGTTTCAGTGCGACGCCGCGAGCCCCGACCCC 
               
               
                   
               
               
                 CTCCACCCCGCCTCCGGGCGCGGGCTCCGGCCCCTGCCCGCGGCTCGCCG 
               
               
                   
               
               
                 CCGCGTCCACTGTCCGCCGCCGGCCGGGGAGGAGGTGGTAGCTGGGGCTG 
               
               
                   
               
               
                 GGGGCGGTGTCTGTCTGTCTGTCCGTCAGCGCGACTGGTCAGCTGCGGGA 
               
               
                   
               
               
                 TCCCAAGGGGGAGGGCTCACGCCGCGCTCCGGCGGTCACCCCCAAAAGCA 
               
               
                   
               
               
                 GGTCACTCACTTTGCCCCTGTCGCTTTCGCTGCTCGCACGCCCGCGCGCT 
               
               
                   
               
               
                 CTCTCTGACCCCGTCTCTCTCTTCCTCGACTTCTCTCTGGAGCTCTTGCT 
               
               
                   
               
               
                 ACCTCTTTCCTCTTTCTGCTGGTTTCCAAAATCCACAGTGATTTGGGGAA 
               
               
                   
               
               
                 GTAGAGCAATCTCCCCAAGCCGTCGGCCCGATTCAAGTGGGGAATGGCAA 
               
               
                   
               
               
                 GCAAAAATAAATTAAAACGAGAAACAATACAGTTTTAAAAAAAAATGTTT 
               
               
                   
               
               
                 AAGAAAAAAGAAGAGGGATAAAACCCGGATCAATGAATATCAAATTCCAG 
               
               
                   
               
               
                 CACCGAGCGCCCTGGCCGGTGAGTCCGCTGACCGGTCCACCTAACCGCTG 
               
               
                   
               
               
                 CGCCTCCCGACAGAGCGCTGGTGCTAGCCCCCAGCGCCACGACCTCCGAG 
               
               
                   
               
               
                 CTACCCGGCTGCCCCAAGCCTCCGCGA  
               
            
           
         
       
     
     In some embodiments, an iRNA described herein includes at least 15 contiguous nucleotides from one of the sequences provided in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B, and may optionally be coupled to additional nucleotide sequences taken from the region contiguous to the selected sequence in VEGF-A. 
     While a target sequence is generally 15-30 nucleotides in length, there is wide variation in the suitability of particular sequences in this range for directing cleavage of any given target RNA. Various software packages and the guidelines set out herein provide guidance for the identification of optimal target sequences for any given gene target, but an empirical approach can also be taken in which a “window” or “mask” of a given size (as a non-limiting example, 21 nucleotides) is literally or figuratively (including, e.g., in silico) placed on the target RNA sequence to identify sequences in the size range that may serve as target sequences. By moving the sequence “window” progressively one nucleotide upstream or downstream of an initial target sequence location, the next potential target sequence can be identified, until the complete set of possible sequences is identified for any given target size selected. This process, coupled with systematic synthesis and testing of the identified sequences (using assays described herein or known in the art) to identify those sequences that perform optimally can identify those RNA sequences that, when targeted with an iRNA agent, mediate the best inhibition of target gene expression. Thus, it is contemplated that further optimization of inhibition efficiency can be achieved by progressively “walking the window” one nucleotide upstream or downstream of the given sequences to identify sequences with equal or better inhibition characteristics. 
     Further, it is contemplated that for any sequence identified, e.g., in Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B, further optimization can be achieved by systematically either adding or removing nucleotides to generate longer or shorter sequences and testing those and sequences generated by walking a window of the longer or shorter size up or down the target RNA from that point. Again, coupling this approach to generating new candidate targets with testing for effectiveness of iRNAs based on those target sequences in an inhibition assay as known in the art or as described herein can lead to further improvements in the efficiency of inhibition. Further still, such optimized sequences can be adjusted by, e.g., the introduction of modified nucleotides as described herein or as known in the art, addition or changes in overhang, or other modifications as known in the art and/or discussed herein to further optimize the molecule (e.g., increasing serum stability or circulating half-life, increasing thermal stability, enhancing transmembrane delivery, targeting to a particular location or cell type, increasing interaction with silencing pathway enzymes, increasing release from endosomes, etc.) as an expression inhibitor. 
     In some embodiments, the disclosure provides an iRNA of any of Tables 2B, 3B, 4B, 5B, 8B, 10B, 14, or 18B that un-modified or un-conjugated. In some embodiments, an RNAi agent of the disclosure has a nucleotide sequence as provided in any of Tables 2A, 3A, 4A, 5A, 8A, 10A, 12, 13 14, and 18A but lacks one or more ligand or moiety shown in the table. A ligand or moiety (e.g., a lipophilic ligand or moiety) can be included in any of the positions provided in the instant application. 
     An iRNA as described herein can contain one or more mismatches to the target sequence. In some embodiments, an iRNA as described herein contains no more than 3 mismatches. In some embodiments, when the antisense strand of the iRNA contains mismatches to a target sequence, the area of mismatch is not located in the center of the region of complementarity. In some embodiments, when the antisense strand of the iRNA contains mismatches to the target sequence, the mismatch is restricted to be within the last 5 nucleotides from either the 5′ or 3′ end of the region of complementarity. For example, for a 23 nucleotide iRNA agent RNA strand which is complementary to a region of VEGF-A, the RNA strand generally does not contain any mismatch within the central 13 nucleotides. The methods described herein, or methods known in the art can be used to determine whether an iRNA containing a mismatch to a target sequence is effective in inhibiting the expression of VEGF-A. Consideration of the efficacy of iRNAs with mismatches in inhibiting expression of VEGF-A is important, especially if the particular region of complementarity in a VEGF-A gene is known to have polymorphic sequence variation within the population. 
     In some embodiments, at least one end of a dsRNA has a single-stranded nucleotide overhang of 1 to 4, generally 1 or 2 nucleotides. In some embodiments, dsRNAs having at least one nucleotide overhang have superior inhibitory properties relative to their blunt-ended counterparts. In some embodiments, the RNA of an iRNA (e.g., a dsRNA) is chemically modified to enhance stability or other beneficial characteristics. The nucleic acids featured in the disclosure may be synthesized and/or modified by methods well established in the art, such as those described in “Current protocols in nucleic acid chemistry,” Beaucage, S. L. et al. (Edrs.), John Wiley &amp; Sons, Inc., New York, N.Y., USA, which is hereby incorporated herein by reference. Modifications include, for example, (a) end modifications, e.g., 5′ end modifications (phosphorylation, conjugation, inverted linkages, etc.) 3′ end modifications (conjugation, DNA nucleotides, inverted linkages, etc.), (b) base modifications, e.g., replacement with stabilizing bases, destabilizing bases, or bases that base pair with an expanded repertoire of partners, removal of bases (abasic nucleotides), or conjugated bases, (c) sugar modifications (e.g., at the 2′ position or 4′ position, or having an acyclic sugar) or replacement of the sugar, as well as (d) backbone modifications, including modification or replacement of the phosphodiester linkages. Specific examples of RNA compounds useful in this disclosure include, but are not limited to, RNAs containing modified backbones or no natural internucleoside linkages. RNAs having modified backbones include, among others, those that do not have a phosphorus atom in the backbone. For the purposes of this specification, and as sometimes referenced in the art, modified RNAs that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides. In particular embodiments, the modified RNA will have a phosphorus atom in its internucleoside backbone. 
     Modified RNA backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates including 3′-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3′-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs of these, and those) having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3′-5′ to 5′-3′ or 2′-5′ to 5′-2′. Various salts, mixed salts and free acid forms are also included. 
     Representative U.S. patents that teach the preparation of the above phosphorus-containing linkages include, but are not limited to, U.S. Pat. Nos. 3,687,808; 4,469,863; 4,476,301; 5,023,243; 5,177,195; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,316; 5,550,111; 5,563,253; 5,571,799; 5,587,361; 5,625,050; 6,028,188; 6,124,445; 6,160,109; 6,169,170; 6,172,209; 6,239,265; 6,277,603; 6,326,199; 6,346,614; 6,444,423; 6,531,590; 6,534,639; 6,608,035; 6,683,167; 6,858,715; 6,867,294; 6,878,805; 7,015,315; 7,041,816; 7,273,933; 7,321,029; and RE39464, each of which is herein incorporated by reference. 
     Modified RNA backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatoms and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH 2  component parts. 
     Representative U.S. patents that teach the preparation of the above oligonucleosides include, but are not limited to, U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,64,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; and, 5,677,439, each of which is herein incorporated by reference. 
     In other RNA mimetics suitable or contemplated for use in iRNAs, both the sugar and the internucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for hybridization with an appropriate nucleic acid target compound. One such oligomeric compound, an RNA mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA compounds, the sugar backbone of an RNA is replaced with an amide containing backbone, in particular an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone. Representative U.S. patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Further teaching of PNA compounds can be found, for example, in Nielsen et al., Science, 1991, 254, 1497-1500. 
     Some embodiments featured in the disclosure include RNAs with phosphorothioate backbones and oligonucleosides with heteroatom backbones, and in particular —CH 2 —NH—CH 2 —, —CH 2 —N(CH 3 )—O—CH 2 —[known as a methylene (methylimino) or MMI backbone], —CH 2 —O—N(CH 3 )—CH 2 —, —CH 2 —N(CH 3 )—N(CH 3 )—CH 2 — and —N(CH 3 )—CH 2 —CH 2 — [wherein the native phosphodiester backbone is represented as —O—P—O—CH 2 —] of the above-referenced U.S. Pat. No. 5,489,677, and the amide backbones of the above-referenced U.S. Pat. No. 5,602,240. In some embodiments, the RNAs featured herein have morpholino backbone structures of the above-referenced U.S. Pat. No. 5,034,506. 
     Modified RNAs may also contain one or more substituted sugar moieties. The iRNAs, e.g., dsRNAs, featured herein can include one of the following at the 2′ position: OH; F; O-, S-, or N-alkyl; O-, S-, or N-alkenyl; O-, S- or N-alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted C 1  to C 10  alkyl or C 2  to C 10  alkenyl and alkynyl. Exemplary suitable modifications include O[(CH 2 ) n O] m CH 3 , O(CH 2 ). n OCH 3 , O(CH 2 ) n NH 2 , O(CH 2 ) n CH 3 , O(CH 2 ) n ONH 2 , and O(CH 2 ) n ON[(CH 2 ) n CH 3 )] 2 , where n and m are from 1 to about 10. In other embodiments, dsRNAs include one of the following at the 2′ position: C 1  to C 10  lower alkyl, substituted lower alkyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH, SCH 3 , OCN, Cl, Br, CN, CF 3 , OCF 3 , SOCH 3 , SO 2 CH 3 , ONO 2 , N 3 , NH 2 , heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an iRNA, or a group for improving the pharmacodynamic properties of an iRNA, and other substituents having similar properties. In some embodiments, the modification includes a 2′-methoxyethoxy (2′-O—CH 2 CH 2 OCH 3 , also known as 2′-O-(2-methoxyethyl) or 2′-MOE) (Martin et al.,  Helv. Chim. Acta,  1995, 78:486-504) i.e., an alkoxy-alkoxy group. Another exemplary modification is 2′-dimethylaminooxyethoxy, i.e., a O(CH 2 ) 2 ON(CH 3 ) 2  group, also known as 2′-DMAOE, and 2′-dimethylaminoethoxyethoxy (also known in the art as 2′-O-dimethylaminoethoxyethyl or 2′-DMAEOE), i.e., 2′-O—CH 2 —O—CH 2 —N(CH 2 ) 2 . 
     In other embodiments, an iRNA agent comprises one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) acyclic nucleotides (or nucleosides). In certain embodiments, the sense strand or the antisense strand, or both sense strand and antisense strand, include less than five acyclic nucleotides per strand (e.g., four, three, two or one acyclic nucleotides per strand). The one or more acyclic nucleotides can be found, for example, in the double-stranded region, of the sense or antisense strand, or both strands; at the 5′-end, the 3′-end, both of the 5′ and 3′-ends of the sense or antisense strand, or both strands, of the iRNA agent. In some embodiments, one or more acyclic nucleotides are present at positions 1 to 8 of the sense or antisense strand, or both. In some embodiments, one or more acyclic nucleotides are found in the antisense strand at positions 4 to 10 (e.g., positions 6-8) from the 5′-end of the antisense strand. In some embodiments, the one or more acyclic nucleotides are found at one or both 3′-terminal overhangs of the iRNA agent. 
     The term “acyclic nucleotide” or “acyclic nucleoside” as used herein refers to any nucleotide or nucleoside having an acyclic sugar, e.g., an acyclic ribose. An exemplary acyclic nucleotide or nucleoside can include a nucleobase, e.g., a naturally occurring or a modified nucleobase (e.g., a nucleobase as described herein). In certain embodiments, a bond between any of the ribose carbons (C1, C2, C3, C4, or C5), is independently or in combination absent from the nucleotide. In some embodiments, the bond between C2-C3 carbons of the ribose ring is absent, e.g., an acyclic 2′-3′-seco-nucleotide monomer. In other embodiments, the bond between C1-C2, C3-C4, or C4-05 is absent (e.g., a 1′-2′, 3′-4′ or 4′-5′-seco nucleotide monomer). Exemplary acyclic nucleotides are disclosed in U.S. Pat. No. 8,314,227, incorporated herein by reference in its entirely. For example, an acyclic nucleotide can include any of monomers D-J in FIGS. 1-2 of U.S. Pat. No. 8,314,227. In some embodiments, the acyclic nucleotide includes the following monomer: 
     
       
         
         
             
             
         
       
     
     wherein Base is a nucleobase, e.g., a naturally occurring or a modified nucleobase (e.g., a nucleobase as described herein). 
     In certain embodiments, the acyclic nucleotide can be modified or derivatized, e.g., by coupling the acyclic nucleotide to another moiety, e.g., a ligand (e.g., a GalNAc, a cholesterol ligand), an alkyl, a polyamine, a sugar, a polypeptide, among others. 
     In other embodiments, the iRNA agent includes one or more acyclic nucleotides and one or more LNAs (e.g., an LNA as described herein). For example, one or more acyclic nucleotides and/or one or more LNAs can be present in the sense strand, the antisense strand, or both. The number of acyclic nucleotides in one strand can be the same or different from the number of LNAs in the opposing strand. In certain embodiments, the sense strand and/or the antisense strand comprises less than five LNAs (e.g., four, three, two or one LNAs) located in the double stranded region or a 3′-overhang. In other embodiments, one or two LNAs are located in the double stranded region or the 3′-overhang of the sense strand. Alternatively, or in combination, the sense strand and/or antisense strand comprises less than five acyclic nucleotides (e.g., four, three, two or one acyclic nucleotides) in the double-stranded region or a 3′-overhang. In some embodiments, the sense strand of the iRNA agent comprises one or two LNAs in the 3′-overhang of the sense strand, and one or two acyclic nucleotides in the double-stranded region of the antisense strand (e.g., at positions 4 to 10 (e.g., positions 6-8) from the 5′-end of the antisense strand) of the iRNA agent. 
     In other embodiments, inclusion of one or more acyclic nucleotides (alone or in addition to one or more LNAs) in the iRNA agent results in one or more (or all) of: (i) a reduction in an off-target effect; (ii) a reduction in passenger strand participation in RNAi; (iii) an increase in specificity of the guide strand for its target mRNA; (iv) a reduction in a microRNA off-target effect; (v) an increase in stability; or (vi) an increase in resistance to degradation, of the iRNA molecule. 
     Other modifications include 2′-methoxy (2′-OCH 3 ), 2′-5 aminopropoxy (2′-OCH 2 CH 2 CH 2 NH 2 ) and 2′-fluoro (2′-F). Similar modifications may also be made at other positions on the RNA of an iRNA, particularly the 3′ position of the sugar on the 3′ terminal nucleotide or in 2′-5′ linked dsRNAs and the 5′ position of 5′ terminal nucleotide. iRNAs may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar. Representative U.S. patents that teach the preparation of such modified sugar structures include, but are not limited to, U.S. Pat. Nos. 4,981,957; 5,118,800; 5,319,080; 5,359,044; 5,393,878; 5,446,137; 5,466,786; 5,514,785; 5,519,134; 5,567,811; 5,576,427; 5,591,722; 5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,658,873; 5,670,633; and 5,700,920, certain of which are commonly owned with the instant application, and each of which is herein incorporated by reference. 
     An iRNA may also include nucleobase (often referred to in the art simply as “base”) modifications or substitutions. As used herein, “unmodified” or “natural” nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl anal other 8-substituted adenines and guanines, 5-halo, particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-daazaadenine and 3-deazaguanine and 3-deazaadenine. 
     Further nucleobases include those disclosed in U.S. Pat. No. 3,687,808, those disclosed in Modified Nucleosides in Biochemistry, Biotechnology and Medicine, Herdewijn, P. ed. Wiley-VCH, 2008; those disclosed in The Concise Encyclopedia of Polymer Science and Engineering, pages 858-859, Kroschwitz, J. L, ed. John Wiley &amp; Sons, 1990, these disclosed by Englisch et al.,  Angewandte Chemie , International Edition, 1991, 30, 613, and those disclosed by Sanghvi, Y S., Chapter 15 , dsRNA Research and Applications , pages 289-302, Crooke, S. T. and Lebleu, B., Ed., CRC Press, 1993. Certain of these nucleobases are particularly useful for increasing the binding affinity of the oligomeric compounds featured in the disclosure. These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2° C. (Sanghvi, Y. S., Crooke, S. T. and Lebleu, B., Eds., dsRNA Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are exemplary base substitutions, even more particularly when combined with 2′-O-methoxyethyl sugar modifications. 
     Representative U.S. patents that teach the preparation of certain of the above noted modified nucleobases as well as other modified nucleobases include, but are not limited to, the above noted U.S. Pat. No. 3,687,808, as well as U.S. Pat. Nos. 4,845,205; 5,130,30; 5,134,066; 5,175,273; 5,367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908; 5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,594,121, 5,596,091; 5,614,617; 5,681,941; 6,015,886; 6,147,200; 6,166,197; 6,222,025; 6,235,887; 6,380,368; 6,528,640; 6,639,062; 6,617,438; 7,045,610; 7,427,672; and 7,495,088, each of which is herein incorporated by reference, and U.S. Pat. No. 5,750,692, also herein incorporated by reference. 
     The RNA of an iRNA can also be modified to include one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) bicyclic sugar moities. A “bicyclic sugar” is a furanosyl ring modified by the bridging of two atoms. A “bicyclic nucleoside” (“BNA”) is a nucleoside having a sugar moiety comprising a bridge connecting two carbon atoms of the sugar ring, thereby forming a bicyclic ring system. In certain embodiments, the bridge connects the 4′-carbon and the 2′-carbon of the sugar ring. Thus, in some embodiments an agent of the disclosure may include one or more locked nucleic acids (LNAs) (also referred to herein as “locked nucleotides”). In some embodiments, a locked nucleic acid is a nucleotide having a modified ribose moiety in which the ribose moiety comprises an extra bridge connecting, e.g., the 2′ and 4′ carbons. This structure effectively “locks” the ribose in the 3′-endo structural conformation. The addition of locked nucleic acids to siRNAs has been shown to increase siRNA stability in serum, increase thermal stability, and to reduce off-target effects (Elmen, J. et al., (2005)  Nucleic Acids Research  33(1):439-447; Mook, O R. et al., (2007)  Mol Canc Ther  6(3):833-843; Grunweller, A. et al., (2003)  Nucleic Acids Research  31(12):3185-3193). 
     Examples of bicyclic nucleosides for use in the polynucleotides of the disclosure include without limitation nucleosides comprising a bridge between the 4′ and the 2′ ribosyl ring atoms. 
     In certain embodiments, the antisense polynucleotide agents of the disclosure include one or more bicyclic nucleosides comprising a 4′ to 2′ bridge. Examples of such 4′ to 2′ bridged bicyclic nucleosides, include but are not limited to 4′-(CH2)-O-2′ (LNA); 4′-(CH2)-S-2′; 4′-(CH2)2-O-2′ (ENA); 4′-CH(CH3)-O-2′ (also referred to as “constrained ethyl” or “cEt”) and 4′-CH(CH2OCH3)-O-2′ (and analogs thereof; see, e.g., U.S. Pat. No. 7,399,845); 4′-C(CH3)(CH3)-O-2′ (and analogs thereof; see e.g., U.S. Pat. No. 8,278,283); 4′-CH2-N(OCH3)-2′ (and analogs thereof; see e.g., U.S. Pat. No. 8,278,425); 4′-CH2-O—N(CH3)-2′ (see, e.g., U.S. Patent Publication No. 2004/0171570); 4′-CH2-N(R)—O-2′, wherein R is H, C1-C12 alkyl, or a protecting group (see, e.g., U.S. Pat. No. 7,427,672); 4′-CH2-C(H)(CH3)-2′ (see, e.g., Chattopadhyaya et al.,  J. Org. Chem.,  2009, 74, 118-134); and 4′-CH2-C(═CH2)-2′ (and analogs thereof; see, e.g., U.S. Pat. No. 8,278,426). The contents of each of the foregoing are incorporated herein by reference for the methods provided therein. Representative U.S. Patents that teach the preparation of locked nucleic acids include, but are not limited to, the following: U.S. Pat. Nos. 6,268,490; 6,670,461; 6,794,499; 6,998,484; 7,053,207; 7,084,125; 7,399,845, and 8,314,227, each of which is herein incorporated by reference in its entirety. Exemplary LNAs include but are not limited to, a 2′, 4′-C methylene bicyclo nucleotide (see for example Wengel et al., International PCT 5 Publication No. WO 00/66604 and WO 99/14226). 
     Any of the foregoing bicyclic nucleosides can be prepared having one or more stereochemical sugar configurations including for example α-L-ribofuranose and β-D-ribofuranose (see WO 99/14226). 
     A RNAi agent of the disclosure can also be modified to include one or more constrained ethyl nucleotides. As used herein, a “constrained ethyl nucleotide” or “cEt” is a locked nucleic acid comprising a bicyclic sugar moiety comprising a 4′-CH(CH3)-O-2′ bridge. In some embodiments, a constrained ethyl nucleotide is in the S conformation referred to herein as “S-cEt.” 
     A RNAi agent of the disclosure may also include one or more “conformationally restricted nucleotides” (“CRN”). CRN are nucleotide analogs with a linker connecting the C2′ and C4′ carbons of ribose or the C3 and —C5′ carbons of ribose. CRN lock the ribose ring into a stable conformation and increase the hybridization affinity to mRNA. The linker is of sufficient length to place the oxygen in an optimal position for stability and affinity resulting in less ribose ring puckering. 
     Representative publications that teach the preparation of certain of the above noted CRN include, but are not limited to, US 2013/0190383; and WO 2013/036868, the contents of each of which are hereby incorporated herein by reference for the methods provided therein. In some embodiments, a RNAi agent of the disclosure comprises one or more monomers that are UNA (unlocked nucleic acid) nucleotides. UNA is unlocked acyclic nucleic acid, wherein any of the bonds of the sugar has been removed, forming an unlocked “sugar” residue. In one example, UNA also encompasses monomer with bonds between C1′-C4′ have been removed (i.e. the covalent carbon-oxygen-carbon bond between the C1′ and C4′ carbons). In another example, the C2′-C3′ bond (i.e. the covalent carbon-carbon bond between the C2′ and C3′ carbons) of the sugar has been removed (see  Nuc. Acids Symp. Series,  52, 133-134 (2008) and Fluiter et al.,  Mol. Biosyst.,  2009, 10, 1039). 
     Representative U.S. publications that teach the preparation of UNA include, but are not limited to, U.S. Pat. No. 8,314,227; and US Patent Publication Nos. 2013/0096289; 2013/0011922; and 2011/0313020, the contents of each of which are hereby incorporated herein by reference for the methods provided therein. 
     In other embodiments, the iRNA agents include one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) G-clamp nucleotides. A G-clamp nucleotide is a modified cytosine analog wherein the modifications confer the ability to hydrogen bond both Watson-Crick and Hoogsteen faces of a complementary guanine within a duplex, see for example Lin and Matteucci, 1998 , J. Am. Chem. Soc.,  120, 8531-8532. A single G-clamp analog substitution within an oligonucleotide can result in substantially enhanced helical thermal stability and mismatch discrimination when hybridized to complementary oligonucleotides. The inclusion of such nucleotides in the iRNA molecules can result in enhanced affinity and specificity to nucleic acid targets, complementary sequences, or template strands. 
     Potentially stabilizing modifications to the ends of RNA molecules can include N-(acetylaminocaproyl)-4-hydroxyprolinol (Hyp-C6-NHAc), N-(caproyl-4-hydroxyprolinol (Hyp-C6), N-(acetyl-4-hydroxyprolinol (Hyp-NHAc), thymidine-2′-O-deoxythymidine (ether), N-(aminocaproyl)-4-hydroxyprolinol (Hyp-C6-amino), 2-docosanoyl-uridine-3″-phosphate, inverted base dT(idT) and others. Disclosure of this modification can be found in PCT Publication No. WO 2011/005861. 
     Other modifications of a RNAi agent of the disclosure include a 5′ phosphate or 5′ phosphate mimic, e.g., a 5′-terminal phosphate or phosphate mimic on the antisense strand of a RNAi agent. Suitable phosphate mimics are disclosed in, for example US 2012/0157511, the contents of which are incorporated herein by reference for the methods provided therein. 
     iRNA Motifs 
     In certain aspects of the disclosure, the double-stranded RNAi agents of the disclosure include agents with chemical modifications as disclosed, for example, in WO 2013/075035, the contents of which are incorporated herein by reference for the methods provided therein. As shown herein and in WO 2013/075035, a superior result may be obtained by introducing one or more motifs of three identical modifications on three consecutive nucleotides into a sense strand or antisense strand of an RNAi agent, particularly at or near the cleavage site. In some embodiments, the sense strand and antisense strand of the RNAi agent may otherwise be completely modified. The introduction of these motifs interrupts the modification pattern, if present, of the sense or antisense strand. The RNAi agent may be optionally conjugated with a lipophilic moiety or ligand, e.g., a C16 moiety or ligand, for instance on the sense strand. The RNAi agent may be optionally modified with a (S)-glycol nucleic acid (GNA) modification, for instance on one or more residues of the antisense strand. The resulting RNAi agents present superior gene silencing activity. 
     In some embodiments, the sense strand sequence may be represented by formula (I): 
       5′n p -N a -(XXX) i -N b -YYY-N b -(ZZZ) j -N a -n q 3′  (I)
 
     wherein: 
     i and j are each independently 0 or 1; 
     p and q are each independently 0-6; 
     each N a  independently represents an oligonucleotide sequence comprising 0-25 modified nucleotides, each sequence comprising at least two differently modified nucleotides; 
     each N b  independently represents an oligonucleotide sequence comprising 0-10 modified nucleotides; 
     each n p  and n q  independently represent an overhang nucleotide; 
     wherein N b  and Y do not have the same modification; and 
     XXX, YYY and ZZZ each independently represent one motif of three identical modifications on three consecutive nucleotides. In some embodiments, YYY is all 2′-F modified nucleotides. 
     In some embodiments, the N a  and/or N b  comprise modifications of alternating pattern. 
     In some embodiments, the YYY motif occurs at or near the cleavage site of the sense strand. For example, when the RNAi agent has a duplex region of 17-23 nucleotides in length, the YYY motif can occur at or the vicinity of the cleavage site (e.g.: can occur at positions 6, 7, 8; 7, 8, 9; 8, 9, 10; 9, 10, 11; 10, 11,12 or 11, 12, 13) of the sense strand, the count starting from the 1 st  nucleotide, from the 5′-end; or optionally, the count starting at the 1 st  paired nucleotide within the duplex region, from the 5′-end. 
     In some embodiments, i is 1 and j is 0, or i is 0 and j is 1, or both i and j are 1. The sense strand can therefore be represented by the following formulas: 
       5′n p -N a -YYY-N b -ZZZ-N a -n q 3′  (Ib);
 
       5′n p -N a -XXX-N b -YYY-N a -n q 3′  (Ic); or
 
       5′n p -N a -XXX-N b -YYY-N b -ZZZ-N a -n q 3′  (Id).
 
     When the sense strand is represented by formula (Ib), N b  represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. Each N a  independently can represent an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. 
     When the sense strand is represented as formula (Ic), N b  represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. Each N a  can independently represent an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. 
     When the sense strand is represented as formula (Id), each N b  independently represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. In some embodiments, N b  1S 0, 1, 2, 3, 4, 5 or 6. Each N a  can independently represent an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. 
     Each of X, Y and Z may be the same or different from each other. 
     In other embodiments, i is 0 and j is 0, and the sense strand may be represented by the formula: 
       5′n p -N a -YYY-N a -n q 3′  (Ia).
 
     When the sense strand is represented by formula (Ia), each N a  independently can represent an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. 
     In some embodiments, the antisense strand sequence of the RNAi may be represented by formula (II): 
       5′n q ′-N a ′-(Z′Z′Z′) k -N b ′-Y′Y′Y′-N b ′-(X′X′X′) l -N′ a -n p ′3′  (II)
 
     wherein: 
     k and l are each independently 0 or 1; 
     p′ and q′ are each independently 0-6; 
     each N a ′ independently represents an oligonucleotide sequence comprising 0-25 modified nucleotides, each sequence comprising at least two differently modified nucleotides; 
     each N b ′ independently represents an oligonucleotide sequence comprising 0-10 modified nucleotides; 
     each n p ′ and n q ′ independently represent an overhang nucleotide; 
     wherein N b ′ and Y′ do not have the same modification; 
     and 
     X′X′X′, Y′Y′Y′, and Z′Z′Z′ each independently represent one of three identical modification on three consecutive nucleotides. 
     In some embodiments, the N a ′ and/or N b ′ comprise modification of alternating pattern. 
     The Y′Y′Y′ motif occurs at or near the cleavage site of the antisense strand. For example, when the RNAi agent has a duplex region of 17-23 nucleotides in length, the Y′Y′Y′ motif can occur at positions 9, 10, 11; 10, 11, 12; 11, 12, 13; 12, 13, 14; or 13, 14, 15 of the antisense strand, with the count starting from the 1 st  nucleotide, from the 5′-end; or optionally, the count starting at the 1 st  paired nucleotide within the duplex region, from the 5′-end. In some embodiments, the Y′Y′Y′ motif occurs at positions 11, 12, 13. 
     In some embodiments, Y′Y′Y′ motif is all 2′-Ome modified nucleotides. 
     In on embodiment, k is 1 and l is 0, or k is 0 and l is 1, or both 5 k and l are 1. 
     The antisense strand can therefore be represented by the following formulas: 
       5′n q ′-N a ′-Z′Z′Z′-N b ′-Y′Y′Y′-N a ′-n p ′3′  (IIb);
 
       5′n q ′-N a ′-Y′Y′Y′-N b ′-X′X′X′-n p ′3′  (IIc); or
 
       5′n q ′-N a ′-Z′Z′Z′-N b ′-Y′Y′Y′-N b ′-X′X′X′-N a ′-n p ′3′  (IId).
 
     When the antisense strand is represented by formula (IIb), N b ′ represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. Each N a ′ independently represents an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. 
     When the antisense strand is represented as formula (IId), each N b ′ independently represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. Each N a ′ independently represents an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. In some embodiments, N b  is 0, 1, 2, 3, 4, 5 or 6. 
     In other embodiments, k is 0 and l is 0 and the antisense strand may be represented by the formula: 
       5′n p ′-N a ′-Y′Y′Y′-N a ′-n q ′3′  (Ia).
 
     When the antisense strand is represented as formula (IIa), each N a ′ independently represents an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. 
     Each of X′, Y′ and Z′ may be the same or different from each other. 
     Each nucleotide of the sense strand and antisense strand may be independently modified with LNA, HNA, CeNA, GNA, 2′-methoxyethyl, 2′-O-methyl, 2′-O-allyl, 2′-C-allyl, 2′-hydroxyl, or 2′-fluoro. For example, each nucleotide of the sense strand and antisense strand is independently modified with 2′-O-methyl or 2′-fluoro. Each X, Y, Z, X′, Y′ and Z′, in particular, may represent a 2′-O-methyl modification or a 2′-fluoro modification. 
     In some embodiments, the sense strand of the RNAi agent may contain YYY motif occurring at 9, 10 and 11 positions of the strand when the duplex region is 21 nt, the count starting from the 1 st  nucleotide from the 5′-end, or optionally, the count starting at the 1 st  paired nucleotide within the duplex region, from the 5′-end; and Y represents 2′-F modification. The sense strand may additionally contain XXX motif or ZZZ motifs as wing modifications at the opposite end of the duplex region; and XXX and ZZZ each independently represents a 2′-OMe modification or 2′-F modification. 
     In some embodiments the antisense strand may Y′Y′Y′ motif occurring at positions 11, 12, 13 of the strand, the count starting from the 1 st  nucleotide from the 5′-end, or optionally, the count starting at the 1 st  paired nucleotide within the duplex region, from the 5′-end; and Y′ represents 2′-O-methyl modification. The antisense strand may additionally contain X′X′X′ motif or Z′Z′Z′ motifs as wing modifications at the opposite end of the duplex region; and X′X′X′ and Z′Z′Z′ each independently represents a 2′-OMe modification or 2′-F modification. 
     The sense strand represented by any one of the above formulas (Ia), (Ib), (Ic), and (Id) forms a duplex with an antisense strand being represented by any one of formulas (IIa), (IIb), (IIc), and (IId), respectively. 
     Accordingly, certain RNAi agents for use in the methods of the disclosure may comprise a sense strand and an antisense strand, each strand having 14 to 30 nucleotides, the RNAi duplex represented by formula (III): 
       sense: 5′n p -N a -(XXX) i -N b -YYY-N b -(ZZZ) j -N a -n q 3′
 
       antisense: 3′n p ′-N a ′-(X′X′X′) k -N b ′-Y′Y′Y′-N b ′-(Z′Z′Z′) l -N a ′-n q ′5′   (III)
 
     wherein, 
     i, j, k, and l are each independently 0 or 1; 
     p, p′, q, and q′ are each independently 0-6; 
     each N a  and N a ′ independently represents an oligonucleotide sequence comprising 0-25 modified nucleotides, each sequence comprising at least two differently modified nucleotides; 
     each N b  and N b ′ independently represents an oligonucleotide sequence comprising 0-10 modified nucleotides; 
     wherein 
     each n p ′, n p , n q ′, and n q , each of which may or may not be present independently represents an overhang nucleotide; and 
     XXX, YYY, ZZZ, X′X′X′, Y′Y′Y′, and Z′Z′Z′ each independently represent one motif of three identical modification on three consecutive nucleotides. 
     In some embodiments, i is 0 and j is 0; or i is 1 and j is 0; or i is 0 and j is 1; or both i and j are 0; or both i and j are 1. In some embodiments, k is 0 and l is 0; or k is 1 and l is 0; k is 0 and l is 1; or both k and l are 0; or both k and l are 1. 
     Exemplary combinations of the sense strand and antisense strand forming a RNAi duplex include the formulas below: 
       5′n p -N a -YYY-N a -n q 3′
 
       3′n p ′-N a ′-Y′Y′Y′-N a ′n q ′5′   (IIIa)
 
       5′n p -N a -YYY-N b -ZZZ-N a -n q 3′
 
       3′n p -N a ′-Y′Y′Y′-N b ′-Z′Z′Z′-N a ′-n q ′5′   (IIIb)
 
       5′n p -N a -XXX-N b -YYY-N a -n q 3′
 
       3′n p -N a ′-X′X′X′-N b ′-Y′Y′Y′-N a ′-n q ′5′   (IIIc)
 
       5′n p -N a -XXX-N b -YYY-N b -ZZZ-N a -n q 3′
 
       3′n p -N a ′-X′X′X′-N b ′-Y′Y′Y′-N b ′-Z′Z′Z′-N a ′-n q ′5′   (IIId)
 
     When the RNAi agent is represented by formula (IIIa), each N a  independently represents an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. 
     When the RNAi agent is represented by formula (IIIb), each N b  independently represents an oligonucleotide sequence comprising 1-10, 1-7, 1-5 or 1-4 modified nucleotides. Each N a  independently represents an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. 
     When the RNAi agent is represented as formula (IIIc), each N b , N b ′ independently represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. Each N a  independently represents an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. 
     When the RNAi agent is represented as formula (IIId), each N b , N b ′ independently represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. Each N a , N a ′ independently represents an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. Each of N a , N a ′, N b  and N b ′ independently comprises modifications of alternating pattern. 
     Each of X, Y and Z in formulas (III), (IIIa), (IIIb), (IIIc), and (IIId) may be the same or different from each other. 
     When the RNAi agent is represented by formula (III), (IIIa), (IIIb), (IIIc), and (IIId), at least one of the Y nucleotides may form a base pair with one of the Y′ nucleotides. Alternatively, at least two of the Y nucleotides form base pairs with the corresponding Y′ nucleotides; or all three of the Y nucleotides all form base pairs with the corresponding Y′ nucleotides. 
     When the RNAi agent is represented by formula (IIIb) or (IIId), at least one of the Z nucleotides may form a base pair with one of the Z′ nucleotides. Alternatively, at least two of the Z nucleotides form base pairs with the corresponding Z′ nucleotides; or all three of the Z nucleotides all form base pairs with the corresponding Z′ nucleotides. 
     When the RNAi agent is represented as formula (IIIc) or (IIId), at least one of the X nucleotides may form a base pair with one of the X′ nucleotides. Alternatively, at least two of the X nucleotides form base pairs with the corresponding X′ nucleotides; or all three of the X nucleotides all form base pairs with the corresponding X′ nucleotides. 
     In some embodiments, the modification on the Y nucleotide is different than the modification on the Y′ nucleotide, the modification on the Z nucleotide is different than the modification on the Z′ nucleotide, and/or the modification on the X nucleotide is different than the modification on the X′ nucleotide. 
     In some embodiments, when the RNAi agent is represented by formula (IIId), the N a  modifications are 2′-O-methyl or 2′-fluoro modifications. In some embodiments, when the RNAi agent is represented by formula (IIId), the N a  modifications are 2′-O-methyl or 2′-fluoro modifications and n p ′&gt;0 and at least one n p ′ is linked to a neighboring nucleotide a via phosphorothioate linkage. In some embodiments, when the RNAi agent is represented by formula (IIId), the N a  modifications are 2′-O-methyl or 2′-fluoro modifications, n p ′&gt;0 and at least one n p ′ is linked to a neighboring nucleotide via phosphorothioate linkage, and the sense strand is conjugated to one or more moieties or ligands (e.g., one or more lipophilic moieties, optionally one or more C16 moieties, or one or more GalNAc moieties) attached through a bivalent or trivalent branched linker. In some embodiments, when the RNAi agent is represented by formula (IIId), the N a  modifications are 2′-O-methyl or 2′-fluoro modifications, n p ′&gt;0 and at least one n p ′ is linked to a neighboring nucleotide via phosphorothioate linkage, the sense strand comprises at least one phosphorothioate linkage, and the sense strand is conjugated to one or more moieties or ligands (e.g., one or more lipophilic moieties, optionally one or more C16 moieties, or one or more GalNAc moieties) attached through a bivalent or trivalent branched linker. 
     In some embodiments, when the RNAi agent is represented by formula (IIIa), the N a  modifications are 2′-O-methyl or 2′-fluoro modifications, n p ′&gt;0 and at least one n p ′ is linked to a neighboring nucleotide via phosphorothioate linkage, the sense strand comprises at least one phosphorothioate linkage, and the sense strand is conjugated to one or more moieties or ligands (e.g., one or more lipophilic moieties, optionally one or more C16 moieties, or one or more GalNAc moieties) attached through a bivalent or trivalent branched linker. 
     In some embodiments, the RNAi agent is a multimer containing at least two duplexes represented by formula (III), (IIIa), (IIIb), (IIIc), and (IIId), wherein the duplexes are connected by a linker. The linker can be cleavable or non-cleavable. Optionally, the multimer further comprises a ligand. Each of the duplexes can target the same gene or two different genes; or each of the duplexes can target same gene at two different target sites. 
     In some embodiments, the RNAi agent is a multimer containing three, four, five, six or more duplexes represented by formula (III), (IIIa), (IIIb), (IIIc), and (IIId), wherein the duplexes are connected by a linker. The linker can be cleavable or non-cleavable. Optionally, the multimer further comprises a ligand. Each of the duplexes can target the same gene or two different genes; or each of the duplexes can target same gene at two different target sites. 
     In some embodiments, two RNAi agents represented by formula (III), (IIIa), (IIIb), (IIIc), and (IIId) are linked to each other at the 5′ end, and one or both of the 3′ ends and are optionally conjugated to a ligand. Each of the agents can target the same gene or two different genes; or each of the agents can target same gene at two different target sites. 
     Various publications describe multimeric RNAi agents that can be used in the methods of the disclosure. Such publications include WO2007/091269, WO2010/141511, WO2007/117686, WO2009/014887, and WO2011/031520; and U.S. Pat. No. 7,858,769, the contents of each of which are hereby incorporated herein by reference for the methods provided therein. In certain embodiments, the RNAi agents of the disclosure may include GalNAc ligands. 
     As described in more detail below, the RNAi agent that contains conjugations of one or more carbohydrate moieties to a RNAi agent can optimize one or more properties of the RNAi agent. In many cases, the carbohydrate moiety will be attached to a modified subunit of the RNAi agent. For example, the ribose sugar of one or more ribonucleotide subunits of a dsRNA agent can be replaced with another moiety, e.g., a non-carbohydrate (preferably cyclic) carrier to which is attached a carbohydrate ligand. A ribonucleotide subunit in which the ribose sugar of the subunit has been so replaced is referred to herein as a ribose replacement modification subunit (RRMS). A cyclic carrier may be a carbocyclic ring system, i.e., all ring atoms are carbon atoms, or a heterocyclic ring system, i.e., one or more ring atoms may be a heteroatom, e.g., nitrogen, oxygen, sulfur. The cyclic carrier may be a monocyclic ring system, or may contain two or more rings, e.g. fused rings. The cyclic carrier may be a fully saturated ring system, or it may contain one or more double bonds. 
     The ligand may be attached to the polynucleotide via a carrier. The carriers include (i) at least one “backbone attachment point,” preferably two “backbone attachment points” and (ii) at least one “tethering attachment point.” A “backbone attachment point” as used herein refers to a functional group, e.g. a hydroxyl group, or generally, a bond available for, and that is suitable for incorporation of the carrier into the backbone, e.g., the phosphate, or modified phosphate, e.g., sulfur containing, backbone, of a ribonucleic acid. A “tethering attachment point” (TAP) in some embodiments refers to a constituent ring atom of the cyclic carrier, e.g., a carbon atom or a heteroatom (distinct from an atom which provides a backbone attachment point), that connects a selected moiety. The moiety can be, e.g., a carbohydrate, e.g. monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, and polysaccharide. Optionally, the selected moiety is connected by an intervening tether to the cyclic carrier. Thus, the cyclic carrier will often include a functional group, e.g., an amino group, or generally, provide a bond, that is suitable for incorporation or tethering of another chemical entity, e.g., a ligand to the constituent ring. 
     The RNAi agents may be conjugated to a ligand via a carrier, wherein the carrier can be cyclic group or acyclic group; preferably, the cyclic group is selected from pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, [1,3]dioxolane, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, quinoxalinyl, pyridazinonyl, tetrahydrofuryl and decalin; preferably, the acyclic group is selected from serinol backbone or diethanolamine backbone. 
     In certain specific embodiments, the RNAi agent for use in the methods of the disclosure is an agent selected from the group of agents listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. These agents may further comprise a ligand. The ligand can be attached to the sense strand, antisense strand or both strands, at the 3′-end, 5′-end, or both ends. For instance, the ligand may be conjugated to the sense strand, in particular, the 3′-end of the sense strand. 
     iRNA Conjugates 
     The iRNA agents disclosed herein can be in the form of conjugates. The conjugate may be attached at any suitable location in the iRNA molecule, e.g., at the 3′ end or the 5′ end of the sense or the antisense strand. The conjugates are optionally attached via a linker. 
     In some embodiments, an iRNA agent described herein is chemically linked to one or more ligands, moieties or conjugates, which may confer functionality, e.g., by affecting (e.g., enhancing) the activity, cellular distribution or cellular uptake of the iRNA. Such moieties include but are not limited to lipid moieties such as a cholesterol moiety (Letsinger et al.,  Proc. Natl. Acid. Sci. USA,  1989, 86: 6553-6556), cholic acid (Manoharan et al.,  Biorg. Med. Chem. Let.,  1994, 4:1053-1060), a thioether, e.g., beryl-S-tritylthiol (Manoharan et al.,  Ann. N.Y. Acad. Sci.,  1992, 660:306-309; Manoharan et al.,  Biorg. Med. Chem. Let.,  1993, 3:2765-2770), a thiocholesterol (Oberhauser et al.,  Nucl. Acids Res.,  1992, 20:533-538), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al.,  EMBO J,  1991, 10:1111-1118; Kabanov et al.,  FEBS Lett.,  1990, 259:327-330; Svinarchuk et al.,  Biochimie,  1993, 75:49-54), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethyl-ammonium 1,2-di-O-hexadecyl-rac-glycero-3-phosphonate (Manoharan et al.,  Tetrahedron Lett.,  1995, 36:3651-3654; Shea et al.,  Nucl. Acids Res.,  1990, 18:3777-3783), a polyamine or a polyethylene glycol chain (Manoharan et al.,  Nucleosides  &amp;  Nucleotides,  1995, 14:969-973), or adamantane acetic acid (Manoharan et al.,  Tetrahedron Lett.,  1995, 36:3651-3654), a palmityl moiety (Mishra et al.,  Biochim. Biophys. Acta,  1995, 1264:229-237), or an octadecylamine or hexylamino-carbonyloxycholesterol moiety (Crooke et al.,  J. Pharmacol. Exp. Ther.,  1996, 277:923-937). 
     In some embodiments, a ligand alters the distribution, targeting or lifetime of an iRNA agent into which it is incorporated. In some embodiments, a ligand provides an enhanced affinity for a selected target, e.g., molecule, cell or cell type, compartment, e.g., a cellular or organ compartment, tissue, organ or region of the body, as, e.g., compared to a species absent such a ligand. Typical ligands will not take part in duplex pairing in a duplexed nucleic acid. 
     Ligands can include a naturally occurring substance, such as a protein (e.g., human serum albumin (HSA), low-density lipoprotein (LDL), or globulin); carbohydrate (e.g., a dextran, pullulan, chitin, chitosan, inulin, cyclodextrin or hyaluronic acid); or a lipid. The ligand may also be a recombinant or synthetic molecule, such as a synthetic polymer, e.g., a synthetic polyamino acid. Examples of polyamino acids include polyamino acid is a polylysine (PLL), poly L-aspartic acid, poly L-glutamic acid, styrene-maleic acid anhydride copolymer, poly(L-lactide-co-glycolide) copolymer, divinyl ether-maleic anhydride copolymer, N-(2-hydroxypropyl)methacrylamide copolymer (HMPA), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyurethane, poly(2-ethylacrylic acid), N-isopropylacrylamide polymers, or polyphosphazine. Examples of polyamines include: polyethylenimine, polylysine (PLL), spermine, spermidine, polyamine, pseudopeptide-polyamine, peptidomimetic polyamine, dendrimer polyamine, arginine, amidine, protamine, cationic lipid, cationic porphyrin, quaternary salt of a polyamine, or an a helical peptide. 
     Ligands can also include targeting groups, e.g., a cell or tissue targeting agent, e.g., a lectin, glycoprotein, lipid or protein, e.g., an antibody, that binds to a specified cell type such as a kidney cell. A targeting group can be a thyrotropin, melanotropin, lectin, glycoprotein, surfactant protein A, Mucin carbohydrate, multivalent lactose, multivalent galactose, N-acetyl-galactosamine, N-acetyl-gulucosamine multivalent mannose, multivalent fucose, glycosylated polyaminoacids, multivalent galactose, transferrin, bisphosphonate, polyglutamate, polyaspartate, a lipid, cholesterol, a steroid, bile acid, folate, vitamin B12, biotin, or an RGD peptide or RGD peptide mimetic. 
     Other examples of ligands include dyes, intercalating agents (e.g. acridines), cross-linkers (e.g. psoralene, mitomycin C), porphyrins (TPPC4, texaphyrin, Sapphyrin), polycyclic aromatic hydrocarbons (e.g., phenazine, dihydrophenazine), artificial endonucleases (e.g. EDTA), lipophilic molecules, e.g, cholesterol, cholic acid, adamantane acetic acid, 1-pyrene butyric acid, dihydrotestosterone, 1,3-Bis-O(hexadecyl)glycerol, geranyloxyhexyl group, hexadecylglycerol, borneol, menthol, 1,3-propanediol, heptadecyl group, palmitic acid, myristic acid, O3-(oleoyl)lithocholic acid, O3-(oleoyl)cholenic acid, dimethoxytrityl, or phenoxazine) and peptide conjugates (e.g., antennapedia peptide, Tat peptide), alkylating agents, phosphate, amino, mercapto, PEG (e.g., PEG-40K), MPEG, [MPEG] 2 , polyamino, alkyl, substituted alkyl, radiolabeled markers, enzymes, haptens (e.g. biotin), transport/absorption facilitators (e.g., aspirin, vitamin E, folic acid), synthetic ribonucleases (e.g., imidazole, bisimidazole, histamine, imidazole clusters, acridine-imidazole conjugates, Eu3+ complexes of tetraazamacrocycles), dinitrophenyl, HRP, or AP. 
     Ligands can be proteins, e.g., glycoproteins, or peptides, e.g., molecules having a specific affinity for a co-ligand, or antibodies e.g., an antibody, that binds to a specified cell type such as an ocular cell. Ligands may also include hormones and hormone receptors. They can also include non-peptidic species, such as lipids, lectins, carbohydrates, vitamins, cofactors, multivalent lactose, multivalent galactose, N-acetyl-galactosamine, N-acetyl-glucosamine multivalent mannose, or multivalent fucose. The ligand can be, for example, a lipopolysaccharide, an activator of p38 MAP kinase, or an activator of NF-κB. 
     The ligand can be a substance, e.g., a drug, which can increase the uptake of the iRNA agent into the cell, for example, by disrupting the cell&#39;s cytoskeleton, e.g., by disrupting the cell&#39;s microtubules, microfilaments, and/or intermediate filaments. The drug can be, for example, taxon, vincristine, vinblastine, cytochalasin, nocodazole, japlakinolide, latrunculin A, phalloidin, swinholide A, indanocine, or myoservin. 
     In some embodiments, a ligand attached to an iRNA as described herein acts as a pharmacokinetic modulator (PK modulator). PK modulators include lipophiles, bile acids, steroids, phospholipid analogues, peptides, protein binding agents, PEG, vitamins etc. Exemplary PK modulators include, but are not limited to, cholesterol, fatty acids, cholic acid, lithocholic acid, dialkylglycerides, diacylglyceride, phospholipids, sphingolipids, naproxen, ibuprofen, vitamin E, biotin etc. Oligonucleotides that comprise a number of phosphorothioate linkages are also known to bind to serum protein, thus short oligonucleotides, e.g., oligonucleotides of about 5 bases, 10 bases, 15 bases or 20 bases, comprising multiple of phosphorothioate linkages in the backbone are also amenable to the present disclosure as ligands (e.g. as PK modulating ligands). In addition, aptamers that bind serum components (e.g. serum proteins) are also suitable for use as PK modulating ligands in the embodiments described herein. 
     Ligand-conjugated oligonucleotides of the disclosure may be synthesized by the use of an oligonucleotide that bears a pendant reactive functionality, such as that derived from the attachment of a linking molecule onto the oligonucleotide (described below). This reactive oligonucleotide may be reacted directly with commercially available ligands, ligands that are synthesized bearing any of a variety of protecting groups, or ligands that have a linking moiety attached thereto. 
     The oligonucleotides used in the conjugates of the present disclosure may be conveniently and routinely made through the well-known technique of solid-phase synthesis. Equipment for such synthesis is sold by several vendors including, for example, Applied Biosystems (Foster City, Calif.). Any other means for such synthesis known in the art may additionally or alternatively be employed. It is also known to use similar techniques to prepare other oligonucleotides, such as the phosphorothioates and alkylated derivatives. 
     In the ligand-conjugated oligonucleotides and ligand-molecule bearing sequence-specific linked nucleosides of the present disclosure, the oligonucleotides and oligonucleosides may be assembled on a suitable DNA synthesizer utilizing standard nucleotide or nucleoside precursors, or nucleotide or nucleoside conjugate precursors that already bear the linking moiety, ligand-nucleotide or nucleoside-conjugate precursors that already bear the ligand molecule, or non-nucleoside ligand-bearing building blocks. 
     When using nucleotide-conjugate precursors that already bear a linking moiety, the synthesis of the sequence-specific linked nucleosides is typically completed, and the ligand molecule is then reacted with the linking moiety to form the ligand-conjugated oligonucleotide. In some embodiments, the oligonucleotides or linked nucleosides of the present disclosure are synthesized by an automated synthesizer using phosphoramidites derived from ligand-nucleoside conjugates in addition to the standard phosphoramidites and non-standard phosphoramidites that are commercially available and routinely used in oligonucleotide synthesis. 
     A. Lipophilic Moieties 
     In certain embodiments, the lipophilic moiety is an aliphatic, cyclic such as alicyclic, or polycyclic such as polyalicyclic compound, such as a steroid (e.g., sterol) or a linear or branched aliphatic hydrocarbon. The lipophilic moiety may generally comprise a hydrocarbon chain, which may be cyclic or acyclic. The hydrocarbon chain may comprise various substituents or one or more heteroatoms, such as an oxygen or nitrogen atom. Such lipophilic aliphatic moieties include, without limitation, saturated or unsaturated C 4 -C 30  hydrocarbon (e.g., C 6 -C 18  hydrocarbon), saturated or unsaturated fatty acids, waxes (e.g., monohydric alcohol esters of fatty acids and fatty diamides), terpenes (e.g., C 10  terpenes, C 15  sesquiterpenes, C 20  diterpenes, C 30  triterpenes, and C 40  tetraterpenes), and other polyalicyclic hydrocarbons. For instance, the lipophilic moiety may contain a C 4 -C 30  hydrocarbon chain (e.g., C 4 -C 30  alkyl or alkenyl). In some embodiments the lipophilic moiety contains a saturated or unsaturated C 6 -C 18  hydrocarbon chain (e.g., a linear C 6 -C 18  alkyl or alkenyl). In some embodiments, the lipophilic moiety contains a saturated or unsaturated C 16  hydrocarbon chain (e.g., a linear C 16  alkyl or alkenyl). 
     The lipophilic moiety may be attached to the RNAi agent by any method known in the art, including via a functional grouping already present in the lipophilic moiety or introduced into the RNAi agent, such as a hydroxy group (e.g., —CO—CH 2 —OH). The functional groups already present in the lipophilic moiety or introduced into the RNAi agent include, but are not limited to, hydroxyl, amine, carboxylic acid, sulfonate, phosphate, thiol, azide, and alkyne. 
     Conjugation of the RNAi agent and the lipophilic moiety may occur, for example, through formation of an ether or a carboxylic or carbamoyl ester linkage between the hydroxy and an alkyl group R—, an alkanoyl group RCO— or a substituted carbamoyl group RNHCO—. The alkyl group R may be cyclic (e.g., cyclohexyl) or acyclic (e.g., straight-chained or branched; and saturated or unsaturated). Alkyl group R may be a butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl or octadecyl group, or the like. 
     In some embodiments, the lipophilic moiety is conjugated to the double-stranded RNAi agent via a linker a linker containing an ether, thioether, urea, carbonate, amine, amide, maleimide-thioether, disulfide, phosphodiester, sulfonamide linkage, a product of a click reaction (e.g., a triazole from the azide-alkyne cycloaddition), or carbamate. 
     In another embodiment, the lipophilic moiety is a steroid, such as sterol. Steroids are polycyclic compounds containing a perhydro-1,2-cyclopentanophenanthrene ring system. Steroids include, without limitation, bile acids (e.g., cholic acid, deoxycholic acid and dehydrocholic acid), cortisone, digoxigenin, testosterone, cholesterol, and cationic steroids, such as cortisone. A “cholesterol derivative” refers to a compound derived from cholesterol, for example by substitution, addition or removal of substituents. 
     In another embodiment, the lipophilic moiety is an aromatic moiety. In this context, the term “aromatic” refers broadly to mono- and polyaromatic hydrocarbons. Aromatic groups include, without limitation, C6-C14 aryl moieties comprising one to three aromatic rings, which may be optionally substituted; “aralkyl” or “arylalkyl” groups comprising an aryl group covalently linked to an alkyl group, either of which may independently be optionally substituted or unsubstituted; and “heteroaryl” groups. As used herein, the term “heteroaryl” refers to groups having 5 to 14 ring atoms, preferably 5, 6, 9, or 10 ring atoms; having 6, 10, or 14n electrons shared in a cyclic array, and having, in addition to carbon atoms, one to about three heteroatoms selected from the group consisting of nitrogen (N), oxygen (O), and sulfur (S). 
     As employed herein, a “substituted” alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group is one having one to about four, preferably one to about three, more preferably one or two, non-hydrogen substituents. Suitable substituents include, without limitation, halo, hydroxy, nitro, haloalkyl, alkyl, alkaryl, aryl, aralkyl, alkoxy, aryloxy, amino, acylamino, alkylcarbamoyl, arylcarbamoyl, aminoalkyl, alkoxycarbonyl, carboxy, hydroxyalkyl, alkanesulfonyl, arenesulfonyl, alkanesulfonamido, arenesulfonamido, aralkylsulfonamido, alkylcarbonyl, acyloxy, cyano, and ureido groups. 
     In some embodiments, the lipophilic moiety is an aralkyl group, e.g., a 2-arylpropanoyl moiety. The structural features of the aralkyl group are selected so that the lipophilic moiety will bind to at least one protein in vivo. In certain embodiments, the structural features of the aralkyl group are selected so that the lipophilic moiety binds to serum, vascular, or cellular proteins. In certain embodiments, the structural features of the aralkyl group promote binding to albumin, an immunoglobulin, a lipoprotein, α-2-macroglubulin, or α-1-glycoprotein. 
     In certain embodiments, the ligand is naproxen or a structural derivative of naproxen. Procedures for the synthesis of naproxen can be found in U.S. Pat. Nos. 3,904,682 and 4,009,197, which are hereby incorporated by reference in their entirety. Naproxen has the chemical name (S)-6-Methoxy-α-methyl-2-naphthaleneacetic acid and the structure is 
     
       
         
         
             
             
         
       
     
     In certain embodiments, the ligand is ibuprofen or a structural derivative of ibuprofen. Procedures for the synthesis of ibuprofen can be found in U.S. Pat. No. 3,228,831, which is incorporated herein by reference for the methods provided therein. The structure of ibuprofen is 
     
       
         
         
             
             
         
       
     
     Additional exemplary aralkyl groups are illustrated in U.S. Pat. No. 7,626,014, which is incorporated herein by reference for the methods provided therein. 
     In another embodiment, suitable lipophilic moieties include lipid, cholesterol, retinoic acid, cholic acid, adamantane acetic acid, 1-pyrene butyric acid, dihydrotestosterone, 1,3-bis-O(hexadecyl)glycerol, geranyloxyhexyanol, hexadecylglycerol, borneol, menthol, 1,3-propanediol, heptadecyl group, palmitic acid, myristic acid, O3-(oleoyl)lithocholic acid, O3-(oleoyl)cholenic acid, ibuprofen, naproxen, dimethoxytrityl, or phenoxazine. 
     In certain embodiments, more than one lipophilic moiety can be incorporated into the double-strand RNAi agent, particularly when the lipophilic moiety has a low lipophilicity or hydrophobicity. In some embodiments, two or more lipophilic moieties are incorporated into the same strand of the double-strand RNAi agent. In some embodiments, each strand of the double-strand RNAi agent has one or more lipophilic moieties incorporated. In some embodiments, two or more lipophilic moieties are incorporated into the same position (i.e., the same nucleobase, same sugar moiety, or same internucleosidic linkage) of the double-strand RNAi agent. This can be achieved by, e.g., conjugating the two or more lipophilic moieties via a carrier, or conjugating the two or more lipophilic moieties via a branched linker, or conjugating the two or more lipophilic moieties via one or more linkers, with one or more linkers linking the lipophilic moieties consecutively. 
     The lipophilic moiety may be conjugated to the RNAi agent via a direct attachment to the ribosugar of the RNAi agent. Alternatively, the lipophilic moiety may be conjugated to the double-strand RNAi agent via a linker or a carrier. 
     In certain embodiments, the lipophilic moiety may be conjugated to the RNAi agent via one or more linkers (tethers). 
     In some embodiments, the lipophilic moiety is conjugated to the double-stranded RNAi agent via a linker containing an ether, thioether, urea, carbonate, amine, amide, maleimide-thioether, disulfide, phosphodiester, sulfonamide linkage, a product of a click reaction (e.g., a triazole from the azide-alkyne cycloaddition), or carbamate. 
     B. Lipid Conjugates 
     In some embodiments, the ligand is a lipid or lipid-based molecule. Such a lipid or lipid-based molecule can typically bind a serum protein, such as human serum albumin (HSA). An HSA binding ligand allows for vascular distribution of the conjugate to a target tissue. For example, the target tissue can be the eye. Other molecules that can bind HSA can also be used as ligands. For example, neproxin or aspirin can be used. A lipid or lipid-based ligand can (a) increase resistance to degradation of the conjugate, (b) increase targeting or transport into a target cell or cell membrane, and/or (c) can be used to adjust binding to a serum protein, e.g., HSA. 
     A lipid-based ligand can be used to modulate, e.g., control (e.g., inhibit) the binding of the conjugate to a target tissue. For example, a lipid or lipid-based ligand that binds to HSA more strongly will be less likely to be targeted to the kidney and therefore less likely to be cleared from the body. A lipid or lipid-based ligand that binds to HSA less strongly can be used to target the conjugate to the kidney. 
     In some embodiments, the lipid-based ligand binds HSA. For example, the ligand can bind HSA with a sufficient affinity such that distribution of the conjugate to a non-kidney tissue is enhanced. However, the affinity is typically not so strong that the HSA-ligand binding cannot be reversed. 
     In some embodiments, the lipid-based ligand binds HSA weakly or not at all, such that distribution of the conjugate to the kidney is enhanced. Other moieties that target to kidney cells can also be used in place of or in addition to the lipid-based ligand. 
     In another aspect, the ligand is a moiety, e.g., a vitamin, which is taken up by a target cell, e.g., a proliferating cell. These are particularly useful for treating disorders characterized by unwanted cell proliferation, e.g., of the malignant or non-malignant type, e.g., cancer cells. Exemplary vitamins include vitamin A, E, and K. Other exemplary vitamins include are B vitamin, e.g., folic acid, B12, riboflavin, biotin, pyridoxal or other vitamins or nutrients taken up by cancer cells. Also included are HSA and low-density lipoprotein (LDL). 
     Cell Permeation Agents 
     In another aspect, the ligand is a cell-permeation agent, such as a helical cell-permeation agent. In some embodiments, the agent is amphipathic. An exemplary agent is a peptide such as tat or antennopedia. If the agent is a peptide, it can be modified, including a peptidylmimetic, invertomers, non-peptide or pseudo-peptide linkages, and use of D-amino acids. The helical agent is typically an α-helical agent, and can have a lipophilic and a lipophobic phase. 
     The ligand can be a peptide or peptidomimetic. A peptidomimetic (also referred to herein as an oligopeptidomimetic) is a molecule capable of folding into a defined three-dimensional structure similar to a natural peptide. The attachment of peptide and peptidomimetics to iRNA agents can affect pharmacokinetic distribution of the iRNA, such as by enhancing cellular recognition and absorption. The peptide or peptidomimetic moiety can be about 5-50 amino acids long, e.g., about 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 amino acids long. 
     A peptide or peptidomimetic can be, for example, a cell permeation peptide, cationic peptide, amphipathic peptide, or hydrophobic peptide (e.g., consisting primarily of Tyr, Trp or Phe). The peptide moiety can be a dendrimer peptide, constrained peptide or crosslinked peptide. In another alternative, the peptide moiety can include a hydrophobic membrane translocation sequence (MTS). An exemplary hydrophobic MTS-containing peptide is RFGF having the amino acid sequence AAVALLPAVLLALLAP (SEQ ID NO: 4158). An RFGF analogue (e.g., amino acid sequence AALLPVLLAAP (SEQ ID NO: 4159)) containing a hydrophobic MTS can also be a targeting moiety. The peptide moiety can be a “delivery” peptide, which can carry large polar molecules including peptides, oligonucleotides, and protein across cell membranes. For example, sequences from the HIV Tat protein (GRKKRRQRRRPPQ (SEQ ID NO: 4160)) and the  Drosophila Antennapedia  protein (RQIKIWFQNRRMKWKK (SEQ ID NO: 4161)) have been found to be capable of functioning as delivery peptides. A peptide or peptidomimetic can be encoded by a random sequence of DNA, such as a peptide identified from a phage-display library, or one-bead-one-compound (OBOC) combinatorial library (Lam et al.,  Nature,  354:82-84, 1991). Typically, the peptide or peptidomimetic tethered to a dsRNA agent via an incorporated monomer unit is a cell targeting peptide such as an arginine-glycine-aspartic acid (RGD)-peptide, or RGD mimic. A peptide moiety can range in length from about 5 amino acids to about 40 amino acids. The peptide moieties can have a structural modification, such as to increase stability or direct conformational properties. Any of the structural modifications described below can be utilized. 
     An RGD peptide for use in the compositions and methods of the disclosure may be linear or cyclic, and may be modified, e.g., glycosylated or methylated, to facilitate targeting to a specific tissue(s). RGD-containing peptides and peptidomimetics may include D-amino acids, as well as synthetic RGD mimics. In addition to RGD, one can use other moieties that target the integrin ligand. In some embodiments, conjugates of this ligand target PECAM-1 or VEGF. 
     An RGD peptide moiety can be used to target a particular cell type, e.g., a tumor cell, such as an endothelial tumor cell or a breast cancer tumor cell (Zitzmann et al.,  Cancer Res.,  62:5139-43, 2002). An RGD peptide can facilitate targeting of an dsRNA agent to tumors of a variety of other tissues, including the lung, kidney, spleen, or liver (Aoki et al.,  Cancer Gene Therapy  8:783-787, 2001). Typically, the RGD peptide will facilitate targeting of an iRNA agent to the kidney. The RGD peptide can be linear or cyclic, and can be modified, e.g., glycosylated or methylated to facilitate targeting to specific tissues. For example, a glycosylated RGD peptide can deliver a iRNA agent to a tumor cell expressing α v β 3  (Haubner et al.,  Jour. Nucl. Med.,  42:326-336, 2001). 
     A “cell permeation peptide” is capable of permeating a cell, e.g., a microbial cell, such as a bacterial or fungal cell, or a mammalian cell, such as a human cell. A microbial cell-permeating peptide can be, for example, an α-helical linear peptide (e.g., LL-37 or Ceropin P1), a disulfide bond-containing peptide (e.g., α-defensin, β-defensin or bactenecin), or a peptide containing only one or two dominating amino acids (e.g., PR-39 or indolicidin). A cell permeation peptide can also include a nuclear localization signal (NLS). For example, a cell permeation peptide can be a bipartite amphipathic peptide, such as MPG, which is derived from the fusion peptide domain of HIV-1 gp41 and the NLS of SV40 large T antigen (Simeoni et al.,  Nucl. Acids Res.  31:2717-2724, 2003). 
     Carbohydrate Conjugates and Ligands 
     In some embodiments of the compositions and methods of the disclosure, an iRNA oligonucleotide further comprises a carbohydrate. The carbohydrate conjugated iRNA are advantageous for the in vivo delivery of nucleic acids, as well as compositions suitable for in vivo therapeutic use, as described herein. As used herein, “carbohydrate” refers to a compound which is either a carbohydrate per se made up of one or more monosaccharide units having at least 6 carbon atoms (which can be linear, branched or cyclic) with an oxygen, nitrogen or sulfur atom bonded to each carbon atom; or a compound having as a part thereof a carbohydrate moiety made up of one or more monosaccharide units each having at least six carbon atoms (which can be linear, branched or cyclic), with an oxygen, nitrogen or sulfur atom bonded to each carbon atom. Representative carbohydrates include the sugars (mono-, di-, tri- and oligosaccharides containing from about 4, 5, 6, 7, 8, or 9 monosaccharide units), and polysaccharides such as starches, glycogen, cellulose and polysaccharide gums. Specific monosaccharides include C5 and above (e.g., C5, C6, C7, or C8) sugars; di- and trisaccharides include sugars having two or three monosaccharide units (e.g., C5, C6, C7, or C8). 
     In certain embodiments, the compositions and methods of the disclosure include a C16 ligand. In exemplary embodiments, the C16 ligand of the disclosure has the following structure (exemplified here below for a uracil base, yet attachment of the C16 ligand is contemplated for a nucleotide presenting any base (C, G, A, etc.) or possessing any other modification as presented herein, provided that 2′ ribo attachment is preserved) and is attached at the 2′ position of the ribo within a residue that is so modified: 
     
       
         
         
             
             
         
       
     
     As shown above, a C16 ligand-modified residue presents a straight chain alkyl at the 2′-ribo position of an exemplary residue (here, a Uracil) that is so modified. 
     In some embodiments, a carbohydrate conjugate of a RNAi agent of the instant disclosure further comprises one or more additional ligands as described above, such as, but not limited to, a PK modulator or a cell permeation peptide. 
     Additional carbohydrate conjugates (and linkers) suitable for use in the present disclosure include those described in WO 2014/179620 and WO 2014/179627, the entire contents of each of which are incorporated herein by reference. 
     In certain embodiments, the compositions and methods of the disclosure include a vinyl phosponate (VP) modification of an RNAi agent as described herein. In exemplary embodiments, a vinyl phosphonate of the disclosure has the following structure: 
     
       
         
         
             
             
         
       
     
     A vinyl phosponate of the instant disclosure may be attached to either the antisense or the sense strand of a dsRNA of the disclosure. In certain preferred embodiments, a vinyl phosphonate of the instant disclosure is attached to the antisense strand of a dsRNA, optionally at the 5′ end of the antisense strand of the dsRNA. 
     Vinyl phosphate modifications are also contemplated for the compositions and methods of the instant disclosure. An exemplary vinyl phosphate structure is: 
     
       
         
         
             
             
         
       
     
     In some embodiments, a carbohydrate conjugate comprises a monosaccharide. In some embodiments, the monosaccharide is an N-acetylgalactosamine (GalNAc). GalNAc conjugates, which comprise one or more N-acetylgalactosamine (GalNAc) derivatives, are described, for example, in U.S. Pat. No. 8,106,022, the entire content of which is hereby incorporated herein by reference. In some embodiments, the GalNAc conjugate serves as a ligand that targets the iRNA to particular cells. In some embodiments, the GalNAc conjugate targets the iRNA to liver cells, e.g., by serving as a ligand for the asialoglycoprotein receptor of liver cells (e.g., hepatocytes). 
     In some embodiments, the carbohydrate conjugate comprises one or more GalNAc derivatives. The GalNAc derivatives may be attached via a linker, e.g., a bivalent or trivalent branched linker. In some embodiments the GalNAc conjugate is conjugated to the 3′ end of the sense strand. In some embodiments, the GalNAc conjugate is conjugated to the iRNA agent (e.g., to the 3′ end of the sense strand) via a linker, e.g., a linker as described herein. 
     In some embodiments, the GalNAc conjugate is 
     
       
         
         
             
             
         
       
     
     In some embodiments, the RNAi agent is attached to the carbohydrate conjugate via a linker as shown in the following schematic, wherein X is O or S: 
     
       
         
         
             
             
         
       
     
     In some embodiments, the RNAi agent is conjugated to L96 as defined in Table 1 and shown below: 
     
       
         
         
             
             
         
       
     
     In some embodiments, a carbohydrate conjugate for use in the compositions and methods of the disclosure is selected from the group consisting of: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Another representative carbohydrate conjugate for use in the embodiments described herein includes, but is not limited to, 
     
       
         
         
             
             
         
       
     
     when one of X or Y is an oligonucleotide, the other is a hydrogen. 
     In some embodiments, the carbohydrate conjugate further comprises one or more additional ligands as described above, such as, but not limited to, a PK modulator and/or a cell permeation peptide. 
     In some embodiments, an iRNA of the disclosure is conjugated to a carbohydrate through a linker. Non-limiting examples of iRNA carbohydrate conjugates with linkers of the compositions and methods of the disclosure include, but are not limited to, 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     when one of X or Y is an oligonucleotide, the other is a hydrogen. 
     E. Thermally Destabilizing Modifications 
     In certain embodiments, a dsRNA molecule can be optimized for RNA interference by incorporating thermally destabilizing modifications in the seed region of the antisense strand (i.e., at positions 2-9 of the 5′-end of the antisense strand) to reduce or inhibit off-target gene silencing. It has been discovered that dsRNAs with an antisense strand comprising at least one thermally destabilizing modification of the duplex within the first 9 nucleotide positions, counting from the 5′ end, of the antisense strand have reduced off-target gene silencing activity. Accordingly, in some embodiments, the antisense strand comprises at least one (e.g., one, two, three, four, five, or more) thermally destabilizing modification of the duplex within the first 9 nucleotide positions of the 5′ region of the antisense strand. In some embodiments, one or more thermally destabilizing modification(s) of the duplex is/are located in positions 2-9, or preferably positions 4-8, from the 5′-end of the antisense strand. In some further embodiments, the thermally destabilizing modification(s) of the duplex is/are located at position 6, 7, or 8 from the 5′-end of the antisense strand. In still some further embodiments, the thermally destabilizing modification of the duplex is located at position 7 from the 5′-end of the antisense strand. The term “thermally destabilizing modification(s)” includes modification(s) that would result with a dsRNA with a lower overall melting temperature (Tm) (preferably a Tm with one, two, three, or four degrees lower than the Tm of the dsRNA without having such modification(s). In some embodiments, the thermally destabilizing modification of the duplex is located at position 2, 3, 4, 5, or 9 from the 5′-end of the antisense strand. 
     The thermally destabilizing modifications can include, but are not limited to, abasic modification; mismatch with the opposing nucleotide in the opposing strand; and sugar modification such as 2′-deoxy modification or acyclic nucleotide, e.g., unlocked nucleic acids (UNA) or glycol nucleic acid (GNA). 
     Exemplified abasic modifications include, but are not limited to, the following: 
     
       
         
         
             
             
         
       
     
     Wherein R═H, Me, Et or OMe; R′═H, Me, Et or OMe; R″═H, Me, Et or OMe 
     
       
         
         
             
             
         
       
     
     wherein B is a modified or unmodified nucleobase. 
     Exemplified sugar modifications include, but are not limited to the following: 
     
       
         
         
             
             
         
       
     
     wherein B is a modified or unmodified nucleobase. 
     In some embodiments the thermally destabilizing modification of the duplex is selected from the group consisting of: 
     
       
         
         
             
             
         
       
     
     wherein B is a modified or unmodified nucleobase and the asterisk on each structure represents either R, S or racemic. 
     The term “acyclic nucleotide” refers to any nucleotide having an acyclic ribose sugar, for example, where any of bonds between the ribose carbons (e.g., C1′-C2′, C2′-C3′, C3′-C4′, C4′-O4′, or C1′-O4′) is absent or at least one of ribose carbons or oxygen (e.g., C1′, C2′, C3′, C4′, or O4′) are independently or in combination absent from the nucleotide. In some embodiments, acyclic nucleotide is 
     
       
         
         
             
             
         
       
     
     wherein B is a modified or unmodified nucleobase, R 1  and R 2  independently are H, halogen, OR 3 , or alkyl; and R 3  is H, alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or sugar). The term “UNA” refers to unlocked acyclic nucleic acid, wherein any of the bonds of the sugar has been removed, forming an unlocked “sugar” residue. In one example, UNA also encompasses monomers with bonds between C1′-C4′ being removed (i.e. the covalent carbon-oxygen-carbon bond between the C1′ and C4′ carbons). In another example, the C2′-C3′ bond (i.e. the covalent carbon-carbon bond between the C2′ and C3′ carbons) of the sugar is removed (see Mikhailov et. al., Tetrahedron Letters, 26 (17): 2059 (1985); and Fluiter et al., Mol. Biosyst., 10: 1039 (2009), which are hereby incorporated by reference in their entirety). The acyclic derivative provides greater backbone flexibility without affecting the Watson-Crick pairings. The acyclic nucleotide can be linked via 2′-5′ or 3′-5′ linkage. 
     The term ‘GNA’ refers to glycol nucleic acid which is a polymer similar to DNA or RNA but differing in the composition of its “backbone” in that is composed of repeating glycerol units linked by phosphodiester bonds: 
     
       
         
         
             
             
         
       
     
     The thermally destabilizing modification of the duplex can be mismatches (i.e., noncomplementary base pairs) between the thermally destabilizing nucleotide and the opposing nucleotide in the opposite strand within the dsRNA duplex. Exemplary mismatch base pairs include G:G, G:A, G:U, G:T, A:A, A:C, C:C, C:U, C:T, U:U, T:T, U:T, or a combination thereof. Other mismatch base pairings known in the art are also amenable to the present invention. A mismatch can occur between nucleotides that are either naturally occurring nucleotides or modified nucleotides, i.e., the mismatch base pairing can occur between the nucleobases from respective nucleotides independent of the modifications on the ribose sugars of the nucleotides. In certain embodiments, the dsRNA molecule contains at least one nucleobase in the mismatch pairing that is a 2′-deoxy nucleobase; e.g., the 2′-deoxy nucleobase is in the sense strand. 
     In some embodiments, the thermally destabilizing modification of the duplex in the seed region of the antisense strand includes nucleotides with impaired W-C H-bonding to complementary base on the target mRNA, such as: 
     
       
         
         
             
             
         
       
     
     More examples of abasic nucleotide, acyclic nucleotide modifications (including UNA and GNA), and mismatch modifications have been described in detail in WO 2011/133876, which is herein incorporated by reference in its entirety. 
     The thermally destabilizing modifications may also include universal base with reduced or abolished capability to form hydrogen bonds with the opposing bases, and phosphate modifications. 
     In some embodiments, the thermally destabilizing modification of the duplex includes nucleotides with non-canonical bases such as, but not limited to, nucleobase modifications with impaired or completely abolished capability to form hydrogen bonds with bases in the opposite strand. These nucleobase modifications have been evaluated for destabilization of the central region of the dsRNA duplex as described in WO 2010/0011895, which is herein incorporated by reference in its entirety. Exemplary nucleobase modifications are: 
     
       
         
         
             
             
         
       
     
     In some embodiments, the thermally destabilizing modification of the duplex in the seed region of the antisense strand includes one or more α-nucleotide complementary to the base on the target mRNA, such as: 
     
       
         
         
             
             
         
       
     
     wherein R is H, OH, OCH 3 , F, NH 2 , NHMe, NMe 2  or O-alkyl. 
     Exemplary phosphate modifications known to decrease the thermal stability of dsRNA duplexes compared to natural phosphodiester linkages are: 
     
       
         
         
             
             
         
       
     
     The alkyl for the R group can be a C 1 -C 6 alkyl. Specific alkyls for the R group include, but are not limited to methyl, ethyl, propyl, isopropyl, butyl, pentyl and hexyl. 
     As the skilled artisan will recognize, in view of the functional role of nucleobases is defining specificity of a RNAi agent of the disclosure, while nucleobase modifications can be performed in the various manners as described herein, e.g., to introduce destabilizing modifications into a RNAi agent of the disclosure, e.g., for purpose of enhancing on-target effect relative to off-target effect, the range of modifications available and, in general, present upon RNAi agents of the disclosure tends to be much greater for non-nucleobase modifications, e.g., modifications to sugar groups or phosphate backbones of polyribonucleotides. Such modifications are described in greater detail in other sections of the instant disclosure and are expressly contemplated for RNAi agents of the disclosure, either possessing native nucleobases or modified nucleobases as described above or elsewhere herein. 
     In addition to the antisense strand comprising a thermally destabilizing modification, the dsRNA can also comprise one or more stabilizing modifications. For example, the dsRNA can comprise at least two (e.g., two, three, four, five, six, seven, eight, nine, ten, or more) stabilizing modifications. Without limitations, the stabilizing modifications all can be present in one strand. In some embodiments, both the sense and the antisense strands comprise at least two stabilizing modifications. The stabilizing modification can occur on any nucleotide of the sense strand or antisense strand. For instance, the stabilizing modification can occur on every nucleotide on the sense strand or antisense strand; each stabilizing modification can occur in an alternating pattern on the sense strand or antisense strand; or the sense strand or antisense strand comprises both stabilizing modification in an alternating pattern. The alternating pattern of the stabilizing modifications on the sense strand may be the same or different from the antisense strand, and the alternating pattern of the stabilizing modifications on the sense strand can have a shift relative to the alternating pattern of the stabilizing modifications on the antisense strand. 
     In some embodiments, the antisense strand comprises at least two (e.g., two, three, four, five, six, seven, eight, nine, ten, or more) stabilizing modifications. Without limitations, a stabilizing modification in the antisense strand can be present at any positions. 
     In some embodiments, the antisense strand comprises stabilizing modifications at positions 2, 6, 8, 9, 14, and 16 from the 5′-end. In some other embodiments, the antisense strand comprises stabilizing modifications at positions 2, 6, 14, and 16 from the 5′-end. In still some other embodiments, the antisense strand comprises stabilizing modifications at positions 2, 14, and 16 from the 5′-end. 
     In some embodiments, the antisense strand comprises at least one stabilizing modification adjacent to the destabilizing modification. For example, the stabilizing modification can be the nucleotide at the 5′-end or the 3′-end of the destabilizing modification, i.e., at position −1 or +1 from the position of the destabilizing modification. In some embodiments, the antisense strand comprises a stabilizing modification at each of the 5′-end and the 3′-end of the destabilizing modification, i.e., positions −1 and +1 from the position of the destabilizing modification. 
     In some embodiments, the antisense strand comprises at least two stabilizing modifications at the 3′-end of the destabilizing modification, i.e., at positions +1 and +2 from the position of the destabilizing modification. 
     In some embodiments, the sense strand comprises at least two (e.g., two, three, four, five, six, seven, eight, nine, ten or more) stabilizing modifications. Without limitations, a stabilizing modification in the sense strand can be present at any positions. In some embodiments, the sense strand comprises stabilizing modifications at positions 7, 10, and 11 from the 5′-end. In some other embodiments, the sense strand comprises stabilizing modifications at positions 7, 9, 10, and 11 from the 5′-end. In some embodiments, the sense strand comprises stabilizing modifications at positions opposite or complimentary to positions 11, 12, and 15 of the antisense strand, counting from the 5′-end of the antisense strand. In some other embodiments, the sense strand comprises stabilizing modifications at positions opposite or complimentary to positions 11, 12, 13, and 15 of the antisense strand, counting from the 5′-end of the antisense strand. In some embodiments, the sense strand comprises a block of two, three, or four stabilizing modifications. 
     In some embodiments, the sense strand does not comprise a stabilizing modification in position opposite or complimentary to the thermally destabilizing modification of the duplex in the antisense strand. 
     Exemplary thermally stabilizing modifications include, but are not limited to, 2′-fluoro modifications. Other thermally stabilizing modifications include, but are not limited to, LNA. 
     In some embodiments, the dsRNA of the disclosure comprises at least four (e.g., four, five, six, seven, eight, nine, ten, or more) 2′-fluoro nucleotides. Without limitations, the 2′-fluoro nucleotides all can be present in one strand. In some embodiments, both the sense and the antisense strands comprise at least two 2′-fluoro nucleotides. The 2′-fluoro modification can occur on any nucleotide of the sense strand or antisense strand. For instance, the 2′-fluoro modification can occur on every nucleotide on the sense strand or antisense strand; each 2′-fluoro modification can occur in an alternating pattern on the sense strand or antisense strand; or the sense strand or antisense strand comprises both 2′-fluoro modifications in an alternating pattern. The alternating pattern of the 2′-fluoro modifications on the sense strand may be the same or different from the antisense strand, and the alternating pattern of the 2′-fluoro modifications on the sense strand can have a shift relative to the alternating pattern of the 2′-fluoro modifications on the antisense strand. 
     In some embodiments, the antisense strand comprises at least two (e.g., two, three, four, five, six, seven, eight, nine, ten, or more) 2′-fluoro nucleotides. Without limitations, a 2′-fluoro modification in the antisense strand can be present at any positions. In some embodiments, the antisense comprises 2′-fluoro nucleotides at positions 2, 6, 8, 9, 14, and 16 from the 5′-end. In some other embodiments, the antisense comprises 2′-fluoro nucleotides at positions 2, 6, 14, and 16 from the 5′-end. In still some other embodiments, the antisense comprises 2′-fluoro nucleotides at positions 2, 14, and 16 from the 5′-end. 
     In some embodiments, the antisense strand comprises at least one 2′-fluoro nucleotide adjacent to the destabilizing modification. For example, the 2′-fluoro nucleotide can be the nucleotide at the 5′-end or the 3′-end of the destabilizing modification, i.e., at position −1 or +1 from the position of the destabilizing modification. In some embodiments, the antisense strand comprises a 2′-fluoro nucleotide at each of the 5′-end and the 3′-end of the destabilizing modification, i.e., positions −1 and +1 from the position of the destabilizing modification. 
     In some embodiments, the antisense strand comprises at least two 2′-fluoro nucleotides at the 3′-end of the destabilizing modification, i.e., at positions +1 and +2 from the position of the destabilizing modification. 
     In some embodiments, the sense strand comprises at least two (e.g., two, three, four, five, six, seven, eight, nine, ten, or more) 2′-fluoro nucleotides. Without limitations, a 2′-fluoro modification in the sense strand can be present at any positions. In some embodiments, the antisense comprises 2′-fluoro nucleotides at positions 7, 10, and 11 from the 5′-end. In some other embodiments, the sense strand comprises 2′-fluoro nucleotides at positions 7, 9, 10, and 11 from the 5′-end. In some embodiments, the sense strand comprises 2′-fluoro nucleotides at positions opposite or complimentary to positions 11, 12, and 15 of the antisense strand, counting from the 5′-end of the antisense strand. In some other embodiments, the sense strand comprises 2′-fluoro nucleotides at positions opposite or complimentary to positions 11, 12, 13, and 15 of the antisense strand, counting from the 5′-end of the antisense strand. In some embodiments, the sense strand comprises a block of two, three, or four 2′-fluoro nucleotides. 
     In some embodiments, the sense strand does not comprise a 2′-fluoro nucleotide in position opposite or complimentary to the thermally destabilizing modification of the duplex in the antisense strand. 
     In some embodiments, the dsRNA molecule of the disclosure comprises a 21 nucleotides (nt) sense strand and a 23 nucleotides (nt) antisense, wherein the antisense strand contains at least one thermally destabilizing nucleotide, where the at least one thermally destabilizing nucleotide occurs in the seed region of the antisense strand (i.e., at position 2-9 of the 5′-end of the antisense strand), wherein one end of the dsRNA is blunt, while the other end is comprises a 2 nt overhang, and wherein the dsRNA optionally further has at least one (e.g., one, two, three, four, five, six, or all seven) of the following characteristics: (i) the antisense comprises 2, 3, 4, 5, or 6 2′-fluoro modifications; (ii) the antisense comprises 1, 2, 3, 4, or 5 phosphorothioate internucleotide linkages; (iii) the sense strand is conjugated with a ligand; (iv) the sense strand comprises 2, 3, 4, or 5 2′-fluoro modifications; (v) the sense strand comprises 1, 2, 3, 4, or 5 phosphorothioate internucleotide linkages; (vi) the dsRNA comprises at least four 2′-fluoro modifications; and (vii) the dsRNA comprises a blunt end at 5′-end of the antisense strand. Preferably, the 2 nt overhang is at the 3′-end of the antisense. 
     In some embodiments, every nucleotide in the sense strand and antisense strand of the dsRNA molecule may be modified. Each nucleotide may be modified with the same or different modification which can include one or more alteration of one or both of the non-linking phosphate oxygens or of one or more of the linking phosphate oxygens; alteration of a constituent of the ribose sugar, e.g., of the 2′ hydroxyl on the ribose sugar; wholesale replacement of the phosphate moiety with “dephospho” linkers; modification or replacement of a naturally occurring base; and replacement or modification of the ribose-phosphate backbone. 
     As nucleic acids are polymers of subunits, many of the modifications occur at a position which is repeated within a nucleic acid, e.g., a modification of a base, or a phosphate moiety, or a non-linking O of a phosphate moiety. In some cases, the modification will occur at all of the subject positions in the nucleic acid but in many cases it will not. By way of example, a modification may only occur at a 3′ or 5′ terminal position, may only occur in a terminal region, e.g., at a position on a terminal nucleotide or in the last 2, 3, 4, 5, or 10 nucleotides of a strand. A modification may occur in a double strand region, a single strand region, or in both. A modification may occur only in the double strand region of an RNA or may only occur in a single strand region of an RNA. E.g., a phosphorothioate modification at a non-linking O position may only occur at one or both termini, may only occur in a terminal region, e.g., at a position on a terminal nucleotide or in the last 2, 3, 4, 5, or 10 nucleotides of a strand, or may occur in double strand and single strand regions, particularly at termini. The 5′ end or ends can be phosphorylated. 
     It may be possible, e.g., to enhance stability, to include particular bases in overhangs, or to include modified nucleotides or nucleotide surrogates, in single strand overhangs, e.g., in a 5′ or 3′ overhang, or in both. E.g., it can be desirable to include purine nucleotides in overhangs. In some embodiments all or some of the bases in a 3′ or 5′ overhang may be modified, e.g., with a modification described herein. Modifications can include, e.g., the use of modifications at the 2′ position of the ribose sugar with modifications that are known in the art, e.g., the use of deoxyribonucleotides, 2′-deoxy-2′-fluoro (2′-F) or 2′-O-methyl modified instead of the ribosugar of the nucleobase, and modifications in the phosphate group, e.g., phosphorothioate modifications. Overhangs need not be homologous with the target sequence. 
     In some embodiments, each residue of the sense strand and antisense strand is independently modified with LNA, HNA, CeNA, 2′-methoxyethyl, 2′-O-methyl, 2′-O-allyl, 2′-C-allyl, 2′-deoxy, or 2′-fluoro. The strands can contain more than one modification. In some embodiments, each residue of the sense strand and antisense strand is independently modified with 2′-O-methyl or 2′-fluoro. It is to be understood that these modifications are in addition to the at least one thermally destabilizing modification of the duplex present in the antisense strand. 
     At least two different modifications are typically present on the sense strand and antisense strand. Those two modifications may be the 2′-deoxy, 2′-O-methyl, or 2′-fluoro modifications, acyclic nucleotides or others. In some embodiments, the sense strand and antisense strand each comprises two differently modified nucleotides selected from 2′-O-methyl or 2′-deoxy. In some embodiments, each residue of the sense strand and antisense strand is independently modified with 2′-O-methyl nucleotide, 2′-deoxy nucleotide, 2′-deoxy-2′-fluoro nucleotide, 2′-O-N-methylacetamido (2′-O-NMA) nucleotide, a 2′-O-dimethylaminoethoxyethyl (2′-O-DMAEOE) nucleotide, 2′-O-aminopropyl (2′-O-AP) nucleotide, or 2′-ara-F nucleotide. Again, it is to be understood that these modifications are in addition to the at least one thermally destabilizing modification of the duplex present in the antisense strand. 
     In some embodiments, the dsRNA molecule of the disclosure comprises modifications of an alternating pattern, particular in the B1, B2, B3, B1′, B2′, B3′, B4′ regions. The term “alternating motif” or “alternative pattern” as used herein refers to a motif having one or more modifications, each modification occurring on alternating nucleotides of one strand. The alternating nucleotide may refer to one per every other nucleotide or one per every three nucleotides, or a similar pattern. For example, if A, B and C each represent one type of modification to the nucleotide, the alternating motif can be “ABABABABABAB . . . ,” “AABBAABBAABB . . . ,” “AABAABAABAAB . . . ,” “AAABAAABAAAB . . . ,” “AAABBBAAABBB . . . ,” or “ABCABCABCABC . . . ,” etc. 
     The type of modifications contained in the alternating motif may be the same or different. For example, if A, B, C, D each represent one type of modification on the nucleotide, the alternating pattern, i.e., modifications on every other nucleotide, may be the same, but each of the sense strand or antisense strand can be selected from several possibilities of modifications within the alternating motif such as “ABABAB . . . ”, “ACACAC . . . ” “BDBDBD . . . ” or “CDCDCD . . . ,” etc. 
     In some embodiments, the dsRNA molecule of the disclosure comprises the modification pattern for the alternating motif on the sense strand relative to the modification pattern for the alternating motif on the antisense strand is shifted. The shift may be such that the modified group of nucleotides of the sense strand corresponds to a differently modified group of nucleotides of the antisense strand and vice versa. For example, the sense strand when paired with the antisense strand in the dsRNA duplex, the alternating motif in the sense strand may start with “ABABAB” from 5′-3′ of the strand and the alternating motif in the antisense strand may start with “BABABA” from 3′-5′ of the strand within the duplex region. As another example, the alternating motif in the sense strand may start with “AABBAABB” from 5′-3′ of the strand and the alternating motif in the antisense strand may start with “BBAABBAA” from 3′-5′ of the strand within the duplex region, so that there is a complete or partial shift of the modification patterns between the sense strand and the antisense strand. 
     The dsRNA molecule of the disclosure may further comprise at least one phosphorothioate or methylphosphonate internucleotide linkage. The phosphorothioate or methylphosphonate internucleotide linkage modification may occur on any nucleotide of the sense strand or antisense strand or both in any position of the strand. For instance, the internucleotide linkage modification may occur on every nucleotide on the sense strand or antisense strand; each internucleotide linkage modification may occur in an alternating pattern on the sense strand or antisense strand; or the sense strand or antisense strand comprises both internucleotide linkage modifications in an alternating pattern. The alternating pattern of the internucleotide linkage modification on the sense strand may be the same or different from the antisense strand, and the alternating pattern of the internucleotide linkage modification on the sense strand may have a shift relative to the alternating pattern of the internucleotide linkage modification on the antisense strand. 
     In some embodiments, the dsRNA molecule comprises the phosphorothioate or methylphosphonate internucleotide linkage modification in the overhang region. For example, the overhang region comprises two nucleotides having a phosphorothioate or methylphosphonate internucleotide linkage between the two nucleotides. Internucleotide linkage modifications also may be made to link the overhang nucleotides with the terminal paired nucleotides within duplex region. For example, at least 2, 3, 4, or all the overhang nucleotides may be linked through phosphorothioate or methylphosphonate internucleotide linkage, and optionally, there may be additional phosphorothioate or methylphosphonate internucleotide linkages linking the overhang nucleotide with a paired nucleotide that is next to the overhang nucleotide. For instance, there may be at least two phosphorothioate internucleotide linkages between the terminal three nucleotides, in which two of the three nucleotides are overhang nucleotides, and the third is a paired nucleotide next to the overhang nucleotide. Preferably, these terminal three nucleotides may be at the 3′-end of the antisense strand. 
     In some embodiments, the sense strand of the dsRNA molecule comprises 1-10 blocks of two to ten phosphorothioate or methylphosphonate internucleotide linkages separated by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 phosphate internucleotide linkages, wherein one of the phosphorothioate or methylphosphonate internucleotide linkages is placed at any position in the oligonucleotide sequence and the said sense strand is paired with an antisense strand comprising any combination of phosphorothioate, methylphosphonate, and phosphate internucleotide linkages or an antisense strand comprising either phosphorothioate or methylphosphonate or phosphate linkage. 
     In some embodiments, the antisense strand of the dsRNA molecule comprises two blocks of two phosphorothioate or methylphosphonate internucleotide linkages separated by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 phosphate internucleotide linkages, wherein one of the phosphorothioate or methylphosphonate internucleotide linkages is placed at any position in the oligonucleotide sequence and the said antisense strand is paired with a sense strand comprising any combination of phosphorothioate, methylphosphonate, and phosphate internucleotide linkages or an antisense strand comprising either phosphorothioate or methylphosphonate or phosphate linkage. 
     In some embodiments, the antisense strand of the dsRNA molecule comprises two blocks of three phosphorothioate or methylphosphonate internucleotide linkages separated by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 phosphate internucleotide linkages, wherein one of the phosphorothioate or methylphosphonate internucleotide linkages is placed at any position in the oligonucleotide sequence and the said antisense strand is paired with a sense strand comprising any combination of phosphorothioate, methylphosphonate, and phosphate internucleotide linkages or an antisense strand comprising either phosphorothioate or methylphosphonate or phosphate linkage. 
     In some embodiments, the antisense strand of the dsRNA molecule comprises two blocks of four phosphorothioate or methylphosphonate internucleotide linkages separated by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 phosphate internucleotide linkages, wherein one of the phosphorothioate or methylphosphonate internucleotide linkages is placed at any position in the oligonucleotide sequence and the said antisense strand is paired with a sense strand comprising any combination of phosphorothioate, methylphosphonate, and phosphate internucleotide linkages or an antisense strand comprising either phosphorothioate or methylphosphonate or phosphate linkage. 
     In some embodiments, the antisense strand of the dsRNA molecule comprises two blocks of five phosphorothioate or methylphosphonate internucleotide linkages separated by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 phosphate internucleotide linkages, wherein one of the phosphorothioate or methylphosphonate internucleotide linkages is placed at any position in the oligonucleotide sequence and the said antisense strand is paired with a sense strand comprising any combination of phosphorothioate, methylphosphonate, and phosphate internucleotide linkages or an antisense strand comprising either phosphorothioate or methylphosphonate or phosphate linkage. 
     In some embodiments, the antisense strand of the dsRNA molecule comprises two blocks of six phosphorothioate or methylphosphonate internucleotide linkages separated by 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 phosphate internucleotide linkages, wherein one of the phosphorothioate or methylphosphonate internucleotide linkages is placed at any position in the oligonucleotide sequence and the said antisense strand is paired with a sense strand comprising any combination of phosphorothioate, methylphosphonate, and phosphate internucleotide linkages or an antisense strand comprising either phosphorothioate or methylphosphonate or phosphate linkage. 
     In some embodiments, the antisense strand of the dsRNA molecule comprises two blocks of seven phosphorothioate or methylphosphonate internucleotide linkages separated by 1, 2, 3, 4, 5, 6, 7, or 8 phosphate internucleotide linkages, wherein one of the phosphorothioate or methylphosphonate internucleotide linkages is placed at any position in the oligonucleotide sequence and the said antisense strand is paired with a sense strand comprising any combination of phosphorothioate, methylphosphonate, and phosphate internucleotide linkages or an antisense strand comprising either phosphorothioate or methylphosphonate or phosphate linkage. 
     In some embodiments, the antisense strand of the dsRNA molecule comprises two blocks of eight phosphorothioate or methylphosphonate internucleotide linkages separated by 1, 2, 3, 4, 5, or 6 phosphate internucleotide linkages, wherein one of the phosphorothioate or methylphosphonate internucleotide linkages is placed at any position in the oligonucleotide sequence and the said antisense strand is paired with a sense strand comprising any combination of phosphorothioate, methylphosphonate, and phosphate internucleotide linkages or an antisense strand comprising either phosphorothioate or methylphosphonate or phosphate linkage. 
     In some embodiments, the antisense strand of the dsRNA molecule comprises two blocks of nine phosphorothioate or methylphosphonate internucleotide linkages separated by 1, 2, 3, or 4 phosphate internucleotide linkages, wherein one of the phosphorothioate or methylphosphonate internucleotide linkages is placed at any position in the oligonucleotide sequence and the said antisense strand is paired with a sense strand comprising any combination of phosphorothioate, methylphosphonate, and phosphate internucleotide linkages or an antisense strand comprising either phosphorothioate or methylphosphonate or phosphate linkage. 
     In some embodiments, the dsRNA molecule of the disclosure further comprises one or more phosphorothioate or methylphosphonate internucleotide linkage modification within positions 1-10 of the termini position(s) of the sense or antisense strand. For example, at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides may be linked through phosphorothioate or methylphosphonate internucleotide linkage at one end or both ends of the sense or antisense strand. 
     In some embodiments, the dsRNA molecule of the disclosure further comprises one or more phosphorothioate or methylphosphonate internucleotide linkage modification within positions 1-10 of the internal region of the duplex of each of the sense or antisense strand. For example, at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides may be linked through phosphorothioate methylphosphonate internucleotide linkage at position 8-16 of the duplex region counting from the 5′-end of the sense strand; the dsRNA molecule can optionally further comprise one or more phosphorothioate or methylphosphonate internucleotide linkage modification within positions 1-10 of the termini position(s). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises one to five phosphorothioate or methylphosphonate internucleotide linkage modification(s) within position 1-5 and one to five phosphorothioate or methylphosphonate internucleotide linkage modification(s) within position 18-23 of the sense strand (counting from the 5′-end), and one to five phosphorothioate or methylphosphonate internucleotide linkage modification at positions 1 and 2 and one to five within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises one phosphorothioate internucleotide linkage modification within position 1-5 and one phosphorothioate or methylphosphonate internucleotide linkage modification within position 18-23 of the sense strand (counting from the 5′-end), and one phosphorothioate internucleotide linkage modification at positions 1 and 2 and two phosphorothioate or methylphosphonate internucleotide linkage modifications within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises two phosphorothioate internucleotide linkage modifications within position 1-5 and one phosphorothioate internucleotide linkage modification within position 18-23 of the sense strand (counting from the 5′-end), and one phosphorothioate internucleotide linkage modification at positions 1 and 2 and two phosphorothioate internucleotide linkage modifications within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises two phosphorothioate internucleotide linkage modifications within position 1-5 and two phosphorothioate internucleotide linkage modifications within position 18-23 of the sense strand (counting from the 5′-end), and one phosphorothioate internucleotide linkage modification at positions 1 and 2 and two phosphorothioate internucleotide linkage modifications within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises two phosphorothioate internucleotide linkage modifications within position 1-5 and two phosphorothioate internucleotide linkage modifications within position 18-23 of the sense strand (counting from the 5′-end), and one phosphorothioate internucleotide linkage modification at positions 1 and 2 and one phosphorothioate internucleotide linkage modification within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises one phosphorothioate internucleotide linkage modification within position 1-5 and one phosphorothioate internucleotide linkage modification within position 18-23 of the sense strand (counting from the 5′-end), and two phosphorothioate internucleotide linkage modifications at positions 1 and 2 and two phosphorothioate internucleotide linkage modifications within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises one phosphorothioate internucleotide linkage modification within position 1-5 and one within position 18-23 of the sense strand (counting from the 5′-end), and two phosphorothioate internucleotide linkage modification at positions 1 and 2 and one phosphorothioate internucleotide linkage modification within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises one phosphorothioate internucleotide linkage modification within position 1-5 (counting from the 5′-end) of the sense strand, and two phosphorothioate internucleotide linkage modifications at positions 1 and 2 and one phosphorothioate internucleotide linkage modification within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises two phosphorothioate internucleotide linkage modifications within position 1-5 (counting from the 5′-end) of the sense strand, and one phosphorothioate internucleotide linkage modification at positions 1 and 2 and two phosphorothioate internucleotide linkage modifications within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises two phosphorothioate internucleotide linkage modifications within position 1-5 and one within position 18-23 of the sense strand (counting from the 5′-end), and two phosphorothioate internucleotide linkage modifications at positions 1 and 2 and one phosphorothioate internucleotide linkage modification within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises two phosphorothioate internucleotide linkage modifications within position 1-5 and one phosphorothioate internucleotide linkage modification within position 18-23 of the sense strand (counting from the 5′-end), and two phosphorothioate internucleotide linkage modifications at positions 1 and 2 and two phosphorothioate internucleotide linkage modifications within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises two phosphorothioate internucleotide linkage modifications within position 1-5 and one phosphorothioate internucleotide linkage modification within position 18-23 of the sense strand (counting from the 5′-end), and one phosphorothioate internucleotide linkage modification at positions 1 and 2 and two phosphorothioate internucleotide linkage modifications within positions 18-23 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises two phosphorothioate internucleotide linkage modifications at position 1 and 2, and two phosphorothioate internucleotide linkage modifications at position 20 and 21 of the sense strand (counting from the 5′-end), and one phosphorothioate internucleotide linkage modification at positions 1 and one at position 21 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises one phosphorothioate internucleotide linkage modification at position 1, and one phosphorothioate internucleotide linkage modification at position 21 of the sense strand (counting from the 5′-end), and two phosphorothioate internucleotide linkage modifications at positions 1 and 2 and two phosphorothioate internucleotide linkage modifications at positions 20 and 21 the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises two phosphorothioate internucleotide linkage modifications at position 1 and 2, and two phosphorothioate internucleotide linkage modifications at position 21 and 22 of the sense strand (counting from the 5′-end), and one phosphorothioate internucleotide linkage modification at positions 1 and one phosphorothioate internucleotide linkage modification at position 21 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises one phosphorothioate internucleotide linkage modification at position 1, and one phosphorothioate internucleotide linkage modification at position 21 of the sense strand (counting from the 5′-end), and two phosphorothioate internucleotide linkage modifications at positions 1 and 2 and two phosphorothioate internucleotide linkage modifications at positions 21 and 22 the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises two phosphorothioate internucleotide linkage modifications at position 1 and 2, and two phosphorothioate internucleotide linkage modifications at position 22 and 23 of the sense strand (counting from the 5′-end), and one phosphorothioate internucleotide linkage modification at positions 1 and one phosphorothioate internucleotide linkage modification at position 21 of the antisense strand (counting from the 5′-end). 
     In some embodiments, the dsRNA molecule of the disclosure further comprises one phosphorothioate internucleotide linkage modification at position 1, and one phosphorothioate internucleotide linkage modification at position 21 of the sense strand (counting from the 5′-end), and two phosphorothioate internucleotide linkage modifications at positions 1 and 2 and two phosphorothioate internucleotide linkage modifications at positions 23 and 23 the antisense strand (counting from the 5′-end). 
     In some embodiments, compound of the disclosure comprises a pattern of backbone chiral centers. In some embodiments, a common pattern of backbone chiral centers comprises at least 5 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 6 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 7 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 8 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 9 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 10 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 11 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 12 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 13 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 14 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 15 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 16 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 17 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 18 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises at least 19 internucleotidic linkages in the Sp configuration. In some embodiments, a common pattern of backbone chiral centers comprises no more than 8 internucleotidic linkages in the Rp configuration. In some embodiments, a common pattern of backbone chiral centers comprises no more than 7 internucleotidic linkages in the Rp configuration. In some embodiments, a common pattern of backbone chiral centers comprises no more than 6 internucleotidic linkages in the Rp configuration. In some embodiments, a common pattern of backbone chiral centers comprises no more than 5 internucleotidic linkages in the Rp configuration. In some embodiments, a common pattern of backbone chiral centers comprises no more than 4 internucleotidic linkages in the Rp configuration. In some embodiments, a common pattern of backbone chiral centers comprises no more than 3 internucleotidic linkages in the Rp configuration. In some embodiments, a common pattern of backbone chiral centers comprises no more than 2 internucleotidic linkages in the Rp configuration. In some embodiments, a common pattern of backbone chiral centers comprises no more than 1 internucleotidic linkages in the Rp configuration. In some embodiments, a common pattern of backbone chiral centers comprises no more than 8 internucleotidic linkages which are not chiral (as a non-limiting example, a phosphodiester). In some embodiments, a common pattern of backbone chiral centers comprises no more than 7 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises no more than 6 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises no more than 5 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises no more than 4 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises no more than 3 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises no more than 2 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises no more than 1 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises at least 10 internucleotidic linkages in the Sp configuration, and no more than 8 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises at least 11 internucleotidic linkages in the Sp configuration, and no more than 7 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises at least 12 internucleotidic linkages in the Sp configuration, and no more than 6 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises at least 13 internucleotidic linkages in the Sp configuration, and no more than 6 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises at least 14 internucleotidic linkages in the Sp configuration, and no more than 5 internucleotidic linkages which are not chiral. In some embodiments, a common pattern of backbone chiral centers comprises at least 15 internucleotidic linkages in the Sp configuration, and no more than 4 internucleotidic linkages which are not chiral. In some embodiments, the internucleotidic linkages in the Sp configuration are optionally contiguous or not contiguous. In some embodiments, the internucleotidic linkages in the Rp configuration are optionally contiguous or not contiguous. In some embodiments, the internucleotidic linkages which are not chiral are optionally contiguous or not contiguous. 
     In some embodiments, compound of the disclosure comprises a block is a stereochemistry block. In some embodiments, a block is an Rp block in that each internucleotidic linkage of the block is Rp. In some embodiments, a 5′-block is an Rp block. In some embodiments, a 3′-block is an Rp block. In some embodiments, a block is an Sp block in that each internucleotidic linkage of the block is Sp. In some embodiments, a 5′-block is an Sp block. In some embodiments, a 3′-block is an Sp block. In some embodiments, provided oligonucleotides comprise both Rp and Sp blocks. In some embodiments, provided oligonucleotides comprise one or more Rp but no Sp blocks. In some embodiments, provided oligonucleotides comprise one or more Sp but no Rp blocks. In some embodiments, provided oligonucleotides comprise one or more PO blocks wherein each internucleotidic linkage in a natural phosphate linkage. 
     In some embodiments, compound of the disclosure comprises a 5′-block is an Sp block wherein each sugar moiety comprises a 2′-F modification. In some embodiments, a 5′-block is an Sp block wherein each of internucleotidic linkage is a modified internucleotidic linkage and each sugar moiety comprises a 2′-F modification. In some embodiments, a 5′-block is an Sp block wherein each of internucleotidic linkage is a phosphorothioate linkage and each sugar moiety comprises a 2′-F modification. In some embodiments, a 5′-block comprises 4 or more nucleoside units. In some embodiments, a 5′-block comprises 5 or more nucleoside units. In some embodiments, a 5′-block comprises 6 or more nucleoside units. In some embodiments, a 5′-block comprises 7 or more nucleoside units. In some embodiments, a 3′-block is an Sp block wherein each sugar moiety comprises a 2′-F modification. In some embodiments, a 3′-block is an Sp block wherein each of internucleotidic linkage is a modified internucleotidic linkage and each sugar moiety comprises a 2′-F modification. In some embodiments, a 3′-block is an Sp block wherein each of internucleotidic linkage is a phosphorothioate linkage and each sugar moiety comprises a 2′-F modification. In some embodiments, a 3′-block comprises 4 or more nucleoside units. In some embodiments, a 3′-block comprises 5 or more nucleoside units. In some embodiments, a 3′-block comprises 6 or more nucleoside units. In some embodiments, a 3′-block comprises 7 or more nucleoside units. 
     In some embodiments, compound of the disclosure comprises a type of nucleoside in a region or an oligonucleotide is followed by a specific type of internucleotidic linkage, e.g., natural phosphate linkage, modified internucleotidic linkage, Rp chiral internucleotidic linkage, Sp chiral internucleotidic linkage, etc. In some embodiments, A is followed by Sp. In some embodiments, A is followed by Rp. In some embodiments, A is followed by natural phosphate linkage (PO). In some embodiments, U is followed by Sp. In some embodiments, U is followed by Rp. In some embodiments, U is followed by natural phosphate linkage (PO). In some embodiments, C is followed by Sp. In some embodiments, C is followed by Rp. In some embodiments, C is followed by natural phosphate linkage (PO). In some embodiments, G is followed by Sp. In some embodiments, G is followed by Rp. In some embodiments, G is followed by natural phosphate linkage (PO). In some embodiments, C and U are followed by Sp. In some embodiments, C and U are followed by Rp. In some embodiments, C and U are followed by natural phosphate linkage (PO). In some embodiments, A and G are followed by Sp. In some embodiments, A and G are followed by Rp. 
     In some embodiments, the dsRNA molecule of the disclosure comprises mismatch(es) with the target, within the duplex, or combinations thereof. The mismatch can occur in the overhang region or the duplex region. The base pair can be ranked on the basis of their propensity to promote dissociation or melting (e.g., on the free energy of association or dissociation of a particular pairing, the simplest approach is to examine the pairs on an individual pair basis, though next neighbor or similar analysis can also be used). In terms of promoting dissociation: A:U is preferred over G:C; G:U is preferred over G:C; and I:C is preferred over G:C (I=inosine). Mismatches, e.g., non-canonical or other than canonical pairings (as described elsewhere herein) are preferred over canonical (A:T, A:U, G:C) pairings; and pairings which include a universal base are preferred over canonical pairings. 
     In some embodiments, the dsRNA molecule of the disclosure comprises at least one of the first 1, 2, 3, 4, or 5 base pairs within the duplex regions from the 5′-end of the antisense strand can be chosen independently from the group of: A:U, G:U, I:C, and mismatched pairs, e.g., non-canonical or other than canonical pairings or pairings which include a universal base, to promote the dissociation of the antisense strand at the 5′-end of the duplex. 
     In some embodiments, the nucleotide at the 1 position within the duplex region from the 5′-end in the antisense strand is selected from the group consisting of A, dA, dU, U, and dT. Alternatively, at least one of the first 1, 2 or 3 base pair within the duplex region from the 5′-end of the antisense strand is an AU base pair. For example, the first base pair within the duplex region from the 5′-end of the antisense strand is an AU base pair. 
     It was found that introducing 4′-modified or 5′-modified nucleotide to the 3′-end of a phosphodiester (PO), phosphorothioate (PS), or phosphorodithioate (PS2) linkage of a dinucleotide at any position of single stranded or double stranded oligonucleotide can exert steric effect to the internucleotide linkage and, hence, protecting or stabilizing it against nucleases. 
     In some embodiments, 5′-modified nucleoside is introduced at the 3′-end of a dinucleotide at any position of single stranded or double stranded siRNA. For instance, a 5′-alkylated nucleoside may be introduced at the 3′-end of a dinucleotide at any position of single stranded or double stranded siRNA. The alkyl group at the 5′ position of the ribose sugar can be racemic or chirally pure R or S isomer. An exemplary 5′-alkylated nucleoside is 5′-methyl nucleoside. The 5′-methyl can be either racemic or chirally pure R or S isomer. 
     In some embodiments, 4′-modified nucleoside is introduced at the 3′-end of a dinucleotide at any position of single stranded or double stranded siRNA. For instance, a 4′-alkylated nucleoside may be introduced at the 3′-end of a dinucleotide at any position of single stranded or double stranded siRNA. The alkyl group at the 4′ position of the ribose sugar can be racemic or chirally pure R or S isomer. An exemplary 4′-alkylated nucleoside is 4′-methyl nucleoside. The 4′-methyl can be either racemic or chirally pure R or S isomer. Alternatively, a 4′-O-alkylated nucleoside may be introduced at the 3′-end of a dinucleotide at any position of single stranded or double stranded siRNA. The 4′-O-alkyl of the ribose sugar can be racemic or chirally pure R or S isomer. An exemplary 4′-O-alkylated nucleoside is 4′-O-methyl nucleoside. The 4′-O-methyl can be either racemic or chirally pure R or S isomer. 
     In some embodiments, 5′-alkylated nucleoside is introduced at any position on the sense strand or antisense strand of a dsRNA, and such modification maintains or improves potency of the dsRNA. The 5′-alkyl can be either racemic or chirally pure R or S isomer. An exemplary 5′-alkylated nucleoside is 5′-methyl nucleoside. The 5′-methyl can be either racemic or chirally pure R or S isomer. 
     In some embodiments, 4′-alkylated nucleoside is introduced at any position on the sense strand or antisense strand of a dsRNA, and such modification maintains or improves potency of the dsRNA. The 4′-alkyl can be either racemic or chirally pure R or S isomer. An exemplary 4′-alkylated nucleoside is 4′-methyl nucleoside. The 4′-methyl can be either racemic or chirally pure R or S isomer. 
     In some embodiments, 4′-O-alkylated nucleoside is introduced at any position on the sense strand or antisense strand of a dsRNA, and such modification maintains or improves potency of the dsRNA. The 5′-alkyl can be either racemic or chirally pure R or S isomer. An exemplary 4′-O-alkylated nucleoside is 4′-O-methyl nucleoside. The 4′-O-methyl can be either racemic or chirally pure R or S isomer. 
     In some embodiments, the dsRNA molecule of the disclosure can comprise 2′-5′ linkages (with 2′-H, 2′-OH, and 2′-OMe and with P═O or P═S). For example, the 2′-5′ linkages modifications can be used to promote nuclease resistance or to inhibit binding of the sense to the antisense strand, or can be used at the 5′ end of the sense strand to avoid sense strand activation by RISC. 
     In another embodiment, the dsRNA molecule of the disclosure can comprise L sugars (e.g., L ribose, L-arabinose with 2′-H, 2′-OH and 2′-OMe). For example, these L sugars modifications can be used to promote nuclease resistance or to inhibit binding of the sense to the antisense strand, or can be used at the 5′ end of the sense strand to avoid sense strand activation by RISC. 
     Various publications describe multimeric siRNA which can all be used with the dsRNA of the disclosure. Such publications include WO2007/091269, U.S. Pat. No. 7,858,769, WO2010/141511, WO2007/117686, WO2009/014887, and WO2011/031520 which are hereby incorporated by their entirely. 
     In some embodiments dsRNA molecules of the disclosure are 5′ phosphorylated or include a phosphoryl analog at the 5′ prime terminus. 5′-phosphate modifications include those which are compatible with RISC mediated gene silencing. Suitable modifications include: 5′-monophosphate ((HO) 2 (O)P—O-5′); 5′-diphosphate ((HO) 2 (O)P—O—P(HO)(O)—O-5′); 5′-triphosphate ((HO) 2 (O)P—O—(HO)(O)P—O—P(HO)(O)—O-5′); 5′-guanosine cap (7-methylated or non-methylated) (7m-G-O-5′-(HO)(O)P—O—(HO)(O)P—O—P(HO)(O)—O-5′); 5′-adenosine cap (Appp), and any modified or unmodified nucleotide cap structure (N—O-5′-(HO)(O)P—O—(HO)(O)P—O—P(HO)(O)—O-5′); 5′-monothiophosphate (phosphorothioate; (HO) 2 (S)P—O-5′); 5′-monodithiophosphate (phosphorodithioate; (HO)(HS)(S)P—O-5′), 5′-phosphorothiolate ((HO) 2 (O)P—S-5′); any additional combination of oxygen/sulfur replaced monophosphate, diphosphate and triphosphates (e.g. 5′-alpha-thiotriphosphate, 5′-gamma-thiotriphosphate, etc.), 5′-phosphoramidates ((HO) 2 (O)P—NH-5′, (HO)(NH 2 )(O)P—O-5′), 5′-alkylphosphonates (R=alkyl=methyl, ethyl, isopropyl, propyl, etc., e.g. RP(OH)(O)—O-5′-, 5′-alkenylphosphonates (i.e. vinyl, substituted vinyl), (OH) 2 (O)P-5′-CH 2 -), 5′-alkyletherphosphonates (R=alkylether=methoxymethyl (MeOCH2-), ethoxymethyl, etc., e.g. RP(OH)(O)—O-5′-). In one example, the modification can in placed in the antisense strand of a dsRNA molecule. 
     Linkers 
     In some embodiments, the conjugate or ligand described herein can be attached to an iRNA oligonucleotide with various linkers that can be cleavable or non-cleavable. 
     Linkers typically comprise a direct bond or an atom such as oxygen or sulfur, a unit such as NR8, C(O), C(O)NH, SO, SO 2 , SO 2 NH or a chain of atoms, such as, but not limited to, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkylarylalkyl, alkylarylalkenyl, alkylarylalkynyl, alkenylarylalkyl, alkenylarylalkenyl, alkenylarylalkynyl, alkynylarylalkyl, alkynylarylalkenyl, alkynylarylalkynyl, alkylheteroarylalkyl, alkylheteroarylalkenyl, alkylheteroarylalkynyl, alkenylheteroarylalkyl, alkenylheteroarylalkenyl, alkenylheteroarylalkynyl, alkynylheteroarylalkyl, alkynylheteroarylalkenyl, alkynylheteroarylalkynyl, alkylheterocyclylalkyl, alkylheterocyclylalkenyl, alkylhererocyclylalkynyl, alkenylheterocyclylalkyl, alkenylheterocyclylalkenyl, alkenylheterocyclylalkynyl, alkynylheterocyclylalkyl, alkynylheterocyclylalkenyl, alkynylheterocyclylalkynyl, alkylaryl, alkenylaryl, alkynylaryl, alkylheteroaryl, alkenylheteroaryl, alkynylhereroaryl, which one or more methylenes can be interrupted or terminated by O, S, S(O), SO 2 , N(R8), C(O), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic; where R8 is hydrogen, acyl, aliphatic or substituted aliphatic. In some embodiments, the linker is between about 1-24 atoms, 2-24, 3-24, 4-24, 5-24, 6-24, 6-18, 7-18, 8-18 atoms, 7-17, 8-17, 6-16, 7-16, or 8-16 atoms. 
     In some embodiments, a dsRNA of the disclosure is conjugated to a bivalent or trivalent branched linker selected from the group of structures shown in any of formula (XXXI)-(XXXIV): 
     
       
         
         
             
             
         
       
     
     wherein: 
     q2A, q2B, q3A, q3B, q4A, q4B, q5A, q5B and q5C represent independently for each occurrence 0-20 and wherein the repeating unit can be the same or different; 
     P 2A , P 2B , P 3A , P 3B , P 4A , P 4B , P 5A , P 5B , P 5C , T 2A , T 2B , T 3A , T 3B , T 4A , T 4B , T 4A , T 5B , T 5C  are each independently for each occurrence absent, CO, NH, O, S, OC(O), NHC(O), CH 2 , CH 2 NH or CH 2 O; 
     Q 2A , Q 2B , Q 3A , Q 3B , Q 4A , Q 4B , Q 5A , Q 5B , Q 5C  are independently for each occurrence absent, alkylene, substituted alkylene wherein one or more methylenes can be interrupted or terminated by one or more of O, S, S(O), SO 2 , N(R N ), C(R′)═C(R″), C≡C or C(O); 
     R 2A , R 2B , R 3A , R 3B , R 4A , R 4B , R 5A , R 5B , R 5C  are each independently for each occurrence absent, NH, O, S, CH 2 , C(O)O, C(O)NH, NHCH(R a )C(O), —C(O)—CH(R a )—NH—, CO, CH═N—O, 
     
       
         
         
             
             
         
       
     
     or heterocyclyl; 
     L 2A , L 2B , L 3A , L 3B , L 4A , L 4B , L 5A , L 5B  and L 5C  represent the ligand; i.e. each independently for each occurrence a monosaccharide (such as GalNAc), disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, or polysaccharide; and R a  is H or amino acid side chain. Trivalent conjugating GalNAc derivatives are particularly useful for use with RNAi agents for inhibiting the expression of a target gene, such as those of formula (XXXV): 
     
       
         
         
             
             
         
       
     
     wherein L 5A , L 5B  and L 5C  represent a monosaccharide, such as GalNAc derivative. 
     Examples of suitable bivalent and trivalent branched linker groups conjugating GalNAc derivatives include, but are not limited to, the structures recited above as formulas II, VII, XI, X, and XIII. 
     A cleavable linking group is one which is sufficiently stable outside the cell, but which upon entry into a target cell is cleaved to release the two parts the linker is holding together. In a some embodiments, the cleavable linking group is cleaved at least about 10 times, 20, times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times or more, or at least about 100 times faster in a target cell or under a first reference condition (which can, e.g., be selected to mimic or represent intracellular conditions) than in the blood of a subject, or under a second reference condition (which can, e.g., be selected to mimic or represent conditions found in the blood or serum). 
     Cleavable linking groups are susceptible to cleavage agents, e.g., pH, redox potential or the presence of degradative molecules. Generally, cleavage agents are more prevalent or found at higher levels or activities inside cells than in serum or blood. Examples of such degradative agents include: redox agents which are selected for particular substrates or which have no substrate specificity, including, e.g., oxidative or reductive enzymes or reductive agents such as mercaptans, present in cells, that can degrade a redox cleavable linking group by reduction; esterases; endosomes or agents that can create an acidic environment, e.g., those that result in a pH of five or lower; enzymes that can hydrolyze or degrade an acid cleavable linking group by acting as a general acid, peptidases (which can be substrate specific), and phosphatases. 
     A cleavable linkage group, such as a disulfide bond can be susceptible to pH. The pH of human serum is 7.4, while the average intracellular pH is slightly lower, ranging from about 7.1-7.3. Endosomes have a more acidic pH, in the range of 5.5-6.0, and lysosomes have an even more acidic pH at around 5.0. Some linkers will have a cleavable linking group that is cleaved at a suitable pH, thereby releasing a cationic lipid from the ligand inside the cell, or into the desired compartment of the cell. 
     A linker can include a cleavable linking group that is cleavable by a particular enzyme. The type of cleavable linking group incorporated into a linker can depend on the cell to be targeted. 
     In general, the suitability of a candidate cleavable linking group can be evaluated by testing the ability of a degradative agent (or condition) to cleave the candidate linking group. It will also be desirable to also test the candidate cleavable linking group for the ability to resist cleavage in the blood or when in contact with other non-target tissue. Thus, one can determine the relative susceptibility to cleavage between a first and a second condition, where the first is selected to be indicative of cleavage in a target cell and the second is selected to be indicative of cleavage in other tissues or biological fluids, e.g., blood or serum. The evaluations can be carried out in cell free systems, in cells, in cell culture, in organ or tissue culture, or in whole animals. It can be useful to make initial evaluations in cell-free or culture conditions and to confirm by further evaluations in whole animals. In some embodiments, useful candidate compounds are cleaved at least about 2, 4, 10, 20, 30, 40, 50, 60, 70, 80, 90, or about 100 times faster in the cell (or under in vitro conditions selected to mimic intracellular conditions) as compared to blood or serum (or under in vitro conditions selected to mimic extracellular conditions). 
     Redox Cleavable Linking Groups 
     In some embodiments, a cleavable linking group is a redox cleavable linking group that is cleaved upon reduction or oxidation. An example of reductively cleavable linking group is a disulphide linking group (—S—S—). To determine if a candidate cleavable linking group is a suitable “reductively cleavable linking group,” or for example is suitable for use with a particular iRNA moiety and particular targeting agent one can look to methods described herein. For example, a candidate can be evaluated by incubation with dithiothreitol (DTT), or other reducing agent using reagents know in the art, which mimic the rate of cleavage which would be observed in a cell, e.g., a target cell. The candidates can also be evaluated under conditions which are selected to mimic blood or serum conditions. In one, candidate compounds are cleaved by at most about 10% in the blood. In other embodiments, useful candidate compounds are degraded at least about 2, 4, 10, 20, 30, 40, 50, 60, 70, 80, 90, or about 100 times faster in the cell (or under in vitro conditions selected to mimic intracellular conditions) as compared to blood (or under in vitro conditions selected to mimic extracellular conditions). The rate of cleavage of candidate compounds can be determined using standard enzyme kinetics assays under conditions chosen to mimic intracellular media and compared to conditions chosen to mimic extracellular media. 
     Phosphate-Based Cleavable Linking Groups 
     In some embodiments, a cleavable linker comprises a phosphate-based cleavable linking group. A phosphate-based cleavable linking group is cleaved by agents that degrade or hydrolyze the phosphate group. An example of an agent that cleaves phosphate groups in cells are enzymes such as phosphatases in cells. Examples of phosphate-based linking groups are —O—P(O)(ORk)-O—, —O—P(S)(ORk)-O—, —O—P(S)(SRk)-O—, —S—P(O)(ORk)-O—, —O—P(O)(ORk)-S—, —S—P(O)(ORk)-S—, —O—P(S)(ORk)-S—, —S—P(S)(ORk)-O—, —O—P(O)(Rk)-O—, —O—P(S)(Rk)-O—, —S—P(O)(Rk)-O—, —S—P(S)(Rk)-O—, —S—P(O)(Rk)-S—, —O—P(S)(Rk)-S—. In some embodiments, phosphate-based linking groups are —O—P(O)(OH)—O—, —O—P(S)(OH)—O—, —O—P(S)(SH)—O—, —S—P(O)(OH)—O—, —O—P(O)(OH)—S—, —S—P(O)(OH)—S—, —O—P(S)(OH)—S—, —S—P(S)(OH)—O—, —O—P(O)(H)—O—, —O—P(S)(H)—O—, —S—P(O)(H)—O, —S—P(S)(H)—O—, —S—P(O)(H)—S—, —O—P(S)(H)—S—. In some embodiments, a phosphate-based linking group is —O—P(O)(OH)—O—. These candidates can be evaluated using methods analogous to those described above. 
     Acid Cleavable Linking Groups 
     In some embodiments, a cleavable linker comprises an acid cleavable linking group. An acid cleavable linking group is a linking group that is cleaved under acidic conditions. In some embodiments acid cleavable linking groups are cleaved in an acidic environment with a pH of about 6.5 or lower (e.g., about 6.0, 5.75, 5.5, 5.25, 5.0, or lower), or by agents such as enzymes that can act as a general acid. In a cell, specific low pH organelles, such as endosomes and lysosomes can provide a cleaving environment for acid cleavable linking groups. Examples of acid cleavable linking groups include but are not limited to hydrazones, esters, and esters of amino acids. Acid cleavable groups can have the general formula —C═NN—, C(O)O, or —OC(O). In some embodiments, the carbon attached to the oxygen of the ester (the alkoxy group) is an aryl group, substituted alkyl group, or tertiary alkyl group such as dimethyl pentyl or t-butyl. These candidates can be evaluated using methods analogous to those described above. 
     Ester-Based Cleavable Linking Groups 
     In some embodiments, a cleavable linker comprises an ester-based cleavable linking group. An ester-based cleavable linking group is cleaved by enzymes such as esterases and amidases in cells. Examples of ester-based cleavable linking groups include but are not limited to esters of alkylene, alkenylene and alkynylene groups. Ester cleavable linking groups have the general formula —C(O)O—, or —OC(O)—. These candidates can be evaluated using methods analogous to those described above. 
     Peptide-Based Cleavable Linking Groups 
     In some embodiments, a cleavable linker comprises a peptide-based cleavable linking group. A peptide-based cleavable linking group is cleaved by enzymes such as peptidases and proteases in cells. Peptide-based cleavable linking groups are peptide bonds formed between amino acids to yield oligopeptides (e.g., dipeptides, tripeptides etc.) and polypeptides. Peptide-based cleavable groups do not include the amide group (—C(O)NH—). The amide group can be formed between any alkylene, alkenylene or alkynylene. A peptide bond is a special type of amide bond formed between amino acids to yield peptides and proteins. The peptide-based cleavage group is generally limited to the peptide bond (i.e., the amide bond) formed between amino acids yielding peptides and proteins and does not include the entire amide functional group. Peptide-based cleavable linking groups have the general formula —NHCHRAC(O)NHCHRBC(O)—, where RA and RB are the R groups of the two adjacent amino acids. These candidates can be evaluated using methods analogous to those described above. Representative U.S. patents that teach the preparation of RNA conjugates include, but are not limited to, U.S. Pat. Nos. 4,828,979; 4,948,882; 5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552,538; 5,578,717, 5,580,731; 5,591,584; 5,109,124; 5,118,802; 5,138,045; 5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044; 4,605,735; 4,667,025; 4,762,779; 4,789,737; 4,824,941; 4,835,263; 4,876,335; 4,904,582; 4,958,013; 5,082,830; 5,112,963; 5,214,136; 5,082,830; 5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506; 5,262,536; 5,272,250; 5,292,873; 5,317,098; 5,371,241, 5,391,723; 5,416,203, 5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552; 5,567,810; 5,574,142; 5,585,481; 5,587,371; 5,595,726; 5,597,696; 5,599,923; 5,599,928 and 5,688,941; 6,294,664; 6,320,017; 6,576,752; 6,783,931; 6,900,297; 7,037,646; 8,106,022, the entire contents of each of which is herein incorporated by reference. 
     It is not necessary for all positions in a given compound to be uniformly modified, and in fact more than one of the aforementioned modifications may be incorporated in a single compound or even at a single nucleoside within an iRNA. The present disclosure also includes iRNA compounds that are chimeric compounds. 
     “Chimeric” iRNA compounds, or “chimeras,” in the context of the present disclosure, are iRNA compounds, e.g., dsRNAs, that contain two or more chemically distinct regions, each made up of at least one monomer unit, i.e., a nucleotide in the case of a dsRNA compound. These iRNAs typically contain at least one region wherein the RNA is modified so as to confer upon the iRNA increased resistance to nuclease degradation, increased cellular uptake, and/or increased binding affinity for the target nucleic acid. An additional region of the iRNA may serve as a substrate for enzymes capable of cleaving RNA:DNA or RNA:RNA hybrids. By way of example, RNase H is a cellular endonuclease which cleaves the RNA strand of an RNA:DNA duplex. Activation of RNase H, therefore, results in cleavage of the RNA target, thereby greatly enhancing the efficiency of iRNA inhibition of gene expression. Consequently, comparable results can often be obtained with shorter iRNAs when chimeric dsRNAs are used, compared to phosphorothioate deoxy dsRNAs hybridizing to the same target region. Cleavage of the RNA target can be routinely detected by gel electrophoresis and, if necessary, associated nucleic acid hybridization techniques known in the art. 
     In certain instances, the RNA of an iRNA can be modified by a non-ligand group. A number of non-ligand molecules have been conjugated to iRNAs in order to enhance the activity, cellular distribution or cellular uptake of the iRNA, and procedures for performing such conjugations are available in the scientific literature. Such non-ligand moieties have included lipid moieties, such as cholesterol (Kubo, T. et al.,  Biochem. Biophys. Res. Comm.,  2007, 365(1):54-61; Letsinger et al.,  Proc. Natl. Acad. Sci. USA,  1989, 86:6553), cholic acid (Manoharan et al.,  Bioorg. Med. Chem. Lett.,  1994, 4:1053), a thioether, e.g., hexyl-S-tritylthiol (Manoharan et al.,  Ann. N.Y. Acad. Sci.,  1992, 660:306; Manoharan et al.,  Bioorg. Med. Chem. Let.,  1993, 3:2765), a thiocholesterol (Oberhauser et al.,  Nucl. Acids Res.,  1992, 20:533), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al.,  EMBO J.,  1991, 10:111; Kabanov et al.,  FEBS Lett.,  1990, 259:327; Svinarchuk et al.,  Biochimie,  1993, 75:49), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate (Manoharan et al.,  Tetrahedron Lett.,  1995, 36:3651; Shea et al.,  Nucl. Acids Res.,  1990, 18:3777), a polyamine or a polyethylene glycol chain (Manoharan et al.,  Nucleosides  &amp;  Nucleotides,  1995, 14:969), or adamantane acetic acid (Manoharan et al.,  Tetrahedron Lett.,  1995, 36:3651), a palmityl moiety (Mishra et al.,  Biochim. Biophys. Acta,  1995, 1264:229), or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety (Crooke et al.,  J. Pharmacol. Exp. Ther.,  1996, 277:923). Representative United States patents that teach the preparation of such RNA conjugates have been listed above. Typical conjugation protocols involve the synthesis of an RNAs bearing an aminolinker at one or more positions of the sequence. The amino group is then reacted with the molecule being conjugated using appropriate coupling or activating reagents. The conjugation reaction may be performed either with the RNA still bound to the solid support or following cleavage of the RNA, in solution phase. Purification of the RNA conjugate by HPLC typically affords the pure conjugate. 
     Delivery of iRNA 
     The delivery of an iRNA to a subject in need thereof can be achieved in a number of different ways. In vivo delivery can be performed directly by administering a composition comprising an iRNA, e.g. a dsRNA, to a subject. Alternatively, delivery can be performed indirectly by administering one or more vectors that encode and direct the expression of the iRNA. These alternatives are discussed further below. 
     Direct Delivery 
     In general, any method of delivering a nucleic acid molecule can be adapted for use with an iRNA (see e.g., Akhtar S. and Julian R L. (1992)  Trends Cell. Biol.  2(5):139-144 and WO94/02595, which are incorporated herein by reference in their entireties). However, there are three factors that are important to consider in order to successfully deliver an iRNA molecule in vivo: (a) biological stability of the delivered molecule, (2) preventing non-specific effects, and (3) accumulation of the delivered molecule in the target tissue. The non-specific effects of an iRNA can be minimized by local administration, for example by direct injection or implantation into a tissue (as a non-limiting example, the eye) or topically administering the preparation. Local administration to a treatment site maximizes local concentration of the agent, limits the exposure of the agent to systemic tissues that may otherwise be harmed by the agent or that may degrade the agent, and permits a lower total dose of the iRNA molecule to be administered. Several studies have shown successful knockdown of gene products when an iRNA is administered locally. For example, intraocular delivery of a VEGF dsRNA by intravitreal injection in cynomolgus monkeys (Tolentino, M J., et al (2004)  Retina  24:132-138) and subretinal injections in mice (Reich, S J., et al (2003)  Mol. Vis.  9:210-216) were both shown to prevent neovascularization in an experimental model of age-related macular degeneration. In addition, direct intratumoral injection of a dsRNA in mice reduces tumor volume (Pille, J., et al (2005)  Mol. Ther.  11:267-274) and can prolong survival of tumor-bearing mice (Kim, W J., et al (2006)  Mol. Ther.  14:343-350; Li, S., et al (2007)  Mol. Ther.  15:515-523). RNA interference has also shown success with local delivery to the CNS by direct injection (Dorn, G., et al. (2004)  Nucleic Acids  32:e49; Tan, P H., et al (2005)  Gene Ther.  12:59-66; Makimura, H., et al (2002)  BMC Neurosci.  3:18; Shishkina, G T., et al (2004)  Neuroscience  129:521-528; Thakker, E R., et al (2004)  Proc. Natl. Acad. Sci. U.S.A.  101:17270-17275; Akaneya,Y., et al (2005)  J. Neurophysiol.  93:594-602) and to the lungs by intranasal administration (Howard, K A., et al (2006)  Mol. Ther.  14:476-484; Zhang, X., et al (2004)  J. Biol. Chem.  279:10677-10684; Bitko, V., et al (2005)  Nat. Med.  11:50-55). For administering an iRNA systemically for the treatment of a disease, the RNA can be modified or alternatively delivered using a drug delivery system; both methods act to prevent the rapid degradation of the dsRNA by endo- and exo-nucleases in vivo. 
     Modification of the RNA or the pharmaceutical carrier can also permit targeting of the iRNA composition to the target tissue and avoid undesirable off-target effects. iRNA molecules can be modified by chemical conjugation to other groups, e.g., a lipid or carbohydrate group as described herein. Such conjugates can be used to target iRNA to particular cells, e.g., liver cells, e.g., hepatocytes. For example, GalNAc conjugates or lipid (e.g., LNP) formulations can be used to target iRNA to particular cells, e.g., liver cells, e.g., hepatocytes. 
     iRNA molecules can also be modified by chemical conjugation to lipophilic groups such as cholesterol to enhance cellular uptake and prevent degradation. For example, an iRNA directed against ApoB conjugated to a lipophilic cholesterol moiety was injected systemically into mice and resulted in knockdown of apoB mRNA in both the liver and jejunum (Soutschek, J., et al (2004)  Nature  432:173-178). Conjugation of an iRNA to an aptamer has been shown to inhibit tumor growth and mediate tumor regression in a mouse model of prostate cancer (McNamara, J O., et al (2006)  Nat. Biotechnol.  24:1005-1015). In an alternative embodiment, the iRNA can be delivered using drug delivery systems such as a nanoparticle, a dendrimer, a polymer, liposomes, or a cationic delivery system. Positively charged cationic delivery systems facilitate binding of an iRNA molecule (negatively charged) and also enhance interactions at the negatively charged cell membrane to permit efficient uptake of an iRNA by the cell. Cationic lipids, dendrimers, or polymers can either be bound to an iRNA, or induced to form a vesicle or micelle (see e.g., Kim S H., et al (2008)  Journal of Controlled Release  129(2):107-116) that encases an iRNA. The formation of vesicles or micelles further prevents degradation of the iRNA when administered systemically. Methods for making and administering cationic-iRNA complexes are well within the abilities of one skilled in the art (see e.g., Sorensen, D R., et al (2003)  J. Mol. Biol  327:761-766; Verma, U N., et al (2003)  Clin. Cancer Res.  9:1291-1300; Arnold, A S et al (2007)  J. Hypertens.  25:197-205, which are incorporated herein by reference in their entirety). Some non-limiting examples of drug delivery systems useful for systemic delivery of iRNAs include DOTAP (Sorensen, D R., et al (2003), supra; Verma, U N., et al (2003), supra), Oligofectamine, “solid nucleic acid lipid particles” (Zimmermann, T S., et al (2006)  Nature  441:111-114), cardiolipin (Chien, P Y., et al (2005)  Cancer Gene Ther.  12:321-328; Pal, A., et al (2005)  Int J. Oncol.  26:1087-1091), polyethyleneimine (Bonnet M E., et al (2008)  Pharm. Res . August 16 Epub ahead of print; Aigner, A. (2006)  J. Biomed. Biotechnol.  71659), Arg-Gly-Asp (RGD) peptides (Liu, S. (2006)  Mol. Pharm.  3:472-487), and polyamidoamines (Tomalia, D A., et al (2007)  Biochem. Soc. Trans.  35:61-67; Yoo, H., et al (1999)  Pharm. Res.  16:1799-1804). In some embodiments, an iRNA forms a complex with cyclodextrin for systemic administration. Methods for administration and pharmaceutical compositions of iRNAs and cyclodextrins can be found in U.S. Pat. No. 7,427,605, which is herein incorporated by reference in its entirety. 
     Vector encoded iRNAs In another aspect, iRNA targeting VEGF-A can be expressed from transcription units inserted into DNA or RNA vectors (see, e.g., Couture, A, et al.,  TIG . (1996), 12:5-10; Skillern, A., et al., International PCT Publication No. WO 00/22113, Conrad, International PCT Publication No. WO 00/22114, and Conrad, U.S. Pat. No. 6,054,299). Expression can be transient (on the order of hours to weeks) or sustained (weeks to months or longer), depending upon the specific construct used and the target tissue or cell type. These transgenes can be introduced as a linear construct, a circular plasmid, or a viral vector, which can be an integrating or non-integrating vector. The transgene can also be constructed to permit it to be inherited as an extrachromosomal plasmid (Gassmann, et al.,  Proc. Natl. Acad. Sci. USA  (1995) 92:1292). 
     The individual strand or strands of an iRNA can be transcribed from a promoter on an expression vector. Where two separate strands are to be expressed to generate, for example, a dsRNA, two separate expression vectors can be co-introduced (e.g., by transfection or infection) into a target cell. Alternatively, each individual strand of a dsRNA can be transcribed by promoters both of which are located on the same expression plasmid. In some embodiments, a dsRNA is expressed as an inverted repeat joined by a linker polynucleotide sequence such that the dsRNA has a stem and loop structure. 
     An iRNA expression vector is typically a DNA plasmid or viral vector. An expression vector compatible with eukaryotic cells, e.g., with vertebrate cells, can be used to produce recombinant constructs for the expression of an iRNA as described herein. Eukaryotic cell expression vectors are well known in the art and are available from a number of commercial sources. Typically, such vectors contain convenient restriction sites for insertion of the desired nucleic acid segment. Delivery of iRNA expressing vectors can be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex-planted from the patient followed by reintroduction into the patient, or by any other means that allows for introduction into a desired target cell. 
     An iRNA expression plasmid can be transfected into a target cell as a complex with a cationic lipid carrier (e.g., Oligofectamine) or a non-cationic lipid-based carrier (e.g., Transit-TKO™). Multiple lipid transfections for iRNA-mediated knockdowns targeting different regions of a target RNA over a period of a week or more are also contemplated by the disclosure. Successful introduction of vectors into host cells can be monitored using various known methods. For example, transient transfection can be signaled with a reporter, such as a fluorescent marker, such as Green Fluorescent Protein (GFP). Stable transfection of cells ex vivo can be ensured using markers that provide the transfected cell with resistance to specific environmental factors (e.g., antibiotics and drugs), such as hygromycin B resistance. 
     Viral vector systems which can be utilized with the methods and compositions described herein include, but are not limited to, (a) adenovirus vectors; (b) retrovirus vectors, including but not limited to lentiviral vectors, moloney murine leukemia virus, etc.; (c) adeno-associated virus vectors; (d) herpes simplex virus vectors; (e) SV40 vectors; (f) polyoma virus vectors; (g) papilloma virus vectors; (h) picornavirus vectors; (i) pox virus vectors such as an orthopox, e.g., vaccinia virus vectors or avipox, e.g. canary pox or fowl pox; and (j) a helper-dependent or gutless adenovirus. Replication-defective viruses can also be advantageous. Different vectors will or will not become incorporated into the cells&#39; genome. The constructs can include viral sequences for transfection, if desired. Alternatively, the construct may be incorporated into vectors capable of episomal replication, e.g EPV and EBV vectors. Constructs for the recombinant expression of an iRNA will generally require regulatory elements, e.g., promoters, enhancers, etc., to ensure the expression of the iRNA in target cells. Other aspects to consider for vectors and constructs are further described below. 
     Vectors useful for the delivery of an iRNA will include regulatory elements (promoter, enhancer, etc.) sufficient for expression of the iRNA in the desired target cell or tissue. The regulatory elements can be chosen to provide either constitutive or regulated/inducible expression. 
     Expression of the iRNA can be precisely regulated, for example, by using an inducible regulatory sequence that is sensitive to certain physiological regulators, e.g., circulating glucose levels, or hormones (Docherty et al., 1994 , FASEB J.  8:20-24). Such inducible expression systems, suitable for the control of dsRNA expression in cells or in mammals include, for example, regulation by ecdysone, by estrogen, progesterone, tetracycline, chemical inducers of dimerization, and isopropyl-β-D1-thiogalactopyranoside (IPTG). A person skilled in the art would be able to choose the appropriate regulatory/promoter sequence based on the intended use of the iRNA transgene. 
     In a specific embodiment, viral vectors that contain nucleic acid sequences encoding an iRNA can be used. For example, a retroviral vector can be used (see Miller et al.,  Meth. Enzymol.  217:581-599 (1993)). These retroviral vectors contain the components necessary for the correct packaging of the viral genome and integration into the host cell DNA. The nucleic acid sequences encoding an iRNA are cloned into one or more vectors, which facilitates delivery of the nucleic acid into a patient. More detail about retroviral vectors can be found, for example, in Boesen et al.,  Biotherapy  6:291-302 (1994), which describes the use of a retroviral vector to deliver the mdr1 gene to hematopoietic stem cells in order to make the stem cells more resistant to chemotherapy. Other references illustrating the use of retroviral vectors in gene therapy are: Clowes et al.,  J. Clin. Invest.  93:644-651 (1994); Kiem et al.,  Blood  83:1467-1473 (1994); Salmons and Gunzberg,  Human Gene Therapy  4:129-141 (1993); and Grossman and Wilson,  Curr. Opin. in Genetics and Devel.  3:110-114 (1993). Lentiviral vectors contemplated for use include, for example, the HIV based vectors described in U.S. Pat. Nos. 6,143,520; 5,665,557; and 5,981,276, which are herein incorporated by reference. 
     Adenoviruses are also contemplated for use in delivery of iRNAs. Adenoviruses are especially attractive vehicles, e.g., for delivering genes to respiratory epithelia. Adenoviruses naturally infect respiratory epithelia where they cause a mild disease. Other targets for adenovirus-based delivery systems are liver, the central nervous system, endothelial cells, and muscle. Adenoviruses have the advantage of being capable of infecting non-dividing cells. Kozarsky and Wilson,  Current Opinion in Genetics and Development  3:499-503 (1993) present a review of adenovirus-based gene therapy. Bout et al.,  Human Gene Therapy  5:3-10 (1994) demonstrated the use of adenovirus vectors to transfer genes to the respiratory epithelia of rhesus monkeys. Other instances of the use of adenoviruses in gene therapy can be found in Rosenfeld et al.,  Science  252:431-434 (1991); Rosenfeld et al.,  Cell  68:143-155 (1992); Mastrangeli et al.,  J. Clin. Invest.  91:225-234 (1993); PCT Publication WO94/12649; and Wang, et al.,  Gene Therapy  2:775-783 (1995). A suitable AV vector for expressing an iRNA featured in the disclosure, a method for constructing the recombinant AV vector, and a method for delivering the vector into target cells, are described in Xia H et al. (2002),  Nat. Biotech.  20: 1006-1010. 
     Use of Adeno-associated virus (AAV) vectors is also contemplated (Walsh et al.,  Proc. Soc. Exp. Biol. Med.  204:289-300 (1993); U.S. Pat. No. 5,436,146). In some embodiments, the iRNA can be expressed as two separate, complementary single-stranded RNA molecules from a recombinant AAV vector having, for example, either the U6 or H1 RNA promoters, or the cytomegalovirus (CMV) promoter. Suitable AAV vectors for expressing the dsRNA featured in the disclosure, methods for constructing the recombinant AV vector, and methods for delivering the vectors into target cells are described in Samulski R et al. (1987),  J. Virol.  61: 3096-3101; Fisher K J et al. (1996),  J. Virol.,  70: 520-532; Samulski R et al. (1989),  J. Virol.  63: 3822-3826; U.S. Pat. Nos. 5,252,479; 5,139,941; International Patent Application No. WO 94/13788; and International Patent Application No. WO 93/24641, the entire disclosures of which are herein incorporated by reference. 
     Another typical viral vector is a pox virus such as a vaccinia virus, for example an attenuated vaccinia such as Modified Virus Ankara (MVA) or NYVAC, an avipox such as fowl pox or canary pox. 
     The tropism of viral vectors can be modified by pseudotyping the vectors with envelope proteins or other surface antigens from other viruses, or by substituting different viral capsid proteins, as appropriate. For example, lentiviral vectors can be pseudotyped with surface proteins from vesicular stomatitis virus (VSV), rabies, Ebola, Mokola, and the like. AAV vectors can be made to target different cells by engineering the vectors to express different capsid protein serotypes; see, e.g., Rabinowitz J E et al. (2002),  J Virol  76:791-801, the entire disclosure of which is herein incorporated by reference. 
     The pharmaceutical preparation of a vector can include the vector in an acceptable diluent, or can include a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g., retroviral vectors, the pharmaceutical preparation can include one or more cells which produce the gene delivery system. 
     III. Pharmaceutical Compositions Containing iRNA 
     In some embodiments, the disclosure provides pharmaceutical compositions containing an iRNA, as described herein, and a pharmaceutically acceptable carrier. The pharmaceutical composition containing the iRNA is useful for treating a disease or disorder related to the expression or activity of VEGF-A (e.g., an angiogenic ocular disorder). Such pharmaceutical compositions are formulated based on the mode of delivery. In some embodiments, compositions can be formulated for localized delivery, e.g., by intraocular delivery (e.g., intravitreal administration, e.g., intravitreal injection; transscleral administration, e.g., transscleral injection; subconjunctival administration, e.g., subconjunctival injection; retrobulbar administration, e.g., retrobulbar injection; intracameral administration, e.g., intracameral injection; or subretinal administration, e.g., subretinal injection). In other embodiments, compositions can be formulated for topical delivery. In another example, compositions can be formulated for systemic administration via parenteral delivery, e.g., by intravenous (IV) delivery. In some embodiments, a composition provided herein (e.g., a composition comprising a GalNAc conjugate or an LNP formulation) is formulated for intravenous delivery. 
     The pharmaceutical compositions featured herein are administered in a dosage sufficient to inhibit expression of VEGF-A. In general, a suitable dose of iRNA will be in the range of 0.01 to 200.0 milligrams per kilogram body weight of the recipient per day. The pharmaceutical composition may be administered once daily, or the iRNA may be administered as two, three, or more sub-doses at appropriate intervals throughout the day or even using continuous infusion or delivery through a controlled release formulation. In that case, the iRNA contained in each sub-dose must be correspondingly smaller in order to achieve the total daily dosage. The dosage unit can also be compounded for delivery over several days, e.g., using a conventional sustained release formulation which provides sustained release of the iRNA over a several day period. Sustained release formulations are well known in the art and are particularly useful for delivery of agents at a particular site, such as can be used with the agents of the present disclosure. In this embodiment, the dosage unit contains a corresponding multiple of the daily dose. 
     The effect of a single dose on VEGF-A levels can be long lasting, such that subsequent doses are administered at not more than 3, 4, or 5-day intervals, or at not more than 1, 2, 3, 4, 12, 24, or 36-week intervals. 
     The skilled artisan will appreciate that certain factors may influence the dosage and timing required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general health and/or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of a composition can include a single treatment or a series of treatments. Estimates of effective dosages and in vivo half-lives for the individual iRNAs encompassed by the disclosure can be made using conventional methodologies or on the basis of in vivo testing using a suitable animal model. 
     A suitable animal model, e.g., a mouse or a cynomolgus monkey, e.g., an animal containing a transgene expressing human VEGF-A, can be used to determine the therapeutically effective dose and/or an effective dosage regimen administration of VEGF-A siRNA. 
     The present disclosure also includes pharmaceutical compositions and formulations that include the iRNA compounds featured herein. The pharmaceutical compositions of the present disclosure may be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration may be local (e.g., by intraocular injection), topical (e.g., by an eye drop solution), or parenteral. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; subdermal, e.g., via an implanted device; or intracranial, e.g., by intraparenchymal, intrathecal, or intraventricular administration. 
     Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable. Coated condoms, gloves and the like may also be useful. Suitable topical formulations include those in which the iRNAs featured in the disclosure are in admixture with a topical delivery agent such as lipids, liposomes, fatty acids, fatty acid esters, steroids, chelating agents and surfactants. Suitable lipids and liposomes include neutral (e.g., dioleoylphosphatidyl DOPE ethanolamine, dimyristoylphosphatidyl choline DMPC, distearolyphosphatidyl choline) negative (e.g., dimyristoylphosphatidyl glycerol DMPG) and cationic (e.g., dioleoyltetramethylaminopropyl DOTAP and dioleoylphosphatidyl ethanolamine DOTMA). iRNAs featured in the disclosure may be encapsulated within liposomes or may form complexes thereto, in particular to cationic liposomes. Alternatively, iRNAs may be complexed to lipids, in particular to cationic lipids. Suitable fatty acids and esters include but are not limited to arachidonic acid, oleic acid, eicosanoic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or a C120 alkyl ester (e.g., isopropylmyristate IPM), monoglyceride, diglyceride or pharmaceutically acceptable salt thereof. Topical formulations are described in detail in U.S. Pat. No. 6,747,014, which is incorporated herein by reference. 
     Liposomal Formulations 
     There are many organized surfactant structures besides microemulsions that have been studied and used for the formulation of drugs. These include monolayers, micelles, bilayers and vesicles. Vesicles, such as liposomes, have attracted great interest because of their specificity and the duration of action they offer from the standpoint of drug delivery. As used in the present disclosure, the term “liposome” means a vesicle composed of amphiphilic lipids arranged in a spherical bilayer or bilayers. 
     Liposomes are unilamellar or multilamellar vesicles which have a membrane formed from a lipophilic material and an aqueous interior. The aqueous portion contains the composition to be delivered. Cationic liposomes possess the advantage of being able to fuse to the cell wall. Non-cationic liposomes, although not able to fuse as efficiently with the cell wall, are taken up by macrophages in vivo. 
     In order to traverse intact mammalian skin, lipid vesicles must pass through a series of fine pores, each with a diameter less than 50 nm, under the influence of a suitable transdermal gradient. Therefore, it is desirable to use a liposome which is highly deformable and able to pass through such fine pores. 
     Further advantages of liposomes include; liposomes obtained from natural phospholipids are biocompatible and biodegradable; liposomes can incorporate a wide range of water and lipid soluble drugs; liposomes can protect encapsulated drugs in their internal compartments from metabolism and degradation (Rosoff, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Important considerations in the preparation of liposome formulations are the lipid surface charge, vesicle size and the aqueous volume of the liposomes. 
     Liposomes are useful for the transfer and delivery of active ingredients to the site of action. Because the liposomal membrane is structurally similar to biological membranes, when liposomes are applied to a tissue, the liposomes start to merge with the cellular membranes and as the merging of the liposome and cell progresses, the liposomal contents are emptied into the cell where the active agent may act. 
     Liposomal formulations have been the focus of extensive investigation as the mode of delivery for many drugs. There is growing evidence that for topical administration, liposomes present several advantages over other formulations. Such advantages include reduced side-effects related to high systemic absorption of the administered drug, increased accumulation of the administered drug at the desired target, and the ability to administer a wide variety of drugs, both hydrophilic and hydrophobic, into the skin. 
     Several reports have detailed the ability of liposomes to deliver agents including high-molecular weight DNA into the skin. Compounds including analgesics, antibodies, hormones and high-molecular weight DNAs have been administered to the skin. The majority of applications resulted in the targeting of the upper epidermis 
     Liposomes fall into two broad classes. Cationic liposomes are positively charged liposomes which interact with the negatively charged DNA molecules to form a stable complex. The positively charged DNA/liposome complex binds to the negatively charged cell surface and is internalized in an endosome. Due to the acidic pH within the endosome, the liposomes are ruptured, releasing their contents into the cell cytoplasm (Wang et al.,  Biochem. Biophys. Res. Commun.,  1987, 147, 980-985). 
     Liposomes which are pH-sensitive or negatively charged, entrap DNA rather than complex with it. Since both the DNA and the lipid are similarly charged, repulsion rather than complex formation occurs. Nevertheless, some DNA is entrapped within the aqueous interior of these liposomes. pH-sensitive liposomes have been used to deliver DNA encoding the thymidine kinase gene to cell monolayers in culture. Expression of the exogenous gene was detected in the target cells (Zhou et al.,  Journal of Controlled Release,  1992, 19, 269-274). 
     One major type of liposomal composition includes phospholipids other than naturally derived phosphatidylcholine. Neutral liposome compositions, for example, can be formed from dimyristoyl phosphatidylcholine (DMPC) or dipalmitoyl phosphatidylcholine (DPPC). Anionic liposome compositions generally are formed from dimyristoyl phosphatidylglycerol, while anionic fusogenic liposomes are formed primarily from dioleoyl phosphatidylethanolamine (DOPE). Another type of liposomal composition is formed from phosphatidylcholine (PC) such as, for example, soybean PC, and egg PC. Another type is formed from mixtures of phospholipid and/or phosphatidylcholine and/or cholesterol. 
     Several studies have assessed the topical delivery of liposomal drug formulations to the skin. Application of liposomes containing interferon to guinea pig skin resulted in a reduction of skin herpes sores while delivery of interferon via other means (e.g., as a solution or as an emulsion) were ineffective (Weiner et al.,  Journal of Drug Targeting,  1992, 2, 405-410). Further, an additional study tested the efficacy of interferon administered as part of a liposomal formulation to the administration of interferon using an aqueous system, and concluded that the liposomal formulation was superior to aqueous administration (du Plessis et al.,  Antiviral Research,  1992, 18, 259-265). 
     Non-ionic liposomal systems have also been examined to determine their utility in the delivery of drugs to the skin, in particular systems comprising non-ionic surfactant and cholesterol. Non-ionic liposomal formulations comprising Novasome™ I (glyceryl dilaurate/cholesterol/polyoxyethylene-10-stearyl ether) and Novasome™ II (glyceryl distearate/cholesterol/polyoxyethylene-10-stearyl ether) were used to deliver cyclosporin-A into the dermis of mouse skin. Results indicated that such non-ionic liposomal systems were effective in facilitating the deposition of cyclosporin-A into different layers of the skin (Hu et al. S.T.P.  Pharma. Sci.,  1994, 4, 6, 466). 
     Liposomes also include “sterically stabilized” liposomes, a term which, as used herein, refers to liposomes comprising one or more specialized lipids that, when incorporated into liposomes, result in enhanced circulation lifetimes relative to liposomes lacking such specialized lipids. Examples of sterically stabilized liposomes are those in which part of the vesicle-forming lipid portion of the liposome (A) comprises one or more glycolipids, such as monosialoganglioside G M1 , or (B) is derivatized with one or more hydrophilic polymers, such as a polyethylene glycol (PEG) moiety. While not wishing to be bound by any particular theory, it is thought in the art that, at least for sterically stabilized liposomes containing gangliosides, sphingomyelin, or PEG-derivatized lipids, the enhanced circulation half-life of these sterically stabilized liposomes derives from a reduced uptake into cells of the reticuloendothelial system (RES) (Allen et al.,  FEBS Letters,  1987, 223, 42; Wu et al.,  Cancer Research,  1993, 53, 3765). 
     Various liposomes comprising one or more glycolipids are known in the art. Papahadjopoulos et al. ( Ann. N.Y. Acad. Sci.,  1987, 507, 64) reported the ability of monosialoganglioside G M1 , galactocerebroside sulfate and phosphatidylinositol to improve blood half-lives of liposomes. These findings were expounded upon by Gabizon et al. ( Proc. Natl. Acad. Sci. U.S.A.,  1988, 85, 6949). U.S. Pat. No. 4,837,028 and WO 88/04924, both to Allen et al., disclose liposomes comprising (1) sphingomyelin and (2) the ganglioside G M1  or a galactocerebroside sulfate ester. U.S. Pat. No. 5,543,152 (Webb et al.) discloses liposomes comprising sphingomyelin. Liposomes comprising 1,2-sn-dimyristoylphosphatidylcholine are disclosed in WO 97/13499 (Lim et al). 
     Many liposomes comprising lipids derivatized with one or more hydrophilic polymers, and methods of preparation thereof, are known in the art. Sunamoto et al. ( Bull. Chem. Soc. Jpn.,  1980, 53, 2778) described liposomes comprising a nonionic detergent, 2C1215G, that contains a PEG moiety. Illum et al. ( FEBS Lett.,  1984, 167, 79) noted that hydrophilic coating of polystyrene particles with polymeric glycols results in significantly enhanced blood half-lives. Synthetic phospholipids modified by the attachment of carboxylic groups of polyalkylene glycols (e.g., PEG) are described by Sears (U.S. Pat. Nos. 4,426,330 and 4,534,899). Klibanov et al. ( FEBS Lett.,  1990, 268, 235) described experiments demonstrating that liposomes comprising phosphatidylethanolamine (PE) derivatized with PEG or PEG stearate have significant increases in blood circulation half-lives. Blume et al. ( Biochimica et Biophysica Acta,  1990, 1029, 91) extended such observations to other PEG-derivatized phospholipids, e.g., DSPE-PEG, formed from the combination of distearoylphosphatidylethanolamine (DSPE) and PEG. Liposomes having covalently bound PEG moieties on their external surface are described in European Patent No. EP 0 445 131 B1 and WO 90/04384 to Fisher. Liposome compositions containing 1-20 mole percent of PE derivatized with PEG, and methods of use thereof, are described by Woodle et al. (U.S. Pat. Nos. 5,013,556 and 5,356,633) and Martin et al. (U.S. Pat. No. 5,213,804 and European Patent No. EP 0 496 813 B1). Liposomes comprising a number of other lipid-polymer conjugates are disclosed in WO 91/05545 and U.S. Pat. No. 5,225,212 (both to Martin et al.) and in WO 94/20073 (Zalipsky et al.). Liposomes comprising PEG-modified ceramide lipids are described in WO 96/10391 (Choi et al). U.S. Pat. No. 5,540,935 (Miyazaki et al.) and U.S. Pat. No. 5,556,948 (Tagawa et al.) describe PEG-containing liposomes that can be further derivatized with functional moieties on their surfaces. 
     A number of liposomes comprising nucleic acids are known in the art. WO 96/40062 to Thierry et al. discloses methods for encapsulating high molecular weight nucleic acids in liposomes. U.S. Pat. No. 5,264,221 to Tagawa et al. discloses protein-bonded liposomes and asserts that the contents of such liposomes may include a dsRNA. U.S. Pat. No. 5,665,710 to Rahman et al. describes certain methods of encapsulating oligodeoxynucleotides in liposomes. WO 97/04787 to Love et al. discloses liposomes comprising dsRNAs targeted to the raf gene. 
     Transfersomes are yet another type of liposomes, and are highly deformable lipid aggregates which are attractive candidates for drug delivery vehicles. Transfersomes may be described as lipid droplets which are so highly deformable that they are easily able to penetrate through pores which are smaller than the droplet. Transfersomes are adaptable to the environment in which they are used, e.g., they are self-optimizing (adaptive to the shape of pores in the skin), self-repairing, frequently reach their targets without fragmenting, and often self-loading. To make transfersomes it is possible to add surface edge-activators, usually surfactants, to a standard liposomal composition. Transfersomes have been used to deliver serum albumin to the skin. The transfersome-mediated delivery of serum albumin has been shown to be as effective as subcutaneous injection of a solution containing serum albumin. 
     Surfactants find wide application in formulations such as emulsions (including microemulsions) and liposomes. The most common way of classifying and ranking the properties of the many different types of surfactants, both natural and synthetic, is by the use of the hydrophile/lipophile balance (HLB). The nature of the hydrophilic group (also known as the “head”) provides the most useful means for categorizing the different surfactants used in formulations (Rieger, in  Pharmaceutical Dosage Forms , Marcel Dekker, Inc., New York, N.Y., 1988, p. 285). 
     If the surfactant molecule is not ionized, it is classified as a nonionic surfactant. Nonionic surfactants find wide application in pharmaceutical and cosmetic products and are usable over a wide range of pH values. In general, their HLB values range from 2 to about 18 depending on their structure. Nonionic surfactants include nonionic esters such as ethylene glycol esters, propylene glycol esters, glyceryl esters, polyglyceryl esters, sorbitan esters, sucrose esters, and ethoxylated esters. Nonionic alkanolamides and ethers such as fatty alcohol ethoxylates, propoxylated alcohols, and ethoxylated/propoxylated block polymers are also included in this class. The polyoxyethylene surfactants are the most popular members of the nonionic surfactant class. 
     If the surfactant molecule carries a negative charge when it is dissolved or dispersed in water, the surfactant is classified as anionic. Anionic surfactants include carboxylates such as soaps, acyl lactylates, acyl amides of amino acids, esters of sulfuric acid such as alkyl sulfates and ethoxylated alkyl sulfates, sulfonates such as alkyl benzene sulfonates, acyl isethionates, acyl taurates and sulfosuccinates, and phosphates. The most important members of the anionic surfactant class are the alkyl sulfates and the soaps. 
     If the surfactant molecule carries a positive charge when it is dissolved or dispersed in water, the surfactant is classified as cationic. Cationic surfactants include quaternary ammonium salts and ethoxylated amines. The quaternary ammonium salts are the most used members of this class. 
     If the surfactant molecule has the ability to carry either a positive or negative charge, the surfactant is classified as amphoteric. Amphoteric surfactants include acrylic acid derivatives, substituted alkylamides, N-alkylbetaines and phosphatides. 
     The use of surfactants in drug products, formulations and in emulsions has been reviewed (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, N.Y., 1988, p. 285). 
     Nucleic Acid Lipid Particles 
     In some embodiments, a VEGF-A dsRNA featured in the disclosure is fully encapsulated in the lipid formulation, e.g., to form a SPLP, pSPLP, SNALP, or other nucleic acid-lipid particle. SNALPs and SPLPs typically contain a cationic lipid, a non-cationic lipid, and a lipid that prevents aggregation of the particle (e.g., a PEG-lipid conjugate). SNALPs and SPLPs are extremely useful for systemic applications, as they exhibit extended circulation lifetimes following intravenous (i.v.) injection and accumulate at distal sites (e.g., sites physically separated from the administration site). SPLPs include “pSPLP,” which include an encapsulated condensing agent-nucleic acid complex as set forth in PCT Publication No. WO 00/03683. The particles of the present disclosure typically have a mean diameter of about 50 nm to about 150 nm, more typically about 60 nm to about 130 nm, more typically about 70 nm to about 110 nm, most typically about 70 nm to about 90 nm, and are substantially nontoxic. In addition, the nucleic acids when present in the nucleic acid-lipid particles of the present disclosure are resistant in aqueous solution to degradation with a nuclease. Nucleic acid-lipid particles and their method of preparation are disclosed in, e.g., U.S. Pat. Nos. 5,976,567; 5,981,501; 6,534,484; 6,586,410; 6,815,432; and PCT Publication No. WO 96/40964. 
     In some embodiments, the lipid to drug ratio (mass/mass ratio) (e.g., lipid to dsRNA ratio) will be in the range of from about 1:1 to about 50:1, from about 1:1 to about 25:1, from about 3:1 to about 15:1, from about 4:1 to about 10:1, from about 5:1 to about 9:1, or about 6:1 to about 9:1. 
     The cationic lipid may be, for example, N,N-dioleyl-N,N-dimethylammonium chloride (DODAC), N,N-distearyl-N,N-dimethylammonium bromide (DDAB), N-(I-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP), N-(I-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA), N,N-dimethyl-2,3-dioleyloxy)propylamine (DODMA), 1,2-DiLinoleyloxy-N,N-dimethylaminopropane (DLinDMA), 1,2-Dilinolenyloxy-N,N-dimethylaminopropane (DLenDMA), 1,2-Dilinoleylcarbamoyloxy-3-dimethylaminopropane (DLin-C-DAP), 1,2-Dilinoleyoxy-3-(dimethylamino)acetoxypropane (DLin-DAC), 1,2-Dilinoleyoxy-3-morpholinopropane (DLin-MA), 1,2-Dilinoleoyl-3-dimethylaminopropane (DLinDAP), 1,2-Dilinoleylthio-3-dimethylaminopropane (DLin-S-DMA), 1-Linoleoyl-2-linoleyloxy-3-dimethylaminopropane (DLin-2-DMAP), 1,2-Dilinoleyloxy-3-trimethylaminopropane chloride salt (DLin-TMA.Cl), 1,2-Dilinoleoyl-3-trimethylaminopropane chloride salt (DLin-TAP.Cl), 1,2-Dilinoleyloxy-3-(N-methylpiperazino)propane (DLin-MPZ), or 3-(N,N-Dilinoleylamino)-1,2-propanediol (DLinAP), 3-(N,N-Dioleylamino)-1,2-propanedio (DOAP), 1,2-Dilinoleyloxo-3-(2-N,N-dimethylamino)ethoxypropane (DLin-EG-DMA), 1,2-Dilinolenyloxy-N,N-dimethylaminopropane (DLinDMA), 2,2-Dilinoleyl-4-dimethylaminomethyl-[1,3]-dioxolane (DLin-K-DMA) or analogs thereof, (3aR,5s,6aS)-N,N-dimethyl-2,2-di((9Z,12Z)-octadeca-9,12-dienyl)tetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-amine (ALN100), (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (MC3), 1,1′-(2-(4-(2-((2-(bis(2-hydroxydodecyl)amino)ethyl)(2-hydroxydodecyl)amino)ethyl)piperazin-1-yl)ethylazanediyl)didodecan-2-ol (Tech G1), or a mixture thereof. The cationic lipid may comprise from about 20 mol % to about 50 mol % or about 40 mol % of the total lipid present in the particle. 
     In some embodiments, the compound 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane can be used to prepare lipid-siRNA nanoparticles. Synthesis of 2,2-Dilinoleyl dimethylaminoethyl-[1,3]-dioxolane is described in U.S. provisional patent application No. 61/107,998 filed on Oct. 23, 2008, which is herein incorporated by reference. 
     In some embodiments, the lipid-siRNA particle includes 40% 2, 2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane: 10% DSPC: 40% Cholesterol: 10% PEG-C-DOMG (mole percent) with a particle size of 63.0±20 nm and a 0.027 siRNA/Lipid Ratio. 
     The non-cationic lipid may be an anionic lipid or a neutral lipid including, but not limited to, distearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dioleoyl-phosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoylphosphatidylethanolamine (POPE), dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoyl phosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoyl-phosphatidyl-ethanolamine (DSPE), 16-O-monomethyl PE, 16-O-dimethyl PE, 18-1-trans PE, 1-stearoyl-2-oleoyl-phosphatidyethanolamine (SOPE), cholesterol, or a mixture thereof. The non-cationic lipid may be from about 5 mol % to about 90 mol %, about 10 mol %, or about 58 mol % if cholesterol is included, of the total lipid present in the particle. 
     The conjugated lipid that inhibits aggregation of particles may be, for example, a polyethyleneglycol (PEG)-lipid including, without limitation, a PEG-diacylglycerol (DAG), a PEG-dialkyloxypropyl (DAA), a PEG-phospholipid, a PEG-ceramide (Cer), or a mixture thereof. The PEG-DAA conjugate may be, for example, a PEG-dilauryloxypropyl (Ci 2 ), a PEG-dimyristyloxypropyl (Ci 4 ), a PEG-dipalmityloxypropyl (Ci 6 ), or a PEG-distearyloxypropyl (C] 8 ). The conjugated lipid that prevents aggregation of particles may be from 0 mol % to about 20 mol % or about 2 mol % of the total lipid present in the particle. 
     In some embodiments, the nucleic acid-lipid particle further includes cholesterol at, e.g., about 10 mol % to about 60 mol % or about 48 mol % of the total lipid present in the particle. 
     In some embodiments, the iRNA is formulated in a lipid nanoparticle (LNP). 
     LNP01 
     In some embodiments, the lipidoid ND984HCl (MW 1487) (see U.S. patent application Ser. No. 12/056,230, filed Mar. 26, 2008, which is herein incorporated by reference), Cholesterol (Sigma-Aldrich), and PEG-Ceramide C16 (Avanti Polar Lipids) can be used to prepare lipid-dsRNA nanoparticles (e.g., LNP01 particles). Stock solutions of each in ethanol can be prepared as follows: ND98, 133 mg/ml; Cholesterol, 25 mg/ml, PEG-Ceramide C16, 100 mg/ml. The ND98, Cholesterol, and PEG-Ceramide C16 stock solutions can then be combined in a, e.g., 42:48:10 molar ratio. The combined lipid solution can be mixed with aqueous dsRNA (e.g., in sodium acetate pH 5) such that the final ethanol concentration is about 35-45% and the final sodium acetate concentration is about 100-300 mM. Lipid-dsRNA nanoparticles typically form spontaneously upon mixing. Depending on the desired particle size distribution, the resultant nanoparticle mixture can be extruded through a polycarbonate membrane (e.g., 100 nm cut-off) using, for example, a thermobarrel extruder, such as Lipex Extruder (Northern Lipids, Inc). In some cases, the extrusion step can be omitted. Ethanol removal and simultaneous buffer exchange can be accomplished by, for example, dialysis or tangential flow filtration. Buffer can be exchanged with, for example, phosphate buffered saline (PBS) at about pH 7, e.g., about pH 6.9, about pH 7.0, about pH 7.1, about pH 7.2, about pH 7.3, or about pH 7.4. 
     
       
         
         
             
             
         
       
     
     LNP01 formulations are described, e.g., in International Application Publication No. WO 2008/042973, which is hereby incorporated by reference. 
     Additional exemplary lipid-dsRNA formulations are provided in the following table. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Exemplary lipid formulations 
               
            
           
           
               
               
               
            
               
                   
                   
                 cationic lipid/non-cationic 
               
               
                   
                   
                 lipid/cholesterol/PEG-lipid conjugate 
               
               
                   
                 Cationic Lipid 
                 Lipid:siRNA ratio 
               
               
                   
               
               
                 SNALP 
                 1,2-Dilinolenyloxy-N,N - 
                 DLinDMA/DPPC/Cholesterol/PEG-cDMA 
               
               
                   
                 dimethylaminopropane (DLinDMA) 
                 (57.1/7.1/34.4/1.4) 
               
               
                   
                   
                 lipid:siRNA~7:1 
               
               
                 S-XTC 
                 2,2-Dilinoleyl-4-dimethylaminoethyl- 
                 XTC/DPPC/Cholesterol/PEG-cDMA 
               
               
                   
                 [1,3]-dioxolane (XTC) 
                 57.1/7.1/34.4/1.4 
               
               
                   
                   
                 lipid:siRNA~7:1 
               
               
                 LNP05 
                 2,2-Dilinoleyl-4-dimethylaminoethyl- 
                 XTC/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 [1,3]-dioxolane (XTC) 
                 57.5/7.5/31.5/3.5 
               
               
                   
                   
                 lipid:siRNA~6:1 
               
               
                 LNP06 
                 2,2-Dilinoleyl-4-dimethylaminoethyl- 
                 XTC/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 [1,3]-dioxolane (XTC) 
                 57.5/7.5/31.5/3.5 
               
               
                   
                   
                 lipid:siRNA~11:1 
               
               
                 LNP07 
                 2,2-Dilinoleyl-4-dimethylaminoethyl- 
                 XTC/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 [1,3]-dioxolane (XTC) 
                 60/7.5/31/1.5, 
               
               
                   
                   
                 lipid:siRNA~6:1 
               
               
                 LNP08 
                 2,2-Dilinoleyl-4-dimethylaminoethyl- 
                 XTC/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 [1,3]-dioxolane (XTC) 
                 60/7.5/31/1.5, 
               
               
                   
                   
                 lipid:siRNA~11:1 
               
               
                 LNP09 
                 2,2-Dilinoleyl-4-dimethylaminoethyl- 
                 XTC/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 [1,3]-dioxolane (XTC) 
                 50/10/38.5/1.5 
               
               
                   
                   
                 Lipid:siRNA 10:1 
               
               
                 LNP10 
                 (3aR,5s,6aS)-N,N-dimethyl-2,2- 
                 ALN100/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 di((9Z,12Z)-octadeca-9,12- 
                 50/10/38.5/1.5 
               
               
                   
                 dienyl)tetrahydro-3aH- 
                 Lipid:siRNA 10:1 
               
               
                   
                 cyclopenta[d][1,3]dioxol-5-amine 
                   
               
               
                   
                 (ALN100) 
                   
               
               
                 LNP11 
                 (6Z,9Z,28Z,31Z)-heptatriaconta- 
                 MC-3/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 6,9,28,31-tetraen-19-yl 4- 
                 50/10/38.5/1.5 
               
               
                   
                 (dimethylamino)butanoate (MC3) 
                 Lipid:siRNA 10:1 
               
               
                 LNP12 
                 1,1′-(2-(4-(2-((2-(bis(2- 
                 C12-200/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 hydroxydodecyl)amino)ethyl)(2- 
                 50/10/38.5/1.5 
               
               
                   
                 hydroxydodecyl)amino)ethyl)piperazin- 
                 Lipid:siRNA 10:1 
               
               
                   
                 1-yl)ethylazanediyl)didodecan-2-ol 
                   
               
               
                   
                 (C12-200) 
                   
               
               
                 LNP13 
                 XTC 
                 XTC/DSPC/Chol/PEG-DMG 
               
               
                   
                   
                 50/10/38.5/1.5 
               
               
                   
                   
                 Lipid:siRNA: 33:1 
               
               
                 LNP14 
                 MC3 
                 MC3/DSPC/Chol/PEG-DMG 
               
               
                   
                   
                 40/15/40/5 
               
               
                   
                   
                 Lipid:siRNA: 11:1 
               
               
                 LNP15 
                 MC3 
                 MC3/DSPC/Chol/PEG-DSG/GalNAc- 
               
               
                   
                   
                 PEG-DSG 
               
               
                   
                   
                 50/10/35/4.5/0.5 
               
               
                   
                   
                 Lipid:siRNA: 11:1 
               
               
                 LNP16 
                 MC3 
                 MC3/DSPC/Chol/PEG-DMG 
               
               
                   
                   
                 50/10/38.5/1.5 
               
               
                   
                   
                 Lipid:siRNA: 7:1 
               
               
                 LNP17 
                 MC3 
                 MC3/DSPC/Chol/PEG-DSG 
               
               
                   
                   
                 50/10/38.5/1.5 
               
               
                   
                   
                 Lipid:siRNA: 10:1 
               
               
                 LNP18 
                 MC3 
                 MC3/DSPC/Chol/PEG-DMG 
               
               
                   
                   
                 50/10/38.5/1.5 
               
               
                   
                   
                 Lipid:siRNA: 12:1 
               
               
                 LNP19 
                 MC3 
                 MC3/DSPC/Chol/PEG-DMG 
               
               
                   
                   
                 50/10/35/5 
               
               
                   
                   
                 Lipid:siRNA: 8:1 
               
               
                 LNP20 
                 MC3 
                 MC3/DSPC/Chol/PEG-DPG 
               
               
                   
                   
                 50/10/38.5/1.5 
               
               
                   
                   
                 Lipid:siRNA: 10:1 
               
               
                 LNP21 
                 C12-200 
                 C12-200/DSPC/Chol/PEG-DSG 
               
               
                   
                   
                 50/10/38.5/1.5 
               
               
                   
                   
                 Lipid:siRNA: 7:1 
               
               
                 LNP22 
                 XTC 
                 XTC/DSPC/Chol/PEG-DSG 
               
               
                   
                   
                 50/10/38.5/1.5 
               
               
                   
                   
                 Lipid:siRNA: 10:1 
               
               
                   
               
               
                 DSPC: distearoylphosphatidylcholine 
               
               
                 DPPC: dipalmitoylphosphatidylcholine 
               
               
                 PEG-DMG: PEG-didimyristoyl glycerol (C14-PEG, or PEG-C14) (PEG with avg mol wt of 2000) 
               
               
                 PEG-DSG: PEG-distyryl glycerol (C18-PEG, or PEG-C18) (PEG with avg mol wt of 2000) 
               
               
                 PEG-cDMA: PEG-carbamoyl-1,2-dimyristyloxypropylamine (PEG with avg mol wt of 2000) 
               
            
           
         
       
     
     SNALP (1,2-Dilinolenyloxy-N,N-dimethylaminopropane (DLinDMA)) comprising formulations are described in International Publication No. WO2009/127060, filed Apr. 15, 2009, which is hereby incorporated by reference. 
     XTC comprising formulations are described, e.g., in U.S. Provisional Ser. No. 61/148,366, filed Jan. 29, 2009; U.S. Provisional Ser. No. 61/156,851, filed Mar. 2, 2009; U.S. Provisional Ser. No. 61/185,712, filed Jun. 10, 2009; U.S. Provisional Ser. No. 61/228,373, filed Jul. 24, 2009; U.S. Provisional Ser. No. 61/239,686, filed Sep. 3, 2009, and International Application No. PCT/US2010/022614, filed Jan. 29, 2010, which are hereby incorporated by reference. 
     MC3 comprising formulations are described, e.g., in U.S. Provisional Ser. No. 61/244,834, filed Sep. 22, 2009, U.S. Provisional Ser. No. 61/185,800, filed Jun. 10, 2009, and International Application No. PCT/US10/28224, filed Jun. 10, 2010, which are hereby incorporated by reference. 
     ALNY-100 comprising formulations are described, e.g., International patent application number PCT/US09/63933, filed on Nov. 10, 2009, which is hereby incorporated by reference. 
     C12-200 comprising formulations are described in U.S. Provisional Ser. No. 61/175,770, filed May 5, 2009 and International Application No. PCT/US10/33777, filed May 5, 2010, which are hereby incorporated by reference. 
     Synthesis of Cationic Lipids 
     Any of the compounds, e.g., cationic lipids and the like, used in the nucleic acid-lipid particles featured in the disclosure may be prepared by known organic synthesis techniques. All substituents are as defined below unless indicated otherwise. 
     “Alkyl” means a straight chain or branched, noncyclic or cyclic, saturated aliphatic hydrocarbon containing from 1 to 24 carbon atoms. Representative saturated straight chain alkyls include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, and the like; while saturated branched alkyls include isopropyl, sec-butyl, isobutyl, tert-butyl, isopentyl, and the like. Representative saturated cyclic alkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like; while unsaturated cyclic alkyls include cyclopentenyl and cyclohexenyl, and the like. 
     “Alkenyl” means an alkyl, as defined above, containing at least one double bond between adjacent carbon atoms. Alkenyls include both cis and trans isomers. Representative straight chain and branched alkenyls include ethylenyl, propylenyl, 1-butenyl, 2-butenyl, isobutylenyl, 1-pentenyl, 2-pentenyl, 3-methyl-1-butenyl, 2-methyl-2-butenyl, 2,3-dimethyl-2-butenyl, and the like. 
     “Alkynyl” means any alkyl or alkenyl, as defined above, which additionally contains at least one triple bond between adjacent carbons. Representative straight chain and branched alkynyls include acetylenyl, propynyl, 1-butynyl, 2-butynyl, 1-pentynyl, 2-pentynyl, 3-methyl-1 butynyl, and the like. 
     “Acyl” means any alkyl, alkenyl, or alkynyl wherein the carbon at the point of attachment is substituted with an oxo group, as defined below. For example, —C(═O)alkyl, —C(═O)alkenyl, and —C(═O)alkynyl are acyl groups. 
     “Heterocycle” means a 5- to 7-membered monocyclic, or 7- to 10-membered bicyclic, heterocyclic ring which is either saturated, unsaturated, or aromatic, and which contains from 1 or 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and wherein the nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen heteroatom may be optionally quaternized, including bicyclic rings in which any of the above heterocycles are fused to a benzene ring. The heterocycle may be attached via any heteroatom or carbon atom. Heterocycles include heteroaryls as defined below. Heterocycles include morpholinyl, pyrrolidinonyl, pyrrolidinyl, piperidinyl, piperizynyl, hydantoinyl, valerolactamyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydropyrimidinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, tetrahydropyrimidinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, and the like. 
     The terms “optionally substituted alkyl”, “optionally substituted alkenyl”, “optionally substituted alkynyl”, “optionally substituted acyl”, and “optionally substituted heterocycle” means that, when substituted, at least one hydrogen atom is replaced with a substituent. In the case of an oxo substituent (═O) two hydrogen atoms are replaced. In this regard, substituents include oxo, halogen, heterocycle, —CN, —OR x , —NR x R y , —NR x C(═O)R y , —NR x SO 2 R y , —C(═O)R x , —C(═O)OR x , —C(═O)NR x R y , —SO n R x  and —SO n NR x R y , wherein n is 0, 1 or 2, R x  and R y  are the same or different and independently hydrogen, alkyl or heterocycle, and each of said alkyl and heterocycle substituents may be further substituted with one or more of oxo, halogen, —OH, —CN, alkyl, —OR x , heterocycle, —NR x R y , —NR x C(═O)R y , —NR x SO 2 R y , —C(═O)R x , —C(═O)OR x , —C(═O)NR x R y , —SO n R x  and —SO n NR x R y . 
     “Halogen” means fluoro, chloro, bromo and iodo. 
     In some embodiments, the methods featured in the disclosure may require the use of protecting groups. Protecting group methodology is well known to those skilled in the art (see, for example, P ROTECTIVE  G ROUPS IN  O RGANIC  S YNTHESIS , Green, T. W. et al., Wiley-Interscience, New York City, 1999). Briefly, protecting groups within the context of this disclosure are any group that reduces or eliminates unwanted reactivity of a functional group. A protecting group can be added to a functional group to mask its reactivity during certain reactions and then removed to reveal the original functional group. In some embodiments an “alcohol protecting group” is used. An “alcohol protecting group” is any group which decreases or eliminates unwanted reactivity of an alcohol functional group. Protecting groups can be added and removed using techniques well known in the art. 
     Synthesis of Formula A 
     In some embodiments, nucleic acid-lipid particles featured in the disclosure are formulated using a cationic lipid of formula A: 
     
       
         
         
             
             
         
       
     
     where R1 and R2 are independently alkyl, alkenyl or alkynyl, each can be optionally substituted, and R3 and R4 are independently lower alkyl or R3 and R4 can be taken together to form an optionally substituted heterocyclic ring. In some embodiments, the cationic lipid is XTC (2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane). In general, the lipid of formula A above may be made by the following Reaction Schemes 1 or 2, wherein all substituents are as defined above unless indicated otherwise. 
     
       
         
         
             
             
         
       
     
     Lipid A, where R 1  and R 2  are independently alkyl, alkenyl or alkynyl, each can be optionally substituted, and R 3  and R 4  are independently lower alkyl or R 3  and R 4  can be taken together to form an optionally substituted heterocyclic ring, can be prepared according to Scheme 1. Ketone 1 and bromide 2 can be purchased or prepared according to methods known to those of ordinary skill in the art. Reaction of 1 and 2 yields ketal 3. Treatment of ketal 3 with amine 4 yields lipids of formula A. The lipids of formula A can be converted to the corresponding ammonium salt with an organic salt of formula 5, where X is anion counter ion selected from halogen, hydroxide, phosphate, sulfate, or the like. 
     
       
         
         
             
             
         
       
     
     Alternatively, the ketone 1 starting material can be prepared according to Scheme 2. Grignard reagent 6 and cyanide 7 can be purchased or prepared according to methods known to those of ordinary skill in the art. Reaction of 6 and 7 yields ketone 1. Conversion of ketone 1 to the corresponding lipids of formula A is as described in Scheme 1. 
     Synthesis of MC3 
     Preparation of DLin-M-C3-DMA (i.e., (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate) was as follows. A solution of (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-ol (0.53 g), 4-N,N-dimethylaminobutyric acid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. The solution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractions were dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passed down a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. Fractions containing the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g). 
     Synthesis of ALNY-100 
     Synthesis of ketal 519 [ALNY-100] was performed using the following scheme 3: 
     
       
         
         
             
             
         
       
     
     Synthesis of 515 
     To a stirred suspension of LiAlH4 (3.74 g, 0.09852 mol) in 200 ml anhydrous THF in a two neck RBF (1L), was added a solution of 514 (10 g, 0.04926 mol) in 70 mL of THF slowly at 0 OC under nitrogen atmosphere. After complete addition, reaction mixture was warmed to room temperature and then heated to reflux for 4 h. Progress of the reaction was monitored by TLC. After completion of reaction (by TLC) the mixture was cooled to 0° C. and quenched with careful addition of saturated Na2SO4 solution. Reaction mixture was stirred for 4 h at room temperature and filtered off. Residue was washed well with THF. The filtrate and washings were mixed and diluted with 400 mL dioxane and 26 mL conc. HCl and stirred for 20 minutes at room temperature. The volatilities were stripped off under vacuum to furnish the hydrochloride salt of 515 as a white solid. Yield: 7.12 g 1H-NMR (DMSO, 400 MHz): δ=9.34 (broad, 2H), 5.68 (s, 2H), 3.74 (m, 1H), 2.66-2.60 (m, 2H), 2.50-2.45 (m, 5H). 
     Synthesis of 516 
     To a stirred solution of compound 515 in 100 mL dry DCM in a 250 mL two neck RBF, was added NEt3 (37.2 mL, 0.2669 mol) and cooled to 0° C. under nitrogen atmosphere. After a slow addition of N-(benzyloxy-carbonyloxy)-succinimide (20 g, 0.08007 mol) in 50 mL dry DCM, reaction mixture was allowed to warm to room temperature. After completion of the reaction (2-3 h by TLC) mixture was washed successively with 1N HCl solution (1×100 mL) and saturated NaHCO 3  solution (1×50 mL). The organic layer was then dried over anhyd. Na2SO4 and the solvent was evaporated to give crude material which was purified by silica gel column chromatography to get 516 as sticky mass. Yield: 11 g (89%). 1H-NMR (CDCl3, 400 MHz): δ=7.36-7.27 (m, 5H), 5.69 (s, 2H), 5.12 (s, 2H), 4.96 (br., 1H) 2.74 (s, 3H), 2.60 (m, 2H), 2.30-2.25 (m, 2H). LC-MS [M+H] −232.3 (96.94%). 
     Synthesis of 517A and 517B 
     The cyclopentene 516 (5 g, 0.02164 mol) was dissolved in a solution of 220 mL acetone and water (10:1) in a single neck 500 mL RBF and to it was added N-methyl morpholine-N-oxide (7.6 g, 0.06492 mol) followed by 4.2 mL of 7.6% solution of OsO4 (0.275 g, 0.00108 mol) in tert-butanol at room temperature. After completion of the reaction (— 3 h), the mixture was quenched with addition of solid Na2SO3 and resulting mixture was stirred for 1.5 h at room temperature. Reaction mixture was diluted with DCM (300 mL) and washed with water (2×100 mL) followed by saturated NaHCO 3  (1×50 mL) solution, water (1×30 mL) and finally with brine (1×50 mL). Organic phase was dried over an.Na2SO4 and solvent was removed in vacuum. Silica gel column chromatographic purification of the crude material was afforded a mixture of diastereomers, which were separated by prep HPLC. Yield: −6 g crude 
     517A—Peak-1 (white solid), 5.13 g (96%). 1H-NMR (DMSO, 400 MHz): δ=7.39-7.31 (m, 5H), 5.04 (s, 2H), 4.78-4.73 (m, 1H), 4.48-4.47 (d, 2H), 3.94-3.93 (m, 2H), 2.71 (s, 3H), 1.72-1.67 (m, 4H). LC-MS−[M+H] −266.3, [M+NH4+] −283.5 present, HPLC-97.86%. Stereochemistry confirmed by X-ray. 
     Synthesis of 518 
     Using a procedure analogous to that described for the synthesis of compound 505, compound 518 (1.2 g, 41%) was obtained as a colorless oil. 1H-NMR (CDCl3, 400 MHz): δ=7.35-7.33 (m, 4H), 7.30-7.27 (m, 1H), 5.37-5.27 (m, 8H), 5.12 (s, 2H), 4.75 (m, 1H), 4.58-4.57 (m, 2H), 2.78-2.74 (m, 7H), 2.06-2.00 (m, 8H), 1.96-1.91 (m, 2H), 1.62 (m, 4H), 1.48 (m, 2H), 1.37-1.25 (br m, 36H), 0.87 (m, 6H). HPLC-98.65%. 
     General Procedure for the Synthesis of Compound 519 
     A solution of compound 518 (1 eq) in hexane (15 mL) was added in a drop-wise fashion to an ice-cold solution of LAH in THF (1 M, 2 eq). After complete addition, the mixture was heated at 40° C. over 0.5 h then cooled again on an ice bath. The mixture was carefully hydrolyzed with saturated aqueous Na2SO4 then filtered through celite and reduced to an oil. Column chromatography provided the pure 519 (1.3 g, 68%) which was obtained as a colorless oil. 13C NMR=130.2, 130.1 (×2), 127.9 (×3), 112.3, 79.3, 64.4, 44.7, 38.3, 35.4, 31.5, 29.9 (×2), 29.7, 29.6 (×2), 29.5 (×3), 29.3 (×2), 27.2 (×3), 25.6, 24.5, 23.3, 226, 14.1; Electrospray MS (+ve): Molecular weight for C44H80NO2 (M+H)+ Calc. 654.6, Found 654.6. 
     Formulations prepared by either the standard or extrusion-free method can be characterized in similar manners. For example, formulations are typically characterized by visual inspection. They should be whitish translucent solutions free from aggregates or sediment. Particle size and particle size distribution of lipid-nanoparticles can be measured by light scattering using, for example, a Malvern Zetasizer Nano ZS (Malvern, USA). Particles should be about 20-300 nm, such as 40-100 nm in size. The particle size distribution should be unimodal. The total dsRNA concentration in the formulation, as well as the entrapped fraction, is estimated using a dye exclusion assay. A sample of the formulated dsRNA can be incubated with an RNA-binding dye, such as Ribogreen (Molecular Probes) in the presence or absence of a formulation disrupting surfactant, e.g., 0.5% Triton-X100. The total dsRNA in the formulation can be determined by the signal from the sample containing the surfactant, relative to a standard curve. The entrapped fraction is determined by subtracting the “free” dsRNA content (as measured by the signal in the absence of surfactant) from the total dsRNA content. Percent entrapped dsRNA is typically &gt;85%. For SNALP formulation, the particle size is at least 30 nm, at least 40 nm, at least 50 nm, at least 60 nm, at least 70 nm, at least 80 nm, at least 90 nm, at least 100 nm, at least 110 nm, and at least 120 nm. The suitable range is typically about at least 50 nm to about at least 110 nm, about at least 60 nm to about at least 100 nm, or about at least 80 nm to about at least 90 nm. 
     Compositions and formulations for oral administration include powders or granules, microparticulates, nanoparticulates, suspensions or solutions in water or non-aqueous media, capsules, gel capsules, sachets, tablets or minitablets. Thickeners, flavoring agents, diluents, emulsifiers, dispersing aids or binders may be desirable. In some embodiments, oral formulations are those in which dsRNAs featured in the disclosure are administered in conjunction with one or more penetration enhancers surfactants and chelators. Suitable surfactants include fatty acids and/or esters or salts thereof, bile acids and/or salts thereof. Suitable bile acids/salts include chenodeoxycholic acid (CDCA) and ursodeoxychenodeoxycholic acid (UDCA), cholic acid, dehydrocholic acid, deoxycholic acid, glucholic acid, glycholic acid, glycodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, sodium tauro-24,25-dihydro-fusidate and sodium glycodihydrofusidate. Suitable fatty acids include arachidonic acid, undecanoic acid, oleic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or a monoglyceride, a diglyceride or a pharmaceutically acceptable salt thereof (e.g., sodium). In some embodiments, combinations of penetration enhancers are used, for example, fatty acids/salts in combination with bile acids/salts. One exemplary combination is the sodium salt of lauric acid, capric acid and UDCA. Further penetration enhancers include polyoxyethylene-9-lauryl ether, polyoxyethylene-20-cetyl ether. DsRNAs featured in the disclosure may be delivered orally, in granular form including sprayed dried particles, or complexed to form micro or nanoparticles. DsRNA complexing agents include poly-amino acids; polyimines; polyacrylates; polyalkylacrylates, polyoxethanes, polyalkylcyanoacrylates; cationized gelatins, albumins, starches, acrylates, polyethyleneglycols (PEG) and starches; polyalkylcyanoacrylates; DEAE-derivatized polyimines, pollulans, celluloses and starches. Suitable complexing agents include chitosan, N-trimethylchitosan, poly-L-lysine, polyhistidine, polyornithine, polyspermines, protamine, polyvinylpyridine, polythiodiethylaminomethylethylene P(TDAE), polyaminostyrene (e.g., p-amino), poly(methylcyanoacrylate), poly(ethylcyanoacrylate), poly(butylcyanoacrylate), poly(isobutylcyanoacrylate), poly(isohexylcynaoacrylate), DEAE-methacrylate, DEAE-hexylacrylate, DEAE-acrylamide, DEAE-albumin and DEAE-dextran, polymethylacrylate, polyhexylacrylate, poly(D,L-lactic acid), poly(DL-lactic-co-glycolic acid (PLGA), alginate, and polyethyleneglycol (PEG). Oral formulations for dsRNAs and their preparation are described in detail in U.S. Pat. No. 6,887,906, US Publn. No. 20030027780, and U.S. Pat. No. 6,747,014, each of which is incorporated herein by reference. 
     Compositions and formulations for parenteral, intraparenchymal (into the brain), intrathecal, intravitreal, subretinal, transscleral, subconjunctival, retrobulbar, intracameral, intraventricular, or intrahepatic administration may include sterile aqueous solutions which may also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carrier compounds and other pharmaceutically acceptable carriers or excipients. 
     Pharmaceutical compositions of the present disclosure include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions may be generated from a variety of components that include, but are not limited to, preformed liquids, self-emulsifying solids and self-emulsifying semisolids. 
     The pharmaceutical formulations featured in the present disclosure, which may conveniently be presented in unit dosage form, may be prepared according to conventional techniques well known in the pharmaceutical industry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product. 
     The compositions featured in the present disclosure may be formulated into any of many possible dosage forms such as, but not limited to, tablets, capsules, gel capsules, liquid syrups, soft gels, suppositories, and enemas. The compositions may also be formulated as suspensions in aqueous, non-aqueous or mixed media. Aqueous suspensions may further contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers. 
     Additional Formulations 
     Emulsions 
     The compositions of the present disclosure may be prepared and formulated as emulsions. Emulsions are typically heterogeneous systems of one liquid dispersed in another in the form of droplets usually exceeding 0.1 μm in diameter (see e.g., Ansel&#39;s Pharmaceutical Dosage Forms and Drug Delivery Systems, Allen, LV., Popovich N G., and Ansel H C., 2004, Lippincott Williams &amp; Wilkins (8th ed.), New York, N.Y.; Idson, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199; Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., Volume 1, p. 245; Block in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 2, p. 335; Higuchi et al., in Remington&#39;s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 1985, p. 301). Emulsions are often biphasic systems comprising two immiscible liquid phases intimately mixed and dispersed with each other. In general, emulsions may be of either the water-in-oil (w/o) or the oil-in-water (o/w) variety. When an aqueous phase is finely divided into and dispersed as minute droplets into a bulk oily phase, the resulting composition is called a water-in-oil (w/o) emulsion. Alternatively, when an oily phase is finely divided into and dispersed as minute droplets into a bulk aqueous phase, the resulting composition is called an oil-in-water (o/w) emulsion. Emulsions may contain additional components in addition to the dispersed phases, and the active drug which may be present as a solution in either the aqueous phase, oily phase or itself as a separate phase. Pharmaceutical excipients such as emulsifiers, stabilizers, dyes, and anti-oxidants may also be present in emulsions as needed. Pharmaceutical emulsions may also be multiple emulsions that are comprised of more than two phases such as, for example, in the case of oil-in-water-in-oil (o/w/o) and water-in-oil-in-water (w/o/w) emulsions. Such complex formulations often provide certain advantages that simple binary emulsions do not. Multiple emulsions in which individual oil droplets of an o/w emulsion enclose small water droplets constitute a w/o/w emulsion. Likewise, a system of oil droplets enclosed in globules of water stabilized in an oily continuous phase provides an o/w/o emulsion. 
     Emulsions are characterized by little or no thermodynamic stability. Often, the dispersed or discontinuous phase of the emulsion is well dispersed into the external or continuous phase and maintained in this form through the means of emulsifiers or the viscosity of the formulation. Either of the phases of the emulsion may be a semisolid or a solid, as is the case of emulsion-style ointment bases and creams. Other means of stabilizing emulsions entail the use of emulsifiers that may be incorporated into either phase of the emulsion. Emulsifiers may broadly be classified into four categories: synthetic surfactants, naturally occurring emulsifiers, absorption bases, and finely dispersed solids (see e.g., Ansel&#39;s Pharmaceutical Dosage Forms and Drug Delivery Systems, Allen, LV., Popovich N G., and Ansel H C., 2004, Lippincott Williams &amp; Wilkins (8th ed.), New York, N.Y.; Idson, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). 
     Synthetic surfactants, also known as surface active agents, have found wide applicability in the formulation of emulsions and have been reviewed in the literature (see e.g., Ansel&#39;s  Pharmaceutical Dosage Forms and Drug Delivery Systems , Allen, L V., Popovich N G., and Ansel H C., 2004, Lippincott Williams &amp; Wilkins (8th ed.), New York, N.Y.; Rieger, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285; Idson, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), Marcel Dekker, Inc., New York, N.Y., 1988, volume 1, p. 199). Surfactants are typically amphiphilic and comprise a hydrophilic and a hydrophobic portion. The ratio of the hydrophilic to the hydrophobic nature of the surfactant has been termed the hydrophile/lipophile balance (HLB) and is a valuable tool in categorizing and selecting surfactants in the preparation of formulations. Surfactants may be classified into different classes based on the nature of the hydrophilic group: nonionic, anionic, cationic and amphoteric (see e.g., Ansel&#39;s Pharmaceutical Dosage Forms and Drug Delivery Systems, Allen, L V., Popovich N G., and Ansel H C., 2004, Lippincott Williams &amp; Wilkins (8th ed.), New York, N.Y. Rieger, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285). 
     Naturally occurring emulsifiers used in emulsion formulations include lanolin, beeswax, phosphatides, lecithin and acacia. Absorption bases possess hydrophilic properties such that they can soak up water to form w/o emulsions yet retain their semisolid consistencies, such as anhydrous lanolin and hydrophilic petrolatum. Finely divided solids have also been used as good emulsifiers especially in combination with surfactants and in viscous preparations. These include polar inorganic solids, such as heavy metal hydroxides, nonswelling clays such as bentonite, attapulgite, hectorite, kaolin, montmorillonite, colloidal aluminum silicate and colloidal magnesium aluminum silicate, pigments and nonpolar solids such as carbon or glyceryl tristearate. 
     A large variety of non-emulsifying materials are also included in emulsion formulations and contribute to the properties of emulsions. These include fats, oils, waxes, fatty acids, fatty alcohols, fatty esters, humectants, hydrophilic colloids, preservatives and antioxidants (Block, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335; Idson, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). 
     Hydrophilic colloids or hydrocolloids include naturally occurring gums and synthetic polymers such as polysaccharides (for example, acacia, agar, alginic acid, carrageenan, guar gum, karaya gum, and tragacanth), cellulose derivatives (for example, carboxymethylcellulose and carboxypropylcellulose), and synthetic polymers (for example, carbomers, cellulose ethers, and carboxyvinyl polymers). These disperse or swell in water to form colloidal solutions that stabilize emulsions by forming strong interfacial films around the dispersed-phase droplets and by increasing the viscosity of the external phase. 
     Since emulsions often contain a number of ingredients such as carbohydrates, proteins, sterols and phosphatides that may readily support the growth of microbes, these formulations often incorporate preservatives. Commonly used preservatives included in emulsion formulations include methyl paraben, propyl paraben, quaternary ammonium salts, benzalkonium chloride, esters of p-hydroxybenzoic acid, and boric acid. Antioxidants are also commonly added to emulsion formulations to prevent deterioration of the formulation. Antioxidants used may be free radical scavengers such as tocopherols, alkyl gallates, butylated hydroxyanisole, butylated hydroxytoluene, or reducing agents such as ascorbic acid and sodium metabisulfite, and antioxidant synergists such as citric acid, tartaric acid, and lecithin. 
     The application of emulsion formulations via dermatological, oral and parenteral routes and methods for their manufacture have been reviewed in the literature (see e.g., Ansel&#39;s  Pharmaceutical Dosage Forms and Drug Delivery Systems , Allen, L V., Popovich N G., and Ansel H C., 2004, Lippincott Williams &amp; Wilkins (8th ed.), New York, N.Y.; Idson, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Emulsion formulations for oral delivery have been very widely used because of ease of formulation, as well as efficacy from an absorption and bioavailability standpoint (see e.g., Ansel&#39;s  Pharmaceutical Dosage Forms and Drug Delivery Systems , Allen, L V., Popovich N G., and Ansel H C., 2004, Lippincott Williams &amp; Wilkins (8th ed.), New York, N.Y.; Rosoff, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Idson, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Mineral-oil base laxatives, oil-soluble vitamins and high fat nutritive preparations are among the materials that have commonly been administered orally as o/w emulsions. 
     In some embodiments of the present disclosure, the compositions of iRNAs and nucleic acids are formulated as microemulsions. A microemulsion may be defined as a system of water, oil and amphiphile which is a single optically isotropic and thermodynamically stable liquid solution (see e.g., Ansel&#39;s Pharmaceutical Dosage Forms and Drug Delivery Systems, Allen, L V., Popovich N G., and Ansel H C., 2004, Lippincott Williams &amp; Wilkins (8th ed.), New York, N.Y.; Rosoff, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Typically, microemulsions are systems that are prepared by first dispersing an oil in an aqueous surfactant solution and then adding a sufficient amount of a fourth component, generally an intermediate chain-length alcohol to form a transparent system. Therefore, microemulsions have also been described as thermodynamically stable, isotopically clear dispersions of two immiscible liquids that are stabilized by interfacial films of surface-active molecules (Leung and Shah, in:  Controlled Release of Drugs: Polymers and Aggregate Systems , Rosoff, M., Ed., 1989, VCH Publishers, New York, pages 185-215). Microemulsions commonly are prepared via a combination of three to five components that include oil, water, surfactant, cosurfactant and electrolyte. Whether the microemulsion is of the water-in-oil (w/o) or an oil-in-water (o/w) type is dependent on the properties of the oil and surfactant used and on the structure and geometric packing of the polar heads and hydrocarbon tails of the surfactant molecules (Schott, in Remington&#39;s  Pharmaceutical Sciences , Mack Publishing Co., Easton, Pa., 1985, p. 271). 
     The phenomenological approach utilizing phase diagrams has been extensively studied and has yielded a comprehensive knowledge, to one skilled in the art, of how to formulate microemulsions (see e.g., Ansel&#39;s  Pharmaceutical Dosage Forms and Drug Delivery Systems , Allen, L V., Popovich N G., and Ansel H C., 2004, Lippincott Williams &amp; Wilkins (8th ed.), New York, N.Y.; Rosoff, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Block, in  Pharmaceutical Dosage Forms , Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335). Compared to conventional emulsions, microemulsions offer the advantage of solubilizing water-insoluble drugs in a formulation of thermodynamically stable droplets that are formed spontaneously. 
     Surfactants used in the preparation of microemulsions include, but are not limited to, ionic surfactants, non-ionic surfactants, Brij 96, polyoxyethylene oleyl ethers, polyglycerol fatty acid esters, tetraglycerol monolaurate (ML310), tetraglycerol monooleate (MO310), hexaglycerol monooleate (PO310), hexaglycerol pentaoleate (PO500), decaglycerol monocaprate (MCA750), decaglycerol monooleate (MO750), decaglycerol sequioleate (SO750), decaglycerol decaoleate (DA0750), alone or in combination with cosurfactants. The cosurfactant, usually a short-chain alcohol such as ethanol, 1-propanol, and 1-butanol, serves to increase the interfacial fluidity by penetrating into the surfactant film and consequently creating a disordered film because of the void space generated among surfactant molecules. Microemulsions may, however, be prepared without the use of cosurfactants and alcohol-free self-emulsifying microemulsion systems are known in the art. The aqueous phase may typically be, but is not limited to, water, an aqueous solution of the drug, glycerol, PEG300, PEG400, polyglycerols, propylene glycols, and derivatives of ethylene glycol. The oil phase may include, but is not limited to, materials such as Captex 300, Captex 355, Capmul MCM, fatty acid esters, medium chain (C8-C12) mono, di, and tri-glycerides, polyoxyethylated glyceryl fatty acid esters, fatty alcohols, polyglycolized glycerides, saturated polyglycolized C8-C10 glycerides, vegetable oils and silicone oil. 
     Microemulsions are particularly of interest from the standpoint of drug solubilization and the enhanced absorption of drugs. Lipid based microemulsions (both o/w and w/o) have been proposed to enhance the oral bioavailability of drugs, including peptides (see e.g., U.S. Pat. Nos. 6,191,105; 7,063,860; 7,070,802; 7,157,099; Constantinides et al.,  Pharmaceutical Research,  1994, 11, 1385-1390; Ritschel,  Meth. Find. Exp. Clin. Pharmacol.,  1993, 13, 205). Microemulsions afford advantages of improved drug solubilization, protection of drug from enzymatic hydrolysis, possible enhancement of drug absorption due to surfactant-induced alterations in membrane fluidity and permeability, ease of preparation, ease of oral administration over solid dosage forms, improved clinical potency, and decreased toxicity (see e.g., U.S. Pat. Nos. 6,191,105; 7,063,860; 7,070,802; 7,157,099; Constantinides et al.,  Pharmaceutical Research,  1994, 11, 1385; Ho et al.,  J. Pharm. Sci.,  1996, 85, 138-143). Often microemulsions may form spontaneously when their components are brought together at ambient temperature. This may be particularly advantageous when formulating thermolabile drugs, peptides or iRNAs. Microemulsions have also been effective in the transdermal delivery of active components in both cosmetic and pharmaceutical applications. It is expected that the microemulsion compositions and formulations of the present disclosure will facilitate the increased systemic absorption of iRNAs and nucleic acids from the gastrointestinal tract, as well as improve the local cellular uptake of iRNAs and nucleic acids. 
     Microemulsions of the present disclosure may also contain additional components and additives such as sorbitan monostearate (Grill 3), Labrasol, and penetration enhancers to improve the properties of the formulation and to enhance the absorption of the iRNAs and nucleic acids of the present disclosure. Penetration enhancers used in the microemulsions of the present disclosure may be classified as belonging to one of five broad categories--surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al.,  Critical Reviews in Therapeutic Drug Carrier Systems,  1991, p. 92). Each of these classes has been discussed above. 
     Penetration Enhancers 
     In some embodiments, the present disclosure employs various penetration enhancers to effect the efficient delivery of nucleic acids, particularly iRNAs, to the skin of animals. Most drugs are present in solution in both ionized and nonionized forms. However, usually only lipid soluble or lipophilic drugs readily cross cell membranes. It has been discovered that even non-lipophilic drugs may cross cell membranes if the membrane to be crossed is treated with a penetration enhancer. In addition to aiding the diffusion of non-lipophilic drugs across cell membranes, penetration enhancers also enhance the permeability of lipophilic drugs. 
     Penetration enhancers may be classified as belonging to one of five broad categories, i.e., surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (see e.g., Malmsten, M. Surfactants and polymers in drug delivery,  Informa Health Care , New York, N.Y., 2002; Lee et al.,  Critical Reviews in Therapeutic Drug Carrier Systems,  1991, p. 92). Each of the above-mentioned classes of penetration enhancers are described below in greater detail. 
     Surfactants: In connection with the present disclosure, surfactants (or “surface-active agents”) are chemical entities which, when dissolved in an aqueous solution, reduce the surface tension of the solution or the interfacial tension between the aqueous solution and another liquid, with the result that absorption of iRNAs through the mucosa is enhanced. In addition to bile salts and fatty acids, these penetration enhancers include, for example, sodium lauryl sulfate, polyoxyethylene-9-lauryl ether and polyoxyethylene-20-cetyl ether) (see e.g., Malmsten, M. Surfactants and polymers in drug delivery, Informa Health Care, New York, N.Y., 2002; Lee et al.,  Critical Reviews in Therapeutic Drug Carrier Systems,  1991, p. 92); and perfluorochemical emulsions, such as FC-43. Takahashi et al.,  J. Pharm. Pharmacol.,  1988, 40, 252). 
     Fatty acids: Various fatty acids and their derivatives which act as penetration enhancers include, for example, oleic acid, lauric acid, capric acid (n-decanoic acid), myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein (1-monooleoyl-rac-glycerol), dilaurin, caprylic acid, arachidonic acid, glycerol 1-monocaprate, 1-dodecylazacycloheptan-2-one, acylcarnitines, acylcholines, C 1-20  alkyl esters thereof (e.g., methyl, isopropyl and t-butyl), and mono- and di-glycerides thereof (i.e., oleate, laurate, caprate, myristate, palmitate, stearate, linoleate, etc.) (see e.g., Touitou, E., et al.  Enhancement in Drug Delivery , CRC Press, Danvers, Mass., 2006; Lee et al.,  Critical Reviews in Therapeutic Drug Carrier Systems,  1991, p. 92; Muranishi,  Critical Reviews in Therapeutic Drug Carrier Systems,  1990, 7, 1-33; El Hariri et al.,  J. Pharm. Pharmacol.,  1992, 44, 651-654). 
     Bile salts: The physiological role of bile includes the facilitation of dispersion and absorption of lipids and fat-soluble vitamins (see e.g., Malmsten, M. Surfactants and polymers in drug delivery, Informa Health Care, New York, N.Y., 2002; Brunton, Chapter 38 in: Goodman &amp; Gilman&#39;s  The Pharmacological Basis of Therapeutics,  9th Ed., Hardman et al. Eds., McGraw-Hill, New York, 1996, pp. 934-935). Various natural bile salts, and their synthetic derivatives, act as penetration enhancers. Thus, the term “bile salts” includes any of the naturally occurring components of bile as well as any of their synthetic derivatives. Suitable bile salts include, for example, cholic acid (or its pharmaceutically acceptable sodium salt, sodium cholate), dehydrocholic acid (sodium dehydrocholate), deoxycholic acid (sodium deoxycholate), glucholic acid (sodium glucholate), glycholic acid (sodium glycocholate), glycodeoxycholic acid (sodium glycodeoxycholate), taurocholic acid (sodium taurocholate), taurodeoxycholic acid (sodium taurodeoxycholate), chenodeoxycholic acid (sodium chenodeoxycholate), ursodeoxycholic acid (UDCA), sodium tauro-24,25-dihydro-fusidate (STDHF), sodium glycodihydrofusidate and polyoxyethylene-9-lauryl ether (POE) (see e.g., Malmsten, M. Surfactants and polymers in drug delivery, Informa Health Care, New York, N.Y., 2002; Lee et al.,  Critical Reviews in Therapeutic Drug Carrier Systems,  1991, page 92; Swinyard, Chapter 39 In:  Remington&#39;s Pharmaceutical Sciences,  18th Ed., Gennaro, ed., Mack Publishing Co., Easton, Pa., 1990, pages 782-783; Muranishi,  Critical Reviews in Therapeutic Drug Carrier Systems,  1990, 7, 1-33; Yamamoto et al.,  J. Pharm. Exp. Ther.,  1992, 263, 25; Yamashita et al.,  J. Pharm. Sci.,  1990, 79, 579-583). 
     Chelating Agents: Chelating agents, as used in connection with the present disclosure, can be defined as compounds that remove metallic ions from solution by forming complexes therewith, with the result that absorption of iRNAs through the mucosa is enhanced. With regards to their use as penetration enhancers in the present disclosure, chelating agents have the added advantage of also serving as DNase inhibitors, as most characterized DNA nucleases require a divalent metal ion for catalysis and are thus inhibited by chelating agents (Jarrett,  J. Chromatogr.,  1993, 618, 315-339). Suitable chelating agents include but are not limited to disodium ethylenediaminetetraacetate (EDTA), citric acid, salicylates (e.g., sodium salicylate, 5-methoxysalicylate and homovanilate), N-acyl derivatives of collagen, laureth-9 and N-amino acyl derivatives of β-diketones (enamines)(see e.g., Katdare, A. et al.,  Excipient development for pharmaceutical, biotechnology, and drug delivery , CRC Press, Danvers, Mass., 2006; Lee et al.,  Critical Reviews in Therapeutic Drug Carrier Systems,  1991, page 92; Muranishi,  Critical Reviews in Therapeutic Drug Carrier Systems,  1990, 7, 1-33; Buur et al.,  J. Control Rel.,  1990, 14, 43-51). 
     Non-chelating non-surfactants: As used herein, non-chelating non-surfactant penetration enhancing compounds can be defined as compounds that demonstrate insignificant activity as chelating agents or as surfactants but that nonetheless enhance absorption of iRNAs through the alimentary mucosa (see e.g., Muranishi,  Critical Reviews in Therapeutic Drug Carrier Systems,  1990, 7, 1-33). This class of penetration enhancers include, for example, unsaturated cyclic ureas, 1-alkyl- and 1-alkenylazacyclo-alkanone derivatives (Lee et al.,  Critical Reviews in Therapeutic Drug Carrier Systems,  1991, page 92); and non-steroidal anti-inflammatory agents such as diclofenac sodium, indomethacin and phenylbutazone (Yamashita et al.,  J. Pharm. Pharmacol.,  1987, 39, 621-626). 
     Agents that enhance uptake of iRNAs at the cellular level may also be added to the pharmaceutical and other compositions of the present disclosure. For example, cationic lipids, such as lipofectin (Junichi et al, U.S. Pat. No. 5,705,188), cationic glycerol derivatives, and polycationic molecules, such as polylysine (Lollo et al., PCT Application WO 97/30731), are also known to enhance the cellular uptake of dsRNAs. Examples of commercially available transfection reagents include, for example Lipofectamine™ (Invitrogen; Carlsbad, Calif.), Lipofectamine 2000™ (Invitrogen; Carlsbad, Calif.), 293fectin™ (Invitrogen; Carlsbad, Calif.), Cellfectin™ (Invitrogen; Carlsbad, Calif.), DMRIE-C™ (Invitrogen; Carlsbad, Calif.), FreeStyle™ MAX (Invitrogen; Carlsbad, Calif.), Lipofectamine™ 2000 CD (Invitrogen; Carlsbad, Calif.), Lipofectamine™ (Invitrogen; Carlsbad, Calif.), RNAiMAX (Invitrogen; Carlsbad, Calif.), Oligofectamine™ (Invitrogen; Carlsbad, Calif.), Optifect™ (Invitrogen; Carlsbad, Calif.), X-tremeGENE Q2 Transfection Reagent (Roche; Grenzacherstrasse, Switzerland), DOTAP Liposomal Transfection Reagent (Grenzacherstrasse, Switzerland), DOSPER Liposomal Transfection Reagent (Grenzacherstrasse, Switzerland), or Fugene (Grenzacherstrasse, Switzerland), Transfectam® Reagent (Promega; Madison, Wis.), TransFast™ Transfection Reagent (Promega; Madison, Wis.), Tfx™-20 Reagent (Promega; Madison, Wis.), Tfx™-50 Reagent (Promega; Madison, Wis.), DreamFect™ (OZ Biosciences; Marseille, France), EcoTransfect (OZ Biosciences; Marseille, France), TransPassa D1 Transfection Reagent (New England Biolabs; Ipswich, Mass., USA), LyoVec™/LipoGen™ (Invivogen; San Diego, Calif., USA), PerFectin Transfection Reagent (Genlantis; San Diego, Calif., USA), NeuroPORTER Transfection Reagent (Genlantis; San Diego, Calif., USA), GenePORTER Transfection reagent (Genlantis; San Diego, Calif., USA), GenePORTER 2 Transfection reagent (Genlantis; San Diego, Calif., USA), Cytofectin Transfection Reagent (Genlantis; San Diego, Calif., USA), BaculoPORTER Transfection Reagent (Genlantis; San Diego, Calif., USA), TroganPORTER™ transfection Reagent (Genlantis; San Diego, Calif., USA), RiboFect (Bioline; Taunton, Mass., USA), PlasFect (Bioline; Taunton, Mass., USA), UniFECTOR (B-Bridge International; Mountain View, Calif., USA), SureFECTOR (B-Bridge International; Mountain View, Calif., USA), or HiFect™ (B-Bridge International, Mountain View, Calif., USA), among others. 
     Other agents may be utilized to enhance the penetration of the administered nucleic acids, including glycols such as ethylene glycol and propylene glycol, pyrrols such as 2-pyrrol, azones, and terpenes such as limonene and menthone. 
     Carriers 
     Certain compositions of the present disclosure also incorporate carrier compounds in the formulation. As used herein, “carrier compound” can refer to a nucleic acid, or analog thereof, which is inert (i.e., does not possess biological activity per se) but is recognized as a nucleic acid by in vivo processes that reduce the bioavailability of a nucleic acid having biological activity by, for example, degrading the biologically active nucleic acid or promoting its removal from circulation. The coadministration of a nucleic acid and a carrier compound, typically with an excess of the latter substance, can result in a substantial reduction of the amount of nucleic acid recovered in the liver, kidney or other extracirculatory reservoirs, presumably due to competition between the carrier compound and the nucleic acid for a common receptor. For example, the recovery of a partially phosphorothioate dsRNA in hepatic tissue can be reduced when it is coadministered with polyinosinic acid, dextran sulfate, polycytidic acid or 4-acetamido-4′isothiocyano-stilbene-2,2′-disulfonic acid (Miyao et al.,  DsRNA Res. Dev.,  1995, 5, 115-121; Takakura et al.,  DsRNA  &amp;  Nucl. Acid Drug Dev.,  1996, 6, 177-183). 
     Excipients 
     In contrast to a carrier compound, a pharmaceutical carrier or excipient may comprise, e.g., a pharmaceutically acceptable solvent, suspending agent or any other pharmacologically inert vehicle for delivering one or more nucleic acids to an animal. The excipient may be liquid or solid and is selected, with the planned manner of administration in mind, so as to provide for the desired bulk, consistency, etc., when combined with a nucleic acid and the other components of a given pharmaceutical composition. Typical pharmaceutical carriers include, but are not limited to, binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose, etc.); fillers (e.g., lactose and other sugars, microcrystalline cellulose, pectin, gelatin, calcium sulfate, ethyl cellulose, polyacrylates or calcium hydrogen phosphate, etc.); lubricants (e.g., magnesium stearate, talc, silica, colloidal silicon dioxide, stearic acid, metallic stearates, hydrogenated vegetable oils, corn starch, polyethylene glycols, sodium benzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodium starch glycolate, etc.); and wetting agents (e.g., sodium lauryl sulphate, etc). 
     Pharmaceutically acceptable organic or inorganic excipients suitable for non-parenteral administration which do not deleteriously react with nucleic acids can also be used to formulate the compositions of the present disclosure. Suitable pharmaceutically acceptable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like. 
     Formulations for topical administration of nucleic acids may include sterile and non-sterile aqueous solutions, non-aqueous solutions in common solvents such as alcohols, or solutions of the nucleic acids in liquid or solid oil bases. The solutions may also contain buffers, diluents and other suitable additives. Pharmaceutically acceptable organic or inorganic excipients suitable for non-parenteral administration which do not deleteriously react with nucleic acids can be used. 
     Suitable pharmaceutically acceptable excipients include, but are not limited to, water, salt solutions, alcohol, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like. 
     Other Components 
     The compositions of the present disclosure may additionally contain other adjunct components conventionally found in pharmaceutical compositions, e.g., at their art-established usage levels. Thus, for example, the compositions may contain additional, compatible, pharmaceutically-active materials such as, for example, antipruritics, astringents, local anesthetics or anti-inflammatory agents, or may contain additional materials useful in physically formulating various dosage forms of the compositions of the present disclosure, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers. However, such materials, when added, should not unduly interfere with the biological activities of the components of the compositions of the present disclosure. The formulations can be sterilized and, if desired, mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, colorings, flavorings and/or aromatic substances and the like which do not deleteriously interact with the nucleic acid(s) of the formulation. 
     Aqueous suspensions may contain substances that increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers. 
     In some embodiments, pharmaceutical compositions featured in the disclosure include (a) one or more iRNA compounds and (b) one or more biologic agents which function by a non-RNAi mechanism. Examples of such biologic agents include agents that interfere with an interaction of VEGF-A and at least one VEGF-A binding partner. 
     Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD50/ED50. Compounds that exhibit high therapeutic indices are typical. 
     The data obtained from cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of compositions featured in the disclosure lies generally within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound used in the methods featured in the disclosure, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range of the compound or, when appropriate, of the polypeptide product of a target sequence (e.g., achieving a decreased concentration of the polypeptide) that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography. 
     In addition to their administration, as discussed above, the iRNAs featured in the disclosure can be administered in combination with other known agents effective in treatment of diseases or disorders related to VEGF-A expression (e.g., an angiogenic ocular disorder). In any event, the administering physician can adjust the amount and timing of iRNA administration on the basis of results observed using standard measures of efficacy known in the art or described herein. 
     Methods of Treating Disorders Related to Expression of VEGF-A 
     The present disclosure relates to the use of an iRNA targeting VEGF-A to inhibit VEGF-A expression and/or to treat a disease, disorder, or pathological process that is related to VEGF-A expression (e.g., an angiogenic ocular disorder). 
     In some aspects, a method of treatment of a disorder related to expression of VEGF-A is provided, the method comprising administering an iRNA (e.g., a dsRNA) disclosed herein to a subject in need thereof. In some embodiments, the iRNA inhibits (decreases) VEGF-A expression. 
     In some embodiments, the subject is an animal that serves as a model for a disorder related to VEGF-A expression, e.g., an angiogenic ocular disorder, e.g., AMD, DR, DME, RVO, MEfRVO, CVO, ROP, or mCNV. 
     Angiogenic Ocular Disorders 
     In some embodiments, the disorder related to VEGF-A expression is an angiogenic ocular disorder. Non-limiting examples of angiogenic ocular disorders that are treatable using the methods described herein include AMD (including wet AMD, exudative AMD, etc.), RVO (e.g., CRVO, MEfRVO, retinopathy of prematurity (ROP), or branch retinal vein occlusion (BRVO), DME, CNV (e.g., myopic CNV), iris neovascularization, neovascular glaucoma, post-surgical fibrosis in glaucoma, proliferative retinopathy, proliferative vitreoretinopathy (PVR), optic disc neovascularization, corneal neovascularization, retinal neovascularization, vitreal neovascularization, pannus, pterygium, vascular retinopathy, von Hippel-Lindau disease, histoplasmosis, and diabetic retinopathies. 
     Clinical and pathological features of angiogenic ocular disorders include, but are not limited to, a reduction in visual acuity (e.g., characterized by floating spots, blurriness around the edges or center of field of vision (e.g., scotoma), metamorphopsia, and impaired color vision), increased leakage from the CNV, increased vascular permeability in the eye, collection of fluid or blood beneath the macula, abnormal ocular angiogenesis, and intraretinal hemorrhage. 
     In some embodiments, the subject with the angiogenic ocular disorder is less than 18 years old. In some embodiments, the subject with the angiogenic ocular disorder is an adult. In some embodiments, the subject has, or is identified as having, elevated levels of VEGF-A mRNA or protein relative to a reference level (e.g., a level of VEGF-A that is greater than a reference level). 
     In some embodiments, the angiogenic ocular disorder is diagnosed using analysis of a sample from the subject (e.g., an aqueous ocular fluid sample). In some embodiments, the sample is analyzed using a method selected from one or more of: fluorescent in situ hybridization (FISH), immunohistochemistry, VEGF-A immunoassay, electron microscopy, laser microdissection, and mass spectrometry. In some embodiments, angiogenic ocular disorder is diagnosed using any suitable diagnostic test or technique, e.g., angiography (e.g., fluorescein angiography or indocyanine green angiography), electroretinography, ultrasonography, pachymetry, optical coherence tomography (OCT), computed tomography (CT) and magnetic resonance imaging (MRI), tonometry, color vision testing, visual field testing, slit-lamp examination, ophthalmoscopy, and physical examination (e.g., to assess visual acuity (e.g., by fundoscopy or optical coherence tomography (OCT)). 
     Combination Therapies 
     In some embodiments, an iRNA (e.g., a dsRNA) disclosed herein is administered in combination with a second therapy (e.g., one or more additional therapies) known to be effective in treating a disorder related to VEGF-A expression (e.g., an angiogenic ocular disorder) or a symptom of such a disorder. The iRNA may be administered before, after, or concurrent with the second therapy. In some embodiments, the iRNA is administered before the second therapy. In some embodiments, the iRNA is administered after the second therapy. In some embodiments, the iRNA is administered concurrent with the second therapy. 
     The second therapy may be an additional therapeutic agent. The iRNA and the additional therapeutic agent can be administered in combination in the same composition or the additional therapeutic agent can be administered as part of a separate composition. 
     In some embodiments, the second therapy is a non-iRNA therapeutic agent that is effective to treat the disorder or symptoms of the disorder. 
     In some embodiments, the iRNA is administered in conjunction with a therapy. 
     Exemplary combination therapies include, but are not limited to, photodynamic therapy, photocoagulation therapy, a steroid, a non-steroidal anti-inflammatory agent, an anti-VEGF agent, and a vitrectomy. 
     In some embodiments, the anti-VEGF-A agent comprises a fusion protein. Exemplary anti-VEGF fusion proteins include, but are not limited to, aflibercept (EYLEA®). In some embodiments, the anti-VEGF-A fusion protein has the amino acid sequence of SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKG FIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNC TARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLY TCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL HNHYTQKSLSLSPG (SEQ ID NO: 1905), or a variant thereof having at least about 80%, 85%, 90%, 95%, or 99% sequence identity thereto. 
     In some embodiments, the anti-VEGF-A agent is an antibody or antigen-binding fragment thereof (e.g., an anti-VEGF-A antibody molecule). Exemplary anti-VEGF-A antibody molecules include, but are not limited to, ranibizumab (LUCENTIS®) and brolucizumab (BEOVU®). In some embodiments, an anti-VEGF-A antibody molecule competes for binding to VEGF-A with ranibizumab or brolucizumab. 
     In some embodiments, the anti-VEGF-A antibody molecules comprises one or more (e.g., all three) of a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2) and a heavy chain complementarity determining region 3 (HCDR3). In some embodiments, the anti-VEGF-A antibody molecules comprises one or more (e.g., all three) of a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2) and a light chain complementarity determining region 3 (LCDR3). 
     In some embodiments, the anti-VEGF-A antibody molecule comprises a VH comprising one or more (e.g., all three) of a heavy chain complementarity determining region 1 (HCDR1) of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7, (or a sequence with no more than 1, 2, 3, or 4 mutations, e.g., substitutions, additions, or deletions), a HCDR2 of an anti-VEGF-A antibody or antibody fragment thereof described herein, e.g., in Table 7, (or a sequence with no more than 1, 2, 3, or 4 mutations, e.g., substitutions, additions, or deletions), and a HCDR3 of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7, (or a sequence with no more than 1, 2, 3, or 4 mutations, e.g., substitutions, additions, or deletions). 
     In some embodiments, the anti-VEGF-A antibody molecule comprises a VL comprising one or more (e.g., all three) of a light chain complementarity determining region 1 (LCDR1) of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7, (or a sequence with no more than 1, 2, 3, or 4 mutations, e.g., substitutions, additions, or deletions), a LCDR2 of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7, (or a sequence with no more than 1, 2, 3, or 4 mutations, e.g., substitutions, additions, or deletions), and a LCDR3 of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7, (or a sequence with no more than 1, 2, 3, or 4 mutations, e.g., substitutions, additions, or deletions). 
     In some embodiments, the anti-VEGF-A antibody molecule comprises a VH comprising an amino acid sequence of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7, or an amino acid sequence having at least about 80%, 85%, 90%, 95%, or 99% sequence identity thereto. In some embodiments, the anti-VEGF-A antibody molecule comprises a VL comprising the amino acid sequence of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7, or an amino acid sequence having at least about 80%, 85%, 90%, 95%, or 99% sequence identity thereto. 
     In some embodiments, the anti-VEGF-A antibody molecule comprises a VH comprising the amino acid sequence of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7, (or an amino acid sequence having at least about 80%, 85%, 90%, 95%, or 99% sequence identity thereto) and a VL comprising the amino acid sequence of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7, (or an amino acid sequence having at least about 80%, 85%, 90%, 95%, or 99% sequence identity thereto). 
     In one embodiment, the anti-VEGF-A antibody molecule comprises a scFv comprising a light chain and a heavy chain of an amino acid sequence of anti-VEGF-A antibody molecule described herein, e.g., in Table 7. In one embodiment, the anti-VEGF-A antibody molecule (e.g., an scFv) comprises: a light chain variable region comprising an amino acid sequence having at least one, two, or three modifications (e.g., substitutions) but not more than 30, 20, or 10 modifications (e.g., substitutions) of an amino acid sequence of a light chain variable region of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7, or a sequence with 95-99% identity with an amino acid sequence of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7; and/or a heavy chain variable region comprising an amino acid sequence having at least one, two, or three modifications (e.g., substitutions) but not more than 30, 20, or 10 modifications (e.g., substitutions) of an amino acid sequence of a heavy chain variable region of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7, or a sequence with 95-99% identity to an amino acid sequence of an anti-VEGF-A antibody molecule described herein, e.g., in Table 7. 
     In one embodiment, the anti-VEGF-A antibody molecule is a scFv, and a light chain variable region comprising an amino acid sequence of anti-VEGF-A antibody molecule described herein, e.g., in Table 7, is attached to a heavy chain variable region comprising an amino acid sequence of an anti-VEGF-A antibody molecule described herein, via a linker, e.g., a linker described herein. In one embodiment, the anti-VEGF-A antibody molecule includes a (Gly4-Ser)n linker, wherein n is 1, 2, 3, 4, 5, or 6, preferably 3 or 4 (SEQ ID NO:1951). The light chain variable region and heavy chain variable region of a scFv can be, e.g., in any of the following orientations: light chain variable region-linker-heavy chain variable region or heavy chain variable region-linker-light chain variable region. 
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Exemplary Anti-VEGF Antibody Molecule Sequences 
               
            
           
           
               
               
               
            
               
                 Description 
                 SEQ ID NO. 
                 Sequence 
               
               
                   
               
               
                 Brolucizumab Sequence 
                 1906 
                 MEIVMTQSPSTLSASVGDRVIITCQASEIIHSWL   
               
               
                   
                   
                 WYQQKPGKAPKLLIYLASTLASGVPSRFSGSGSG 
               
               
                   
                   
                 AEFTLTISSLQPDDFATYYCQNVYLASTNGAN  G 
               
               
                   
                   
                 QGTKLTVLGGGGGSGGGGSGGGGSGGGGSEVQ 
               
               
                   
                   
                 LVESGGGLVQPGGSLRLSCTASGFSLTDYYYM   
               
               
                   
                   
                 WVRQAPGKGLEWVGFIDPDDDPYYATWAKG  F 
               
               
                   
                   
                 TISRDNSKNTLYLQMNSLRAEDTAVYYCAGG  H 
               
               
                   
                   
                 NSGWGLDIWGQGTLVTVSS 
               
               
                   
               
               
                 Brolucizumab VH 
                 1907 
                 EVQLVESGGGLVQPGGSLRLSCTASGFSLTDY  Y 
               
               
                   
                   
                 MTWVRQAPGKGLEWVGFIDPDDDPYYATWA   
               
               
                   
                   
                 GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAG 
               
               
                   
                   
                 GDHNSGWGLDIWGQGTLVTVSS 
               
               
                   
               
               
                 Brolucizumab VL 
                 1908 
                 MEIVMTQSPSTLSASVGDRVIITCQASEIIHSWL   
               
               
                   
                   
                 WYQQKPGKAPKLLIYLASTLASGVPSRFSGSG  G 
               
               
                   
                   
                 AEFTLTISSLQPDDFATYYCQNVYLASTNGAN  G 
               
               
                   
                   
                 QGTKLTVLG 
               
               
                   
               
               
                 Brolucizumab Linker 
                 1909 
                 GGGGSGGGGSGGGGSGGGGS 
               
               
                   
               
               
                 Ranibizumab Heavy Chain 
                 1910 
                 EVQLVESGGGLVQPGGSLRLSCAASGYDFT   HYG     
               
               
                   
                   
                     MN   WVRQAPGKGLEWVG   WINTYTGEPTYAA         F     
               
               
                   
                   
                     KR   RFTFSLDTSKSTAYLQMNSLRAEDTAVYY  A 
               
               
                   
                   
                 K   YPYYYGTSHWYFDV   WGOGTLVTVSSASTK  P 
               
               
                   
                   
                 SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV   
               
               
                   
                   
                 WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP  S 
               
               
                   
                   
                 SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT   
               
               
                   
                   
                 L 
               
               
                   
               
               
                 Ranibizumab Light Chain 
                 1911 
                 DIQLTQSPSSLSASVGDRVTITC   SASQDISNYLN       
               
               
                   
                   
                 YQQKPGKAPKVLIY   FTSSLHS   GVPSRFSGSGS   
               
               
                   
                   
                 DFTLTISSLQPEDFATYYC   QQYSTVPWT   FGQG   
               
               
                   
                   
                 KVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL  N 
               
               
                   
                   
                 NFYPREAKVQWKVDNALQSGNSQESVTEQDS   
               
               
                   
                   
                 DSTYSLSSTLTLSKADYEKHKVYACEVTHQGL  S 
               
               
                   
                   
                 PVTKSFNRGEC 
               
               
                   
               
               
                 Ranibizumab VH 
                 1912 
                 EVQLVESGGGLVQPGGSLRLSCAASGYDFT   HYG     
               
               
                   
                   
                     MN   WVRQAPGKGLEWVG   WINTYTGEPTYAA         F     
               
               
                   
                   
                     KR   RFTFSLDTSKSTAYLQMNSLRAEDTAVYYCA 
               
               
                   
                   
                 K   YPYYYGTSHWYFDV   WGQGTLVT 
               
               
                   
                   
                 VSS 
               
               
                   
               
               
                 Ranibizumab VL 
                 1913 
                 DIQLTQSPSSLSASVGDRVTITC   SASQDISNYLN   W 
               
               
                   
                   
                 YQQKPGKAPKVLIY   FTSSLHS   GVPSRFSGSGSGT 
               
               
                   
                   
                 DFTLTISSLQPEDFATYYC   QQYSTVPWT   FGQGT 
               
               
                   
                   
                 KVEIK 
               
               
                   
               
               
                 Note: 
               
               
                 CDR sequences are bolded and underlined 
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     Administration Dosages, Routes, and Timing 
     A subject (e.g., a human subject, e.g., a patient) can be administered a therapeutic amount of iRNA. The therapeutic amount can be, e.g., 0.05-50 mg/kg. 
     In some embodiments, the iRNA is formulated for delivery to a target organ, e.g., to the eye. 
     In some embodiments, the iRNA is formulated as a lipid formulation, e.g., an LNP formulation as described herein. In some such embodiments, the therapeutic amount is 0.05-5 mg/kg dsRNA. In some embodiments, the lipid formulation, e.g., LNP formulation, is administered intravenously. 
     In some embodiments, the iRNA is in the form of a GalNAc conjugate e.g., as described herein. In some such embodiments, the therapeutic amount is 0.5-50 mg dsRNA. In some embodiments, the e.g., GalNAc conjugate is administered subcutaneously. 
     In some embodiments, the administration is repeated, for example, on a regular basis, such as, daily, biweekly (i.e., every two weeks) for one month, two months, three months, four months, six months or longer. After an initial treatment regimen, the treatments can be administered on a less frequent basis. For example, after administration biweekly for three months, administration can be repeated once per month, for six months or a year or longer. 
     In some embodiments, the iRNA agent is administered in two or more doses. In some embodiments, the number or amount of subsequent doses is dependent on the achievement of a desired effect, e.g., to (a) inhibit angiogenesis; (b) inhibit or reduce the expression or activity of VEGF A; (c) inhibit choroidal neovascularization; (d) inhibit growth of new blood vessels in the choriocapillaris; (e) reduce retinal thickness; (f) increase visual acuity; or (g) reduce intraocular inflammation, or the achievement of a therapeutic or prophylactic effect, e.g., reduction or prevention of one or more symptoms associated with the disorder. 
     In some embodiments, the iRNA agent is administered according to a schedule. For example, the iRNA agent may be administered once per week, twice per week, three times per week, four times per week, or five times per week. In some embodiments, the schedule involves regularly spaced administrations, e.g., hourly, every four hours, every six hours, every eight hours, every twelve hours, daily, every 2 days, every 3 days, every 4 days, every 5 days, weekly, biweekly, or monthly. In some embodiments, the iRNA agent is administered at the frequency required to achieve a desired effect. 
     In some embodiments, the schedule involves closely spaced administrations followed by a longer period of time during which the agent is not administered. For example, the schedule may involve an initial set of doses that are administered in a relatively short period of time (e.g., about every 6 hours, about every 12 hours, about every 24 hours, about every 48 hours, or about every 72 hours) followed by a longer time period (e.g., about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 7 weeks, or about 8 weeks) during which the iRNA agent is not administered. In some embodiments, the iRNA agent is initially administered hourly and is later administered at a longer interval (e.g., daily, weekly, biweekly, or monthly). In some embodiments, the iRNA agent is initially administered daily and is later administered at a longer interval (e.g., weekly, biweekly, or monthly). In certain embodiments, the longer interval increases over time or is determined based on the achievement of a desired effect. 
     Before administration of a full dose of the iRNA, patients can be administered a smaller dose, such as a 5% infusion dose, and monitored for adverse effects, such as an allergic reaction, or for elevated lipid levels or blood pressure. In another example, the patient can be monitored for unwanted effects. 
     Methods for Modulating Expression of VEGF-A 
     In some aspects, the disclosure provides a method for modulating (e.g., inhibiting or activating) the expression of VEGF-A, e.g., in a cell, in a tissue, or in a subject. In some embodiments, the cell or tissue is ex vivo, in vitro, or in vivo. In some embodiments, the cell or tissue is in the eye (e.g., retinal pigment epithelium (RPE), a retinal tissue, an astrocyte, a pericyte, a Müller cell, a ganglion cell, an endothelial cell, a photoreceptor cell, a retinal blood vessel (e.g., including endothelial cells and vascular smooth muscle cells), or choroid tissue, e.g., a choroid vessel). In some embodiments, the cell or tissue is in a subject (e.g., a mammal, such as, for example, a human). In some embodiments, the subject (e.g., the human) is at risk, or is diagnosed with a disorder related to expression of VEGF-A expression, as described herein. 
     In some embodiments, the method includes contacting the cell with an iRNA as described herein, in an amount effective to decrease the expression of VEGF-A in the cell. In some embodiments, contacting a cell with an RNAi agent includes contacting a cell in vitro with the RNAi agent or contacting a cell in vivo with the RNAi agent. In some embodiments, the RNAi agent is put into physical contact with the cell by the individual performing the method, or the RNAi agent may be put into a situation that will permit or cause it to subsequently come into contact with the cell. Contacting a cell in vitro may be done, for example, by incubating the cell with the RNAi agent. Contacting a cell in vivo may be done, for example, by injecting the RNAi agent into or near the tissue where the cell is located, or by injecting the RNAi agent into another area, e.g., ocular tissue. For example, the RNAi agent may contain or be coupled to a ligand, e.g., a lipophilic moiety or moieties as described below and further detailed, e.g., in PCT/US2019/031170 which is incorporated herein by reference in its entirety, including the passages therein describing lipophilic moieties, that directs or otherwise stabilizes the RNAi agent at a site of interest. Combinations of in vitro and in vivo methods of contacting are also possible. For example, a cell may also be contacted in vitro with an RNAi agent and subsequently transplanted into a subject. 
     The expression of VEGF-A may be assessed based on the level of expression of VEGF-A mRNA, VEGF-A protein, or the level of another parameter functionally linked to the level of expression of VEGF-A. In some embodiments, the expression of VEGF-A is inhibited by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95%. In some embodiments, the iRNA has an IC50 in the range of 0.001-0.01 nM, 0.001-0.10 nM, 0.001-1.0 nM, 0.001-10 nM, 0.01-0.05 nM, 0.01-0.50 nM, 0.02-0.60 nM, 0.01-1.0 nM, 0.01-1.5 nM, 0.01-10 nM. The IC 50  value may be normalized relative to an appropriate control value, e.g., the IC 50  of a non-targeting iRNA. 
     In some embodiments, the method includes introducing into the cell or tissue an iRNA as described herein and maintaining the cell or tissue for a time sufficient to obtain degradation of the mRNA transcript of VEGF-A, thereby inhibiting the expression of VEGF-A in the cell or tissue. 
     In some embodiments, the method includes administering a composition described herein, e.g., a composition comprising an iRNA that binds VEGF-A, to the mammal such that expression of the target VEGF-A is decreased, such as for an extended duration, e.g., at least two, three, four days or more, e.g., one week, two weeks, three weeks, or four weeks or longer. In some embodiments, the decrease in expression of VEGF-A is detectable within 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, or 24 hours of the first administration. 
     In some embodiments, the method includes administering a composition as described herein to a mammal such that expression of the target VEGF-A is increased by e.g., at least 10% compared to an untreated animal. In some embodiments, the activation of VEGF-A occurs over an extended duration, e.g., at least two, three, four days or more, e.g., one week, two weeks, three weeks, four weeks, or more. Without wishing to be bound by theory, an iRNA can activate VEGF-A expression by stabilizing the VEGF-A mRNA transcript, interacting with a promoter in the genome, or inhibiting an inhibitor of VEGF-A expression. 
     The iRNAs useful for the methods and compositions featured in the disclosure specifically target RNAs (primary or processed) of VEGF-A. Compositions and methods for inhibiting the expression of VEGF-A using iRNAs can be prepared and performed as described elsewhere herein. 
     In some embodiments, the method includes administering a composition containing an iRNA, where the iRNA includes a nucleotide sequence that is complementary to at least a part of an RNA transcript of VEGF-A of the subject, e.g., the mammal, e.g., the human, to be treated. The composition may be administered by any appropriate means known in the art including, but not limited to ocular (e.g., intraocular), topical, and intravenous administration. 
     In certain embodiments, the composition is administered intraocularly (e.g., by intravitreal administration, e.g., intravitreal injection; transscleral administration, e.g., transscleral injection; subconjunctival administration, e.g., subconjunctival injection; retrobulbar administration, e.g., retrobulbar injection; intracameral administration, e.g., intracameral injection; or subretinal administration, e.g., subretinal injection. In other embodiments, the composition is administered topically. In other embodiments, the composition is administered by intravenous infusion or injection. 
     In certain embodiments, the composition is administered by intravenous infusion or injection. In some such embodiments, the composition comprises a lipid formulated siRNA (e.g., an LNP formulation, such as an LNP11 formulation) for intravenous infusion. 
     Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the iRNAs and methods featured in the disclosure, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In the event of a discrepancy between the recited positions of the duplexes presented herein and the alignment of the duplexes to the recited sequences, the alignment of the duplexes to the recited sequence will govern. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. 
     Specific Embodiments 
     1. A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of vascular endothelial growth factor A (VEGF-A), wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region, wherein the sense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of a coding strand of human VEGF-A and the antisense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of the corresponding portion of a non-coding strand of human VEGF-A such that the sense strand is complementary to the at least 15 contiguous nucleotides in the antisense strand. 
     2. The dsRNA agent of embodiment 1, wherein the coding strand of human VEGF-A comprises the sequence SEQ ID NO: 1. 
     3. The dsRNA agent of embodiment 1 or 2, wherein the non-coding strand of human VEGF-A comprises the sequence of SEQ ID NO: 2. 
     4. A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of VEGF-A, wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region, wherein the antisense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of nucleotide sequence of SEQ ID NO: 2 such that the sense strand is complementary to the at least 15 contiguous nucleotides in the antisense strand. 
     5. The dsRNA agent of embodiment 4, wherein the sense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, or 1, 2, or 3 mismatches, of the corresponding portion of the nucleotide sequence of SEQ ID NO: 1. 
     6. The dsRNA of any of the preceding embodiments, wherein the dsRNA agent comprises a sense strand and an antisense strand, wherein the antisense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of nucleotide sequence of SEQ ID NO: 2 such that the sense strand is complementary to the at least 17 contiguous nucleotides in the antisense strand. 
     7. The dsRNA of embodiment 6, wherein the sense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides, with 0, or 1, 2, or 3 mismatches, of the corresponding portion of the nucleotide sequence of SEQ ID NO: 1. 
     8. The dsRNA of any of the preceding embodiments, wherein the dsRNA agent comprises a sense strand and an antisense strand, wherein the antisense strand comprises a nucleotide sequence comprising at least 19 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of nucleotide sequence of SEQ ID NO: 2 such that the sense strand is complementary to the at least 19 contiguous nucleotides in the antisense strand. 
     9. The dsRNA of embodiment 8, wherein the sense strand comprises a nucleotide sequence comprising at least 19 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of the corresponding portion of the nucleotide sequence of SEQ ID NO: 1. 
     10. The dsRNA of any of the preceding embodiments, wherein the dsRNA agent comprises a sense strand and an antisense strand, wherein the antisense strand comprises a nucleotide sequence comprising at least 21 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of nucleotide sequence of SEQ ID NO: 2 such that the sense strand is complementary to the at least 21 contiguous nucleotides in the antisense strand. 
     11. The dsRNA of embodiment 10, wherein the sense strand comprises a nucleotide sequence comprising at least 21 contiguous nucleotides, with 0, or 1, 2, or 3 mismatches, of the corresponding portion of the nucleotide sequence of SEQ ID NO: 1. 
     12. The dsRNA agent of any one of embodiments 1-11, wherein the portion of the sense strand is a portion within nucleotides 1855-1875, 1858-1878, 2178-2198, 2181-2201, 2944-2964, 2946-2966, 2952-2972, 3361-3381, or 3362-3382 of SEQ ID NO: 1. 
     13. The dsRNA agent of any one of embodiments 1-12, wherein the portion of the sense strand is a portion within a sense strand from a duplex chosen from AD-1020574 (CGACAGAACAGUCCUUAAUCA (SEQ ID NO: 4200)), AD-901094 (CAGAACAGUCCUUAAUCCAGA (SEQ ID NO: 4201)), AD-1020575 (CAGAACAGUCCUUAAUCCAGA (SEQ ID NO: 4202)), AD-901100 (AACAGUGCUAAUGUUAUUGGA (SEQ ID NO: 4203)), AD-901101 (AGUGCUAAUGUUAUUGGUGUA (SEQ ID NO: 4204)), AD-901113 (GAGAAAGUGUUUUAUAUACGA (SEQ ID NO: 4205)), AD-901123 (AAAAUAGACAUUGCUAUUCUA (SEQ ID NO: 4206)), AD-901124 (AAAUAGACAUUGCUAUUCUGA (SEQ ID NO: 4207)), AD-901158 (GAAAGUGUUUUAUAUACGGUA (SEQ ID NO: 4208)), AD-901159 (GUUUUAUAUACGGUACUUAUA (SEQ ID NO: 4209)), AD-1020573 (AGUGCUAATGTUAUUGGUGUA (SEQ ID NO: 4210)), or AD-1023143 (AAAAUAGACATUGCUAUUCUA (SEQ ID NO: 4211)). 
     14. The dsRNA agent of any one of embodiments 1-13, wherein the portion of the sense strand is a sense strand chosen from the sense strands of AD-1020574 (CGACAGAACAGUCCUUAAUCA (SEQ ID NO: 4200)), AD-901094 (CAGAACAGUCCUUAAUCCAGA (SEQ ID NO: 4201)), AD-1020575 (CAGAACAGUCCUUAAUCCAGA (SEQ ID NO: 4202)), AD-901100 (AACAGUGCUAAUGUUAUUGGA (SEQ ID NO: 4203)), AD-901101 (AGUGCUAAUGUUAUUGGUGUA (SEQ ID NO: 4204)), AD-901113 (GAGAAAGUGUUUUAUAUACGA (SEQ ID NO: 4205)), AD-901123 (AAAAUAGACAUUGCUAUUCUA (SEQ ID NO: 4206)), AD-901124 (AAAUAGACAUUGCUAUUCUGA (SEQ ID NO: 4207)), AD-901158 (GAAAGUGUUUUAUAUACGGUA (SEQ ID NO: 4208)), AD-901159 (GUUUUAUAUACGGUACUUAUA (SEQ ID NO: 4209)), AD-1020573 (AGUGCUAATGTUAUUGGUGUA (SEQ ID NO: 4210)), or AD-1023143 (AAAAUAGACATUGCUAUUCUA (SEQ ID NO: 4211)). 
     15. The dsRNA of any one of embodiments 1-14, wherein the portion of the antisense strand is a portion within an antisense strand from a duplex chosen from AD-1020574 (UGAUUAAGGACUGUUCUGUCGAU (SEQ ID NO: 4212)), AD-901094 (UCUGGAUUAAGGACUGUUCUGUC (SEQ ID NO: 4213)), AD-1020575 (UCUGGATUAAGGACUGUUCUGUC (SEQ ID NO: 4214)), AD-901100 (UCCAAUAACAUUAGCACUGUUAA (SEQ ID NO: 4215)), AD-901101 (UACACCAAUAACAUUAGCACUGU (SEQ ID NO: 4216)), AD-901113 (UCGUAUAUAAAACACUUUCUCUU (SEQ ID NO: 4217)), AD-901123 (UAGAAUAGCAAUGUCUAUUUUAU (SEQ ID NO: 4218)), AD-901124 (UCAGAAUAGCAAUGUCUAUUUUA (SEQ ID NO: 4219)), AD-901158 (UACCGUAUAUAAAACACUUUCUC (SEQ ID NO: 4220)), AD-901159 (UAUAAGUACCGUAUAUAAAACAC (SEQ ID NO: 4221)), AD-1020573 (UACACCAAUAACATUAGCACUGU (SEQ ID NO: 4222)), or AD-1023143 (UAGAAUAGCAATGTCTAUUUUAU (SEQ ID NO: 4223)). 
     16. The dsRNA of any one of embodiments 1-15, wherein the portion of the antisense strand is an antisense strand chosen the antisense strands of AD-1020574 (UGAUUAAGGACUGUUCUGUCGAU (SEQ ID NO: 4212)), AD-901094 (UCUGGAUUAAGGACUGUUCUGUC (SEQ ID NO: 4213)), AD-1020575 (UCUGGATUAAGGACUGUUCUGUC (SEQ ID NO: 4214)), AD-901100 (UCCAAUAACAUUAGCACUGUUAA (SEQ ID NO: 4215)), AD-901101 (UACACCAAUAACAUUAGCACUGU (SEQ ID NO: 4216)), AD-901113 (UCGUAUAUAAAACACUUUCUCUU (SEQ ID NO: 4217)), AD-901123 (UAGAAUAGCAAUGUCUAUUUUAU (SEQ ID NO: 4218)), AD-901124 (UCAGAAUAGCAAUGUCUAUUUUA (SEQ ID NO: 4219)), AD-901158 (UACCGUAUAUAAAACACUUUCUC (SEQ ID NO: 4220)), AD-901159 (UAUAAGUACCGUAUAUAAAACAC (SEQ ID NO: 4221)), AD-1020573 (UACACCAAUAACATUAGCACUGU (SEQ ID NO: 4222)), or AD-1023143 (UAGAAUAGCAATGTCTAUUUUAU (SEQ ID NO: 4223)). 
     17. The dsRNA of any one of embodiments 1-16, wherein the sense strand and the antisense strand comprise nucleotide sequences of the paired sense strand and antisense strand of a duplex selected from AD-1020574 (SEQ ID NO: 4200 and 4212), AD-901094 (SEQ ID NO: 4201 and 4213), AD-1020575 (SEQ ID NO: 4202 and 4214), AD-901100 (SEQ ID NO: 4203 and 4215), AD-901101 (SEQ ID NO: 4204 and 4216), AD-901113 (SEQ ID NO: 4205 and 4217), AD-901123 (SEQ ID NO: 4206 and 4218), AD-901124 (SEQ ID NO: 4207 and 4219), AD-901158 (SEQ ID NO: 4208 and 4220), AD-901159 (SEQ ID NO: 4209 and 4221), AD-1020573 (SEQ ID NO: 4210 and 4222), or AD-1023143 (SEQ ID NO: 4211 and 4223). 
     18. The dsRNA agent of any one of embodiments 1-11, wherein the portion of the sense strand is a portion within a sense strand from a duplex chosen from AD-953374 (SEQ ID NO: 813), AD-953504 (SEQ ID NO: 1297), AD-953481 (SEQ ID NO: 1298), AD-953351 (SEQ ID NO: 800), AD-901356 (SEQ ID NO: 261), AD-953344 (SEQ ID NO: 787), AD-901355 (SEQ ID NO: 262), AD-953410 (SEQ ID NO: 845), AD-953363 (SEQ ID NO: 779), AD-953411 (SEQ ID NO: 844), AD-953350 (SEQ ID NO: 784), or AD-953375 (SEQ ID NO: 790). 
     19. The dsRNA agent of any one of embodiments 1-11 or 18, wherein the portion of the sense strand is a sense strand chosen from the sense strands of AD-953374 (SEQ ID NO: 813), AD-953504 (SEQ ID NO: 1297), AD-953481 (SEQ ID NO: 1298), AD-953351 (SEQ ID NO: 800), AD-901356 (SEQ ID NO: 261), AD-953344 (SEQ ID NO: 787), AD-901355 (SEQ ID NO: 262), AD-953410 (SEQ ID NO: 845), AD-953363 (SEQ ID NO: 779), AD-953411 (SEQ ID NO: 844), AD-953350 (SEQ ID NO: 784), or AD-953375 (SEQ ID NO: 790). 
     20. The dsRNA of any one of embodiments 1-11 or 18-19, wherein the portion of the antisense strand is a portion within an antisense strand from a duplex chosen from AD-953374 (SEQ ID NO: 943), AD-953504 (SEQ ID NO: 1427), AD-953481 (SEQ ID NO: 1428), AD-953351 (SEQ ID NO: 930), AD-901356 (SEQ ID NO: 390), AD-953344 (SEQ ID NO: 917), AD-901355 (SEQ ID NO: 391), AD-953410 (SEQ ID NO: 975), AD-953363 (SEQ ID NO: 909), AD-953411 (SEQ ID NO: 974), AD-953350 (SEQ ID NO: 914), or AD-953375 (SEQ ID NO: 920). 
     21. The dsRNA of any one of embodiments 1-11 or 18-20, wherein the portion of the antisense strand is an antisense strand chosen from AD-953374 (SEQ ID NO: 943), AD-953504 (SEQ ID NO: 1427), AD-953481 (SEQ ID NO: 1428), AD-953351 (SEQ ID NO: 930), AD-901356 (SEQ ID NO: 390), AD-953344 (SEQ ID NO: 917), AD-901355 (SEQ ID NO: 391), AD-953410 (SEQ ID NO: 975), AD-953363 (SEQ ID NO: 909), AD-953411 (SEQ ID NO: 974), AD-953350 (SEQ ID NO: 914), or AD-953375 (SEQ ID NO: 920). 
     22. The dsRNA of any one of embodiments 1-11, or 18-21 wherein the sense strand and the antisense strand of comprise the nucleotide sequences of the paired sense strand and antisense strand of a duplex selected from AD-953374 (SEQ ID NO: 813 and 943), AD-953504 (SEQ ID NO: 1297 and 1427), AD-953481 (SEQ ID NO: 1298 and 1428), AD-953351 (SEQ ID NO: 800 and 930), AD-901356 (SEQ ID NO: 261 and 390), AD-953344 (SEQ ID NO: 787 and 917), AD-901355 (SEQ ID NO: 262 and 391), AD-953410 (SEQ ID NO: 845 and 975), AD-953363 (SEQ ID NO: 779 and 909), AD-953411 (SEQ ID NO: 844 and 974), AD-953350 (SEQ ID NO: 784 and 914), or AD-953375 (SEQ ID NO: 790 and 920). 
     23. The dsRNA agent of any one of the preceding embodiments, wherein the portion of the sense strand is a portion within a sense strand in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. 
     24. The dsRNA agent of any one of the preceding embodiments, wherein the portion of the antisense strand is a portion within an antisense strand in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. 
     25. The dsRNA agent of any of the preceding embodiments, wherein the antisense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from one of the antisense sequences listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. 
     26. The dsRNA agent of any of the preceding embodiments, wherein the sense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from a sense sequence listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B that corresponds to the antisense sequence. 
     27. The dsRNA agent of any of the preceding embodiments, wherein the antisense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from one of the antisense sequences listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. 
     28. The dsRNA agent of any of the preceding embodiments, wherein the sense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from a sense sequence listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B that corresponds to the antisense sequence. 
     29. The dsRNA agent of any of the preceding embodiments, wherein the antisense strand comprises a nucleotide sequence comprising at least 19 contiguous nucleotides, with 0,1, 2, or 3 mismatches, from one of the antisense sequences listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. 
     30. The dsRNA agent of any of the preceding embodiments, wherein the sense strand comprises a nucleotide sequence comprising at least 19 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from a sense sequence listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B that corresponds to the antisense sequence. 
     31. The dsRNA agent of any of the preceding embodiments, wherein the antisense strand comprises a nucleotide sequence comprising at least 21 contiguous nucleotides, with 0,1, 2, or 3 mismatches, from one of the antisense sequences listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B. 
     32. The dsRNA agent of any of the preceding embodiments, wherein the sense strand comprises a nucleotide sequence comprising at least 21 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, from a sense sequence listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B that corresponds to the antisense sequence. 
     33. A double-stranded ribonucleic acid (dsRNA) agent for inhibiting expression of VEGF-A, wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double-stranded region, wherein the antisense strand comprises a nucleotide sequence of an antisense sequence listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B, and the sense strand comprises a nucleotide sequence of a sense sequence listed in any one of Tables 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 8A, 8B, 10A, 10B, 12, 13, 14, 18A and 18B that corresponds to the antisense sequence. 
     34. The dsRNA agent of embodiment 33, wherein the antisense strand comprises a nucleotide sequence of an antisense sequence listed in Table 2A, and the sense strand comprises a nucleotide sequence of a sense sequence listed in Table 2A that corresponds to the antisense sequence. 
     35. The dsRNA agent of embodiment 33, wherein the antisense strand comprises a nucleotide sequence of an antisense sequence listed in Table 3A, and the sense strand comprises a nucleotide sequence of a sense sequence listed in Table 3A that corresponds to the antisense sequence. 
     36. The dsRNA agent of embodiment 33, wherein the antisense strand comprises a nucleotide sequence of an antisense sequence listed in Table 4A, and the sense strand comprises a nucleotide sequence of a sense sequence listed in Table 4A that corresponds to the antisense sequence. 
     37. The dsRNA agent of embodiment 33, wherein the antisense strand comprises a nucleotide sequence of an antisense sequence listed in Table 18A, and the sense strand comprises a nucleotide sequence of a sense sequence listed in Table 18A that corresponds to the antisense sequence. 
     38. The dsRNA agent of any one of embodiments 33 or 37, wherein the dsRNA agent is AD-1020574, AD-901094, AD-1020575, AD-901100, AD-901101, AD-901113, AD-901123, AD-901124, AD-901158, AD-901159, AD-1020573, or AD-1023143. 
     39. The dsRNA agent of any one of embodiments 33 or 37-38, comprising: 
     (i) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 4164, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4176; 
     (ii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1465, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4177; 
     (iii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1466, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4178; 
     (iv) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1467, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4179; 
     (v) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1468, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4180; 
     (vi) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1469, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4181; 
     (vii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1470, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4182; 
     (viii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1471, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4183; 
     (ix) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1472, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4184; 
     (x) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1473, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4185; 
     (xi) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1474, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4186; or 
     (xii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1475, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4187. 
     40. The dsRNA agent of any one of embodiments 33-36, wherein the dsRNA agent is AD-953374, AD-953504, AD-953481, AD-953351, AD-901356, AD-953344, AD-901355, AD-953410, AD-953363, AD-953411, AD-953350, or AD-953375. 
     41. The dsRNA agent of any one of embodiments 33-36 or 40, comprising: 
     (i) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 553, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 683; 
     (ii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1037, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 1167; 
     (iii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 1038, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 1168; 
     (iv) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 540, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 670; 
     (v) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 3, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 132; 
     (vi) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 527, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 657; 
     (vii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 4, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 133; 
     (viii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 585, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 715; 
     (ix) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 519, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 649; 
     (x) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 584, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 714; 
     (xi) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 524, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 654; or 
     (xii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 530, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 660. 
     42. The dsRNA agent of any of the preceding embodiments, wherein the sense strand is at least 23 nucleotides in length, e.g., 23-30 nucleotides in length. 
     43. The dsRNA agent of any of the preceding embodiments, wherein at least one of the sense strand and the antisense strand is conjugated to one or more lipophilic moieties. 
     44. The dsRNA agent of embodiment 43, wherein the lipophilic moiety is conjugated to one or more positions in the double stranded region of the dsRNA agent. 
     45. The dsRNA agent of embodiment 43 or 44, wherein the lipophilic moiety is conjugated via a linker or carrier. 
     46. The dsRNA agent of any one of embodiments 43-45, wherein lipophilicity of the lipophilic moiety, measured by log Kow, exceeds 0. 
     47. The dsRNA agent of any one of the preceding embodiments, wherein the hydrophobicity of the double-stranded RNAi agent, measured by the unbound fraction in a plasma protein binding assay of the double-stranded RNAi agent, exceeds 0.2. 
     48. The dsRNA agent of embodiment 47, wherein the plasma protein binding assay is an electrophoretic mobility shift assay using human serum albumin protein. 
     49. The dsRNA agent of any of the preceding embodiments, wherein the dsRNA agent comprises at least one modified nucleotide. 
     50. The dsRNA agent of embodiment 49, wherein no more than five of the sense strand nucleotides and not more than five of the nucleotides of the antisense strand are unmodified nucleotides. 
     51. The dsRNA agent of embodiment 50, wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand comprise a modification. 
     52. The dsRNA agent of any one of embodiments 49-51, wherein at least one of the modified nucleotides is selected from the group consisting of a deoxy-nucleotide, a 3′-terminal deoxy-thymine (dT) nucleotide, a 2′-O-methyl modified nucleotide, a 2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an unlocked nucleotide, a conformationally restricted nucleotide, a constrained ethyl nucleotide, an abasic nucleotide, a 2′-amino-modified nucleotide, a 2′-O-allyl-modified nucleotide, 2′-C-alkyl-modified nucleotide, a 2′-methoxyethyl modified nucleotide, a 2′-O-alkyl-modified nucleotide, a morpholino nucleotide, a phosphoramidate, a non-natural base comprising nucleotide, a tetrahydropyran modified nucleotide, a 1,5-anhydrohexitol modified nucleotide, a cyclohexenyl modified nucleotide, a nucleotide comprising a phosphorothioate group, a nucleotide comprising a methylphosphonate group, a nucleotide comprising a 5′-phosphate, a nucleotide comprising a 5′-phosphate mimic, a glycol modified nucleotide, and a 2-O-(N-methylacetamide) modified nucleotide; and combinations thereof. 
     53. The dsRNA agent of any of embodiments 49-51, wherein no more than five of the sense strand nucleotides and not more than five of the nucleotides of the antisense strand include modifications other than 2′-O-methyl modified nucleotide, a 2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, unlocked nucleic acids (UNA) or glycerol nucleic acid (GNA). 
     54. The dsRNA agent of any of the preceding embodiments, which comprises a non-nucleotide spacer (wherein optionally the non-nucleotide spacer comprises a C3-C6 alkyl) between two of the contiguous nucleotides of the sense strand or between two of the contiguous nucleotides of the antisense strand. 
     55. The dsRNA agent of any of the preceding embodiments, wherein each strand is no more than 30 nucleotides in length. 
     56. The dsRNA agent of any of the preceding embodiments, wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide. 
     57. The dsRNA agent of any of the preceding embodiments, wherein at least one strand comprises a 3′ overhang of at least 2 nucleotides. 
     58. The dsRNA agent of any of the preceding embodiments, wherein the double stranded region is 15-30 nucleotide pairs in length. 
     59. The dsRNA agent of embodiment 58, wherein the double stranded region is 17-23 nucleotide pairs in length. 
     60. The dsRNA agent of embodiment 58, wherein the double stranded region is 17-25 nucleotide pairs in length. 
     61. The dsRNA agent of embodiment 58, wherein the double stranded region is 23-27 nucleotide pairs in length. 
     62. The dsRNA agent of embodiment 58, wherein the double stranded region is 19-21 nucleotide pairs in length. 
     63. The dsRNA agent of embodiment 58, wherein the double stranded region is 21-23 nucleotide pairs in length. 
     64. The dsRNA agent of any of the preceding embodiments, wherein each strand has 19-30 nucleotides. 
     65. The dsRNA agent of any of the preceding embodiments, wherein each strand has 19-23 nucleotides. 
     66. The dsRNA agent of any of the preceding embodiments, wherein each strand has 21-23 nucleotides. 
     67. The dsRNA agent of any of the preceding embodiments, wherein the agent comprises at least one phosphorothioate or methylphosphonate internucleotide linkage. 
     68. The dsRNA agent of embodiment 67, wherein the phosphorothioate or methylphosphonate internucleotide linkage is at the 3′-terminus of one strand. 
     69. The dsRNA agent of embodiment 68, wherein the strand is the antisense strand. 
     70. The dsRNA agent of embodiment 68, wherein the strand is the sense strand. 
     71. The dsRNA agent of embodiment 67, wherein the phosphorothioate or methylphosphonate internucleotide linkage is at the 5′-terminus of one strand. 
     72. The dsRNA agent of embodiment 71, wherein the strand is the antisense strand. 
     73. The dsRNA agent of embodiment 71, wherein the strand is the sense strand. 
     74. The dsRNA agent of embodiment 67, wherein each of the 5′- and 3′-terminus of one strand comprises a phosphorothioate or methylphosphonate internucleotide linkage. 
     75. The dsRNA agent of embodiment 74, wherein the strand is the antisense strand. 
     76. The dsRNA agent of any of the preceding embodiments, wherein the base pair at the 1 position of the 5′-end of the antisense strand of the duplex is an AU base pair. 
     77. The dsRNA agent of embodiment 74, wherein the sense strand has a total of 21 nucleotides and the antisense strand has a total of 23 nucleotides. 
     78. The dsRNA agent of any one of embodiments 43-77, wherein one or more lipophilic moieties are conjugated to one or more internal positions on at least one strand. 
     79. The dsRNA agent of embodiment 78, wherein the one or more lipophilic moieties are conjugated to one or more internal positions on at least one strand via a linker or carrier. 
     80. The dsRNA agent of embodiment 79, wherein the internal positions include all positions except the terminal two positions from each end of the at least one strand. 
     81. The dsRNA agent of embodiment 79, wherein the internal positions include all positions except the terminal three positions from each end of the at least one strand. 
     82. The dsRNA agent of any one of embodiments 79-61, wherein the internal positions exclude a cleavage site region of the sense strand. 
     83. The dsRNA agent of embodiment 82, wherein the internal positions include all positions except positions 9-12, counting from the 5′-end of the sense strand. 
     84. The dsRNA agent of embodiment 82, wherein the internal positions include all positions except positions 11-13, counting from the 3′-end of the sense strand. 
     85. The dsRNA agent of any one of embodiments 79-81, wherein the internal positions exclude a cleavage site region of the antisense strand. 
     86. The dsRNA agent of embodiment 85, wherein the internal positions include all positions except positions 12-14, counting from the 5′-end of the antisense strand. 
     87. The dsRNA agent of any one of embodiments 79-81, wherein the internal positions include all positions except positions 11-13 on the sense strand, counting from the 3′-end, and positions 12-14 on the antisense strand, counting from the 5′-end. 
     88. The dsRNA agent of any one of embodiments 43-87, wherein the one or more lipophilic moieties are conjugated to one or more of the internal positions selected from the group consisting of positions 4-8 and 13-18 on the sense strand, and positions 6-10 and 15-18 on the antisense strand, counting from the 5′end of each strand. 
     89. The dsRNA agent of embodiment 88, wherein the one or more lipophilic moieties are conjugated to one or more of the internal positions selected from the group consisting of positions 5, 6, 7, 15, and 17 on the sense strand, and positions 15 and 17 on the antisense strand, counting from the 5′-end of each strand. 
     90. The dsRNA agent of embodiment 44, wherein the positions in the double stranded region exclude a cleavage site region of the sense strand. 
     91. The dsRNA agent of any one of embodiments 43-90, wherein the sense strand is 21 nucleotides in length, the antisense strand is 23 nucleotides in length, and the lipophilic moiety is conjugated to position 21, position 20, position 15, position 1, position 7, position 6, or position 2 of the sense strand or position 16 of the antisense strand. 
     92. The dsRNA agent of embodiment 91, wherein the lipophilic moiety is conjugated to position 21, position 20, position 15, position 1, or position 7 of the sense strand. 
     93. The dsRNA agent of embodiment 91, wherein the lipophilic moiety is conjugated to position 21, position 20, or position 15 of the sense strand. 
     94. The dsRNA agent of embodiment 91, wherein the lipophilic moiety is conjugated to position 20 or position 15 of the sense strand. 
     95. The dsRNA agent of embodiment 91, wherein the lipophilic moiety is conjugated to position 16 of the antisense strand. 
     96. The dsRNA agent of embodiment 91, wherein the lipophilic moiety is conjugated to position 6, counting from the 5′-end of the sense strand. 
     97. The dsRNA agent of any one of embodiments 43-96, wherein the lipophilic moiety is an aliphatic, alicyclic, or polyalicyclic compound. 
     98. The dsRNA agent of embodiment 98, wherein the lipophilic moiety is selected from the group consisting of lipid, cholesterol, retinoic acid, cholic acid, adamantane acetic acid, 1-pyrene butyric acid, dihydrotestosterone, 1,3-bis-O(hexadecyl)glycerol, geranyloxyhexyanol, hexadecylglycerol, borneol, menthol, 1,3-propanediol, heptadecyl group, palmitic acid, myristic acid, O3-(oleoyl)lithocholic acid, O3-(oleoyl)cholenic acid, dimethoxytrityl, or phenoxazine. 
     99. The dsRNA agent of embodiment 98, wherein the lipophilic moiety contains a saturated or unsaturated C4-C30 hydrocarbon chain, and an optional functional group selected from the group consisting of hydroxyl, amine, carboxylic acid, sulfonate, phosphate, thiol, azide, and alkyne. 
     100. The dsRNA agent of embodiment 99, wherein the lipophilic moiety contains a saturated or unsaturated C6-C18 hydrocarbon chain. 
     101. The dsRNA agent of embodiment 99, wherein the lipophilic moiety contains a saturated or unsaturated C16 hydrocarbon chain. 
     102. The dsRNA agent of any one of embodiments 43-101, wherein the lipophilic moiety is conjugated via a carrier that replaces one or more nucleotide(s) in the internal position(s) or the double stranded region. 
     103. The dsRNA agent of embodiment 102, wherein the carrier is a cyclic group selected from the group consisting of pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, [1,3]dioxolanyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, quinoxalinyl, pyridazinonyl, tetrahydrofuranyl, and decalinyl; or is an acyclic moiety based on a serinol backbone or a diethanolamine backbone. 
     104. The dsRNA agent of any one of embodiments 43-101, wherein the lipophilic moiety is conjugated to the double-stranded iRNA agent via a linker containing an ether, thioether, urea, carbonate, amine, amide, maleimide-thioether, disulfide, phosphodiester, sulfonamide linkage, a product of a click reaction, or carbamate. 
     105. The double-stranded iRNA agent of any one of embodiments 43-104, wherein the lipophilic moiety is conjugated to a nucleobase, sugar moiety, or internucleosidic linkage. 
     106. The dsRNA agent of any one of embodiments 43-105, wherein the lipophilic moiety is conjugated via a bio-cleavable linker selected from the group consisting of DNA, RNA, disulfide, amide, functionalized monosaccharides or oligosaccharides of galactosamine, glucosamine, glucose, galactose, mannose, and combinations thereof. 
     107. The dsRNA agent of any one of embodiments 43-106, wherein the 3′ end of the sense strand is protected via an end cap which is a cyclic group having an amine, said cyclic group being selected from the group consisting of pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, [1,3]dioxolanyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, quinoxalinyl, pyridazinonyl, tetrahydrofuranyl, and decalinyl. 
     108. The dsRNA agent of any one of embodiments 43-107, further comprising a targeting ligand, e.g., a ligand that targets an ocular tissue or a liver tissue. 
     109. The dsRNA agent of embodiment 108, wherein the ligand is conjugated to the sense strand. 
     110. The dsRNA agent of embodiment 108 or 109, wherein the ligand is conjugated to the 3′ end or the 5′ end of the sense strand. 
     111. The dsRNA agent of embodiment 108 or 109, wherein the ligand is conjugated to the 3′ end of the sense strand. 
     112. The dsRNA agent of any one of embodiments 108-111, wherein the ocular tissue is a retinal pigment epithelium (RPE) or choroid tissue, e.g., a choroid vessel. 
     113. The dsRNA agent of any one of embodiments 108-111, wherein the targeting ligand comprises N-acetylgalactosamine (GalNAc). 
     114. The dsRNA agent of any one of embodiments 108-111, wherein the targeting ligand is one or more GalNAc conjugates or one or more or GalNAc derivatives. 
     115. The dsRNA agent of embodiment 114, wherein the one or more GalNAc conjugates or one or more GalNAc derivatives are attached through a monovalent linker, or a bivalent, trivalent, or tetravalent branched linker. 
     116. The dsRNA agent of embodiment 114, wherein the ligand is 
     
       
         
         
             
             
         
       
     
     117. The dsRNA agent of embodiment 116, wherein the dsRNA agent is conjugated to the ligand as shown in the following schematic 
     
       
         
         
             
             
         
       
     
     wherein X is O or S. 
     118. The dsRNA agent of embodiment 117, wherein the X is O. 
     119. The dsRNA agent of any one of embodiments 1-118, further comprising a terminal, chiral modification occurring at the first internucleotide linkage at the 3′ end of the antisense strand, having the linkage phosphorus atom in Sp configuration, 
     a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, and 
     a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the sense strand, having the linkage phosphorus atom in either Rp configuration or Sp configuration. 
     120. The dsRNA agent of any one of embodiments 1-118, further comprising 
     a terminal, chiral modification occurring at the first and second internucleotide linkages at the 3′ end of the antisense strand, having the linkage phosphorus atom in Sp configuration, 
     a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, and 
     a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the sense strand, having the linkage phosphorus atom in either Rp or Sp configuration. 
     121. The dsRNA agent of any one of embodiments 1-118, further comprising 
     a terminal, chiral modification occurring at the first, second and third internucleotide linkages at the 3′ end of the antisense strand, having the linkage phosphorus atom in Sp configuration, 
     a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, and 
     a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the sense strand, having the linkage phosphorus atom in either Rp or Sp configuration. 
     122. The dsRNA agent of any one of embodiments 1-118, further comprising 
     a terminal, chiral modification occurring at the first, and second internucleotide linkages at the 3′ end of the antisense strand, having the linkage phosphorus atom in Sp configuration, 
     a terminal, chiral modification occurring at the third internucleotide linkages at the 3′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, 
     a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, and 
     a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the sense strand, having the linkage phosphorus atom in either Rp or Sp configuration. 
     123. The dsRNA agent of any one of embodiments 1-118, further comprising 
     a terminal, chiral modification occurring at the first, and second internucleotide linkages at the 3′ end of the antisense strand, having the linkage phosphorus atom in Sp configuration, 
     a terminal, chiral modification occurring at the first, and second internucleotide linkages at the 5′ end of the antisense strand, having the linkage phosphorus atom in Rp configuration, and 
     a terminal, chiral modification occurring at the first internucleotide linkage at the 5′ end of the sense strand, having the linkage phosphorus atom in either Rp or Sp configuration. 
     124. The dsRNA agent of any one of embodiments 1-123, further comprising a phosphate or phosphate mimic at the 5′-end of the antisense strand. 
     125. The dsRNA agent of embodiment 104, wherein the phosphate mimic is a 5′-vinyl phosphonate (VP). 
     126. A cell containing the dsRNA agent of any one of embodiments 1-125. 
     127. A human ocular cell, e.g., (an RPE cell, an astrocyte, a pericyte, a Müller cell, a ganglion cell, an endothelial cell, or a photoreceptor cell) comprising a reduced level of VEGF-A mRNA or a level of VEGF-A protein as compared to an otherwise similar untreated cell, wherein optionally the level is reduced by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. 
     128. The human cell of embodiment 127, which was produced by a process comprising contacting a human cell with the dsRNA agent of any one of embodiments 1-125. 
     129. A pharmaceutical composition for inhibiting expression of VEGF-A, comprising the dsRNA agent of any one of embodiments 1-125. 
     130. A pharmaceutical composition comprising the dsRNA agent of any one of embodiments 1-125 and a lipid formulation. 
     131. A method of inhibiting expression of VEGF-A in a cell, the method comprising:
         (a) contacting the cell with the dsRNA agent of any one of embodiments 1-125, or a pharmaceutical composition of embodiment 129 or 130; and   (b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of VEGF-A, thereby inhibiting expression of VEGF-A in the cell.       

     132. A method of inhibiting expression of VEGF-A in a cell, the method comprising:
         (a) contacting the cell with the dsRNA agent of any one of embodiments 1-125, or a pharmaceutical composition of embodiment 129 or 130; and   (b) maintaining the cell produced in step (a) for a time sufficient to reduce levels of VEGF-A mRNA, VEGF-A protein, or both of VEGF-A mRNA and protein, thereby inhibiting expression of VEGF-A in the cell.       

     133. The method of embodiment 131 or 132, wherein the cell is within a subject. 
     134. The method of embodiment 133, wherein the subject is a human. 
     135. The method of any one of embodiments 131-134, wherein the level of VEGF-A mRNA is inhibited by at least 50%. 
     136. The method of any one of embodiments 131-134, wherein the level of VEGF-A protein is inhibited by at least 50%. 
     137. The method of embodiment 134-136, wherein inhibiting expression of VEGF-A decreases a VEGF-A protein level in a biological sample (e.g., an aqueous ocular fluid sample) from the subject by at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%. 
     138. The method of any one of embodiments 134-137, wherein the subject has been diagnosed with a VEGF-A-associated disorder, e.g., wet age-related macular degeneration (wet AMD), diabetic retinopathy (DR), diabetic macular edema (DME), retinal vein occlusion (RVO), macular edema following retinal vein occlusion (MEfRVO), retinopathy of prematurity (ROP), or myopic choroidal neovascularization (mCNV). 
     139. A method of inhibiting expression of VEGF-A in an ocular cell or tissue, the method comprising:
         (a) contacting the cell or tissue with a dsRNA agent that binds VEGF-A; and   (b) maintaining the cell or tissue produced in step (a) for a time sufficient to reduce levels of VEGF-A mRNA, VEGF-A protein, or both of VEGF-A mRNA and protein, thereby inhibiting expression of VEGF-A in the cell or tissue.       

     140. The method of embodiment 139, wherein the ocular cell or tissue comprises an RPE cell, a retinal tissue, an astrocyte, a pericyte, a Müller cell, a ganglion cell, an endothelial cell, a photoreceptor cell, a retinal blood vessel (e.g., including endothelial cells and vascular smooth muscle cells), or choroid tissue, e.g., a choroid vessel. 
     141. A method of treating a subject diagnosed with a VEGF-A-associated disorder comprising administering to the subject a therapeutically effective amount of the dsRNA agent of any one of embodiments 1-125 or a pharmaceutical composition of embodiment 129 or 130, thereby treating the disorder. 
     142. The method of embodiment 138 or 141, wherein the VEGF-A-associated disorder is an angiogenic ocular disorder. 
     143. The method of embodiment 142, wherein the angiogenic ocular disorder is selected from the group consisting of AMD, DR, DME, RVO, CVO, MEfRVO, ROP, or mCNV. 
     144. The method of any one of embodiments 141-143, wherein treating comprises amelioration of at least one sign or symptom of the disorder. 
     145. The method of embodiment 144, wherein at least one sign or symptom of the angiogenic ocular disorder comprises a measure of one or more of angiogenesis, choroidal neovascularization, ocular inflammation, visual acuity, or presence, level, or activity of VEGF-A (e.g., VEGF-A gene, VEGF-A mRNA, or VEGF-A protein). 
     146. The method of any one of embodiments 141-143, where treating comprises prevention of progression of the disorder. 
     147. The method of any one of embodiments 144-146, wherein the treating comprises one or more of (a) inhibiting angiogenesis; (b) inhibiting or reducing the expression or activity of VEGF-A; (c) inhibiting choroidal neovascularization; (d) inhibiting growth of new blood vessels in the choriocapillaris; (e) reducing retinal thickness; (f) increasing visual acuity; or (g) reducing intraocular inflammation. 
     148. The method of embodiment 147, wherein the treating results in at least a 30% mean reduction from baseline of VEGF mRNA in the retina, RPE, a retinal blood vessel (e.g., including endothelial cells and vascular smooth muscle cells), or choroid tissue, e.g., a choroid vessel. 
     149. The method of embodiment 148 wherein the treating results in at least a 60% mean reduction from baseline of VEGF mRNA in the retina, RPE, a retinal blood vessel (e.g., including endothelial cells and vascular smooth muscle cells), or choroid tissue, e.g., a choroid vessel. 
     150. The method of embodiment 149, wherein the treating results in at least a 90% mean reduction from baseline of VEGF mRNA in the retina, RPE, a retinal blood vessel (e.g., including endothelial cells and vascular smooth muscle cells), or choroid tissue, e.g., a choroid vessel. 
     151. The method of any one of embodiments 144-149, wherein after treatment the subject experiences at least an 8-week duration of knockdown following a single dose of dsRNA as assessed by VEGF-A protein in the retina. 
     152. The method of embodiment 151, wherein treating results in at least a 12-week duration of knockdown following a single dose of dsRNA as assessed by VEGF-A protein in the retina. 
     153. The method of embodiment 152, wherein treating results in at least a 16-week duration of knockdown following a single dose of dsRNA as assessed by VEGF-A protein in the retina. 
     154. The method of any of embodiments 133-153, wherein the subject is human. 
     155. The method of any one of embodiments 134-154, wherein the dsRNA agent is administered at a dose of about 0.01 mg/kg to about 50 mg/kg. 
     156. The method of any one of embodiments 134-155, wherein the dsRNA agent is administered to the subject intraocularly, intravenously, or topically. 
     157. The method of embodiment 156, wherein the intraocular administration comprises intravitreal administration (e.g., intravitreal injection), transscleral administration (e.g., transscleral injection), subconjunctival administration (e.g., subconjunctival injection), retrobulbar administration (e.g., retrobulbar injection), intracameral administration (e.g., intracameral injection), or subretinal administration (e.g., subretinal injection). 
     158. The method of any one of embodiments 134-157, further comprising measuring level of VEGF-A (e.g., VEGF-A gene, VEGF-A mRNA, or VEGF-A protein) in the subject. 
     159. The method of embodiment 158, where measuring the level of VEGF-A in the subject comprises measuring the level of VEGF-A gene, VEGF-A protein or VEGF-A mRNA in a biological sample from the subject (e.g., an aqueous ocular fluid sample). 
     160. The method of any one of embodiments 134-159, further comprising performing a blood test, an imaging test, or an aqueous ocular fluid biopsy. 
     161. The method of any one of embodiments 158-168, wherein measuring level of VEGF-A (e.g., VEGF-A gene, VEGF-A mRNA, or VEGF-A protein) in the subject is performed prior to treatment with the dsRNA agent or the pharmaceutical composition. 
     162. The method of embodiment 161, wherein, upon determination that a subject has a level of VEGF-A (e.g., VEGF-A gene, VEGF-A mRNA, or VEGF-A protein) that is greater than a reference level, the dsRNA agent or the pharmaceutical composition is administered to the subject. 
     163. The method of any one of embodiments 159-162, wherein measuring level of VEGF-A (e.g., VEGF-A gene, VEGF-A mRNA, or VEGF-A protein) in the subject is performed after treatment with the dsRNA agent or the pharmaceutical composition. 
     164. The method of any one of embodiments 141-163, further comprising administering to the subject an additional agent and/or therapy suitable for treatment or prevention of an VEGF-A-associated disorder. 
     165. The method of embodiment 164, wherein the additional agent and/or therapy comprises one or more of a photodynamic therapy, photocoagulation therapy, a steroid, a non-steroidal anti-inflammatory agent, an anti-VEGF-A agent, and/or a vitrectomy. 
     166. The method of embodiment 165, wherein the anti-VEGF-A agent is a fusion protein or an anti-VEGF-A antibody or antigen-binding fragment thereof (e.g., an anti-VEGF-A antibody molecule). 
     EXAMPLES 
     Example 1. VEGF-A siRNA 
     Nucleic acid sequences provided herein are represented using standard nomenclature. See the abbreviations of Table 1. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Abbreviations of nucleotide monomers used in nucleic acid sequence representation 
               
               
                 It will be understood that these monomers, when present in an oligonucleotide, are mutually 
               
               
                 linked by 5′-3′-phosphodiester bonds. 
               
            
           
           
               
               
               
            
               
                   
                 Abbreviation 
                 Nucleotide(s) 
               
               
                   
                   
               
               
                   
                 A 
                 Adenosine-3′-phosphate 
               
               
                   
                 Ab 
                 beta-L-adenosine-3′-phosphate 
               
               
                   
                 Abs 
                 beta-L-adenosine-3′-phosphorothioate 
               
               
                   
                 Af 
                 2′-fluoroadenosine-3′-phosphate 
               
               
                   
                 Afs 
                 2′-fluoroadenosine-3′-phosphorothioate 
               
               
                   
                 (Ahd) 
                 2′-O-hexadecyl-adenosine-3′-phosphate 
               
               
                   
                 (Ahds) 
                 2′-O-hexadecyl-adenosine-3′-phosphorothioate 
               
               
                   
                 As 
                 adenosine-3′-phosphorothioate 
               
               
                   
                 (A2p) 
                 adenosine 2′-phosphate 
               
               
                   
                 C 
                 cytidine-3′-phosphate 
               
               
                   
                 Cb 
                 beta-L-cytidine-3′-phosphate 
               
               
                   
                 Cbs 
                 beta-L-cytidine-3′-phosphorothioate 
               
               
                   
                 Cf 
                 2′-fluorocytidine-3′-phosphate 
               
               
                   
                 Cfs 
                 2′-fluorocytidine-3′-phosphorothioate 
               
               
                   
                 (Chd) 
                 2’-O-hexadecyl-cytidine-3’-phosphate 
               
               
                   
                 (Chds) 
                 2’-O-hexadecyl-cytidine-3’-phosphorothioate 
               
               
                   
                 Cs 
                 cytidine-3′-phosphorothioate 
               
               
                   
                 (C2p) 
                 cytosine 2′-phosphate 
               
               
                   
                 G 
                 guanosine-3′-phosphate 
               
               
                   
                 Gb 
                 beta-L-guanosine-3′-phosphate 
               
               
                   
                 Gbs 
                 beta-L-guanosine-3′-phosphorothioate 
               
               
                   
                 Gf 
                 2′-fluoroguanosine-3′-phosphate 
               
               
                   
                 Gfs 
                 2′-fluoroguanosine-3′-phosphorothioate 
               
               
                   
                 (Ghd) 
                 2′-O-hexadecyl-guanosine-3′-phosphate 
               
               
                   
                 (Ghds) 
                 2′-O-hexadecyl-guanosine-3′-phosphorothioate 
               
               
                   
                 Gs 
                 guanosine-3′-phosphorothioate 
               
               
                   
                 T 
                 5′-methyluridine-3′-phosphate 
               
               
                   
                 Tb 
                 beta-L-thymidine-3′-phosphate 
               
               
                   
                 Tbs 
                 beta-L-thymidine-3′-phosphorothioate 
               
               
                   
                 Tf 
                 2′-fluoro-5-methyluridine-3′-phosphate 
               
               
                   
                 Tfs 
                 2′-fluoro-5-methyluridine-3′-phosphorothioate 
               
               
                   
                 Tgn 
                 thymidine-glycol nucleic acid (GNA) S-Isomer 
               
               
                   
                 Agn 
                 adenosine-glycol nucleic acid (GNA) S-Isomer 
               
               
                   
                 Cgn 
                 cytidine-glycol nucleic acid (GNA) S-Isomer 
               
               
                   
                 Ggn 
                 guanosine-glycol nucleic acid (GNA) S-Isomer 
               
               
                   
                 Ts 
                 5-methyluridine-3′-phosphorothioate 
               
               
                   
                 U 
                 Uridine-3′-phosphate 
               
               
                   
                 Ub 
                 beta-L-uridine-3′-phosphate 
               
               
                   
                 Ubs 
                 beta-L-uridine-3′-phosphorothioate 
               
               
                   
                 Uf 
                 2′-fluorouridine-3′-phosphate 
               
               
                   
                 Ufs 
                 2′-fluorouridine-3′-phosphorothioate 
               
               
                   
                 (Uhd) 
                 2′-O-hexadecyl-uridine-3′-phosphate 
               
               
                   
                 (Uhds) 
                 2′-O-hexadecyl-uridine-3′-phosphorothioate 
               
               
                   
                 Us 
                 uridine-3′-phosphorothioate 
               
               
                   
                 (U2p) 
                 uracil 2′-phosphate 
               
               
                   
                 N 
                 any nucleotide (G, A, C, T or U) 
               
               
                   
                 VP 
                 Vinyl phosphonate 
               
               
                   
                 a 
                 2′-O-methyladenosine-3′-phosphate 
               
               
                   
                 as 
                 2′-O-methyladenosine-3′-phosphorothioate 
               
               
                   
                 c 
                 2′-O-methylcytidine-3′-phosphate 
               
               
                   
                 cs 
                 2′-O-methylcytidine-3′-phosphorothioate 
               
               
                   
                 g 
                 2′-O-methylguanosine-3′-phosphate 
               
               
                   
                 gs 
                 2′-O-methylguanosine-3′-phosphorothioate 
               
               
                   
                 t 
                 2′-O-methyl-5-methyluridine-3′-phosphate 
               
               
                   
                 ts 
                 2′-O-methyl-5-methyluridine-3′-phosphorothioate 
               
               
                   
                 u 
                 2′-O-methyluridine-3′-phosphate 
               
               
                   
                 us 
                 2′-O-methyluridine-3′-phosphorothioate 
               
               
                   
                 dA 
                 2′-deoxyadenosine-3′-phosphate 
               
               
                   
                 dAs 
                 2′-deoxyadenosine-3′-phosphorothioate 
               
               
                   
                 dC 
                 2′-deoxycytidine-3′-phosphate 
               
               
                   
                 dCs 
                 2′-deoxycytidine-3′-phosphorothioate 
               
               
                   
                 dG 
                 2′-deoxyguanosine-3′-phosphate 
               
               
                   
                 dGs 
                 2′-deoxyguanosine-3′-phosphorothioate 
               
               
                   
                 dT 
                 2′-deoxythymidine 
               
               
                   
                 dTs 
                 2′-deoxythymidine-3′-phosphorothioate 
               
               
                   
                 dU 
                 2′-deoxyuridine 
               
               
                   
                 s 
                 phosphorothioate linkage 
               
               
                   
                 L96 1   
                 N-[tris(GalNAc-alkyl)-amidodecanoyl)]-4-hydroxyprolinol 
               
               
                   
                   
                 Hyp-(GalNAc-alkyl)3 
               
               
                   
                 (Aeo) 
                 2′-O-methoxyethyladenosine-3′-phosphate 
               
               
                   
                 (Aeos) 
                 2′-O-methoxyethyladenosine-3′-phosphorothioate 
               
               
                   
                 (Geo) 
                 2′-O-methoxyethylguanosine-3′-phosphate 
               
               
                   
                 (Geos) 
                 2′-O-methoxyethylguanosine-3′-phosphorothioate 
               
               
                   
                 (Teo) 
                 2′-O-methoxyethyl-5-methyluridine-3′-phosphate 
               
               
                   
                 (Teos) 
                 2′-O-methoxyethyl-5-methyluridine-3′-phosphorothioate 
               
               
                   
                 (m5Ceo) 
                 2′-O-methoxyethyl-5-methylcytidine-3′-phosphate 
               
               
                   
                 (m5Ceos) 
                 2′-O-methoxyethyl-5-methylcytidine-3′-phosphorothioate 
               
               
                   
                   
               
               
                   
                   1 The chemical structure of L96 is as follows: 
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
            
           
         
       
     
     Experimental Methods 
     Bioinformatics 
     Transcripts 
     Three sets of siRNAs targeting the human VEGF-A, “vascular endothelial growth factor A” (human: NCBI refseqID NM_001171623; NCBI GeneID: 7422) were generated. The human NM_001171623 REFSEQ mRNA, version 1, has a length of 3677 bases. Pairs of oligos were generated using bioinformatic methods and ranked, and exemplary pairs of oligos are shown in Table 2A, Table 2B, Table 3A, Table 3B, Table 4A, Table 4B, Table 8A, Table 8B, Table 10A, Table 10B, Table 18A, and Table 18B. Modified sequences are presented in Table 2A, Table 3A, Table 4A, Table 8A, Table 10A, Table 18A. Unmodified sequences are presented in Table 2B, Table 3B, Table 4B, Table 8B, Table 10B, Table 18B. 
     Similarly, a set of siRNAs targeting rat VEGF-A (rat: NCBI refseqID NM_001110333; NCBI GeneID 83785 were generated. The rat NM_001110333.2REFSEQ mRNA, version 2, has a length of 3474 base pairs. Pairs of oligos were generated using bioinformatic methods and ranked, and exemplary pairs of oligos are shown in Table 5A and Table 5B. Modified sequences are presented in Table 5A. Unmodified sequences are presented in Table 5B. 
     
       
         
           
               
             
               
                 TABLE 2A 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Modified Single Strands and Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 SEQ 
                   
                   
                   
               
               
                   
                   
                   
                   
                 Anti- 
                 ID 
                   
                   
                 SEQ ID 
               
               
                   
                 Sense 
                 SEQ 
                   
                 sense 
                 NO: 
                   
                   
                 NO: 
               
               
                 Duplex 
                 Oligo 
                 ID NO: 
                   
                 Oligo 
                 (Anti- 
                   
                 mRNA target 
                 (mRNA 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Name 
                 sense) 
                 Antisense Sequence 
                 sequence 
                 target) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 AD- 
                 A- 
                 4156 
                 asasgac(Uhd)GfaUfAfCfag 
                 A- 
                 130 
                 VPusGfsaucg(Tgn)ucu 
                 GAAAGACUGAUA 
                 4224 
               
               
                 901349.1 
                 1701255. 
                   
                 aacgaucaL96 
                 1701256. 
                   
                 guaUfcAfgucuususc 
                 CAGAACGAUCG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4157 
                 ascsggu(Ahd)CfuUfAfUfuu 
                 A- 
                 131 
                 VPusGfsgaua(Tgn)uaa 
                 AUACGGUACUUA 
                 4225 
               
               
                 901376.1 
                 1701309. 
                   
                 aauauccaL96 
                 1701310. 
                   
                 auaAfgUfaccgusasu 
                 UUUAAUAUCCC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3 
                 csasgaa(Chd)AfgUfCfCfuu 
                 A- 
                 132 
                 VPusCfsugga(Tgn)uaa 
                 GACAGAACAGUCC 
                 4226 
               
               
                 901356.1 
                 1701269. 
                   
                 aauccagaL96 
                 1701270. 
                   
                 ggaCfuGfuucugsusc 
                 UUAAUCCAGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4 
                 csgsaca(Ghd)AfaCfAfGfuc 
                 A- 
                 133 
                 VPusGfsauua(Agn)gg 
                 AUCGACAGAACAG 
                 4227 
               
               
                 901355.1 
                 1701267. 
                   
                 cuuaaucaL96 
                 1701268. 
                   
                 acugUfuCfugucgsasu 
                 UCCUUAAUCC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5 
                 gscsauu(Uhd)GfuUfUfGfua 
                 A- 
                 134 
                 VPusGfsaucu(Tgn)gua 
                 AAGCAUUUGUUU 
                 4228 
               
               
                 901407.1 
                 1701371. 
                   
                 caagaucaL96 
                 1701372. 
                   
                 caaAfcAfaaugcsusu 
                 GUACAAGAUCC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 6 
                 usasuug(Ghd)UfgUfCfUfuc 
                 A- 
                 135 
                 VPusAfsucca(Ggn)ug 
                 GUUAUUGGUGUC 
                 4229 
               
               
                 901367.1 
                 1701291. 
                   
                 acuggauaL96 
                 1701292. 
                   
                 aagaCfaCfcaauasasc 
                 UUCACUGGAUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 7 
                 ascsuga(Uhd)AfcAfGfAfac 
                 A- 
                 136 
                 VPusAfsucga(Tgn)cgu 
                 AGACUGAUACAG 
                 4230 
               
               
                 901352.1 
                 1701261. 
                   
                 gaucgauaL96 
                 1701262. 
                   
                 ucuGfuAfucaguscsu 
                 AACGAUCGAUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 8 
                 asasaga(Chd)UfgAfUfAfca 
                 A- 
                 137 
                 VPusAfsucgu(Tgn)cu 
                 GGAAAGACUGAU 
                 4231 
               
               
                 901348.1 
                 1701253. 
                   
                 gaacgauaL96 
                 1701254. 
                   
                 guauCfaGfucuuuscsc 
                 ACAGAACGAUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 9 
                 asusaca(Ghd)AfaCfGfAfuc 
                 A- 
                 138 
                 VPusCfsugua(Tgn)cga 
                 UGAUACAGAACG 
                 4232 
               
               
                 901354.1 
                 1701265. 
                   
                 gauacagaL96 
                 1701266. 
                   
                 ucgUfuCfuguauscsa 
                 AUCGAUACAGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 10 
                 csusgau(Ahd)CfaGfAfAfcg 
                 A- 
                 139 
                 VPusUfsaucg(Agn)uc 
                 GACUGAUACAGA 
                 4233 
               
               
                 901353.1 
                 1701263. 
                   
                 aucgauaaL96 
                 1701264. 
                   
                 guucUfgUfaucagsusc 
                 ACGAUCGAUAC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 11 
                 gsasgaa(Ahd)GfuGfUfUfuu 
                 A- 
                 140 
                 VPusCfsguau(Agn)ua 
                 AAGAGAAAGUGU 
                 4234 
               
               
                 901375.1 
                 1701307. 
                   
                 auauacgaL96 
                 1701308. 
                   
                 aaacAfcUfuucucsusu 
                 UUUAUAUACGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 12 
                 ascsgaa(Chd)GfuAfCfUfug 
                 A- 
                 141 
                 VPusAfscauc(Tgn)gca 
                 AAACGAACGUACU 
                 4235 
               
               
                 901345.1 
                 1701247. 
                   
                 cagauguaL96 
                 1701248. 
                   
                 aguAfcGfuucgususu 
                 UGCAGAUGUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 13 
                 csusugg(Ahd)AfuUfGfGfa 
                 A- 
                 142 
                 VPusAfsuggc(Ggn)aa 
                 CUCUUGGAAUUG 
                 4236 
               
               
                 901357.1 
                 1701271. 
                   
                 uucgccauaL96 
                 1701272. 
                   
                 uccaAfuUfccaagsasg 
                 GAUUCGCCAUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 14 
                 gsgscag(Chd)UfuGfAfGfuu 
                 A- 
                 143 
                 VPusUfsucgu(Tgn)uaa 
                 GAGGCAGCUUGA 
                 4237 
               
               
                 901334.1 
                 1701225. 
                   
                 aaacgaaaL96 
                 1701226. 
                   
                 cucAfaGfcugccsusc 
                 GUUAAACGAAC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 15 
                 gsgsgca(Ghd)AfaUfCfAfuc 
                 A- 
                 144 
                 VPusAfscuuc(Ggn)ug 
                 GAGGGCAGAAUC 
                 4238 
               
               
                 901313.1 
                 1701183. 
                   
                 acgaaguaL96 
                 1701184. 
                   
                 augaUfuCfugcccsusc 
                 AUCACGAAGUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 16 
                 ususaaa(Chd)GfaAfCfGfua 
                 A- 
                 145 
                 VPusCfsugca(Agn)gu 
                 AGUUAAACGAAC 
                 4239 
               
               
                 901344.1 
                 1701245. 
                   
                 cuugcagaL96 
                 1701246. 
                   
                 acguUfcGfuuuaascsu 
                 GUACUUGCAGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 17 
                 gsusuau(Uhd)GfgUfGfUfc 
                 A- 
                 146 
                 VPusCfscagu(Ggn)aag 
                 AUGUUAUUGGUG 
                 4240 
               
               
                 901366.1 
                 1701289. 
                   
                 uucacuggaL96 
                 1701290. 
                   
                 acaCfcAfauaacsasu 
                 UCUUCACUGGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 18 
                 asgscuu(Ghd)AfgUfUfAfaa 
                 A- 
                 147 
                 VPusAfscguu(Cgn)gu 
                 GCAGCUUGAGUU 
                 4241 
               
               
                 901337.1 
                 1701231. 
                   
                 cgaacguaL96 
                 1701232. 
                   
                 uuaaCfuCfaagcusgsc 
                 AAACGAACGUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 19 
                 gscsagc(Uhd)UfgAfGfUfua 
                 A- 
                 148 
                 VPusGfsuucg(Tgn)uu 
                 AGGCAGCUUGAG 
                 4242 
               
               
                 901335.1 
                 1701227. 
                   
                 aacgaacaL96 
                 1701228. 
                   
                 aacuCfaAfgcugcscsu 
                 UUAAACGAACG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 20 
                 csgsaag(Uhd)GfgUfGfAfag 
                 A- 
                 149 
                 VPusCfscaug(Agn)acu 
                 CACGAAGUGGUG 
                 4243 
               
               
                 901398.1 
                 1701353. 
                   
                 uucauggaL96 
                 1701354. 
                   
                 ucaCfcAfcuucgsusg 
                 AAGUUCAUGGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 21 
                 csasgaa(Uhd)CfaUfCfAfcg 
                 A- 
                 150 
                 VPusAfsccac(Tgn)ucg 
                 GGCAGAAUCAUCA 
                 4244 
               
               
                 901314.1 
                 1701185. 
                   
                 aagugguaL96 
                 1701186. 
                   
                 ugaUfgAfuucugscsc 
                 CGAAGUGGUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 22 
                 asasaau(Ahd)GfaCfAfUfug 
                 A- 
                 151 
                 VPusAfsgaau(Agn)gc 
                 AUAAAAUAGACA 
                 4245 
               
               
                 901386.1 
                 1701329. 
                   
                 cuauucuaL96 
                 1701330. 
                   
                 aaugUfcUfauuuusasu 
                 UUGCUAUUCUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 23 
                 csasgcu(Uhd)GfaGfUfUfaa 
                 A- 
                 152 
                 VPusCfsguuc(Ggn)uu 
                 GGCAGCUUGAGU 
                 4246 
               
               
                 901336.1 
                 1701229. 
                   
                 acgaacgaL96 
                 1701230. 
                   
                 uaacUfcAfagcugscsc 
                 UAAACGAACGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 24 
                 csgscac(Uhd)GfaAfAfCfuu 
                 A- 
                 153 
                 VPusGfsgacg(Agn)aaa 
                 GUCGCACUGAAAC 
                 4247 
               
               
                 901310.1 
                 1701177. 
                   
                 uucguccaL96 
                 1701178. 
                   
                 guuUfcAfgugcgsasc 
                 UUUUCGUCCA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 25 
                 asgsauu(Ahd)UfgCfGfGfau 
                 A- 
                 154 
                 VPusAfsgguu(Tgn)ga 
                 GCAGAUUAUGCG 
                 4248 
               
               
                 901321.1 
                 1701199. 
                   
                 caaaccuaL96 
                 1701200. 
                   
                 uccgCfaUfaaucusgsc 
                 GAUCAAACCUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 26 
                 gscsucu(Chd)UfuAfUfUfug 
                 A- 
                 155 
                 VPusAfsccgg(Tgn)aca 
                 UUGCUCUCUUAUU 
                 4249 
               
               
                 901382.1 
                 1701321. 
                   
                 uaccgguaL96 
                 1701322. 
                   
                 aauAfaGfagagcsasa 
                 UGUACCGGUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 27 
                 usgsaca(Ghd)UfcAfCfUfag 
                 A- 
                 156 
                 VPusAfsgaua(Agn)gc 
                 GGUGACAGUCACU 
                 4250 
               
               
                 901384.1 
                 1701325. 
                   
                 cuuaucuaL96 
                 1701326. 
                   
                 uaguGfaCfugucascsc 
                 AGCUUAUCUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 28 
                 csusuga(Ghd)UfuAfAfAfcg 
                 A- 
                 157 
                 VPusGfsuacg(Tgn)ucg 
                 AGCUUGAGUUAA 
                 4251 
               
               
                 901339.1 
                 1701235. 
                   
                 aacguacaL96 
                 1701236. 
                   
                 uuuAfaCfucaagscsu 
                 ACGAACGUACU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 29 
                 asgsugc(Uhd)AfaUfGfUfua 
                 A- 
                 158 
                 VPusAfscacc(Agn)aua 
                 ACAGUGCUAAUG 
                 4252 
               
               
                 901363.1 
                 1701283. 
                   
                 uugguguaL96 
                 1701284. 
                   
                 acaUfuAfgcacusgsu 
                 UUAUUGGUGUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 30 
                 asusccg(Chd)AfgAfCfGfug 
                 A- 
                 159 
                 VPusAfscauu(Tgn)aca 
                 AGAUCCGCAGACG 
                 4253 
               
               
                 901325.1 
                 1701207. 
                   
                 uaaauguaL96 
                 1701208. 
                   
                 cguCfuGfcggauscsu 
                 UGUAAAUGUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 31 
                 asgsacu(Ghd)AfuAfCfAfga 
                 A- 
                 160 
                 VPusCfsgauc(Ggn)uu 
                 AAAGACUGAUAC 
                 4254 
               
               
                 901350.1 
                 1701257. 
                   
                 acgaucgaL96 
                 1701258. 
                   
                 cuguAfuCfagucususu 
                 AGAACGAUCGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 32 
                 usgsuua(Uhd)UfgGfUfGfu 
                 A- 
                 161 
                 VPusCfsagug(Agn)ag 
                 AAUGUUAUUGGU 
                 4255 
               
               
                 901365.1 
                 1701287. 
                   
                 cuucacugaL96 
                 1701288. 
                   
                 acacCfaAfuaacasusu 
                 GUCUUCACUGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 33 
                 gsusgcu(Ghd)GfaAfUfUfu 
                 A- 
                 162 
                 VPusUfsgaau(Agn)uc 
                 CGGUGCUGGAAU 
                 4256 
               
               
                 901306.1 
                 1701169. 
                   
                 gauauucaaL96 
                 1701170. 
                   
                 aaauUfcCfagcacscsg 
                 UUGAUAUUCAU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 34 
                 ususgcu(Ghd)CfuAfAfAfuc 
                 A- 
                 163 
                 VPusGfscucg(Ggn)ug 
                 UCUUGCUGCUAAA 
                 4257 
               
               
                 901361.1 
                 1701279. 
                   
                 accgagcaL96 
                 1701280. 
                   
                 auuuAfgCfagcaasgsa 
                 UCACCGAGCC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 35 
                 csascca(Uhd)GfcAfGfAfuu 
                 A- 
                 164 
                 VPusUfsccgc(Agn)uaa 
                 AUCACCAUGCAGA 
                 4258 
               
               
                 901320.1 
                 1701197. 
                   
                 augcggaaL96 
                 1701198. 
                   
                 ucuGfcAfuggugsasu 
                 UUAUGCGGAU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 36 
                 gsasaag(Chd)AfuUfUfGfuu 
                 A- 
                 165 
                 VPusUfsugua(Cgn)aaa 
                 GAGAAAGCAUUU 
                 4259 
               
               
                 901405.1 
                 1701367. 
                   
                 uguacaaaL96 
                 1701368. 
                   
                 caaAfuGfcuuucsusc 
                 GUUUGUACAAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 37 
                 gscsuug(Ahd)GfuUfAfAfac 
                 A- 
                 166 
                 VPusUfsacgu(Tgn)cgu 
                 CAGCUUGAGUUA 
                 4260 
               
               
                 901338.1 
                 1701233. 
                   
                 gaacguaaL96 
                 1701234. 
                   
                 uuaAfcUfcaagcsusg 
                 AACGAACGUAC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 38 
                 uscsggu(Ghd)AfcAfGfUfca 
                 A- 
                 167 
                 VPusAfsagcu(Agn)gu 
                 GAUCGGUGACAG 
                 4261 
               
               
                 901383.1 
                 1701323. 
                   
                 cuagcuuaL96 
                 1701324. 
                   
                 gacuGfuCfaccgasusc 
                 UCACUAGCUUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 39 
                 asgsgca(Ghd)CfuUfGfAfgu 
                 A- 
                 168 
                 VPusUfscguu(Tgn)aac 
                 CGAGGCAGCUUGA 
                 4262 
               
               
                 901333.1 
                 1701223. 
                   
                 uaaacgaaL96 
                 1701224. 
                   
                 ucaAfgCfugccuscsg 
                 GUUAAACGAA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 40 
                 csusgca(Ahd)AfaAfCfAfca 
                 A- 
                 169 
                 VPusGfscgag(Tgn)cug 
                 UCCUGCAAAAACA 
                 4263 
               
               
                 901330.1 
                 1701217. 
                   
                 gacucgcaL96 
                 1701218. 
                   
                 uguUfuUfugcagsgsa 
                 CAGACUCGCG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 41 
                 csusugc(Uhd)GfcUfAfAfau 
                 A- 
                 170 
                 VPusCfsucgg(Tgn)gau 
                 UUCUUGCUGCUAA 
                 4264 
               
               
                 901360.1 
                 1701277. 
                   
                 caccgagaL96 
                 1701278. 
                   
                 uuaGfcAfgcaagsasa 
                 AUCACCGAGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 42 
                 ususcuu(Ghd)CfuGfCfUfaa 
                 A- 
                 171 
                 VPusCfsggug(Agn)uu 
                 UUUUCUUGCUGCU 
                 4265 
               
               
                 901358.1 
                 1701273. 
                   
                 aucaccgaL96 
                 1701274. 
                   
                 uagcAfgCfaagaasasa 
                 AAAUCACCGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 43 
                 asasagc(Ahd)UfuUfGfUfuu 
                 A- 
                 172 
                 VPusCfsuugu(Agn)ca 
                 AGAAAGCAUUUG 
                 4266 
               
               
                 901406.1 
                 1701369. 
                   
                 guacaagaL96 
                 1701370. 
                   
                 aacaAfaUfgcuuuscsu 
                 UUUGUACAAGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 44 
                 uscscgc(Ahd)GfaCfGfUfgu 
                 A- 
                 173 
                 VPusAfsacau(Tgn)uac 
                 GAUCCGCAGACGU 
                 4267 
               
               
                 901326.1 
                 1701209. 
                   
                 aaauguuaL96 
                 1701210. 
                   
                 acgUfcUfgcggasusc 
                 GUAAAUGUUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 45 
                 csgsgua(Chd)UfuAfUfUfua 
                 A- 
                 174 
                 VPusGfsggau(Agn)uu 
                 UACGGUACUUAU 
                 4268 
               
               
                 901377.1 
                 1701311. 
                   
                 auaucccaL96 
                 1701312. 
                   
                 aaauAfaGfuaccgsusa 
                 UUAAUAUCCCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 46 
                 gsascug(Ahd)UfaCfAfGfaa 
                 A- 
                 175 
                 VPusUfscgau(Cgn)gu 
                 AAGACUGAUACA 
                 4269 
               
               
                 901351.1 
                 1701259. 
                   
                 cgaucgaaL96 
                 1701260. 
                   
                 ucugUfaUfcagucsusu 
                 GAACGAUCGAU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 47 
                 asasaac(Ahd)CfaGfAfCfuc 
                 A- 
                 176 
                 VPusGfscaac(Ggn)cga 
                 CAAAAACACAGAC 
                 4270 
               
               
                 901415.1 
                 1701387. 
                   
                 gcguugcaL96 
                 1701388. 
                   
                 gucUfgUfguuuususg 
                 UCGCGUUGCA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 48 
                 gsasguu(Ahd)AfaCfGfAfac 
                 A- 
                 177 
                 VPusCfsaagu(Agn)cg 
                 UUGAGUUAAACG 
                 4271 
               
               
                 901342.1 
                 1701241. 
                   
                 guacuugaL96 
                 1701242. 
                   
                 uucgUfuUfaacucsasa 
                 AACGUACUUGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 49 
                 uscsacu(Ghd)GfaUfGfUfau 
                 A- 
                 178 
                 VPusCfsaguc(Agn)aau 
                 CUUCACUGGAUGU 
                 4272 
               
               
                 901420.1 
                 1701397. 
                   
                 uugacugaL96 
                 1701398. 
                   
                 acaUfcCfagugasasg 
                 AUUUGACUGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 50 
                 cscsucc(Ghd)AfaAfCfCfau 
                 A- 
                 179 
                 VPusAfsaagu(Tgn)cau 
                 GGCCUCCGAAACC 
                 4273 
               
               
                 901312.1 
                 1701181. 
                   
                 gaacuuuaL96 
                 1701182. 
                   
                 gguUfuCfggaggscsc 
                 AUGAACUUUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 51 
                 ususgag(Uhd)UfaAfAfCfga 
                 A- 
                 180 
                 VPusAfsguac(Ggn)uu 
                 GCUUGAGUUAAA 
                 4274 
               
               
                 901340.1 
                 1701237. 
                   
                 acguacuaL96 
                 1701238. 
                   
                 cguuUfaAfcucaasgsc 
                 CGAACGUACUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 52 
                 usgscua(Chd)UfgUfUfUfau 
                 A- 
                 181 
                 VPusAfsuuac(Ggn)ga 
                 GGUGCUACUGUU 
                 4275 
               
               
                 901392.1 
                 1701341. 
                   
                 ccguaauaL96 
                 1701342. 
                   
                 uaaaCfaGfuagcascsc 
                 UAUCCGUAAUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 53 
                 cscsgca(Ghd)AfcGfUfGfua 
                 A- 
                 182 
                 VPusGfsaaca(Tgn)uua 
                 AUCCGCAGACGUG 
                 4276 
               
               
                 901327.1 
                 1701211. 
                   
                 aauguucaL96 
                 1701212. 
                   
                 cacGfuCfugcggsasu 
                 UAAAUGUUCC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 54 
                 csgscag(Ahd)CfgUfGfUfaa 
                 A- 
                 183 
                 VPusGfsgaac(Agn)uu 
                 UCCGCAGACGUGU 
                 4277 
               
               
                 901328.1 
                 1701213. 
                   
                 auguuccaL96 
                 1701214. 
                   
                 uacaCfgUfcugcgsgsa 
                 AAAUGUUCCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 55 
                 asgsaga(Ahd)GfaGfAfCfac 
                 A- 
                 184 
                 VPusCfsaaca(Agn)ugu 
                 GAAGAGAAGAGA 
                 4278 
               
               
                 901370.1 
                 1701297. 
                   
                 auuguugaL96 
                 1701298. 
                   
                 gucUfcUfucucususc 
                 CACAUUGUUGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 56 
                 ascsagc(Ahd)CfaAfCfAfaa 
                 A- 
                 185 
                 VPusAfsuuca(Cgn)au 
                 CUACAGCACAACA 
                 4279 
               
               
                 901399.1 
                 1701355. 
                   
                 ugugaauaL96 
                 1701356. 
                   
                 uuguUfgUfgcugusasg 
                 AAUGUGAAUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 57 
                 uscsuug(Chd)UfgCfUfAfaa 
                 A- 
                 186 
                 VPusUfscggu(Ggn)au 
                 UUUCUUGCUGCUA 
                 4280 
               
               
                 901359.1 
                 1701275. 
                   
                 ucaccgaaL96 
                 1701276. 
                   
                 uuagCfaGfcaagasasa 
                 AAUCACCGAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 58 
                 ascsacc(Ahd)UfuGfAfAfac 
                 A- 
                 187 
                 VPusAfscuag(Tgn)gg 
                 UCACACCAUUGAA 
                 4281 
               
               
                 901373.1 
                 1701303. 
                   
                 cacuaguaL96 
                 1701304. 
                   
                 uuucAfaUfggugusgsa 
                 ACCACUAGUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 59 
                 gsasggc(Ahd)GfcUfUfGfag 
                 A- 
                 188 
                 VPusCfsguuu(Agn)ac 
                 GCGAGGCAGCUUG 
                 4282 
               
               
                 901332.1 
                 1701221. 
                   
                 uuaaacgaL96 
                 1701222. 
                   
                 ucaaGfcUfgccucsgsc 
                 AGUUAAACGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 60 
                 gscsacu(Ghd)AfaAfCfUfuu 
                 A- 
                 189 
                 VPusUfsggac(Ggn)aaa 
                 UCGCACUGAAACU 
                 4283 
               
               
                 901311.1 
                 1701179. 
                   
                 ucguccaaL96 
                 1701180. 
                   
                 aguUfuCfagugcsgsa 
                 UUUCGUCCAA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 61 
                 gsusuuu(Ahd)UfaUfAfCfg 
                 A- 
                 190 
                 VPusAfsuaag(Tgn)acc 
                 GUGUUUUAUAUA 
                 4284 
               
               
                 901423.1 
                 1701403. 
                   
                 guacuuauaL96 
                 1701404. 
                   
                 guaUfaUfaaaacsasc 
                 CGGUACUUAUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 62 
                 csascca(Uhd)UfgAfAfAfcc 
                 A- 
                 191 
                 VPusAfsacua(Ggn)ug 
                 CACACCAUUGAAA 
                 4285 
               
               
                 901374.1 
                 1701305. 
                   
                 acuaguuaL96 
                 1701306. 
                   
                 guuuCfaAfuggugsusg 
                 CCACUAGUUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 63 
                 asuscac(Chd)AfuGfCfAfga 
                 A- 
                 192 
                 VPusCfsgcau(Agn)auc 
                 ACAUCACCAUGCA 
                 4286 
               
               
                 901319.1 
                 1701195. 
                   
                 uuaugcgaL96 
                 1701196. 
                   
                 ugcAfuGfgugausgsu 
                 GAUUAUGCGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 64 
                 usgsagu(Uhd)AfaAfCfGfaa 
                 A- 
                 193 
                 VPusAfsagua(Cgn)gu 
                 CUUGAGUUAAAC 
                 4287 
               
               
                 901341.1 
                 1701239. 
                   
                 cguacuuaL96 
                 1701240. 
                   
                 ucguUfuAfacucasasg 
                 GAACGUACUUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 65 
                 gsasaag(Uhd)GfuUfUfUfau 
                 A- 
                 194 
                 VPusAfsccgu(Agn)ua 
                 GAGAAAGUGUUU 
                 4288 
               
               
                 901422.1 
                 1701401. 
                   
                 auacgguaL96 
                 1701402. 
                   
                 uaaaAfcAfcuuucsusc 
                 UAUAUACGGUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 66 
                 ascsagu(Chd)AfcUfAfGfcu 
                 A- 
                 195 
                 VPusCfsaaga(Tgn)aag 
                 UGACAGUCACUAG 
                 4289 
               
               
                 901385.1 
                 1701327. 
                   
                 uaucuugaL96 
                 1701328. 
                   
                 cuaGfuGfacuguscsa 
                 CUUAUCUUGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 67 
                 gsusgcu(Ahd)CfuGfUfUfua 
                 A- 
                 196 
                 VPusUfsuacg(Ggn)au 
                 UGGUGCUACUGU 
                 4290 
               
               
                 901391.1 
                 1701339. 
                   
                 uccguaaaL96 
                 1701340. 
                   
                 aaacAfgUfagcacscsa 
                 UUAUCCGUAAU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 68 
                 cscsugc(Ahd)AfaAfAfCfac 
                 A- 
                 197 
                 VPusCfsgagu(Cgn)ug 
                 UUCCUGCAAAAAC 
                 4291 
               
               
                 901329.1 
                 1701215. 
                   
                 agacucgaL96 
                 1701216. 
                   
                 uguuUfuUfgcaggsasa 
                 ACAGACUCGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 69 
                 csasaaa(Ahd)CfaCfAfGfac 
                 A- 
                 198 
                 VPusAfsacgc(Ggn)ag 
                 UGCAAAAACACAG 
                 4292 
               
               
                 901331.1 
                 1701219. 
                   
                 ucgcguuaL96 
                 1701220. 
                   
                 ucugUfgUfuuuugscsa 
                 ACUCGCGUUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 70 
                 usgscug(Uhd)GfgAfCfUfu 
                 A- 
                 199 
                 VPusCfsccaa(Cgn)uca 
                 ACUGCUGUGGACU 
                 4293 
               
               
                 901368.1 
                 1701293. 
                   
                 gaguugggaL96 
                 1701294. 
                   
                 aguCfcAfcagcasgsu 
                 UGAGUUGGGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 71 
                 gsusgcu(Ahd)AfuGfUfUfa 
                 A- 
                 200 
                 VPusGfsacac(Cgn)aau 
                 CAGUGCUAAUGU 
                 4294 
               
               
                 901364.1 
                 1701285. 
                   
                 uuggugucaL96 
                 1701286. 
                   
                 aacAfuUfagcacsusg 
                 UAUUGGUGUCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 72 
                 usgsgug(Chd)UfaCfUfGfuu 
                 A- 
                 201 
                 VPusAfscgga(Tgn)aaa 
                 AUUGGUGCUACU 
                 4295 
               
               
                 901389.1 
                 1701335. 
                   
                 uauccguaL96 
                 1701336. 
                   
                 cagUfaGfcaccasasu 
                 GUUUAUCCGUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 73 
                 asgsaaa(Ghd)UfgUfUfUfua 
                 A- 
                 202 
                 VPusCfscgua(Tgn)aua 
                 AGAGAAAGUGUU 
                 4296 
               
               
                 901421.1 
                 1701399. 
                   
                 uauacggaL96 
                 1701400. 
                   
                 aaaCfaCfuuucuscsu 
                 UUAUAUACGGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 74 
                 asascua(Uhd)UfuAfUfGfag 
                 A- 
                 203 
                 VPusGfsauac(Agn)uc 
                 UCAACUAUUUAU 
                 4297 
               
               
                 901380.1 
                 1701317. 
                   
                 auguaucaL96 
                 1701318. 
                   
                 ucauAfaAfuaguusgsa 
                 GAGAUGUAUCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 75 
                 asgsuua(Ahd)AfcGfAfAfcg 
                 A- 
                 204 
                 VPusGfscaag(Tgn)acg 
                 UGAGUUAAACGA 
                 4298 
               
               
                 901343.1 
                 1701243. 
                   
                 uacuugcaL96 
                 1701244. 
                   
                 uucGfuUfuaacuscsa 
                 ACGUACUUGCA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 76 
                 csasucu(Uhd)CfaAfGfCfca 
                 A- 
                 205 
                 VPusCfsacag(Ggn)aug 
                 UACAUCUUCAAGC 
                 4299 
               
               
                 901317.1 
                 1701191. 
                   
                 uccugugaL96 
                 1701192. 
                   
                 gcuUfgAfagaugsusa 
                 CAUCCUGUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 77 
                 ususuuu(Uhd)UfuCfAfGfu 
                 A- 
                 206 
                 VPusCfscaag(Agn)aua 
                 GGUUUUUUUUCA 
                 4300 
               
               
                 901424.1 
                 1701405. 
                   
                 auucuuggaL96 
                 1701406. 
                   
                 cugAfaAfaaaaascsc 
                 GUAUUCUUGGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 78 
                 ususauc(Chd)GfuAfAfUfaa 
                 A- 
                 207 
                 VPusCfsccac(Agn)auu 
                 GUUUAUCCGUAA 
                 4301 
               
               
                 901431.1 
                 1701419. 
                   
                 uugugggaL96 
                 1701420. 
                   
                 auuAfcGfgauaasasc 
                 UAAUUGUGGGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 79 
                 gsgsuac(Uhd)UfaUfUfUfaa 
                 A- 
                 208 
                 VPusAfsggga(Tgn)au 
                 ACGGUACUUAUU 
                 4302 
               
               
                 901378.1 
                 1701313. 
                   
                 uaucccuaL96 
                 1701314. 
                   
                 uaaaUfaAfguaccsgsu 
                 UAAUAUCCCUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 80 
                 csascgu(Chd)UfuUfGfUfcu 
                 A- 
                 209 
                 VPusGfscacu(Agn)ga 
                 AUCACGUCUUUGU 
                 4303 
               
               
                 901434.1 
                 1701425. 
                   
                 cuagugcaL96 
                 1701426. 
                   
                 gacaAfaGfacgugsasu 
                 CUCUAGUGCA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 81 
                 usgscaa(Ahd)AfaCfAfCfag 
                 A- 
                 210 
                 VPusCfsgcga(Ggn)uc 
                 CCUGCAAAAACAC 
                 4304 
               
               
                 901412.1 
                 1701381. 
                   
                 acucgcgaL96 
                 1701382. 
                   
                 ugugUfuUfuugcasgsg 
                 AGACUCGCGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 82 
                 ascsuau(Uhd)UfaUfGfAfga 
                 A- 
                 211 
                 VPusAfsgaua(Cgn)auc 
                 CAACUAUUUAUG 
                 4305 
               
               
                 901426.1 
                 1701409. 
                   
                 uguaucuaL96 
                 1701410. 
                   
                 ucaUfaAfauagususg 
                 AGAUGUAUCUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 83 
                 asgsggg(Chd)AfaAfAfAfcg 
                 A- 
                 212 
                 VPusGfscgcu(Tgn)ucg 
                 AAAGGGGCAAAA 
                 4306 
               
               
                 901322.1 
                 1701201. 
                   
                 aaagcgcaL96 
                 1701202. 
                   
                 uuuUfuGfccccususu 
                 ACGAAAGCGCA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 84 
                 ususgcu(Chd)UfcUfUfAfuu 
                 A- 
                 213 
                 VPusCfsggua(Cgn)aaa 
                 UCUUGCUCUCUUA 
                 4307 
               
               
                 901381.1 
                 1701319. 
                   
                 uguaccgaL96 
                 1701320. 
                   
                 uaaGfaGfagcaasgsa 
                 UUUGUACCGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 85 
                 asusuug(Uhd)UfuGfUfAfca 
                 A- 
                 214 
                 VPusCfsggau(Cgn)uu 
                 GCAUUUGUUUGU 
                 4308 
               
               
                 901324.1 
                 1701205. 
                   
                 agauccgaL96 
                 1701206. 
                   
                 guacAfaAfcaaausgsc 
                 ACAAGAUCCGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 86 
                 ususgca(Ghd)AfuGfUfGfac 
                 A- 
                 215 
                 VPusUfscggc(Tgn)ug 
                 ACUUGCAGAUGU 
                 4309 
               
               
                 901347.1 
                 1701251. 
                   
                 aagccgaaL96 
                 1701252. 
                   
                 ucacAfuCfugcaasgsu 
                 GACAAGCCGAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 87 
                 csasacu(Ahd)UfuUfAfUfga 
                 A- 
                 216 
                 VPusAfsuaca(Tgn)cuc 
                 UUCAACUAUUUA 
                 4310 
               
               
                 901379.1 
                 1701315. 
                   
                 gauguauaL96 
                 1701316. 
                   
                 auaAfaUfaguugsasa 
                 UGAGAUGUAUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 88 
                 asasuuc(Uhd)AfcAfUfAfcu 
                 A- 
                 217 
                 VPusGfsagau(Tgn)uag 
                 AGAAUUCUACAU 
                 4311 
               
               
                 901428.1 
                 1701413. 
                   
                 aaaucucaL96 
                 1701414. 
                   
                 uauGfuAfgaauuscsu 
                 ACUAAAUCUCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 89 
                 asusguc(Chd)UfcAfCfAfcc 
                 A- 
                 218 
                 VPusUfsuuca(Agn)ug 
                 CUAUGUCCUCACA 
                 4312 
               
               
                 901371.1 
                 1701299. 
                   
                 auugaaaaL96 
                 1701300. 
                   
                 guguGfaGfgacausasg 
                 CCAUUGAAAC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 90 
                 ususguu(Uhd)GfuAfCfAfa 
                 A- 
                 219 
                 VPusUfsgcgg(Agn)uc 
                 AUUUGUUUGUAC 
                 4313 
               
               
                 901408.1 
                 1701373. 
                   
                 gauccgcaaL96 
                 1701374. 
                   
                 uuguAfcAfaacaasasu 
                 AAGAUCCGCAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 91 
                 usasauc(Chd)AfgAfAfAfcc 
                 A- 
                 220 
                 VPusCfsauuu(Cgn)ag 
                 CUUAAUCCAGAAA 
                 4314 
               
               
                 901417.1 
                 1701391. 
                   
                 ugaaaugaL96 
                 1701392. 
                   
                 guuuCfuGfgauuasasg 
                 CCUGAAAUGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 92 
                 gsasaaa(Ahd)AfaAfUfCfag 
                 A- 
                 221 
                 VPusCfscucg(Agn)acu 
                 AAGAAAAAAAAU 
                 4315 
               
               
                 901400.1 
                 1701357. 
                   
                 uucgaggaL96 
                 1701358. 
                   
                 gauUfuUfuuuucsusu 
                 CAGUUCGAGGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 93 
                 gsgsgca(Ahd)AfaAfCfGfaa 
                 A- 
                 222 
                 VPusUfsugcg(Cgn)uu 
                 AGGGGCAAAAAC 
                 4316 
               
               
                 901323.1 
                 1701203. 
                   
                 agcgcaaaL96 
                 1701204. 
                   
                 ucguUfuUfugcccscsu 
                 GAAAGCGCAAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 94 
                 usgsaag(Uhd)UfcAfUfGfga 
                 A- 
                 223 
                 VPusAfsuaga(Cgn)auc 
                 GGUGAAGUUCAU 
                 4317 
               
               
                 901316.1 
                 1701189. 
                   
                 ugucuauaL96 
                 1701190. 
                   
                 cauGfaAfcuucascsc 
                 GGAUGUCUAUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 95 
                 csascga(Ahd)GfuGfGfUfga 
                 A- 
                 224 
                 VPusAfsugaa(Cgn)uu 
                 AUCACGAAGUGG 
                 4318 
               
               
                 901315.1 
                 1701187. 
                   
                 aguucauaL96 
                 1701188. 
                   
                 caccAfcUfucgugsasu 
                 UGAAGUUCAUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 96 
                 ascsguc(Uhd)UfuGfUfCfuc 
                 A- 
                 225 
                 VPusUfsgcac(Tgn)aga 
                 UCACGUCUUUGUC 
                 4319 
               
               
                 901395.1 
                 1701347. 
                   
                 uagugcaaL96 
                 1701348. 
                   
                 gacAfaAfgacgusgsa 
                 UCUAGUGCAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 97 
                 asascau(Chd)AfcCfAfUfgc 
                 A- 
                 226 
                 VPusAfsuaau(Cgn)ug 
                 CCAACAUCACCAU 
                 4320 
               
               
                 901318.1 
                 1701193. 
                   
                 agauuauaL96 
                 1701194. 
                   
                 caugGfuGfauguusgsg 
                 GCAGAUUAUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 98 
                 gsgsugc(Uhd)AfcUfGfUfu 
                 A- 
                 227 
                 VPusUfsacgg(Agn)ua 
                 UUGGUGCUACUG 
                 4321 
               
               
                 901390.1 
                 1701337. 
                   
                 uauccguaaL96 
                 1701338. 
                   
                 aacaGfuAfgcaccsasa 
                 UUUAUCCGUAA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 99 
                 asasaua(Ghd)AfcAfUfUfgc 
                 A- 
                 228 
                 VPusCfsagaa(Tgn)agc 
                 UAAAAUAGACAU 
                 4322 
               
               
                 901387.1 
                 1701331. 
                   
                 uauucugaL96 
                 1701332. 
                   
                 aauGfuCfuauuususa 
                 UGCUAUUCUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 100 
                 ususccc(Chd)AfaAfUfCfac 
                 A- 
                 229 
                 VPusAfsucca(Cgn)agu 
                 ACUUCCCCAAAUC 
                 4323 
               
               
                 901307.1 
                 1701171. 
                   
                 uguggauaL96 
                 1701172. 
                   
                 gauUfuGfgggaasgsu 
                 ACUGUGGAUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 101 
                 gsasucc(Ghd)CfaGfAfCfgu 
                 A- 
                 230 
                 VPusCfsauuu(Agn)cac 
                 AAGAUCCGCAGAC 
                 4324 
               
               
                 901410.1 
                 1701377. 
                   
                 guaaaugaL96 
                 1701378. 
                   
                 gucUfgCfggaucsusu 
                 GUGUAAAUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 102 
                 ususaac(Ahd)UfcAfCfGfuc 
                 A- 
                 231 
                 VPusAfsgaca(Agn)aga 
                 UAUUAACAUCACG 
                 4325 
               
               
                 901433.1 
                 1701423. 
                   
                 uuugucuaL96 
                 1701424. 
                   
                 cguGfaUfguuaasusa 
                 UCUUUGUCUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 103 
                 asasagu(Ghd)AfgUfGfAfcc 
                 A- 
                 232 
                 VPusAfsaaag(Cgn)agg 
                 GCAAAGUGAGUG 
                 4326 
               
               
                 901308.1 
                 1701173. 
                   
                 ugcuuuuaL96 
                 1701174. 
                   
                 ucaCfuCfacuuusgsc 
                 ACCUGCUUUUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 104 
                 asasaaa(Chd)AfcAfGfAfcu 
                 A- 
                 233 
                 VPusCfsaacg(Cgn)gag 
                 GCAAAAACACAGA 
                 4327 
               
               
                 901414.1 
                 1701385. 
                   
                 cgcguugaL96 
                 1701386. 
                   
                 ucuGfuGfuuuuusgsc 
                 CUCGCGUUGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 105 
                 csgsucg(Chd)AfcUfGfAfaa 
                 A- 
                 234 
                 VPusCfsgaaa(Agn)gu 
                 GGCGUCGCACUGA 
                 4328 
               
               
                 901309.1 
                 1701175. 
                   
                 cuuuucgaL96 
                 1701176. 
                   
                 uucaGfuGfcgacgscsc 
                 AACUUUUCGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 106 
                 asascag(Uhd)GfcUfAfAfug 
                 A- 
                 235 
                 VPusCfscaau(Agn)aca 
                 UUAACAGUGCUA 
                 4329 
               
               
                 901362.1 
                 1701281. 
                   
                 uuauuggaL96 
                 1701282. 
                   
                 uuaGfcAfcuguusasa 
                 AUGUUAUUGGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 107 
                 ususcgu(Chd)CfaAfCfUfuc 
                 A- 
                 236 
                 VPusCfsagcc(Cgn)aga 
                 UUUUCGUCCAACU 
                 4330 
               
               
                 901397.1 
                 1701351. 
                   
                 ugggcugaL96 
                 1701352. 
                   
                 aguUfgGfacgaasasa 
                 UCUGGGCUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 108 
                 asusugg(Uhd)GfuCfUfUfca 
                 A- 
                 237 
                 VPusCfsaucc(Agn)gu 
                 UUAUUGGUGUCU 
                 4331 
               
               
                 901419.1 
                 1701395. 
                   
                 cuggaugaL96 
                 1701396. 
                   
                 gaagAfcAfccaausasa 
                 UCACUGGAUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 109 
                 gscsaaa(Ahd)AfcAfCfAfga 
                 A- 
                 238 
                 VPusAfscgcg(Agn)gu 
                 CUGCAAAAACACA 
                 4332 
               
               
                 901413.1 
                 1701383. 
                   
                 cucgcguaL96 
                 1701384. 
                   
                 cuguGfuUfuuugcsasg 
                 GACUCGCGUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 110 
                 asasaaa(Uhd)CfaGfUfUfcg 
                 A- 
                 239 
                 VPusCfsuuuc(Cgn)uc 
                 AAAAAAAUCAGU 
                 4333 
               
               
                 901401.1 
                 1701359. 
                   
                 aggaaagaL96 
                 1701360. 
                   
                 gaacUfgAfuuuuususu 
                 UCGAGGAAAGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 ill 
                 csasgac(Ghd)UfgUfAfAfau 
                 A- 
                 240 
                 VPusCfsagga(Agn)cau 
                 CGCAGACGUGUAA 
                 4334 
               
               
                 901411.1 
                 1701379. 
                   
                 guuccugaL96 
                 1701380. 
                   
                 uuaCfaCfgucugscsg 
                 AUGUUCCUGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 112 
                 usgsucc(Uhd)CfaCfAfCfca 
                 A- 
                 241 
                 VPusGfsuuuc(Agn)au 
                 UAUGUCCUCACAC 
                 4335 
               
               
                 901372.1 
                 1701301. 
                   
                 uugaaacaL96 
                 1701302. 
                   
                 ggugUfgAfggacasusa 
                 CAUUGAAACC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 113 
                 ususuuu(Uhd)UfcAfGfUfa 
                 A- 
                 242 
                 VPusAfsccaa(Ggn)aau 
                 GUUUUUUUUCAG 
                 4336 
               
               
                 901425.1 
                 1701407. 
                   
                 uucuugguaL96 
                 1701408. 
                   
                 acuGfaAfaaaaasasc 
                 UAUUCUUGGUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 114 
                 asgsauc(Chd)GfcAfGfAfcg 
                 A- 
                 243 
                 VPusAfsuuua(Cgn)ac 
                 CAAGAUCCGCAGA 
                 4337 
               
               
                 901409.1 
                 1701375. 
                   
                 uguaaauaL96 
                 1701376. 
                   
                 gucuGfcGfgaucususg 
                 CGUGUAAAUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 115 
                 cscscuc(Uhd)UfgGfAfAfuu 
                 A- 
                 244 
                 VPusCfsgaau(Cgn)caa 
                 GUCCCUCUUGGAA 
                 4338 
               
               
                 901418.1 
                 1701393. 
                   
                 ggauucgaL96 
                 1701394. 
                   
                 uucCfaAfgagggsasc 
                 UUGGAUUCGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 116 
                 gsasuau(Uhd)AfaCfAfUfca 
                 A- 
                 245 
                 VPusAfsaaga(Cgn)gu 
                 AAGAUAUUAACA 
                 4339 
               
               
                 901393.1 
                 1701343. 
                   
                 cgucuuuaL96 
                 1701344. 
                   
                 gaugUfuAfauaucsusu 
                 UCACGUCUUUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 117 
                 ususggu(Ghd)CfuAfCfUfg 
                 A- 
                 246 
                 VPusCfsggau(Agn)aac 
                 UAUUGGUGCUAC 
                 4340 
               
               
                 901388.1 
                 1701333. 
                   
                 uuuauccgaL96 
                 1701334. 
                   
                 aguAfgCfaccaasusa 
                 UGUUUAUCCGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 118 
                 asasggg(Ghd)CfaAfAfAfac 
                 A- 
                 247 
                 VPusCfsgcuu(Tgn)cgu 
                 GAAAGGGGCAAA 
                 4341 
               
               
                 901404.1 
                 1701365. 
                   
                 gaaagcgaL96 
                 1701366. 
                   
                 uuuUfgCfcccuususc 
                 AACGAAAGCGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 119 
                 csusugc(Ahd)GfaUfGfUfga 
                 A- 
                 248 
                 VPusCfsggcu(Tgn)guc 
                 UACUUGCAGAUG 
                 4342 
               
               
                 901346.1 
                 1701249. 
                   
                 caagccgaL96 
                 1701250. 
                   
                 acaUfcUfgcaagsusa 
                 UGACAAGCCGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 120 
                 asasauc(Ahd)GfuUfCfGfag 
                 A- 
                 249 
                 VPusCfsccuu(Tgn)ccu 
                 AAAAAUCAGUUC 
                 4343 
               
               
                 901403.1 
                 1701363. 
                   
                 gaaagggaL96 
                 1701364. 
                   
                 cgaAfcUfgauuususu 
                 GAGGAAAGGGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 121 
                 ascsuuu(Uhd)CfgUfCfCfaa 
                 A- 
                 250 
                 VPusCfscaga(Agn)gu 
                 AAACUUUUCGUCC 
                 4344 
               
               
                 901396.1 
                 1701349. 
                   
                 cuucuggaL96 
                 1701350. 
                   
                 uggaCfgAfaaagususu 
                 AACUUCUGGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 122 
                 asusuaa(Chd)AfuCfAfCfgu 
                 A- 
                 251 
                 VPusGfsacaa(Agn)gac 
                 AUAUUAACAUCAC 
                 4345 
               
               
                 901432.1 
                 1701421. 
                   
                 cuuugucaL96 
                 1701422. 
                   
                 gugAfuGfuuaausasu 
                 GUCUUUGUCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 123 
                 csgsucu(Uhd)UfgUfCfUfcu 
                 A- 
                 252 
                 VPusCfsugca(Cgn)uag 
                 CACGUCUUUGUCU 
                 4346 
               
               
                 901435.1 
                 1701427. 
                   
                 agugcagaL96 
                 1701428. 
                   
                 agaCfaAfagacgsusg 
                 CUAGUGCAGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 124 
                 asascac(Ahd)GfaCfUfCfgc 
                 A- 
                 253 
                 VPusUfsugca(Agn)cg 
                 AAAACACAGACUC 
                 4347 
               
               
                 901416.1 
                 1701389. 
                   
                 guugcaaaL96 
                 1701390. 
                   
                 cgagUfcUfguguususu 
                 GCGUUGCAAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 125 
                 asusauu(Ahd)AfcAfUfCfac 
                 A- 
                 254 
                 VPusCfsaaag(Agn)cgu 
                 AGAUAUUAACAU 
                 4348 
               
               
                 901394.1 
                 1701345. 
                   
                 gucuuugaL96 
                 1701346. 
                   
                 gauGfuUfaauauscsu 
                 CACGUCUUUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 126 
                 gsusuua(Uhd)CfcGfUfAfau 
                 A- 
                 255 
                 VPusCfsacaa(Tgn)uau 
                 CUGUUUAUCCGUA 
                 4349 
               
               
                 901429.1 
                 1701415. 
                   
                 aauugugaL96 
                 1701416. 
                   
                 uacGfgAfuaaacsasg 
                 AUAAUUGUGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 127 
                 asasaau(Chd)AfgUfUfCfga 
                 A- 
                 256 
                 VPusCfscuuu(Cgn)cuc 
                 AAAAAAUCAGUU 
                 4350 
               
               
                 901402.1 
                 1701361. 
                   
                 ggaaaggaL96 
                 1701362. 
                   
                 gaaCfuGfauuuususu 
                 CGAGGAAAGGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 128 
                 ususuau(Chd)CfgUfAfAfua 
                 A- 
                 257 
                 VPusCfscaca(Agn)uua 
                 UGUUUAUCCGUA 
                 4351 
               
               
                 901430.1 
                 1701417. 
                   
                 auuguggaL96 
                 1701418. 
                   
                 uuaCfgGfauaaascsa 
                 AUAAUUGUGGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 129 
                 asgsgac(Ahd)UfuGfCfUfgu 
                 A- 
                 258 
                 VPusCfscaaa(Ggn)cac 
                 UCAGGACAUUGCU 
                 4352 
               
               
                 901369.1 
                 1701295. 
                   
                 gcuuuggaL96 
                 1701296. 
                   
                 agcAfaUfguccusgsa 
                 GUGCUUUGGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2B 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Unmodified Single Strands and Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 Sense 
                 SEQ ID 
                   
                 mRNA 
                 Antisense 
                 SEQ ID 
                   
                 mRNA 
               
               
                 Duplex 
                 Oligo 
                 NO: 
                   
                 Target 
                 Oligo 
                 NO: 
                   
                 Target 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Range 
                 Name 
                 (Antisense) 
                 Antisense Sequence 
                 Range 
               
               
                   
               
               
                 AD- 
                 A- 
                 259 
                 AAGACUGAUACAGAA 
                 1796- 
                 A- 
                 388 
                 UGAUCGTUCUGUAUCAGU 
                 1794- 
               
               
                 901349. 
                 1701255. 
                   
                 CGAUCA 
                 1816 
                 1701256. 
                   
                 CUUUC 
                 1816 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 260 
                 ACGGUACUUAUUUAA 
                 2961- 
                 A- 
                 389 
                 UGGAUATUAAAUAAGUAC 
                 2959- 
               
               
                 901376. 
                 1701309. 
                   
                 UAUCCA 
                 2981 
                 1701310. 
                   
                 CGUAU 
                 2981 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 261 
                 CAGAACAGUCCUUAA 
                 1858- 
                 A- 
                 390 
                 UCUGGATUAAGGACUGUU 
                 1856- 
               
               
                 901356. 
                 1701269. 
                   
                 UCCAGA 
                 1878 
                 1701270. 
                   
                 CUGUC 
                 1878 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 262 
                 CGACAGAACAGUCCU 
                 1855- 
                 A- 
                 391 
                 UGAUUAAGGACUGUUCU 
                 1853- 
               
               
                 901355. 
                 1701267. 
                   
                 UAAUCA 
                 1875 
                 1701268. 
                   
                 GUCGAU 
                 1875 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 263 
                 GCAUUUGUUUGUACA 
                 1614- 
                 A- 
                 392 
                 UGAUCUTGUACAAACAAA 
                 1612- 
               
               
                 901407. 
                 1701371. 
                   
                 AGAUCA 
                 1634 
                 1701372. 
                   
                 UGCUU 
                 1634 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 264 
                 UAUUGGUGUCUUCAC 
                 2192- 
                 A- 
                 393 
                 UAUCCAGUGAAGACACCA 
                 2190- 
               
               
                 901367. 
                 1701291. 
                   
                 UGGAUA 
                 2212 
                 1701292. 
                   
                 AUAAC 
                 2212 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 265 
                 ACUGAUACAGAACGA 
                 1799- 
                 A- 
                 394 
                 UAUCGATCGUUCUGUAUC 
                 1797- 
               
               
                 901352. 
                 1701261. 
                   
                 UCGAUA 
                 1819 
                 1701262. 
                   
                 AGUCU 
                 1819 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 266 
                 AAAGACUGAUACAGA 
                 1795- 
                 A- 
                 395 
                 UAUCGUTCUGUAUCAGUC 
                 1793- 
               
               
                 901348. 
                 1701253. 
                   
                 ACGAUA 
                 1815 
                 1701254. 
                   
                 UUUCC 
                 1815 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 267 
                 AUACAGAACGAUCGA 
                 1803- 
                 A- 
                 396 
                 UCUGUATCGAUCGUUCUG 
                 1801- 
               
               
                 901354. 
                 1701265. 
                   
                 UACAGA 
                 1823 
                 1701266. 
                   
                 UAUCA 
                 1823 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 268 
                 CUGAUACAGAACGAU 
                 1800- 
                 A- 
                 397 
                 UUAUCGAUCGUUCUGUAU 
                 1798- 
               
               
                 901353. 
                 1701263. 
                   
                 CGAUAA 
                 1820 
                 1701264. 
                   
                 CAGUC 
                 1820 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 269 
                 GAGAAAGUGUUUUA 
                 2944- 
                 A- 
                 398 
                 UCGUAUAUAAAACACUUU 
                 2942- 
               
               
                 901375. 
                 1701307. 
                   
                 UAUACGA 
                 2964 
                 1701308. 
                   
                 CUCUU 
                 2964 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 270 
                 ACGAACGUACUUGCA 
                 1700- 
                 A- 
                 399 
                 UACAUCTGCAAGUACGUU 
                 1698- 
               
               
                 901345. 
                 1701247. 
                   
                 GAUGUA 
                 1720 
                 1701248. 
                   
                 CGUUU 
                 1720 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 271 
                 CUUGGAAUUGGAUUC 
                 1982- 
                 A- 
                 400 
                 UAUGGCGAAUCCAAUUCC 
                 1980- 
               
               
                 901357. 
                 1701271. 
                   
                 GCCAUA 
                 2002 
                 1701272. 
                   
                 AAGAG 
                 2002 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 272 
                 GGCAGCUUGAGUUAA 
                 1685- 
                 A- 
                 401 
                 UUUCGUTUAACUCAAGCU 
                 1683- 
               
               
                 901334. 
                 1701225. 
                   
                 ACGAAA 
                 1705 
                 1701226. 
                   
                 GCCUC 
                 1705 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 273 
                 GGGCAGAAUCAUCAC 
                 1138- 
                 A- 
                 402 
                 UACUUCGUGAUGAUUCUG 
                 1136- 
               
               
                 901313. 
                 1701183. 
                   
                 GAAGUA 
                 1158 
                 1701184. 
                   
                 CCCUC 
                 1158 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 274 
                 UUAAACGAACGUACU 
                 1696- 
                 A- 
                 403 
                 UCUGCAAGUACGUUCGUU 
                 1694- 
               
               
                 901344. 
                 1701245. 
                   
                 UGCAGA 
                 1716 
                 1701246. 
                   
                 UAACU 
                 1716 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 275 
                 GUUAUUGGUGUCUUC 
                 2190- 
                 A- 
                 404 
                 UCCAGUGAAGACACCAAU 
                 2188- 
               
               
                 901366. 
                 1701289. 
                   
                 ACUGGA 
                 2210 
                 1701290. 
                   
                 AACAU 
                 2210 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 276 
                 AGCUUGAGUUAAACG 
                 1688- 
                 A- 
                 405 
                 UACGUUCGUUUAACUCAA 
                 1686- 
               
               
                 901337. 
                 1701231. 
                   
                 AACGUA 
                 1708 
                 1701232. 
                   
                 GCUGC 
                 1708 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 277 
                 GCAGCUUGAGUUAAA 
                 1686- 
                 A- 
                 406 
                 UGUUCGTUUAACUCAAGC 
                 1684- 
               
               
                 901335. 
                 1701227. 
                   
                 CGAACA 
                 1706 
                 1701228. 
                   
                 UGCCU 
                 1706 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 278 
                 CGAAGUGGUGAAGUU 
                 1152- 
                 A- 
                 407 
                 UCCAUGAACUUCACCACU 
                 1150- 
               
               
                 901398. 
                 1701353. 
                   
                 CAUGGA 
                 1172 
                 1701354. 
                   
                 UCGUG 
                 1172 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 279 
                 CAGAAUCAUCACGAA 
                 1141- 
                 A- 
                 408 
                 UACCACTUCGUGAUGAUU 
                 1139- 
               
               
                 901314. 
                 1701185. 
                   
                 GUGGUA 
                 1161 
                 1701186. 
                   
                 CUGCC 
                 1161 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 280 
                 AAAAUAGACAUUGCU 
                 3361- 
                 A- 
                 409 
                 UAGAAUAGCAAUGUCUA 
                 3359- 
               
               
                 901386. 
                 1701329. 
                   
                 AUUCUA 
                 3381 
                 1701330. 
                   
                 UUUUAU 
                 3381 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 281 
                 CAGCUUGAGUUAAAC 
                 1687- 
                 A- 
                 410 
                 UCGUUCGUUUAACUCAAG 
                 1685- 
               
               
                 901336. 
                 1701229. 
                   
                 GAACGA 
                 1707 
                 1701230. 
                   
                 CUGCC 
                 1707 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 282 
                 CGCACUGAAACUUUU 
                  648- 
                 A- 
                 411 
                 UGGACGAAAAGUUUCAG 
                  646- 
               
               
                 901310. 
                 1701177. 
                   
                 CGUCCA 
                  668 
                 1701178. 
                   
                 UGCGAC 
                  668 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 283 
                 AGAUUAUGCGGAUCA 
                 1352- 
                 A- 
                 412 
                 UAGGUUTGAUCCGCAUAA 
                 1350- 
               
               
                 901321. 
                 1701199. 
                   
                 AACCUA 
                 1372 
                 1701200. 
                   
                 UCUGC 
                 1372 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 284 
                 GCUCUCUUAUUUGUA 
                 3096- 
                 A- 
                 413 
                 UACCGGTACAAAUAAGAG 
                 3094- 
               
               
                 901382. 
                 1701321. 
                   
                 CCGGUA 
                 3116 
                 1701322. 
                   
                 AGCAA 
                 3116 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 285 
                 UGACAGUCACUAGCU 
                 3162- 
                 A- 
                 414 
                 UAGAUAAGCUAGUGACU 
                 3160- 
               
               
                 901384. 
                 1701325. 
                   
                 UAUCUA 
                 3182 
                 1701326. 
                   
                 GUCACC 
                 3182 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 286 
                 CUUGAGUUAAACGAA 
                 1690- 
                 A- 
                 415 
                 UGUACGTUCGUUUAACUC 
                 1688- 
               
               
                 901339. 
                 1701235. 
                   
                 CGUACA 
                 1710 
                 1701236. 
                   
                 AAGCU 
                 1710 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 287 
                 AGUGCUAAUGUUAUU 
                 2181- 
                 A- 
                 416 
                 UACACCAAUAACAUUAGC 
                 2179- 
               
               
                 901363. 
                 1701283. 
                   
                 GGUGUA 
                 2201 
                 1701284. 
                   
                 ACUGU 
                 2201 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 288 
                 AUCCGCAGACGUGUA 
                 1631- 
                 A- 
                 417 
                 UACAUUTACACGUCUGCG 
                 1629- 
               
               
                 901325. 
                 1701207. 
                   
                 AAUGUA 
                 1651 
                 1701208. 
                   
                 GAUCU 
                 1651 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 289 
                 AGACUGAUACAGAAC 
                 1797- 
                 A- 
                 418 
                 UCGAUCGUUCUGUAUCAG 
                 1795- 
               
               
                 901350. 
                 1701257. 
                   
                 GAUCGA 
                 1817 
                 1701258. 
                   
                 UCUUU 
                 1817 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 290 
                 UGUUAUUGGUGUCUU 
                 2189- 
                 A- 
                 419 
                 UCAGUGAAGACACCAAUA 
                 2187- 
               
               
                 901365. 
                 1701287. 
                   
                 CACUGA 
                 2209 
                 1701288. 
                   
                 ACAUU 
                 2209 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 291 
                 GUGCUGGAAUUUGAU 
                  125- 
                 A- 
                 420 
                 UUGAAUAUCAAAUUCCAG 
                  123- 
               
               
                 901306. 
                 1701169. 
                   
                 AUUCAA 
                  145 
                 1701170. 
                   
                 CACCG 
                  145 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 292 
                 UUGCUGCUAAAUCAC 
                 2012- 
                 A- 
                 421 
                 UGCUCGGUGAUUUAGCAG 
                 2010- 
               
               
                 901361. 
                 1701279. 
                   
                 CGAGCA 
                 2032 
                 1701280. 
                   
                 CAAGA 
                 2032 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 293 
                 CACCAUGCAGAUUAU 
                 1344- 
                 A- 
                 422 
                 UUCCGCAUAAUCUGCAUG 
                 1342- 
               
               
                 901320. 
                 1701197. 
                   
                 GCGGAA 
                 1364 
                 1701198. 
                   
                 GUGAU 
                 1364 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 294 
                 GAAAGCAUUUGUUUG 
                 1610- 
                 A- 
                 423 
                 UUUGUACAAACAAAUGCU 
                 1608- 
               
               
                 901405. 
                 1701367. 
                   
                 UACAAA 
                 1630 
                 1701368. 
                   
                 UUCUC 
                 1630 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 295 
                 GCUUGAGUUAAACGA 
                 1689- 
                 A- 
                 424 
                 UUACGUTCGUUUAACUCA 
                 1687- 
               
               
                 901338. 
                 1701233. 
                   
                 ACGUAA 
                 1709 
                 1701234. 
                   
                 AGCUG 
                 1709 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 296 
                 UCGGUGACAGUCACU 
                 3158- 
                 A- 
                 425 
                 UAAGCUAGUGACUGUCAC 
                 3156- 
               
               
                 901383. 
                 1701323. 
                   
                 AGCUUA 
                 3178 
                 1701324. 
                   
                 CGAUC 
                 3178 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 297 
                 AGGCAGCUUGAGUUA 
                 1684- 
                 A- 
                 426 
                 UUCGUUTAACUCAAGCUG 
                 1682- 
               
               
                 901333. 
                 1701223. 
                   
                 AACGAA 
                 1704 
                 1701224. 
                   
                 CCUCG 
                 1704 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 298 
                 CUGCAAAAACACAGA 
                 1653- 
                 A- 
                 427 
                 UGCGAGTCUGUGUUUUUG 
                 1651- 
               
               
                 901330. 
                 1701217. 
                   
                 CUCGCA 
                 1673 
                 1701218. 
                   
                 CAGGA 
                 1673 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 299 
                 CUUGCUGCUAAAUCA 
                 2011- 
                 A- 
                 428 
                 UCUCGGTGAUUUAGCAGC 
                 2009- 
               
               
                 901360. 
                 1701277. 
                   
                 CCGAGA 
                 2031 
                 1701278. 
                   
                 AAGAA 
                 2031 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 300 
                 UUCUUGCUGCUAAAU 
                 2009- 
                 A- 
                 429 
                 UCGGUGAUUUAGCAGCAA 
                 2007- 
               
               
                 901358. 
                 1701273. 
                   
                 CACCGA 
                 2029 
                 1701274. 
                   
                 GAAAA 
                 2029 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 301 
                 AAAGCAUUUGUUUGU 
                 1611- 
                 A- 
                 430 
                 UCUUGUACAAACAAAUGC 
                 1609- 
               
               
                 901406. 
                 1701369. 
                   
                 ACAAGA 
                 1631 
                 1701370. 
                   
                 uuucu 
                 1631 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 302 
                 UCCGCAGACGUGUAA 
                 1632- 
                 A- 
                 431 
                 UAACAUTUACACGUCUGC 
                 1630- 
               
               
                 901326. 
                 1701209. 
                   
                 AUGUUA 
                 1652 
                 1701210. 
                   
                 GGAUC 
                 1652 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 303 
                 CGGUACUUAUUUAAU 
                 2962- 
                 A- 
                 432 
                 UGGGAUAUUAAAUAAGU 
                 2960- 
               
               
                 901377. 
                 1701311. 
                   
                 AUCCCA 
                 2982 
                 1701312. 
                   
                 ACCGUA 
                 2982 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 304 
                 GACUGAUACAGAACG 
                 1798- 
                 A- 
                 433 
                 UUCGAUCGUUCUGUAUCA 
                 1796- 
               
               
                 901351. 
                 1701259. 
                   
                 AUCGAA 
                 1818 
                 1701260. 
                   
                 GUCUU 
                 1818 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 305 
                 AAAACACAGACUCGC 
                 1658- 
                 A- 
                 434 
                 UGCAACGCGAGUCUGUGU 
                 1656- 
               
               
                 901415. 
                 1701387. 
                   
                 GUUGCA 
                 1678 
                 1701388. 
                   
                 UUUUG 
                 1678 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 306 
                 GAGUUAAACGAACGU 
                 1693- 
                 A- 
                 435 
                 UCAAGUACGUUCGUUUAA 
                 1691- 
               
               
                 901342. 
                 1701241. 
                   
                 ACUUGA 
                 1713 
                 1701242. 
                   
                 CUCAA 
                 1713 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 307 
                 UCACUGGAUGUAUUU 
                 2203- 
                 A- 
                 436 
                 UCAGUCAAAUACAUCCAG 
                 2201- 
               
               
                 901420. 
                 1701397. 
                   
                 GACUGA 
                 2223 
                 1701398. 
                   
                 UGAAG 
                 2223 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 308 
                 CCUCCGAAACCAUGA 
                 1028- 
                 A- 
                 437 
                 UAAAGUTCAUGGUUUCGG 
                 1026- 
               
               
                 901312. 
                 1701181. 
                   
                 ACUUUA 
                 1048 
                 1701182. 
                   
                 AGGCC 
                 1048 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 309 
                 UUGAGUUAAACGAAC 
                 1691- 
                 A- 
                 438 
                 UAGUACGUUCGUUUAACU 
                 1689- 
               
               
                 901340. 
                 1701237. 
                   
                 GUACUA 
                 1711 
                 1701238. 
                   
                 CAAGC 
                 1711 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 310 
                 UGCUACUGUUUAUCC 
                 3482- 
                 A- 
                 439 
                 UAUUACGGAUAAACAGU 
                 3480- 
               
               
                 901392. 
                 1701341. 
                   
                 GUAAUA 
                 3502 
                 1701342. 
                   
                 AGCACC 
                 3502 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 311 
                 CCGCAGACGUGUAAA 
                 1633- 
                 A- 
                 440 
                 UGAACATUUACACGUCUG 
                 1631- 
               
               
                 901327. 
                 1701211. 
                   
                 UGUUCA 
                 1653 
                 1701212. 
                   
                 CGGAU 
                 1653 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 312 
                 CGCAGACGUGUAAAU 
                 1634- 
                 A- 
                 441 
                 UGGAACAUUUACACGUCU 
                 1632- 
               
               
                 901328. 
                 1701213. 
                   
                 GUUCCA 
                 1654 
                 1701214. 
                   
                 GCGGA 
                 1654 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 313 
                 AGAGAAGAGACACAU 
                 2673- 
                 A- 
                 442 
                 UCAACAAUGUGUCUCUUC 
                 2671- 
               
               
                 901370. 
                 1701297. 
                   
                 UGUUGA 
                 2693 
                 1701298. 
                   
                 UCUUC 
                 2693 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 314 
                 ACAGCACAACAAAUG 
                 1407- 
                 A- 
                 443 
                 UAUUCACAUUUGUUGUGC 
                 1405- 
               
               
                 901399. 
                 1701355. 
                   
                 UGAAUA 
                 1427 
                 1701356. 
                   
                 UGUAG 
                 1427 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 315 
                 UCUUGCUGCUAAAUC 
                 2010- 
                 A- 
                 444 
                 UUCGGUGAUUUAGCAGCA 
                 2008- 
               
               
                 901359. 
                 1701275. 
                   
                 ACCGAA 
                 2030 
                 1701276. 
                   
                 AGAAA 
                 2030 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 316 
                 ACACCAUUGAAACCA 
                 2790- 
                 A- 
                 445 
                 UACUAGTGGUUUCAAUGG 
                 2788- 
               
               
                 901373. 
                 1701303. 
                   
                 CUAGUA 
                 2810 
                 1701304. 
                   
                 UGUGA 
                 2810 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 317 
                 GAGGCAGCUUGAGUU 
                 1683- 
                 A- 
                 446 
                 UCGUUUAACUCAAGCUGC 
                 1681- 
               
               
                 901332. 
                 1701221. 
                   
                 AAACGA 
                 1703 
                 1701222. 
                   
                 CUCGC 
                 1703 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 318 
                 GCACUGAAACUUUUC 
                  649- 
                 A- 
                 447 
                 UUGGACGAAAAGUUUCA 
                  647- 
               
               
                 901311. 
                 1701179. 
                   
                 GUCCAA 
                  669 
                 1701180. 
                   
                 GUGCGA 
                  669 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 319 
                 GUUUUAUAUACGGUA 
                 2952- 
                 A- 
                 448 
                 UAUAAGTACCGUAUAUAA 
                 2950- 
               
               
                 901423. 
                 1701403. 
                   
                 CUUAUA 
                 2972 
                 1701404. 
                   
                 AACAC 
                 2972 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 320 
                 CACCAUUGAAACCAC 
                 2791- 
                 A- 
                 449 
                 UAACUAGUGGUUUCAAU 
                 2789- 
               
               
                 901374. 
                 1701305. 
                   
                 UAGUUA 
                 2811 
                 1701306. 
                   
                 GGUGUG 
                 2811 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 321 
                 AUCACCAUGCAGAUU 
                 1342- 
                 A- 
                 450 
                 UCGCAUAAUCUGCAUGGU 
                 1340- 
               
               
                 901319. 
                 1701195. 
                   
                 AUGCGA 
                 1362 
                 1701196. 
                   
                 GAUGU 
                 1362 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 322 
                 UGAGUUAAACGAACG 
                 1692- 
                 A- 
                 451 
                 UAAGUACGUUCGUUUAAC 
                 1690- 
               
               
                 901341. 
                 1701239. 
                   
                 UACUUA 
                 1712 
                 1701240. 
                   
                 UCAAG 
                 1712 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 323 
                 GAAAGUGUUUUAUA 
                 2946- 
                 A- 
                 452 
                 UACCGUAUAUAAAACACU 
                 2944- 
               
               
                 901422. 
                 1701401. 
                   
                 UACGGUA 
                 2966 
                 1701402. 
                   
                 UUCUC 
                 2966 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 324 
                 ACAGUCACUAGCUUA 
                 3164- 
                 A- 
                 453 
                 UCAAGATAAGCUAGUGAC 
                 3162- 
               
               
                 901385. 
                 1701327. 
                   
                 UCUUGA 
                 3184 
                 1701328. 
                   
                 UGUCA 
                 3184 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 325 
                 GUGCUACUGUUUAUC 
                 3481- 
                 A- 
                 454 
                 UUUACGGAUAAACAGUA 
                 3479- 
               
               
                 901391. 
                 1701339. 
                   
                 CGUAAA 
                 3501 
                 1701340. 
                   
                 GCACCA 
                 3501 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 326 
                 CCUGCAAAAACACAG 
                 1652- 
                 A- 
                 455 
                 UCGAGUCUGUGUUUUUGC 
                 1650- 
               
               
                 901329. 
                 1701215. 
                   
                 ACUCGA 
                 1672 
                 1701216. 
                   
                 AGGAA 
                 1672 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 327 
                 CAAAAACACAGACUC 
                 1656- 
                 A- 
                 456 
                 UAACGCGAGUCUGUGUUU 
                 1654- 
               
               
                 901331. 
                 1701219. 
                   
                 GCGUUA 
                 1676 
                 1701220. 
                   
                 UUGCA 
                 1676 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 328 
                 UGCUGUGGACUUGAG 
                 2221- 
                 A- 
                 457 
                 UCCCAACUCAAGUCCACA 
                 2219- 
               
               
                 901368. 
                 1701293. 
                   
                 UUGGGA 
                 2241 
                 1701294. 
                   
                 GCAGU 
                 2241 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 329 
                 GUGCUAAUGUUAUUG 
                 2182- 
                 A- 
                 458 
                 UGACACCAAUAACAUUAG 
                 2180- 
               
               
                 901364. 
                 1701285. 
                   
                 GUGUCA 
                 2202 
                 1701286. 
                   
                 CACUG 
                 2202 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 330 
                 UGGUGCUACUGUUUA 
                 3479- 
                 A- 
                 459 
                 UACGGATAAACAGUAGCA 
                 3477- 
               
               
                 901389. 
                 1701335. 
                   
                 UCCGUA 
                 3499 
                 1701336. 
                   
                 CCAAU 
                 3499 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 331 
                 AGAAAGUGUUUUAU 
                 2945- 
                 A- 
                 460 
                 UCCGUATAUAAAACACUU 
                 2943- 
               
               
                 901421. 
                 1701399. 
                   
                 AUACGGA 
                 2965 
                 1701400. 
                   
                 UCUCU 
                 2965 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 332 
                 AACUAUUUAUGAGAU 
                 3062- 
                 A- 
                 461 
                 UGAUACAUCUCAUAAAUA 
                 3060- 
               
               
                 901380. 
                 1701317. 
                   
                 GUAUCA 
                 3082 
                 1701318. 
                   
                 GUUGA 
                 3082 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 333 
                 AGUUAAACGAACGUA 
                 1694- 
                 A- 
                 462 
                 UGCAAGTACGUUCGUUUA 
                 1692- 
               
               
                 901343. 
                 1701243. 
                   
                 CUUGCA 
                 1714 
                 1701244. 
                   
                 ACUCA 
                 1714 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 334 
                 CAUCUUCAAGCCAUC 
                 1251- 
                 A- 
                 463 
                 UCACAGGAUGGCUUGAAG 
                 1249- 
               
               
                 901317. 
                 1701191. 
                   
                 CUGUGA 
                 1271 
                 1701192. 
                   
                 AUGUA 
                 1271 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 335 
                 UUUUUUUUCAGUAUU 
                 3027- 
                 A- 
                 464 
                 UCCAAGAAUACUGAAAAA 
                 3025- 
               
               
                 901424. 
                 1701405. 
                   
                 CUUGGA 
                 3047 
                 1701406. 
                   
                 AAACC 
                 3047 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 336 
                 UUAUCCGUAAUAAUU 
                 3491- 
                 A- 
                 465 
                 UCCCACAAUUAUUACGGA 
                 3489- 
               
               
                 901431. 
                 1701419. 
                   
                 GUGGGA 
                 3511 
                 1701420. 
                   
                 UAAAC 
                 3511 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 337 
                 GGUACUUAUUUAAUA 
                 2963- 
                 A- 
                 466 
                 UAGGGATAUUAAAUAAG 
                 2961- 
               
               
                 901378. 
                 1701313. 
                   
                 UCCCUA 
                 2983 
                 1701314. 
                   
                 UACCGU 
                 2983 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 338 
                 CACGUCUUUGUCUCU 
                 3527- 
                 A- 
                 467 
                 UGCACUAGAGACAAAGAC 
                 3525- 
               
               
                 901434. 
                 1701425. 
                   
                 AGUGCA 
                 3547 
                 1701426. 
                   
                 GUGAU 
                 3547 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 339 
                 UGCAAAAACACAGAC 
                 1654- 
                 A- 
                 468 
                 UCGCGAGUCUGUGUUUUU 
                 1652- 
               
               
                 901412. 
                 1701381. 
                   
                 UCGCGA 
                 1674 
                 1701382. 
                   
                 GCAGG 
                 1674 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 340 
                 ACUAUUUAUGAGAUG 
                 3063- 
                 A- 
                 469 
                 UAGAUACAUCUCAUAAAU 
                 3061- 
               
               
                 901426. 
                 1701409. 
                   
                 UAUCUA 
                 3083 
                 1701410. 
                   
                 AGUUG 
                 3083 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 341 
                 AGGGGCAAAAACGAA 
                 1484- 
                 A- 
                 470 
                 UGCGCUTUCGUUUUUGCC 
                 1482- 
               
               
                 901322. 
                 1701201. 
                   
                 AGCGCA 
                 1504 
                 1701202. 
                   
                 CCUUU 
                 1504 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 342 
                 UUGCUCUCUUAUUUG 
                 3094- 
                 A- 
                 471 
                 UCGGUACAAAUAAGAGA 
                 3092- 
               
               
                 901381. 
                 1701319. 
                   
                 UACCGA 
                 3114 
                 1701320. 
                   
                 GCAAGA 
                 3114 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 343 
                 AUUUGUUUGUACAAG 
                 1616- 
                 A- 
                 472 
                 UCGGAUCUUGUACAAACA 
                 1614- 
               
               
                 901324. 
                 1701205. 
                   
                 AUCCGA 
                 1636 
                 1701206. 
                   
                 AAUGC 
                 1636 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 344 
                 UUGCAGAUGUGACAA 
                 1710- 
                 A- 
                 473 
                 UUCGGCTUGUCACAUCUG 
                 1708- 
               
               
                 901347. 
                 1701251. 
                   
                 GCCGAA 
                 1730 
                 1701252. 
                   
                 CAAGU 
                 1730 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 345 
                 CAACUAUUUAUGAGA 
                 3061- 
                 A- 
                 474 
                 UAUACATCUCAUAAAUAG 
                 3059- 
               
               
                 901379. 
                 1701315. 
                   
                 UGUAUA 
                 3081 
                 1701316. 
                   
                 UUGAA 
                 3081 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 346 
                 AAUUCUACAUACUAA 
                 3419- 
                 A- 
                 475 
                 UGAGAUTUAGUAUGUAG 
                 3417- 
               
               
                 901428. 
                 1701413. 
                   
                 AUCUCA 
                 3439 
                 1701414. 
                   
                 AAUUCU 
                 3439 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 347 
                 AUGUCCUCACACCAU 
                 2782- 
                 A- 
                 476 
                 UUUUCAAUGGUGUGAGG 
                 2780- 
               
               
                 901371. 
                 1701299. 
                   
                 UGAAAA 
                 2802 
                 1701300. 
                   
                 ACAUAG 
                 2802 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 348 
                 UUGUUUGUACAAGAU 
                 1618- 
                 A- 
                 477 
                 UUGCGGAUCUUGUACAAA 
                 1616- 
               
               
                 901408. 
                 1701373. 
                   
                 CCGCAA 
                 1638 
                 1701374. 
                   
                 CAAAU 
                 1638 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 349 
                 UAAUCCAGAAACCUG 
                 1870- 
                 A- 
                 478 
                 UCAUUUCAGGUUUCUGGA 
                 1868- 
               
               
                 901417. 
                 1701391. 
                   
                 AAAUGA 
                 1890 
                 1701392. 
                   
                 UUAAG 
                 1890 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 350 
                 GAAAAAAAAUCAGUU 
                 1456- 
                 A- 
                 479 
                 UCCUCGAACUGAUUUUUU 
                 1454- 
               
               
                 901400. 
                 1701357. 
                   
                 CGAGGA 
                 1476 
                 1701358. 
                   
                 UUCUU 
                 1476 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 351 
                 GGGCAAAAACGAAAG 
                 1486- 
                 A- 
                 480 
                 UUUGCGCUUUCGUUUUUG 
                 1484- 
               
               
                 901323. 
                 1701203. 
                   
                 CGCAAA 
                 1506 
                 1701204. 
                   
                 CCCCU 
                 1506 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 352 
                 UGAAGUUCAUGGAUG 
                 1160- 
                 A- 
                 481 
                 UAUAGACAUCCAUGAACU 
                 1158- 
               
               
                 901316. 
                 1701189. 
                   
                 UCUAUA 
                 1180 
                 1701190. 
                   
                 UCACC 
                 1180 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 353 
                 CACGAAGUGGUGAAG 
                 1150- 
                 A- 
                 482 
                 UAUGAACUUCACCACUUC 
                 1148- 
               
               
                 901315. 
                 1701187. 
                   
                 UUCAUA 
                 1170 
                 1701188. 
                   
                 GUGAU 
                 1170 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 354 
                 ACGUCUUUGUCUCUA 
                 3528- 
                 A- 
                 483 
                 UUGCACTAGAGACAAAGA 
                 3526- 
               
               
                 901395. 
                 1701347. 
                   
                 GUGCAA 
                 3548 
                 1701348. 
                   
                 CGUGA 
                 3548 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 355 
                 AACAUCACCAUGCAG 
                 1339- 
                 A- 
                 484 
                 UAUAAUCUGCAUGGUGA 
                 1337- 
               
               
                 901318. 
                 1701193. 
                   
                 AUUAUA 
                 1359 
                 1701194. 
                   
                 UGUUGG 
                 1359 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 356 
                 GGUGCUACUGUUUAU 
                 3480- 
                 A- 
                 485 
                 UUACGGAUAAACAGUAGC 
                 3478- 
               
               
                 901390. 
                 1701337. 
                   
                 CCGUAA 
                 3500 
                 1701338. 
                   
                 ACCAA 
                 3500 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 357 
                 AAAUAGACAUUGCUA 
                 3362- 
                 A- 
                 486 
                 UCAGAATAGCAAUGUCUA 
                 3360- 
               
               
                 901387. 
                 1701331. 
                   
                 UUCUGA 
                 3382 
                 1701332. 
                   
                 UUUUA 
                 3382 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 358 
                 UUCCCCAAAUCACUG 
                  278- 
                 A- 
                 487 
                 UAUCCACAGUGAUUUGGG 
                  276- 
               
               
                 901307. 
                 1701171. 
                   
                 UGGAUA 
                  298 
                 1701172. 
                   
                 GAAGU 
                  298 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 359 
                 GAUCCGCAGACGUGU 
                 1630- 
                 A- 
                 488 
                 UCAUUUACACGUCUGCGG 
                 1628- 
               
               
                 901410. 
                 1701377. 
                   
                 AAAUGA 
                 1650 
                 1701378. 
                   
                 AUCUU 
                 1650 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 360 
                 UUAACAUCACGUCUU 
                 3520- 
                 A- 
                 489 
                 UAGACAAAGACGUGAUG 
                 3518- 
               
               
                 901433. 
                 1701423. 
                   
                 UGUCUA 
                 3540 
                 1701424. 
                   
                 UUAAUA 
                 3540 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 361 
                 AAAGUGAGUGACCUG 
                  415- 
                 A- 
                 490 
                 UAAAAGCAGGUCACUCAC 
                  413- 
               
               
                 901308. 
                 1701173. 
                   
                 CUUUUA 
                  435 
                 1701174. 
                   
                 UUUGC 
                  435 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 362 
                 AAAAACACAGACUCG 
                 1657- 
                 A- 
                 491 
                 UCAACGCGAGUCUGUGUU 
                 1655- 
               
               
                 901414. 
                 1701385. 
                   
                 CGUUGA 
                 1677 
                 1701386. 
                   
                 UUUGC 
                 1677 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 363 
                 CGUCGCACUGAAACU 
                  645- 
                 A- 
                 492 
                 UCGAAAAGUUUCAGUGCG 
                  643- 
               
               
                 901309. 
                 1701175. 
                   
                 UUUCGA 
                  665 
                 1701176. 
                   
                 ACGCC 
                  665 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 364 
                 AACAGUGCUAAUGUU 
                 2178- 
                 A- 
                 493 
                 UCCAAUAACAUUAGCACU 
                 2176- 
               
               
                 901362. 
                 1701281. 
                   
                 AUUGGA 
                 2198 
                 1701282. 
                   
                 GUUAA 
                 2198 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 365 
                 UUCGUCCAACUUCUG 
                  661- 
                 A- 
                 494 
                 UCAGCCCAGAAGUUGGAC 
                  659- 
               
               
                 901397. 
                 1701351. 
                   
                 GGCUGA 
                  681 
                 1701352. 
                   
                 GAAAA 
                  681 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 366 
                 AUUGGUGUCUUCACU 
                 2193- 
                 A- 
                 495 
                 UCAUCCAGUGAAGACACC 
                 2191- 
               
               
                 901419. 
                 1701395. 
                   
                 GGAUGA 
                 2213 
                 1701396. 
                   
                 AAUAA 
                 2213 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 367 
                 GCAAAAACACAGACU 
                 1655- 
                 A- 
                 496 
                 UACGCGAGUCUGUGUUUU 
                 1653- 
               
               
                 901413. 
                 1701383. 
                   
                 CGCGUA 
                 1675 
                 1701384. 
                   
                 UGCAG 
                 1675 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 368 
                 AAAAAUCAGUUCGAG 
                 1460- 
                 A- 
                 497 
                 UCUUUCCUCGAACUGAUU 
                 1458- 
               
               
                 901401. 
                 1701359. 
                   
                 GAAAGA 
                 1480 
                 1701360. 
                   
                 UUUUU 
                 1480 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 369 
                 CAGACGUGUAAAUGU 
                 1636- 
                 A- 
                 498 
                 UCAGGAACAUUUACACGU 
                 1634- 
               
               
                 901411. 
                 1701379. 
                   
                 UCCUGA 
                 1656 
                 1701380. 
                   
                 CUGCG 
                 1656 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 370 
                 UGUCCUCACACCAUU 
                 2783- 
                 A- 
                 499 
                 UGUUUCAAUGGUGUGAG 
                 2781- 
               
               
                 901372. 
                 1701301. 
                   
                 GAAACA 
                 2803 
                 1701302. 
                   
                 GACAUA 
                 2803 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 371 
                 UUUUUUUCAGUAUUC 
                 3028- 
                 A- 
                 500 
                 UACCAAGAAUACUGAAAA 
                 3026- 
               
               
                 901425. 
                 1701407. 
                   
                 UUGGUA 
                 3048 
                 1701408. 
                   
                 AAAAC 
                 3048 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 372 
                 AGAUCCGCAGACGUG 
                 1629- 
                 A- 
                 501 
                 UAUUUACACGUCUGCGGA 
                 1627- 
               
               
                 901409. 
                 1701375. 
                   
                 UAAAUA 
                 1649 
                 1701376. 
                   
                 UCUUG 
                 1649 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 373 
                 CCCUCUUGGAAUUGG 
                 1978- 
                 A- 
                 502 
                 UCGAAUCCAAUUCCAAGA 
                 1976- 
               
               
                 901418. 
                 1701393. 
                   
                 AUUCGA 
                 1998 
                 1701394. 
                   
                 GGGAC 
                 1998 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 374 
                 GAUAUUAACAUCACG 
                 3516- 
                 A- 
                 503 
                 UAAAGACGUGAUGUUAA 
                 3514- 
               
               
                 901393. 
                 1701343. 
                   
                 UCUUUA 
                 3536 
                 1701344. 
                   
                 UAUCUU 
                 3536 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 375 
                 UUGGUGCUACUGUUU 
                 3478- 
                 A- 
                 504 
                 UCGGAUAAACAGUAGCAC 
                 3476- 
               
               
                 901388. 
                 1701333. 
                   
                 AUCCGA 
                 3498 
                 1701334. 
                   
                 CAAUA 
                 3498 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 376 
                 AAGGGGCAAAAACGA 
                 1483- 
                 A- 
                 505 
                 UCGCUUTCGUUUUUGCCC 
                 1481- 
               
               
                 901404. 
                 1701365. 
                   
                 AAGCGA 
                 1503 
                 1701366. 
                   
                 cuuuc 
                 1503 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 377 
                 CUUGCAGAUGUGACA 
                 1709- 
                 A- 
                 506 
                 UCGGCUTGUCACAUCUGC 
                 1707- 
               
               
                 901346. 
                 1701249. 
                   
                 AGCCGA 
                 1729 
                 1701250. 
                   
                 AAGUA 
                 1729 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 378 
                 AAAUCAGUUCGAGGA 
                 1462- 
                 A- 
                 507 
                 UCCCUUTCCUCGAACUGA 
                 1460- 
               
               
                 901403. 
                 1701363. 
                   
                 AAGGGA 
                 1482 
                 1701364. 
                   
                 UUUUU 
                 1482 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 379 
                 ACUUUUCGUCCAACU 
                  657- 
                 A- 
                 508 
                 UCCAGAAGUUGGACGAAA 
                  655- 
               
               
                 901396. 
                 1701349. 
                   
                 UCUGGA 
                  677 
                 1701350. 
                   
                 AGUUU 
                  677 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 380 
                 AUUAACAUCACGUCU 
                 3519- 
                 A- 
                 509 
                 UGACAAAGACGUGAUGU 
                 3517- 
               
               
                 901432. 
                 1701421. 
                   
                 UUGUCA 
                 3539 
                 1701422. 
                   
                 UAAUAU 
                 3539 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 381 
                 CGUCUUUGUCUCUAG 
                 3529- 
                 A- 
                 510 
                 UCUGCACUAGAGACAAAG 
                 3527- 
               
               
                 901435. 
                 1701427. 
                   
                 UGCAGA 
                 3549 
                 1701428. 
                   
                 ACGUG 
                 3549 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 382 
                 AACACAGACUCGCGU 
                 1660- 
                 A- 
                 511 
                 UUUGCAACGCGAGUCUGU 
                 1658- 
               
               
                 901416. 
                 1701389. 
                   
                 UGCAAA 
                 1680 
                 1701390. 
                   
                 GUUUU 
                 1680 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 383 
                 AUAUUAACAUCACGU 
                 3517- 
                 A- 
                 512 
                 UCAAAGACGUGAUGUUA 
                 3515- 
               
               
                 901394. 
                 1701345. 
                   
                 CUUUGA 
                 3537 
                 1701346. 
                   
                 AUAUCU 
                 3537 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 384 
                 GUUUAUCCGUAAUAA 
                 3489- 
                 A- 
                 513 
                 UCACAATUAUUACGGAUA 
                 3487- 
               
               
                 901429. 
                 1701415. 
                   
                 UUGUGA 
                 3509 
                 1701416. 
                   
                 AACAG 
                 3509 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 385 
                 AAAAUCAGUUCGAGG 
                 1461- 
                 A- 
                 514 
                 UCCUUUCCUCGAACUGAU 
                 1459- 
               
               
                 901402. 
                 1701361. 
                   
                 AAAGGA 
                 1481 
                 1701362. 
                   
                 UUUUU 
                 1481 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 386 
                 UUUAUCCGUAAUAAU 
                 3490- 
                 A- 
                 515 
                 UCCACAAUUAUUACGGAU 
                 3488- 
               
               
                 901430. 
                 1701417. 
                   
                 UGUGGA 
                 3510 
                 1701418. 
                   
                 AAACA 
                 3510 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 387 
                 AGGACAUUGCUGUGC 
                 2518- 
                 A- 
                 516 
                 UCCAAAGCACAGCAAUGU 
                 2516- 
               
               
                 901369. 
                 1701295. 
                   
                 UUUGGA 
                 2538 
                 1701296. 
                   
                 CCUGA 
                 2538 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3A 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Modified Single Strands and Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                 Anti- 
                 SEQ 
                   
                   
                 SEQ ID 
               
               
                   
                 Sense 
                 SEQ 
                   
                 sense 
                 ID NO: 
                   
                   
                 NO: 
               
               
                 Duplex 
                 Oligo 
                 ID NO: 
                   
                 Oligo 
                 (Anti- 
                   
                 mRNA target 
                 (mRNA 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Name 
                 sense) 
                 Antisense Sequence 
                 sequence 
                 target) 
               
               
                   
               
               
                 AD- 
                 A- 
                 517 
                 ascsuga(Uhd)AfcAfGfAfac 
                 A- 
                 647 
                 VPusAfsucgAfuCfGfu 
                 AGACUGAUACAG 
                 4353 
               
               
                 953340.1 
                 1701261. 
                   
                 gaucgauaL96 
                 1068804. 
                   
                 ucuGfuAfucaguscsu 
                 AACGAUCGAUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 518 
                 asasaga(Chd)UfgAfUfAfca 
                 A- 
                 648 
                 VPusAfsucgUfuCfUfg 
                 GGAAAGACUGAU 
                 4354 
               
               
                 953336.1 
                 1701253. 
                   
                 gaacgauaL96 
                 1068796. 
                   
                 uauCfaGfucuuuscsc 
                 ACAGAACGAUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 519 
                 gsasgaa(Ahd)GfuGfUfUfuu 
                 A- 
                 649 
                 VPusCfsguaUfaUfAfaa 
                 AAGAGAAAGUGU 
                 4355 
               
               
                 953363.1 
                 1701307. 
                   
                 auauacgaL96 
                 1070290. 
                   
                 acAfcUfuucucsusu 
                 UUUAUAUACGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 520 
                 asgsacu(Ghd)AfuAfCfAfga 
                 A- 
                 650 
                 VPusCfsgauCfgUfUfcu 
                 AAAGACUGAUAC 
                 4356 
               
               
                 953338.1 
                 1701257. 
                   
                 acgaucgaL96 
                 1068800. 
                   
                 guAfuCfagucususu 
                 AGAACGAUCGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 521 
                 csasacu(Ahd)UfuUfAfUfga 
                 A- 
                 651 
                 VPusAfsuacAfuCfUfca 
                 UUCAACUAUUUA 
                 4357 
               
               
                 953367.1 
                 1701315. 
                   
                 gauguauaL96 
                 1070376. 
                   
                 uaAfaUfaguugsasa 
                 UGAGAUGUAUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 522 
                 asasgac(Uhd)GfaUfAfCfag 
                 A- 
                 652 
                 VPusGfsaucGfuUfCfug 
                 GAAAGACUGAUA 
                 4358 
               
               
                 953337.1 
                 1701255. 
                   
                 aacgaucaL96 
                 1068798. 
                   
                 uaUfcAfgucuususc 
                 CAGAACGAUCG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 523 
                 asusaca(Ghd)AfaCfGfAfuc 
                 A- 
                 653 
                 VPusCfsuguAfuCfGfau 
                 UGAUACAGAACG 
                 4359 
               
               
                 953342.1 
                 1701265. 
                   
                 gauacagaL96 
                 1068812. 
                   
                 cgUfuCfuguauscsa 
                 AUCGAUACAGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 524 
                 asascag(Uhd)GfcUfAfAfug 
                 A- 
                 654 
                 VPusCfscaaUfaAfCfau 
                 UUAACAGUGCUA 
                 4360 
               
               
                 953350.1 
                 1701281. 
                   
                 uuauuggaL96 
                 1069342. 
                   
                 uaGfcAfcuguusasa 
                 AUGUUAUUGGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 525 
                 gsusgcu(Ahd)AfuGfUfUfau 
                 A- 
                 655 
                 VPusGfsacaCfcAfAfua 
                 CAGUGCUAAUGU 
                 4361 
               
               
                 953352.1 
                 1701285. 
                   
                 uggugucaL96 
                 1069350. 
                   
                 acAfuUfagcacsusg 
                 UAUUGGUGUCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 526 
                 asascua(Uhd)UfuAfUfGfag 
                 A- 
                 656 
                 VPusGfsauaCfaUfCfuc 
                 UCAACUAUUUAU 
                 4362 
               
               
                 953368.1 
                 1701317. 
                   
                 auguaucaL96 
                 1070378. 
                   
                 auAfaAfuaguusgsa 
                 GAGAUGUAUCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 527 
                 csasgaa(Chd)AfgUfCfCfuu 
                 A- 
                 657 
                 VPusCfsuggAfuUfAfa 
                 GACAGAACAGUCC 
                 4363 
               
               
                 953344.1 
                 1701269. 
                   
                 aauccagaL96 
                 1068918. 
                   
                 ggaCfuGfuucugsusc 
                 UUAAUCCAGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 528 
                 gsascug(Ahd)UfaCfAfGfaa 
                 A- 
                 658 
                 VPusUfscgaUfcGfUfuc 
                 AAGACUGAUACA 
                 4364 
               
               
                 953339.1 
                 1701259. 
                   
                 cgaucgaaL96 
                 1068802. 
                   
                 ugUfaUfcagucsusu 
                 GAACGAUCGAU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 529 
                 ascsagc(Ahd)CfaAfCfAfaa 
                 A- 
                 659 
                 VPusAfsuucAfcAfUfu 
                 CUACAGCACAACA 
                 4365 
               
               
                 953387.1 
                 1701355. 
                   
                 ugugaauaL96 
                 1068170. 
                   
                 uguUfgUfgcugusasg 
                 AAUGUGAAUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 530 
                 asasaua(Ghd)AfcAfUfUfgc 
                 A- 
                 660 
                 VPusCfsagaAfuAfGfca 
                 UAAAAUAGACAU 
                 4366 
               
               
                 953375.1 
                 1701331. 
                   
                 uauucugaL96 
                 1070792. 
                   
                 auGfuCfuauuususa 
                 UGCUAUUCUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 531 
                 usasuug(Ghd)UfgUfCfUfuc 
                 A- 
                 661 
                 VPusAfsuccAfgUfGfaa 
                 GUUAUUGGUGUC 
                 4367 
               
               
                 953355.1 
                 1701291. 
                   
                 acuggauaL96 
                 1069370. 
                   
                 gaCfaCfcaauasasc 
                 UUCACUGGAUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 532 
                 csusgau(Ahd)CfaGfAfAfcg 
                 A- 
                 662 
                 VPusUfsaucGfaUfCfgu 
                 GACUGAUACAGA 
                 4368 
               
               
                 953341.1 
                 1701263. 
                   
                 aucgauaaL96 
                 1068806. 
                   
                 ucUfgUfaucagsusc 
                 ACGAUCGAUAC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 533 
                 gscsucu(Chd)UfuAfUfUfug 
                 A- 
                 663 
                 VPusAfsccgGfuAfCfaa 
                 UUGCUCUCUUAUU 
                 4369 
               
               
                 953370.1 
                 1701321. 
                   
                 uaccgguaL96 
                 1070446. 
                   
                 auAfaGfagagcsasa 
                 UGUACCGGUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 534 
                 csascca(Uhd)UfgAfAfAfcc 
                 A- 
                 664 
                 VPusAfsacuAfgUfGfg 
                 CACACCAUUGAAA 
                 4370 
               
               
                 953362.1 
                 1701305. 
                   
                 acuaguuaL96 
                 1070096. 
                   
                 uuuCfaAfuggugsusg 
                 CCACUAGUUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 535 
                 gsgscag(Chd)UfuGfAfGfuu 
                 A- 
                 665 
                 VPusUfsucgUfuUfAfac 
                 GAGGCAGCUUGA 
                 4371 
               
               
                 953322.1 
                 1701225. 
                   
                 aaacgaaaL96 
                 1068596. 
                   
                 ucAfaGfcugccsusc 
                 GUUAAACGAAC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 536 
                 ususaaa(Chd)GfaAfCfGfua 
                 A- 
                 666 
                 VPusCfsugcAfaGfUfac 
                 AGUUAAACGAAC 
                 4372 
               
               
                 953332.1 
                 1701245. 
                   
                 cuugcagaL96 
                 1068618. 
                   
                 guUfcGfuuuaascsu 
                 GUACUUGCAGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 537 
                 uscsggu(Ghd)AfcAfGfUfca 
                 A- 
                 667 
                 VPusAfsagcUfaGfUfga 
                 GAUCGGUGACAG 
                 4373 
               
               
                 953371.1 
                 1701323. 
                   
                 cuagcuuaL96 
                 1070550. 
                   
                 cuGfuCfaccgasusc 
                 UCACUAGCUUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 538 
                 asgsuua(Ahd)AfcGfAfAfcg 
                 A- 
                 668 
                 VPusGfscaaGfuAfCfgu 
                 UGAGUUAAACGA 
                 4374 
               
               
                 953331.1 
                 1701243. 
                   
                 uacuugcaL96 
                 1068614. 
                   
                 ucGfuUfuaacuscsa 
                 ACGUACUUGCA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 539 
                 gscsagc(Uhd)UfgAfGfUfua 
                 A- 
                 669 
                 VPusGfsuucGfuUfUfaa 
                 AGGCAGCUUGAG 
                 4375 
               
               
                 953323.1 
                 1701227. 
                   
                 aacgaacaL96 
                 1068598. 
                   
                 cuCfaAfgcugcscsu 
                 UUAAACGAACG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 540 
                 asgsugc(Uhd)AfaUfGfUfua 
                 A- 
                 670 
                 VPusAfscacCfaAfUfaa 
                 ACAGUGCUAAUG 
                 4376 
               
               
                 953351.1 
                 1701283. 
                   
                 uugguguaL96 
                 1069348. 
                   
                 caUfuAfgcacusgsu 
                 UUAUUGGUGUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 541 
                 csgsaag(Uhd)GfgUfGfAfag 
                 A- 
                 671 
                 VPusCfscauGfaAfCfuu 
                 CACGAAGUGGUG 
                 4377 
               
               
                 953386.1 
                 1701353. 
                   
                 uucauggaL96 
                 1067728. 
                   
                 caCfcAfcuucgsusg 
                 AAGUUCAUGGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 542 
                 asasagc(Ahd)UfuUfGfUfuu 
                 A- 
                 672 
                 VPusCfsuugUfaCfAfaa 
                 AGAAAGCAUUUG 
                 4378 
               
               
                 953394.1 
                 1701369. 
                   
                 guacaagaL96 
                 1068448. 
                   
                 caAfaUfgcuuuscsu 
                 UUUGUACAAGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 543 
                 asusguc(Chd)UfcAfCfAfcc 
                 A- 
                 673 
                 VPusUfsuucAfaUfGfg 
                 CUAUGUCCUCACA 
                 4379 
               
               
                 953359.1 
                 1701299. 
                   
                 auugaaaaL96 
                 1070078. 
                   
                 uguGfaGfgacausasg 
                 CCAUUGAAAC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 544 
                 usgsagu(Uhd)AfaAfCfGfaa 
                 A- 
                 674 
                 VPusAfsaguAfcGfUfuc 
                 CUUGAGUUAAAC 
                 4380 
               
               
                 953329.1 
                 1701239. 
                   
                 cguacuuaL96 
                 1068610. 
                   
                 guUfuAfacucasasg 
                 GAACGUACUUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 545 
                 ascsacc(Ahd)UfuGfAfAfac 
                 A- 
                 675 
                 VPusAfscuaGfuGfGfu 
                 UCACACCAUUGAA 
                 4381 
               
               
                 953361.1 
                 1701303. 
                   
                 cacuaguaL96 
                 1070094. 
                   
                 uucAfaUfggugusgsa 
                 ACCACUAGUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 546 
                 csasaaa(Ahd)CfaCfAfGfac 
                 A- 
                 676 
                 VPusAfsacgCfgAfGfuc 
                 UGCAAAAACACAG 
                 4382 
               
               
                 953319.1 
                 1701219. 
                   
                 ucgcguuaL96 
                 1068538. 
                   
                 ugUfgUfuuuugscsa 
                 ACUCGCGUUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 547 
                 usgsucc(Uhd)CfaCfAfCfca 
                 A- 
                 677 
                 VPusGfsuuuCfaAfUfg 
                 UAUGUCCUCACAC 
                 4383 
               
               
                 953360.1 
                 1701301. 
                   
                 uugaaacaL96 
                 1070080. 
                   
                 gugUfgAfggacasusa 
                 CAUUGAAACC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 548 
                 csasgcu(Uhd)GfaGfUfUfaa 
                 A- 
                 678 
                 VPusCfsguuCfgUfUfua 
                 GGCAGCUUGAGU 
                 4384 
               
               
                 953324.1 
                 1701229. 
                   
                 acgaacgaL96 
                 1068600. 
                   
                 acUfcAfagcugscsc 
                 UAAACGAACGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 549 
                 gsgsugc(Uhd)AfcUfGfUfuu 
                 A- 
                 679 
                 VPusUfsacgGfaUfAfaa 
                 UUGGUGCUACUG 
                 4385 
               
               
                 953378.1 
                 1701337. 
                   
                 auccguaaL96 
                 1070874. 
                   
                 caGfuAfgcaccsasa 
                 UUUAUCCGUAA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 550 
                 ususgcu(Chd)UfcUfUfAfuu 
                 A- 
                 680 
                 VPusCfsgguAfcAfAfau 
                 UCUUGCUCUCUUA 
                 4386 
               
               
                 953369.1 
                 1701319. 
                   
                 uguaccgaL96 
                 1070442. 
                   
                 aaGfaGfagcaasgsa 
                 UUUGUACCGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 551 
                 uscsuug(Chd)UfgCfUfAfaa 
                 A- 
                 681 
                 VPusUfscggUfgAfUfu 
                 UUUCUUGCUGCUA 
                 4387 
               
               
                 953347.1 
                 1701275. 
                   
                 ucaccgaaL96 
                 1069188. 
                   
                 uagCfaGfcaagasasa 
                 AAUCACCGAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 552 
                 csgsgua(Chd)UfuAfUfUfua 
                 A- 
                 682 
                 VPusGfsggaUfaUfUfaa 
                 UACGGUACUUAU 
                 4388 
               
               
                 953365.1 
                 1701311. 
                   
                 auaucccaL96 
                 1070326. 
                   
                 auAfaGfuaccgsusa 
                 UUAAUAUCCCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 553 
                 asasaau(Ahd)GfaCfAfUfug 
                 A- 
                 683 
                 VPusAfsgaaUfaGfCfaa 
                 AUAAAAUAGACA 
                 4389 
               
               
                 953374.1 
                 1701329. 
                   
                 cuauucuaL96 
                 1070790. 
                   
                 ugUfcUfauuuusasu 
                 UUGCUAUUCUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 554 
                 ascsuuu(Uhd)CfgUfCfCfaa 
                 A- 
                 684 
                 VPusCfscagAfaGfUfug 
                 AAACUUUUCGUCC 
                 4390 
               
               
                 953384.1 
                 1701349. 
                   
                 cuucuggaL96 
                 1067266. 
                   
                 gaCfgAfaaagususu 
                 AACUUCUGGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 555 
                 ususggu(Ghd)CfuAfCfUfgu 
                 A- 
                 685 
                 VPusCfsggaUfaAfAfca 
                 UAUUGGUGCUAC 
                 4391 
               
               
                 953376.1 
                 1701333. 
                   
                 uuauccgaL96 
                 1070870. 
                   
                 guAfgCfaccaasusa 
                 UGUUUAUCCGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 556 
                 gsusuau(Uhd)GfgUfGfUfcu 
                 A- 
                 686 
                 VPusCfscagUfgAfAfga 
                 AUGUUAUUGGUG 
                 4392 
               
               
                 953354.1 
                 1701289. 
                   
                 ucacuggaL96 
                 1069366. 
                   
                 caCfcAfauaacsasu 
                 UCUUCACUGGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 557 
                 ususcgu(Chd)CfaAfCfUfuc 
                 A- 
                 687 
                 VPusCfsagcCfcAfGfaa 
                 UUUUCGUCCAACU 
                 4393 
               
               
                 953385.1 
                 1701351. 
                   
                 ugggcugaL96 
                 1067274. 
                   
                 guUfgGfacgaasasa 
                 UCUGGGCUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 558 
                 ususcuu(Ghd)CfuGfCfUfaa 
                 A- 
                 688 
                 VPusCfsgguGfaUfUfua 
                 UUUUCUUGCUGCU 
                 4394 
               
               
                 953346.1 
                 1701273. 
                   
                 aucaccgaL96 
                 1069186. 
                   
                 gcAfgCfaagaasasa 
                 AAAUCACCGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 559 
                 gsgsuac(Uhd)UfaUfUfUfaa 
                 A- 
                 689 
                 VPusAfsgggAfuAfUfu 
                 ACGGUACUUAUU 
                 4395 
               
               
                 953366.1 
                 1701313. 
                   
                 uaucccuaL96 
                 1070328. 
                   
                 aaaUfaAfguaccsgsu 
                 UAAUAUCCCUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 560 
                 asusauu(Ahd)AfcAfUfCfac 
                 A- 
                 690 
                 VPusCfsaaaGfaCfGfug 
                 AGAUAUUAACAU 
                 4396 
               
               
                 953382.1 
                 1701345. 
                   
                 gucuuugaL96 
                 1070912. 
                   
                 auGfuUfaauauscsu 
                 CACGUCUUUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 561 
                 gsasggc(Ahd)GfcUfUfGfag 
                 A- 
                 691 
                 VPusCfsguuUfaAfCfuc 
                 GCGAGGCAGCUUG 
                 4397 
               
               
                 953320.1 
                 1701221. 
                   
                 uuaaacgaL96 
                 1068592. 
                   
                 aaGfcUfgccucsgsc 
                 AGUUAAACGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 562 
                 gsusgcu(Ahd)CfuGfUfUfua 
                 A- 
                 692 
                 VPusUfsuacGfgAfUfaa 
                 UGGUGCUACUGU 
                 4398 
               
               
                 953379.1 
                 1701339. 
                   
                 uccguaaaL96 
                 1070876. 
                   
                 acAfgUfagcacscsa 
                 UUAUCCGUAAU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 563 
                 asgsgca(Ghd)CfuUfGfAfgu 
                 A- 
                 693 
                 VPusUfscguUfuAfAfc 
                 CGAGGCAGCUUGA 
                 4399 
               
               
                 953321.1 
                 1701223. 
                   
                 uaaacgaaL96 
                 1068594. 
                   
                 ucaAfgCfugccuscsg 
                 GUUAAACGAA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 564 
                 usgsgug(Chd)UfaCfUfGfuu 
                 A- 
                 694 
                 VPusAfscggAfuAfAfac 
                 AUUGGUGCUACU 
                 4400 
               
               
                 953377.1 
                 1701335. 
                   
                 uauccguaL96 
                 1070872. 
                   
                 agUfaGfcaccasasu 
                 GUUUAUCCGUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 565 
                 asasggg(Ghd)CfaAfAfAfac 
                 A- 
                 695 
                 VPusCfsgcuUfuCfGfuu 
                 GAAAGGGGCAAA 
                 4401 
               
               
                 953392.1 
                 1701365. 
                   
                 gaaagcgaL96 
                 1700876. 
                   
                 uuUfgCfcccuususc 
                 AACGAAAGCGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 566 
                 ascsagu(Chd)AfcUfAfGfcu 
                 A- 
                 696 
                 VPusCfsaagAfuAfAfgc 
                 UGACAGUCACUAG 
                 4402 
               
               
                 953373.1 
                 1701327. 
                   
                 uaucuugaL96 
                 1070562. 
                   
                 uaGfuGfacuguscsa 
                 CUUAUCUUGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 567 
                 ascsggu(Ahd)CfuUfAfUfuu 
                 A- 
                 697 
                 VPusGfsgauAfuUfAfaa 
                 AUACGGUACUUA 
                 4403 
               
               
                 953364.1 
                 1701309. 
                   
                 aauauccaL96 
                 1070324. 
                   
                 uaAfgUfaccgusasu 
                 UUUAAUAUCCC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 568 
                 gsasguu(Ahd)AfaCfGfAfac 
                 A- 
                 698 
                 VPusCfsaagUfaCfGfuu 
                 UUGAGUUAAACG 
                 4404 
               
               
                 953330.1 
                 1701241. 
                   
                 guacuugaL96 
                 1068612. 
                   
                 cgUfuUfaacucsasa 
                 AACGUACUUGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 569 
                 usgsuua(Uhd)UfgGfUfGfuc 
                 A- 
                 699 
                 VPusCfsaguGfaAfGfac 
                 AAUGUUAUUGGU 
                 4405 
               
               
                 953353.1 
                 1701287. 
                   
                 uucacugaL96 
                 1069364. 
                   
                 acCfaAfuaacasusu 
                 GUCUUCACUGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 570 
                 csgsaca(Ghd)AfaCfAfGfuc 
                 A- 
                 700 
                 VPusGfsauuAfaGfGfac 
                 AUCGACAGAACAG 
                 4406 
               
               
                 953343.1 
                 1701267. 
                   
                 cuuaaucaL96 
                 1068912. 
                   
                 ugUfuCfugucgsasu 
                 UCCUUAAUCC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 571 
                 asasaau(Chd)AfgUfUfCfga 
                 A- 
                 701 
                 VPusCfscuuUfcCfUfcg 
                 AAAAAAUCAGUU 
                 4407 
               
               
                 953390.1 
                 1701361. 
                   
                 ggaaaggaL96 
                 1700873. 
                   
                 aaCfuGfauuuususu 
                 CGAGGAAAGGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 572 
                 csusugg(Ahd)AfuUfGfGfau 
                 A- 
                 702 
                 VPusAfsuggCfgAfAfu 
                 CUCUUGGAAUUG 
                 4408 
               
               
                 953345.1 
                 1701271. 
                   
                 ucgccauaL96 
                 1069132. 
                   
                 ccaAfuUfccaagsasg 
                 GAUUCGCCAUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 573 
                 asgsaga(Ahd)GfaGfAfCfac 
                 A- 
                 703 
                 VPusCfsaacAfaUfGfug 
                 GAAGAGAAGAGA 
                 4409 
               
               
                 953358.1 
                 1701297. 
                   
                 auuguugaL96 
                 1069954. 
                   
                 ucUfcUfucucususc 
                 CACAUUGUUGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 574 
                 ascsguc(Uhd)UfuGfUfCfuc 
                 A- 
                 704 
                 VPusUfsgcaCfuAfGfag 
                 UCACGUCUUUGUC 
                 4410 
               
               
                 953383.1 
                 1701347. 
                   
                 uagugcaaL96 
                 1070934. 
                   
                 acAfaAfgacgusgsa 
                 UCUAGUGCAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 575 
                 usgsaca(Ghd)UfcAfCfUfag 
                 A- 
                 705 
                 VPusAfsgauAfaGfCfua 
                 GGUGACAGUCACU 
                 4411 
               
               
                 953372.1 
                 1701325. 
                   
                 cuuaucuaL96 
                 1070558. 
                   
                 guGfaCfugucascsc 
                 AGCUUAUCUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 576 
                 ususgag(Uhd)UfaAfAfCfga 
                 A- 
                 706 
                 VPusAfsguaCfgUfUfcg 
                 GCUUGAGUUAAA 
                 4412 
               
               
                 953328.1 
                 1701237. 
                   
                 acguacuaL96 
                 1068608. 
                   
                 uuUfaAfcucaasgsc 
                 CGAACGUACUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 577 
                 gsasaag(Chd)AfuUfUfGfuu 
                 A- 
                 707 
                 VPusUfsuguAfcAfAfac 
                 GAGAAAGCAUUU 
                 4413 
               
               
                 953393.1 
                 1701367. 
                   
                 uguacaaaL96 
                 1068446. 
                   
                 aaAfuGfcuuucsusc 
                 GUUUGUACAAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 578 
                 asuscac(Chd)AfuGfCfAfga 
                 A- 
                 708 
                 VPusCfsgcaUfaAfUfcu 
                 ACAUCACCAUGCA 
                 4414 
               
               
                 953307.1 
                 1701195. 
                   
                 uuaugcgaL96 
                 1068040. 
                   
                 gcAfuGfgugausgsu 
                 GAUUAUGCGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 579 
                 csascca(Uhd)GfcAfGfAfuu 
                 A- 
                 709 
                 VPusUfsccgCfaUfAfau 
                 AUCACCAUGCAGA 
                 4415 
               
               
                 953308.1 
                 1701197. 
                   
                 augcggaaL96 
                 1068044. 
                   
                 cuGfcAfuggugsasu 
                 UUAUGCGGAU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 580 
                 csusuga(Ghd)UfuAfAfAfcg 
                 A- 
                 710 
                 VPusGfsuacGfuUfCfgu 
                 AGCUUGAGUUAA 
                 4416 
               
               
                 953327.1 
                 1701235. 
                   
                 aacguacaL96 
                 1068606. 
                   
                 uuAfaCfucaagscsu 
                 ACGAACGUACU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 581 
                 ususgca(Ghd)AfuGfUfGfac 
                 A- 
                 711 
                 VPusUfscggCfuUfGfuc 
                 ACUUGCAGAUGU 
                 4417 
               
               
                 953335.1 
                 1701251. 
                   
                 aagccgaaL96 
                 1068646. 
                   
                 acAfuCfugcaasgsu 
                 GACAAGCCGAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 582 
                 ascsuau(Uhd)UfaUfGfAfga 
                 A- 
                 712 
                 VPusAfsgauAfcAfUfcu 
                 CAACUAUUUAUG 
                 4418 
               
               
                 953414.1 
                 1701409. 
                   
                 uguaucuaL96 
                 1070380. 
                   
                 caUfaAfauagususg 
                 AGAUGUAUCUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 583 
                 ususuuu(Uhd)UfuCfAfGfua 
                 A- 
                 713 
                 VPusCfscaaGfaAfUfac 
                 GGUUUUUUUUCA 
                 4419 
               
               
                 953412.1 
                 1701405. 
                   
                 uucuuggaL96 
                 1700897. 
                   
                 ugAfaAfaaaaascsc 
                 GUAUUCUUGGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 584 
                 gsusuuu(Ahd)UfaUfAfCfgg 
                 A- 
                 714 
                 VPusAfsuaaGfuAfCfcg 
                 GUGUUUUAUAUA 
                 4420 
               
               
                 953411.1 
                 1701403. 
                   
                 uacuuauaL96 
                 1070306. 
                   
                 uaUfaUfaaaacsasc 
                 CGGUACUUAUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 585 
                 gsasaag(Uhd)GfuUfUfUfau 
                 A- 
                 715 
                 VPusAfsccgUfaUfAfua 
                 GAGAAAGUGUUU 
                 4421 
               
               
                 953410.1 
                 1701401. 
                   
                 auacgguaL96 
                 1070294. 
                   
                 aaAfcAfcuuucsusc 
                 UAUAUACGGUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 586 
                 uscsacu(Ghd)GfaUfGfUfau 
                 A- 
                 716 
                 VPusCfsaguCfaAfAfua 
                 CUUCACUGGAUGU 
                 4422 
               
               
                 953408.1 
                 1701397. 
                   
                 uugacugaL96 
                 1069392. 
                   
                 caUfcCfagugasasg 
                 AUUUGACUGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 587 
                 gscsuug(Ahd)GfuUfAfAfac 
                 A- 
                 717 
                 VPusUfsacgUfuCfGfuu 
                 CAGCUUGAGUUA 
                 4423 
               
               
                 953326.1 
                 1701233. 
                   
                 gaacguaaL96 
                 1068604. 
                   
                 uaAfcUfcaagcsusg 
                 AACGAACGUAC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 588 
                 cscsucc(Ghd)AfaAfCfCfau 
                 A- 
                 718 
                 VPusAfsaagUfuCfAfug 
                 GGCCUCCGAAACC 
                 4424 
               
               
                 953300.1 
                 1701181. 
                   
                 gaacuuuaL96 
                 1067482. 
                   
                 guUfuCfggaggscsc 
                 AUGAACUUUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 589 
                 asasaaa(Uhd)CfaGfUfUfcg 
                 A- 
                 719 
                 VPusCfsuuuCfcUfCfga 
                 AAAAAAAUCAGU 
                 4425 
               
               
                 953389.1 
                 1701359. 
                   
                 aggaaagaL96 
                 1700871. 
                   
                 acUfgAfuuuuususu 
                 UCGAGGAAAGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 590 
                 gsasgaa(Uhd)UfcUfAfCfau 
                 A- 
                 720 
                 VPusAfsuuuAfgUfAfu 
                 UAGAGAAUUCUA 
                 4426 
               
               
                 953415.1 
                 1701411. 
                   
                 acuaaauaL96 
                 1070816. 
                   
                 guaGfaAfuucucsusa 
                 CAUACUAAAUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 591 
                 asgsauu(Ahd)UfgCfGfGfau 
                 A- 
                 721 
                 VPusAfsgguUfuGfAfu 
                 GCAGAUUAUGCG 
                 4427 
               
               
                 953309.1 
                 1701199. 
                   
                 caaaccuaL96 
                 1068060. 
                   
                 ccgCfaUfaaucusgsc 
                 GAUCAAACCUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 592 
                 asasauc(Ahd)GfuUfCfGfag 
                 A- 
                 722 
                 VPusCfsccuUfuCfCfuc 
                 AAAAAUCAGUUC 
                 4428 
               
               
                 953391.1 
                 1701363. 
                   
                 gaaagggaL96 
                 1068240. 
                   
                 gaAfcUfgauuususu 
                 GAGGAAAGGGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 593 
                 gscsauu(Uhd)GfuUfUfGfua 
                 A- 
                 723 
                 VPusGfsaucUfuGfUfac 
                 AAGCAUUUGUUU 
                 4429 
               
               
                 953395.1 
                 1701371. 
                   
                 caagaucaL96 
                 1068454. 
                   
                 aaAfcAfaaugcsusu 
                 GUACAAGAUCC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 594 
                 csascga(Ahd)GfuGfGfUfga 
                 A- 
                 724 
                 VPusAfsugaAfcUfUfca 
                 AUCACGAAGUGG 
                 4430 
               
               
                 953303.1 
                 1701187. 
                   
                 aguucauaL96 
                 1067724. 
                   
                 ccAfcUfucgugsasu 
                 UGAAGUUCAUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 595 
                 usasauc(Chd)AfgAfAfAfcc 
                 A- 
                 725 
                 VPusCfsauuUfcAfGfgu 
                 CUUAAUCCAGAAA 
                 4431 
               
               
                 953405.1 
                 1701391. 
                   
                 ugaaaugaL96 
                 1068942. 
                   
                 uuCfuGfgauuasasg 
                 CCUGAAAUGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 596 
                 csasucu(Uhd)CfaAfGfCfca 
                 A- 
                 726 
                 VPusCfsacaGfgAfUfgg 
                 UACAUCUUCAAGC 
                 4432 
               
               
                 953305.1 
                 1701191. 
                   
                 uccugugaL96 
                 1067926. 
                   
                 cuUfgAfagaugsusa 
                 CAUCCUGUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 597 
                 usgscua(Chd)UfgUfUfUfau 
                 A- 
                 727 
                 VPusAfsuuaCfgGfAfua 
                 GGUGCUACUGUU 
                 4433 
               
               
                 953380.1 
                 1701341. 
                   
                 ccguaauaL96 
                 1070878. 
                   
                 aaCfaGfuagcascsc 
                 UAUCCGUAAUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 598 
                 ususgcu(Ghd)CfuAfAfAfuc 
                 A- 
                 728 
                 VPusGfscucGfgUfGfau 
                 UCUUGCUGCUAAA 
                 4434 
               
               
                 953349.1 
                 1701279. 
                   
                 accgagcaL96 
                 1069192. 
                   
                 uuAfgCfagcaasgsa 
                 UCACCGAGCC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 599 
                 gsasuau(Uhd)AfaCfAfUfca 
                 A- 
                 729 
                 VPusAfsaagAfcGfUfga 
                 AAGAUAUUAACA 
                 4435 
               
               
                 953381.1 
                 1701343. 
                   
                 cgucuuuaL96 
                 1070910. 
                   
                 ugUfuAfauaucsusu 
                 UCACGUCUUUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 600 
                 csusgca(Ahd)AfaAfCfAfca 
                 A- 
                 730 
                 VPusGfscgaGfuCfUfgu 
                 UCCUGCAAAAACA 
                 4436 
               
               
                 953318.1 
                 1701217. 
                   
                 gacucgcaL96 
                 1068532. 
                   
                 guUfuUfugcagsgsa 
                 CAGACUCGCG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 601 
                 csusugc(Uhd)GfcUfAfAfau 
                 A- 
                 731 
                 VPusCfsucgGfuGfAfu 
                 UUCUUGCUGCUAA 
                 4437 
               
               
                 953348.1 
                 1701277. 
                   
                 caccgagaL96 
                 1069190. 
                   
                 uuaGfcAfgcaagsasa 
                 AUCACCGAGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 602 
                 asgsaaa(Ghd)UfgUfUfUfua 
                 A- 
                 732 
                 VPusCfscguAfuAfUfaa 
                 AGAGAAAGUGUU 
                 4438 
               
               
                 953409.1 
                 1701399. 
                   
                 uauacggaL96 
                 1070292. 
                   
                 aaCfaCfuuucuscsu 
                 UUAUAUACGGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 603 
                 asascau(Chd)AfcCfAfUfgc 
                 A- 
                 733 
                 VPusAfsuaaUfcUfGfca 
                 CCAACAUCACCAU 
                 4439 
               
               
                 953306.1 
                 1701193. 
                   
                 agauuauaL96 
                 1068034. 
                   
                 ugGfuGfauguusgsg 
                 GCAGAUUAUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 604 
                 csgscag(Ahd)CfgUfGfUfaa 
                 A- 
                 734 
                 VPusGfsgaaCfaUfUfua 
                 UCCGCAGACGUGU 
                 4440 
               
               
                 953316.1 
                 1701213. 
                   
                 auguuccaL96 
                 1068494. 
                   
                 caCfgUfcugcgsgsa 
                 AAAUGUUCCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 605 
                 asgscuu(Ghd)AfgUfUfAfaa 
                 A- 
                 735 
                 VPusAfscguUfcGfUfu 
                 GCAGCUUGAGUU 
                 4441 
               
               
                 953325.1 
                 1701231. 
                   
                 cgaacguaL96 
                 1068602. 
                   
                 uaaCfuCfaagcusgsc 
                 AAACGAACGUA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 606 
                 gscsacu(Ghd)AfaAfCfUfuu 
                 A- 
                 736 
                 VPusUfsggaCfgAfAfaa 
                 UCGCACUGAAACU 
                 4442 
               
               
                 953299.1 
                 1701179. 
                   
                 ucguccaaL96 
                 1067250. 
                   
                 guUfuCfagugcsgsa 
                 UUUCGUCCAA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 607 
                 asasuuc(Uhd)AfcAfUfAfcu 
                 A- 
                 737 
                 VPusGfsagaUfuUfAfg 
                 AGAAUUCUACAU 
                 4443 
               
               
                 953416.1 
                 1701413. 
                   
                 aaaucucaL96 
                 1070822. 
                   
                 uauGfuAfgaauuscsu 
                 ACUAAAUCUCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 608 
                 cscsgca(Ghd)AfcGfUfGfua 
                 A- 
                 738 
                 VPusGfsaacAfuUfUfac 
                 AUCCGCAGACGUG 
                 4444 
               
               
                 953315.1 
                 1701211. 
                   
                 aauguucaL96 
                 1068492. 
                   
                 acGfuCfugcggsasu 
                 UAAAUGUUCC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 609 
                 uscscgc(Ahd)GfaCfGfUfgu 
                 A- 
                 739 
                 VPusAfsacaUfuUfAfca 
                 GAUCCGCAGACGU 
                 4445 
               
               
                 953314.1 
                 1701209. 
                   
                 aaauguuaL96 
                 1068490. 
                   
                 cgUfcUfgcggasusc 
                 GUAAAUGUUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 610 
                 csgscac(Uhd)GfaAfAfCfuu 
                 A- 
                 740 
                 VPusGfsgacGfaAfAfag 
                 GUCGCACUGAAAC 
                 4446 
               
               
                 953298.1 
                 1701177. 
                   
                 uucguccaL96 
                 1067248. 
                   
                 uuUfcAfgugcgsasc 
                 UUUUCGUCCA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 611 
                 cscscuc(Uhd)UfgGfAfAfuu 
                 A- 
                 741 
                 VPusCfsgaaUfcCfAfau 
                 GUCCCUCUUGGAA 
                 4447 
               
               
                 953406.1 
                 1701393. 
                   
                 ggauucgaL96 
                 1069124. 
                   
                 ucCfaAfgagggsasc 
                 UUGGAUUCGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 612 
                 csasgac(Ghd)UfgUfAfAfau 
                 A- 
                 742 
                 VPusCfsaggAfaCfAfuu 
                 CGCAGACGUGUAA 
                 4448 
               
               
                 953399.1 
                 1701379. 
                   
                 guuccugaL96 
                 1068498. 
                   
                 uaCfaCfgucugscsg 
                 AUGUUCCUGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 613 
                 ascsgaa(Chd)GfuAfCfUfug 
                 A- 
                 743 
                 VPusAfscauCfuGfCfaa 
                 AAACGAACGUACU 
                 4449 
               
               
                 953333.1 
                 1701247. 
                   
                 cagauguaL96 
                 1068626. 
                   
                 guAfcGfuucgususu 
                 UGCAGAUGUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 614 
                 asusccg(Chd)AfgAfCfGfug 
                 A- 
                 744 
                 VPusAfscauUfuAfCfac 
                 AGAUCCGCAGACG 
                 4450 
               
               
                 953313.1 
                 1701207. 
                   
                 uaaauguaL96 
                 1068488. 
                   
                 guCfuGfcggauscsu 
                 UGUAAAUGUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 615 
                 csasgaa(Uhd)CfaUfCfAfcg 
                 A- 
                 745 
                 VPusAfsccaCfuUfCfgu 
                 GGCAGAAUCAUCA 
                 4451 
               
               
                 953302.1 
                 1701185. 
                   
                 aagugguaL96 
                 1067706. 
                   
                 gaUfgAfuucugscsc 
                 CGAAGUGGUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 616 
                 cscsugc(Ahd)AfaAfAfCfac 
                 A- 
                 746 
                 VPusCfsgagUfcUfGfug 
                 UUCCUGCAAAAAC 
                 4452 
               
               
                 953317.1 
                 1701215. 
                   
                 agacucgaL96 
                 1068530. 
                   
                 uuUfuUfgcaggsasa 
                 ACAGACUCGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 617 
                 asgsgac(Ahd)UfuGfCfUfgu 
                 A- 
                 747 
                 VPusCfscaaAfgCfAfca 
                 UCAGGACAUUGCU 
                 4453 
               
               
                 953357.1 
                 1701295. 
                   
                 gcuuuggaL96 
                 1069740. 
                   
                 gcAfaUfguccusgsa 
                 GUGCUUUGGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 618 
                 gsgsgca(Ghd)AfaUfCfAfuc 
                 A- 
                 748 
                 VPusAfscuuCfgUfGfau 
                 GAGGGCAGAAUC 
                 4454 
               
               
                 953301.1 
                 1701183. 
                   
                 acgaaguaL96 
                 1067700. 
                   
                 gaUfuCfugcccsusc 
                 AUCACGAAGUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 619 
                 usgsaag(Uhd)UfcAfUfGfga 
                 A- 
                 749 
                 VPusAfsuagAfcAfUfcc 
                 GGUGAAGUUCAU 
                 4455 
               
               
                 953304.1 
                 1701189. 
                   
                 ugucuauaL96 
                 1067744. 
                   
                 auGfaAfcuucascsc 
                 GGAUGUCUAUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 620 
                 csgsucg(Chd)AfcUfGfAfaa 
                 A- 
                 750 
                 VPusCfsgaaAfaGfUfuu 
                 GGCGUCGCACUGA 
                 4456 
               
               
                 953297.1 
                 1701175. 
                   
                 cuuuucgaL96 
                 1067242. 
                   
                 caGfuGfcgacgscsc 
                 AACUUUUCGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 621 
                 gsasaaa(Ahd)AfaAfUfCfag 
                 A- 
                 751 
                 VPusCfscucGfaAfCfug 
                 AAGAAAAAAAAU 
                 4457 
               
               
                 953388.1 
                 1701357. 
                   
                 uucgaggaL96 
                 1700869. 
                   
                 auUfuUfuuuucsusu 
                 CAGUUCGAGGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 622 
                 asusugg(Uhd)GfuCfUfUfca 
                 A- 
                 752 
                 VPusCfsaucCfaGfUfga 
                 UUAUUGGUGUCU 
                 4458 
               
               
                 953407.1 
                 1701395. 
                   
                 cuggaugaL96 
                 1069372. 
                   
                 agAfcAfccaausasa 
                 UCACUGGAUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 623 
                 asgsauc(Chd)GfcAfGfAfcg 
                 A- 
                 753 
                 VPusAfsuuuAfcAfCfg 
                 CAAGAUCCGCAGA 
                 4459 
               
               
                 953397.1 
                 1701375. 
                   
                 uguaaauaL96 
                 1068484. 
                   
                 ucuGfcGfgaucususg 
                 CGUGUAAAUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 624 
                 gsasucc(Ghd)CfaGfAfCfgu 
                 A- 
                 754 
                 VPusCfsauuUfaCfAfcg 
                 AAGAUCCGCAGAC 
                 4460 
               
               
                 953398.1 
                 1701377. 
                   
                 guaaaugaL96 
                 1068486. 
                   
                 ucUfgCfggaucsusu 
                 GUGUAAAUGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 625 
                 ususguu(Uhd)GfuAfCfAfag 
                 A- 
                 755 
                 VPusUfsgcgGfaUfCfuu 
                 AUUUGUUUGUAC 
                 4461 
               
               
                 953396.1 
                 1701373. 
                   
                 auccgcaaL96 
                 1068462. 
                   
                 guAfcAfaacaasasu 
                 AAGAUCCGCAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 626 
                 usgscug(Uhd)GfgAfCfUfug 
                 A- 
                 756 
                 VPusCfsccaAfcUfCfaa 
                 ACUGCUGUGGACU 
                 4462 
               
               
                 953356.1 
                 1701293. 
                   
                 aguugggaL96 
                 1069428. 
                   
                 guCfcAfcagcasgsu 
                 UGAGUUGGGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 627 
                 csascgu(Chd)UfuUfGfUfcu 
                 A- 
                 757 
                 VPusGfscacUfaGfAfga 
                 AUCACGUCUUUGU 
                 4463 
               
               
                 953422.1 
                 1701425. 
                   
                 cuagugcaL96 
                 1070932. 
                   
                 caAfaGfacgugsasu 
                 CUCUAGUGCA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 628 
                 ususuuu(Uhd)UfcAfGfUfau 
                 A- 
                 758 
                 VPusAfsccaAfgAfAfua 
                 GUUUUUUUUCAG 
                 4464 
               
               
                 953413.1 
                 1701407. 
                   
                 ucuugguaL96 
                 1700899. 
                   
                 cuGfaAfaaaaasasc 
                 UAUUCUUGGUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 629 
                 gsusgcu(Ghd)GfaAfUfUfug 
                 A- 
                 759 
                 VPusUfsgaaUfaUfCfaa 
                 CGGUGCUGGAAU 
                 4465 
               
               
                 953294.1 
                 1701169. 
                   
                 auauucaaL96 
                 1066884. 
                   
                 auUfcCfagcacscsg 
                 UUGAUAUUCAU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 630 
                 ususaac(Ahd)UfcAfCfGfuc 
                 A- 
                 760 
                 VPusAfsgacAfaAfGfac 
                 UAUUAACAUCACG 
                 4466 
               
               
                 953421.1 
                 1701423. 
                   
                 uuugucuaL96 
                 1070918. 
                   
                 guGfaUfguuaasusa 
                 UCUUUGUCUC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 631 
                 asgsggg(Chd)AfaAfAfAfcg 
                 A- 
                 761 
                 VPusGfscgcUfuUfCfgu 
                 AAAGGGGCAAAA 
                 4467 
               
               
                 953310.1 
                 1701201. 
                   
                 aaagcgcaL96 
                 1700793. 
                   
                 uuUfuGfccccususu 
                 ACGAAAGCGCA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 632 
                 asasagu(Ghd)AfgUfGfAfcc 
                 A- 
                 762 
                 VPusAfsaaaGfcAfGfgu 
                 GCAAAGUGAGUG 
                 4468 
               
               
                 953296.1 
                 1701173. 
                   
                 ugcuuuuaL96 
                 1067146. 
                   
                 caCfuCfacuuusgsc 
                 ACCUGCUUUUG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 633 
                 asasaaa(Chd)AfcAfGfAfcu 
                 A- 
                 763 
                 VPusCfsaacGfcGfAfgu 
                 GCAAAAACACAGA 
                 4469 
               
               
                 953402.1 
                 1701385. 
                   
                 cgcguugaL96 
                 1068540. 
                   
                 cuGfuGfuuuuusgsc 
                 CUCGCGUUGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 634 
                 asusuug(Uhd)UfuGfUfAfca 
                 A- 
                 764 
                 VPusCfsggaUfcUfUfgu 
                 GCAUUUGUUUGU 
                 4470 
               
               
                 953312.1 
                 1701205. 
                   
                 agauccgaL96 
                 1068458. 
                   
                 acAfaAfcaaausgsc 
                 ACAAGAUCCGC 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 635 
                 ususccc(Chd)AfaAfUfCfac 
                 A- 
                 765 
                 VPusAfsuccAfcAfGfug 
                 ACUUCCCCAAAUC 
                 4471 
               
               
                 953295.1 
                 1701171. 
                   
                 uguggauaL96 
                 1700778. 
                   
                 auUfuGfgggaasgsu 
                 ACUGUGGAUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 636 
                 asusuaa(Chd)AfuCfAfCfgu 
                 A- 
                 766 
                 VPusGfsacaAfaGfAfcg 
                 AUAUUAACAUCAC 
                 4472 
               
               
                 953420.1 
                 1701421. 
                   
                 cuuugucaL96 
                 1070916. 
                   
                 ugAfuGfuuaausasu 
                 GUCUUUGUCU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 637 
                 csgsucu(Uhd)UfgUfCfUfcu 
                 A- 
                 767 
                 VPusCfsugcAfcUfAfga 
                 CACGUCUUUGUCU 
                 4473 
               
               
                 953423.1 
                 1701427. 
                   
                 agugcagaL96 
                 1070936. 
                   
                 gaCfaAfagacgsusg 
                 CUAGUGCAGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 638 
                 asasaac(Ahd)CfaGfAfCfuc 
                 A- 
                 768 
                 VPusGfscaaCfgCfGfag 
                 CAAAAACACAGAC 
                 4474 
               
               
                 953403.1 
                 1701387. 
                   
                 gcguugcaL96 
                 1068542. 
                   
                 ucUfgUfguuuususg 
                 UCGCGUUGCA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 639 
                 usgscaa(Ahd)AfaCfAfCfag 
                 A- 
                 769 
                 VPusCfsgcgAfgUfCfug 
                 CCUGCAAAAACAC 
                 4475 
               
               
                 953400.1 
                 1701381. 
                   
                 acucgcgaL96 
                 1068534. 
                   
                 ugUfuUfuugcasgsg 
                 AGACUCGCGU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 640 
                 asascac(Ahd)GfaCfUfCfgc 
                 A- 
                 770 
                 VPusUfsugcAfaCfGfcg 
                 AAAACACAGACUC 
                 4476 
               
               
                 953404.1 
                 1701389. 
                   
                 guugcaaaL96 
                 1068546. 
                   
                 agUfcUfguguususu 
                 GCGUUGCAAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 641 
                 csusugc(Ahd)GfaUfGfUfga 
                 A- 
                 771 
                 VPusCfsggcUfuGfUfca 
                 UACUUGCAGAUG 
                 4477 
               
               
                 953334.1 
                 1701249. 
                   
                 caagccgaL96 
                 1068644. 
                   
                 caUfcUfgcaagsusa 
                 UGACAAGCCGA 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 642 
                 ususuau(Chd)CfgUfAfAfua 
                 A- 
                 772 
                 VPusCfscacAfaUfUfau 
                 UGUUUAUCCGUA 
                 4478 
               
               
                 953418.1 
                 1701417. 
                   
                 auuguggaL96 
                 1070894. 
                   
                 uaCfgGfauaaascsa 
                 AUAAUUGUGGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 643 
                 gscsaaa(Ahd)AfcAfCfAfga 
                 A- 
                 773 
                 VPusAfscgcGfaGfUfcu 
                 CUGCAAAAACACA 
                 4479 
               
               
                 953401.1 
                 1701383. 
                   
                 cucgcguaL96 
                 1068536. 
                   
                 guGfuUfuuugcsasg 
                 GACUCGCGUU 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 644 
                 gsusuua(Uhd)CfcGfUfAfau 
                 A- 
                 774 
                 VPusCfsacaAfuUfAfuu 
                 CUGUUUAUCCGUA 
                 4480 
               
               
                 953417.1 
                 1701415. 
                   
                 aauugugaL96 
                 1070892. 
                   
                 acGfgAfuaaacsasg 
                 AUAAUUGUGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 645 
                 gsgsgca(Ahd)AfaAfCfGfaa 
                 A- 
                 775 
                 VPusUfsugcGfcUfUfuc 
                 AGGGGCAAAAAC 
                 4481 
               
               
                 953311.1 
                 1701203. 
                   
                 agcgcaaaL96 
                 1068252. 
                   
                 guUfuUfugcccscsu 
                 GAAAGCGCAAG 
                   
               
               
                   
                 1 
                   
                   
                 1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 646 
                 ususauc(Chd)GfuAfAfUfaa 
                 A- 
                 776 
                 VPusCfsccaCfaAfUfua 
                 GUUUAUCCGUAA 
                 4482 
               
               
                 953419.1 
                 1701419. 
                   
                 uugugggaL96 
                 1700905. 
                   
                 uuAfcGfgauaasasc 
                 UAAUUGUGGGG 
                   
               
               
                   
                 1 
                   
                   
                 1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3B 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Unmodified Single Strandsand Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                 SEQ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                 ID 
                   
                   
               
               
                   
                 Sense 
                 SEQ ID 
                   
                 mRNA 
                 Antisense 
                 NO: 
                   
                 mRNA 
               
               
                 Duplex 
                 Oligo 
                 NO: 
                   
                 Target 
                 Oligo 
                 (Anti- 
                   
                 Target 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Range 
                 Name 
                 sense) 
                 Antisense Sequence 
                 Range 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 AD- 
                 A- 
                 777 
                 ACUGAUACAGAACG 
                 1799- 
                 A- 
                 907 
                 UAUCGAUCGUUCUGUAUC 
                 1797- 
               
               
                 953340. 
                 1701261. 
                   
                 AUCGAUA 
                 1819 
                 1068804. 
                   
                 AGUCU 
                 1819 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 778 
                 AAAGACUGAUACAG 
                 1795- 
                 A- 
                 908 
                 UAUCGUUCUGUAUCAGUC 
                 1793- 
               
               
                 953336. 
                 1701253. 
                   
                 AACGAUA 
                 1815 
                 1068796. 
                   
                 UUUCC 
                 1815 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 779 
                 GAGAAAGUGUUUU 
                 2944- 
                 A- 
                 909 
                 UCGUAUAUAAAACACUUU 
                 2942- 
               
               
                 953363. 
                 1701307. 
                   
                 AUAUACGA 
                 2964 
                 1070290. 
                   
                 CUCUU 
                 2964 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 780 
                 AGACUGAUACAGAA 
                 1797- 
                 A- 
                 910 
                 UCGAUCGUUCUGUAUCAG 
                 1795- 
               
               
                 953338. 
                 1701257. 
                   
                 CGAUCGA 
                 1817 
                 1068800. 
                   
                 UCUUU 
                 1817 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 781 
                 CAACUAUUUAUGAG 
                 3061- 
                 A- 
                 911 
                 UAUACAUCUCAUAAAUAG 
                 3059- 
               
               
                 953367. 
                 1701315. 
                   
                 AUGUAUA 
                 3081 
                 1070376. 
                   
                 UUGAA 
                 3081 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 782 
                 AAGACUGAUACAGA 
                 1796- 
                 A- 
                 912 
                 UGAUCGUUCUGUAUCAGU 
                 1794- 
               
               
                 953337. 
                 1701255. 
                   
                 ACGAUCA 
                 1816 
                 1068798. 
                   
                 CUUUC 
                 1816 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 783 
                 AUACAGAACGAUCG 
                 1803- 
                 A- 
                 913 
                 UCUGUAUCGAUCGUUCUG 
                 1801- 
               
               
                 953342. 
                 1701265. 
                   
                 AUACAGA 
                 1823 
                 1068812. 
                   
                 UAUCA 
                 1823 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 784 
                 AACAGUGCUAAUGU 
                 2178- 
                 A- 
                 914 
                 UCCAAUAACAUUAGCACU 
                 2176- 
               
               
                 953350. 
                 1701281. 
                   
                 UAUUGGA 
                 2198 
                 1069342. 
                   
                 GUUAA 
                 2198 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 785 
                 GUGCUAAUGUUAUU 
                 2182- 
                 A- 
                 915 
                 UGACACCAAUAACAUUAG 
                 2180- 
               
               
                 953352. 
                 1701285. 
                   
                 GGUGUCA 
                 2202 
                 1069350. 
                   
                 CACUG 
                 2202 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 786 
                 AACUAUUUAUGAGA 
                 3062- 
                 A- 
                 916 
                 UGAUACAUCUCAUAAAUA 
                 3060- 
               
               
                 953368. 
                 1701317. 
                   
                 UGUAUCA 
                 3082 
                 1070378. 
                   
                 GUUGA 
                 3082 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 787 
                 CAGAACAGUCCUUA 
                 1858- 
                 A- 
                 917 
                 UCUGGAUUAAGGACUGUU 
                 1856- 
               
               
                 953344. 
                 1701269. 
                   
                 AUCCAGA 
                 1878 
                 1068918. 
                   
                 CUGUC 
                 1878 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 788 
                 GACUGAUACAGAAC 
                 1798- 
                 A- 
                 918 
                 UUCGAUCGUUCUGUAUCA 
                 1796- 
               
               
                 953339. 
                 1701259. 
                   
                 GAUCGAA 
                 1818 
                 1068802. 
                   
                 GUCUU 
                 1818 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 789 
                 ACAGCACAACAAAU 
                 1407- 
                 A- 
                 919 
                 UAUUCACAUUUGUUGUGC 
                 1405- 
               
               
                 953387. 
                 1701355. 
                   
                 GUGAAUA 
                 1427 
                 1068170. 
                   
                 UGUAG 
                 1427 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 790 
                 AAAUAGACAUUGCU 
                 3362- 
                 A- 
                 920 
                 UCAGAAUAGCAAUGUCUA 
                 3360- 
               
               
                 953375. 
                 1701331. 
                   
                 AUUCUGA 
                 3382 
                 1070792. 
                   
                 UUUUA 
                 3382 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 791 
                 UAUUGGUGUCUUCA 
                 2192- 
                 A- 
                 921 
                 UAUCCAGUGAAGACACCA 
                 2190- 
               
               
                 953355. 
                 1701291. 
                   
                 CUGGAUA 
                 2212 
                 1069370. 
                   
                 AUAAC 
                 2212 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 792 
                 CUGAUACAGAACGA 
                 1800- 
                 A- 
                 922 
                 UUAUCGAUCGUUCUGUAU 
                 1798- 
               
               
                 953341. 
                 1701263. 
                   
                 UCGAUAA 
                 1820 
                 1068806. 
                   
                 CAGUC 
                 1820 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 793 
                 GCUCUCUUAUUUGU 
                 3096- 
                 A- 
                 923 
                 UACCGGUACAAAUAAGAG 
                 3094- 
               
               
                 953370. 
                 1701321. 
                   
                 ACCGGUA 
                 3116 
                 1070446. 
                   
                 AGCAA 
                 3116 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 794 
                 CACCAUUGAAACCA 
                 2791- 
                 A- 
                 924 
                 UAACUAGUGGUUUCAAUG 
                 2789- 
               
               
                 953362. 
                 1701305. 
                   
                 CUAGUUA 
                 2811 
                 1070096. 
                   
                 GUGUG 
                 2811 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 795 
                 GGCAGCUUGAGUUA 
                 1685- 
                 A- 
                 925 
                 UUUCGUUUAACUCAAGCU 
                 1683- 
               
               
                 953322. 
                 1701225. 
                   
                 AACGAAA 
                 1705 
                 1068596. 
                   
                 GCCUC 
                 1705 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 796 
                 UUAAACGAACGUAC 
                 1696- 
                 A- 
                 926 
                 UCUGCAAGUACGUUCGUU 
                 1694- 
               
               
                 953332. 
                 1701245. 
                   
                 UUGCAGA 
                 1716 
                 1068618. 
                   
                 UAACU 
                 1716 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 797 
                 UCGGUGACAGUCAC 
                 3158- 
                 A- 
                 927 
                 UAAGCUAGUGACUGUCAC 
                 3156- 
               
               
                 953371. 
                 1701323. 
                   
                 UAGCUUA 
                 3178 
                 1070550. 
                   
                 CGAUC 
                 3178 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 798 
                 AGUUAAACGAACGU 
                 1694- 
                 A- 
                 928 
                 UGCAAGUACGUUCGUUUA 
                 1692- 
               
               
                 953331. 
                 1701243. 
                   
                 ACUUGCA 
                 1714 
                 1068614. 
                   
                 ACUCA 
                 1714 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 799 
                 GCAGCUUGAGUUAA 
                 1686- 
                 A- 
                 929 
                 UGUUCGUUUAACUCAAGC 
                 1684- 
               
               
                 953323. 
                 1701227. 
                   
                 ACGAACA 
                 1706 
                 1068598. 
                   
                 UGCCU 
                 1706 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 800 
                 AGUGCUAAUGUUAU 
                 2181- 
                 A- 
                 930 
                 UACACCAAUAACAUUAGC 
                 2179- 
               
               
                 953351. 
                 1701283. 
                   
                 UGGUGUA 
                 2201 
                 1069348. 
                   
                 ACUGU 
                 2201 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 801 
                 CGAAGUGGUGAAGU 
                 1152- 
                 A- 
                 931 
                 UCCAUGAACUUCACCACU 
                 1150- 
               
               
                 953386. 
                 1701353. 
                   
                 UCAUGGA 
                 1172 
                 1067728. 
                   
                 UCGUG 
                 1172 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 802 
                 AAAGCAUUUGUUUG 
                 1611- 
                 A- 
                 932 
                 UCUUGUACAAACAAAUGC 
                 1609- 
               
               
                 953394. 
                 1701369. 
                   
                 UACAAGA 
                 1631 
                 1068448. 
                   
                 UUUCU 
                 1631 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 803 
                 AUGUCCUCACACCA 
                 2782- 
                 A- 
                 933 
                 UUUUCAAUGGUGUGAGG 
                 2780- 
               
               
                 953359. 
                 1701299. 
                   
                 UUGAAAA 
                 2802 
                 1070078. 
                   
                 ACAUAG 
                 2802 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 804 
                 UGAGUUAAACGAAC 
                 1692- 
                 A- 
                 934 
                 UAAGUACGUUCGUUUAAC 
                 1690- 
               
               
                 953329. 
                 1701239. 
                   
                 GUACUUA 
                 1712 
                 1068610. 
                   
                 UCAAG 
                 1712 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 805 
                 ACACCAUUGAAACC 
                 2790- 
                 A- 
                 935 
                 UACUAGUGGUUUCAAUGG 
                 2788- 
               
               
                 953361. 
                 1701303. 
                   
                 ACUAGUA 
                 2810 
                 1070094. 
                   
                 UGUGA 
                 2810 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 806 
                 CAAAAACACAGACU 
                 1656- 
                 A- 
                 936 
                 UAACGCGAGUCUGUGUUU 
                 1654- 
               
               
                 953319. 
                 1701219. 
                   
                 CGCGUUA 
                 1676 
                 1068538. 
                   
                 UUGCA 
                 1676 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 807 
                 UGUCCUCACACCAU 
                 2783- 
                 A- 
                 937 
                 UGUUUCAAUGGUGUGAG 
                 2781- 
               
               
                 953360. 
                 1701301. 
                   
                 UGAAACA 
                 2803 
                 1070080. 
                   
                 GACAUA 
                 2803 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 808 
                 CAGCUUGAGUUAAA 
                 1687- 
                 A- 
                 938 
                 UCGUUCGUUUAACUCAAG 
                 1685- 
               
               
                 953324. 
                 1701229. 
                   
                 CGAACGA 
                 1707 
                 1068600. 
                   
                 CUGCC 
                 1707 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 809 
                 GGUGCUACUGUUUA 
                 3480- 
                 A- 
                 939 
                 UUACGGAUAAACAGUAGC 
                 3478- 
               
               
                 953378. 
                 1701337. 
                   
                 UCCGUAA 
                 3500 
                 1070874. 
                   
                 ACCAA 
                 3500 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 810 
                 UUGCUCUCUUAUUU 
                 3094- 
                 A- 
                 940 
                 UCGGUACAAAUAAGAGAG 
                 3092- 
               
               
                 953369. 
                 1701319. 
                   
                 GUACCGA 
                 3114 
                 1070442. 
                   
                 CAAGA 
                 3114 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 811 
                 UCUUGCUGCUAAAU 
                 2010- 
                 A- 
                 941 
                 UUCGGUGAUUUAGCAGCA 
                 2008- 
               
               
                 953347. 
                 1701275. 
                   
                 CACCGAA 
                 2030 
                 1069188. 
                   
                 AGAAA 
                 2030 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 812 
                 CGGUACUUAUUUAA 
                 2962- 
                 A- 
                 942 
                 UGGGAUAUUAAAUAAGU 
                 2960- 
               
               
                 953365. 
                 1701311. 
                   
                 UAUCCCA 
                 2982 
                 1070326. 
                   
                 ACCGUA 
                 2982 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 813 
                 AAAAUAGACAUUGC 
                 3361- 
                 A- 
                 943 
                 UAGAAUAGCAAUGUCUAU 
                 3359- 
               
               
                 953374. 
                 1701329. 
                   
                 UAUUCUA 
                 3381 
                 1070790. 
                   
                 UUUAU 
                 3381 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 814 
                 ACUUUUCGUCCAAC 
                  657- 
                 A- 
                 944 
                 UCCAGAAGUUGGACGAAA 
                  655- 
               
               
                 953384. 
                 1701349. 
                   
                 UUCUGGA 
                  677 
                 1067266. 
                   
                 AGUUU 
                  677 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 815 
                 UUGGUGCUACUGUU 
                 3478- 
                 A- 
                 945 
                 UCGGAUAAACAGUAGCAC 
                 3476- 
               
               
                 953376. 
                 1701333. 
                   
                 UAUCCGA 
                 3498 
                 1070870. 
                   
                 CAAUA 
                 3498 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 816 
                 GUUAUUGGUGUCUU 
                 2190- 
                 A- 
                 946 
                 UCCAGUGAAGACACCAAU 
                 2188- 
               
               
                 953354. 
                 1701289. 
                   
                 CACUGGA 
                 2210 
                 1069366. 
                   
                 AACAU 
                 2210 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 817 
                 UUCGUCCAACUUCU 
                  661- 
                 A- 
                 947 
                 UCAGCCCAGAAGUUGGAC 
                  659- 
               
               
                 953385. 
                 1701351. 
                   
                 GGGCUGA 
                  681 
                 1067274. 
                   
                 GAAAA 
                  681 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 818 
                 UUCUUGCUGCUAAA 
                 2009- 
                 A- 
                 948 
                 UCGGUGAUUUAGCAGCAA 
                 2007- 
               
               
                 953346. 
                 1701273. 
                   
                 UCACCGA 
                 2029 
                 1069186. 
                   
                 GAAAA 
                 2029 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 819 
                 GGUACUUAUUUAAU 
                 2963- 
                 A- 
                 949 
                 UAGGGAUAUUAAAUAAG 
                 2961- 
               
               
                 953366. 
                 1701313. 
                   
                 AUCCCUA 
                 2983 
                 1070328. 
                   
                 UACCGU 
                 2983 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 820 
                 AUAUUAACAUCACG 
                 3517- 
                 A- 
                 950 
                 UCAAAGACGUGAUGUUAA 
                 3515- 
               
               
                 953382. 
                 1701345. 
                   
                 UCUUUGA 
                 3537 
                 1070912. 
                   
                 UAUCU 
                 3537 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 821 
                 GAGGCAGCUUGAGU 
                 1683- 
                 A- 
                 951 
                 UCGUUUAACUCAAGCUGC 
                 1681- 
               
               
                 953320. 
                 1701221. 
                   
                 UAAACGA 
                 1703 
                 1068592. 
                   
                 CUCGC 
                 1703 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 822 
                 GUGCUACUGUUUAU 
                 3481- 
                 A- 
                 952 
                 UUUACGGAUAAACAGUAG 
                 3479- 
               
               
                 953379. 
                 1701339. 
                   
                 CCGUAAA 
                 3501 
                 1070876. 
                   
                 CACCA 
                 3501 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 823 
                 AGGCAGCUUGAGUU 
                 1684- 
                 A- 
                 953 
                 UUCGUUUAACUCAAGCUG 
                 1682- 
               
               
                 953321. 
                 1701223. 
                   
                 AAACGAA 
                 1704 
                 1068594. 
                   
                 CCUCG 
                 1704 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 824 
                 UGGUGCUACUGUUU 
                 3479- 
                 A- 
                 954 
                 UACGGAUAAACAGUAGCA 
                 3477- 
               
               
                 953377. 
                 1701335. 
                   
                 AUCCGUA 
                 3499 
                 1070872. 
                   
                 CCAAU 
                 3499 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 825 
                 AAGGGGCAAAAACG 
                 1483- 
                 A- 
                 955 
                 UCGCUUUCGUUUUUGCCC 
                 1481- 
               
               
                 953392. 
                 1701365. 
                   
                 AAAGCGA 
                 1503 
                 1700876. 
                   
                 CUUUC 
                 1503 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 826 
                 ACAGUCACUAGCUU 
                 3164- 
                 A- 
                 956 
                 UCAAGAUAAGCUAGUGAC 
                 3162- 
               
               
                 953373. 
                 1701327. 
                   
                 AUCUUGA 
                 3184 
                 1070562. 
                   
                 UGUCA 
                 3184 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 827 
                 ACGGUACUUAUUUA 
                 2961- 
                 A- 
                 957 
                 UGGAUAUUAAAUAAGUA 
                 2959- 
               
               
                 953364. 
                 1701309. 
                   
                 AUAUCCA 
                 2981 
                 1070324. 
                   
                 CCGUAU 
                 2981 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 828 
                 GAGUUAAACGAACG 
                 1693- 
                 A- 
                 958 
                 UCAAGUACGUUCGUUUAA 
                 1691- 
               
               
                 953330. 
                 1701241. 
                   
                 UACUUGA 
                 1713 
                 1068612. 
                   
                 CUCAA 
                 1713 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 829 
                 UGUUAUUGGUGUCU 
                 2189- 
                 A- 
                 959 
                 UCAGUGAAGACACCAAUA 
                 2187- 
               
               
                 953353. 
                 1701287. 
                   
                 UCACUGA 
                 2209 
                 1069364. 
                   
                 ACAUU 
                 2209 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 830 
                 CGACAGAACAGUCC 
                 1855- 
                 A- 
                 960 
                 UGAUUAAGGACUGUUCUG 
                 1853- 
               
               
                 953343. 
                 1701267. 
                   
                 UUAAUCA 
                 1875 
                 1068912. 
                   
                 UCGAU 
                 1875 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 831 
                 AAAAUCAGUUCGAG 
                 1461- 
                 A- 
                 961 
                 UCCUUUCCUCGAACUGAU 
                 1459- 
               
               
                 953390. 
                 1701361. 
                   
                 GAAAGGA 
                 1481 
                 1700873. 
                   
                 UUUUU 
                 1481 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 832 
                 CUUGGAAUUGGAUU 
                 1982- 
                 A- 
                 962 
                 UAUGGCGAAUCCAAUUCC 
                 1980- 
               
               
                 953345. 
                 1701271. 
                   
                 CGCCAUA 
                 2002 
                 1069132. 
                   
                 AAGAG 
                 2002 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 833 
                 AGAGAAGAGACACA 
                 2673- 
                 A- 
                 963 
                 UCAACAAUGUGUCUCUUC 
                 2671- 
               
               
                 953358. 
                 1701297. 
                   
                 UUGUUGA 
                 2693 
                 1069954. 
                   
                 UCUUC 
                 2693 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 834 
                 ACGUCUUUGUCUCU 
                 3528- 
                 A- 
                 964 
                 UUGCACUAGAGACAAAGA 
                 3526- 
               
               
                 953383. 
                 1701347. 
                   
                 AGUGCAA 
                 3548 
                 1070934. 
                   
                 CGUGA 
                 3548 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 835 
                 UGACAGUCACUAGC 
                 3162- 
                 A- 
                 965 
                 UAGAUAAGCUAGUGACUG 
                 3160- 
               
               
                 953372. 
                 1701325. 
                   
                 UUAUCUA 
                 3182 
                 1070558. 
                   
                 UCACC 
                 3182 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 836 
                 UUGAGUUAAACGAA 
                 1691- 
                 A- 
                 966 
                 UAGUACGUUCGUUUAACU 
                 1689- 
               
               
                 953328. 
                 1701237. 
                   
                 CGUACUA 
                 1711 
                 1068608. 
                   
                 CAAGC 
                 1711 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 837 
                 GAAAGCAUUUGUUU 
                 1610- 
                 A- 
                 967 
                 UUUGUACAAACAAAUGCU 
                 1608- 
               
               
                 953393. 
                 1701367. 
                   
                 GUACAAA 
                 1630 
                 1068446. 
                   
                 UUCUC 
                 1630 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 838 
                 AUCACCAUGCAGAU 
                 1342- 
                 A- 
                 968 
                 UCGCAUAAUCUGCAUGGU 
                 1340- 
               
               
                 953307. 
                 1701195. 
                   
                 UAUGCGA 
                 1362 
                 1068040. 
                   
                 GAUGU 
                 1362 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 839 
                 CACCAUGCAGAUUA 
                 1344- 
                 A- 
                 969 
                 UUCCGCAUAAUCUGCAUG 
                 1342- 
               
               
                 953308. 
                 1701197. 
                   
                 UGCGGAA 
                 1364 
                 1068044. 
                   
                 GUGAU 
                 1364 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 840 
                 CUUGAGUUAAACGA 
                 1690- 
                 A- 
                 970 
                 UGUACGUUCGUUUAACUC 
                 1688- 
               
               
                 953327. 
                 1701235. 
                   
                 ACGUACA 
                 1710 
                 1068606. 
                   
                 AAGCU 
                 1710 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 841 
                 UUGCAGAUGUGACA 
                 1710- 
                 A- 
                 971 
                 UUCGGCUUGUCACAUCUG 
                 1708- 
               
               
                 953335. 
                 1701251. 
                   
                 AGCCGAA 
                 1730 
                 1068646. 
                   
                 CAAGU 
                 1730 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 842 
                 ACUAUUUAUGAGAU 
                 3063- 
                 A- 
                 972 
                 UAGAUACAUCUCAUAAAU 
                 3061- 
               
               
                 953414. 
                 1701409. 
                   
                 GUAUCUA 
                 3083 
                 1070380. 
                   
                 AGUUG 
                 3083 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 843 
                 UUUUUUUUCAGUAU 
                 3027- 
                 A- 
                 973 
                 UCCAAGAAUACUGAAAAA 
                 3025- 
               
               
                 953412. 
                 1701405. 
                   
                 UCUUGGA 
                 3047 
                 1700897. 
                   
                 AAACC 
                 3047 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 844 
                 GUUUUAUAUACGGU 
                 2952- 
                 A- 
                 974 
                 UAUAAGUACCGUAUAUAA 
                 2950- 
               
               
                 953411. 
                 1701403. 
                   
                 ACUUAUA 
                 2972 
                 1070306. 
                   
                 AACAC 
                 2972 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 845 
                 GAAAGUGUUUUAU 
                 2946- 
                 A- 
                 975 
                 UACCGUAUAUAAAACACU 
                 2944- 
               
               
                 953410. 
                 1701401. 
                   
                 AUACGGUA 
                 2966 
                 1070294. 
                   
                 UUCUC 
                 2966 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 846 
                 UCACUGGAUGUAUU 
                 2203- 
                 A- 
                 976 
                 UCAGUCAAAUACAUCCAG 
                 2201- 
               
               
                 953408. 
                 1701397. 
                   
                 UGACUGA 
                 2223 
                 1069392. 
                   
                 UGAAG 
                 2223 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 847 
                 GCUUGAGUUAAACG 
                 1689- 
                 A- 
                 977 
                 UUACGUUCGUUUAACUCA 
                 1687- 
               
               
                 953326. 
                 1701233. 
                   
                 AACGUAA 
                 1709 
                 1068604. 
                   
                 AGCUG 
                 1709 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 848 
                 CCUCCGAAACCAUG 
                 1028- 
                 A- 
                 978 
                 UAAAGUUCAUGGUUUCGG 
                 1026- 
               
               
                 953300. 
                 1701181. 
                   
                 AACUUUA 
                 1048 
                 1067482. 
                   
                 AGGCC 
                 1048 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 849 
                 AAAAAUCAGUUCGA 
                 1460- 
                 A- 
                 979 
                 UCUUUCCUCGAACUGAUU 
                 1458- 
               
               
                 953389. 
                 1701359. 
                   
                 GGAAAGA 
                 1480 
                 1700871. 
                   
                 UUUUU 
                 1480 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 850 
                 GAGAAUUCUACAUA 
                 3416- 
                 A- 
                 980 
                 UAUUUAGUAUGUAGAAU 
                 3414- 
               
               
                 953415. 
                 1701411. 
                   
                 CUAAAUA 
                 3436 
                 1070816. 
                   
                 UCUCUA 
                 3436 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 851 
                 AGAUUAUGCGGAUC 
                 1352- 
                 A- 
                 981 
                 UAGGUUUGAUCCGCAUAA 
                 1350- 
               
               
                 953309. 
                 1701199. 
                   
                 AAACCUA 
                 1372 
                 1068060. 
                   
                 UCUGC 
                 1372 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 852 
                 AAAUCAGUUCGAGG 
                 1462- 
                 A- 
                 982 
                 UCCCUUUCCUCGAACUGA 
                 1460- 
               
               
                 953391. 
                 1701363. 
                   
                 AAAGGGA 
                 1482 
                 1068240. 
                   
                 UUUUU 
                 1482 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 853 
                 GCAUUUGUUUGUAC 
                 1614- 
                 A- 
                 983 
                 UGAUCUUGUACAAACAAA 
                 1612- 
               
               
                 953395. 
                 1701371. 
                   
                 AAGAUCA 
                 1634 
                 1068454. 
                   
                 UGCUU 
                 1634 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 854 
                 CACGAAGUGGUGAA 
                 1150- 
                 A- 
                 984 
                 UAUGAACUUCACCACUUC 
                 1148- 
               
               
                 953303. 
                 1701187. 
                   
                 GUUCAUA 
                 1170 
                 1067724. 
                   
                 GUGAU 
                 1170 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 855 
                 UAAUCCAGAAACCU 
                 1870- 
                 A- 
                 985 
                 UCAUUUCAGGUUUCUGGA 
                 1868- 
               
               
                 953405. 
                 1701391. 
                   
                 GAAAUGA 
                 1890 
                 1068942. 
                   
                 UUAAG 
                 1890 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 856 
                 CAUCUUCAAGCCAU 
                 1251- 
                 A- 
                 986 
                 UCACAGGAUGGCUUGAAG 
                 1249- 
               
               
                 953305. 
                 1701191. 
                   
                 CCUGUGA 
                 1271 
                 1067926. 
                   
                 AUGUA 
                 1271 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 857 
                 UGCUACUGUUUAUC 
                 3482- 
                 A- 
                 987 
                 UAUUACGGAUAAACAGUA 
                 3480- 
               
               
                 953380. 
                 1701341. 
                   
                 CGUAAUA 
                 3502 
                 1070878. 
                   
                 GCACC 
                 3502 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 858 
                 UUGCUGCUAAAUCA 
                 2012- 
                 A- 
                 988 
                 UGCUCGGUGAUUUAGCAG 
                 2010- 
               
               
                 953349. 
                 1701279. 
                   
                 CCGAGCA 
                 2032 
                 1069192. 
                   
                 CAAGA 
                 2032 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 859 
                 GAUAUUAACAUCAC 
                 3516- 
                 A- 
                 989 
                 UAAAGACGUGAUGUUAA 
                 3514- 
               
               
                 953381. 
                 1701343. 
                   
                 GUCUUUA 
                 3536 
                 1070910. 
                   
                 UAUCUU 
                 3536 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 860 
                 CUGCAAAAACACAG 
                 1653- 
                 A- 
                 990 
                 UGCGAGUCUGUGUUUUUG 
                 1651- 
               
               
                 953318. 
                 1701217. 
                   
                 ACUCGCA 
                 1673 
                 1068532. 
                   
                 CAGGA 
                 1673 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 861 
                 CUUGCUGCUAAAUC 
                 2011- 
                 A- 
                 991 
                 UCUCGGUGAUUUAGCAGC 
                 2009- 
               
               
                 953348. 
                 1701277. 
                   
                 ACCGAGA 
                 2031 
                 1069190. 
                   
                 AAGAA 
                 2031 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 862 
                 AGAAAGUGUUUUA 
                 2945- 
                 A- 
                 992 
                 UCCGUAUAUAAAACACUU 
                 2943- 
               
               
                 953409. 
                 1701399. 
                   
                 UAUACGGA 
                 2965 
                 1070292. 
                   
                 UCUCU 
                 2965 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 863 
                 AACAUCACCAUGCA 
                 1339- 
                 A- 
                 993 
                 UAUAAUCUGCAUGGUGAU 
                 1337- 
               
               
                 953306. 
                 1701193. 
                   
                 GAUUAUA 
                 1359 
                 1068034. 
                   
                 GUUGG 
                 1359 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 864 
                 CGCAGACGUGUAAA 
                 1634- 
                 A- 
                 994 
                 UGGAACAUUUACACGUCU 
                 1632- 
               
               
                 953316. 
                 1701213. 
                   
                 UGUUCCA 
                 1654 
                 1068494. 
                   
                 GCGGA 
                 1654 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 865 
                 AGCUUGAGUUAAAC 
                 1688- 
                 A- 
                 995 
                 UACGUUCGUUUAACUCAA 
                 1686- 
               
               
                 953325. 
                 1701231. 
                   
                 GAACGUA 
                 1708 
                 1068602. 
                   
                 GCUGC 
                 1708 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 866 
                 GCACUGAAACUUUU 
                  649- 
                 A- 
                 996 
                 UUGGACGAAAAGUUUCAG 
                  647- 
               
               
                 953299. 
                 1701179. 
                   
                 CGUCCAA 
                  669 
                 1067250. 
                   
                 UGCGA 
                  669 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 867 
                 AAUUCUACAUACUA 
                 3419- 
                 A- 
                 997 
                 UGAGAUUUAGUAUGUAG 
                 3417- 
               
               
                 953416. 
                 1701413. 
                   
                 AAUCUCA 
                 3439 
                 1070822. 
                   
                 AAUUCU 
                 3439 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 868 
                 CCGCAGACGUGUAA 
                 1633- 
                 A- 
                 998 
                 UGAACAUUUACACGUCUG 
                 1631- 
               
               
                 953315. 
                 1701211. 
                   
                 AUGUUCA 
                 1653 
                 1068492. 
                   
                 CGGAU 
                 1653 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 869 
                 UCCGCAGACGUGUA 
                 1632- 
                 A- 
                 999 
                 UAACAUUUACACGUCUGC 
                 1630- 
               
               
                 953314. 
                 1701209. 
                   
                 AAUGUUA 
                 1652 
                 1068490. 
                   
                 GGAUC 
                 1652 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 870 
                 CGCACUGAAACUUU 
                  648- 
                 A- 
                 1000 
                 UGGACGAAAAGUUUCAGU 
                  646- 
               
               
                 953298. 
                 1701177. 
                   
                 UCGUCCA 
                  668 
                 1067248. 
                   
                 GCGAC 
                  668 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 871 
                 CCCUCUUGGAAUUG 
                 1978- 
                 A- 
                 1001 
                 UCGAAUCCAAUUCCAAGA 
                 1976- 
               
               
                 953406. 
                 1701393. 
                   
                 GAUUCGA 
                 1998 
                 1069124. 
                   
                 GGGAC 
                 1998 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 872 
                 CAGACGUGUAAAUG 
                 1636- 
                 A- 
                 1002 
                 UCAGGAACAUUUACACGU 
                 1634- 
               
               
                 953399. 
                 1701379. 
                   
                 UUCCUGA 
                 1656 
                 1068498. 
                   
                 CUGCG 
                 1656 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 873 
                 ACGAACGUACUUGC 
                 1700- 
                 A- 
                 1003 
                 UACAUCUGCAAGUACGUU 
                 1698- 
               
               
                 953333. 
                 1701247. 
                   
                 AGAUGUA 
                 1720 
                 1068626. 
                   
                 CGUUU 
                 1720 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 874 
                 AUCCGCAGACGUGU 
                 1631- 
                 A- 
                 1004 
                 UACAUUUACACGUCUGCG 
                 1629- 
               
               
                 953313. 
                 1701207. 
                   
                 AAAUGUA 
                 1651 
                 1068488. 
                   
                 GAUCU 
                 1651 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 875 
                 CAGAAUCAUCACGA 
                 1141- 
                 A- 
                 1005 
                 UACCACUUCGUGAUGAUU 
                 1139- 
               
               
                 953302. 
                 1701185. 
                   
                 AGUGGUA 
                 1161 
                 1067706. 
                   
                 CUGCC 
                 1161 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 876 
                 CCUGCAAAAACACA 
                 1652- 
                 A- 
                 1006 
                 UCGAGUCUGUGUUUUUGC 
                 1650- 
               
               
                 953317. 
                 1701215. 
                   
                 GACUCGA 
                 1672 
                 1068530. 
                   
                 AGGAA 
                 1672 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 877 
                 AGGACAUUGCUGUG 
                 2518- 
                 A- 
                 1007 
                 UCCAAAGCACAGCAAUGU 
                 2516- 
               
               
                 953357. 
                 1701295. 
                   
                 CUUUGGA 
                 2538 
                 1069740. 
                   
                 CCUGA 
                 2538 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 878 
                 GGGCAGAAUCAUCA 
                 1138- 
                 A- 
                 1008 
                 UACUUCGUGAUGAUUCUG 
                 1136- 
               
               
                 953301. 
                 1701183. 
                   
                 CGAAGUA 
                 1158 
                 1067700. 
                   
                 CCCUC 
                 1158 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 879 
                 UGAAGUUCAUGGAU 
                 1160- 
                 A- 
                 1009 
                 UAUAGACAUCCAUGAACU 
                 1158- 
               
               
                 953304. 
                 1701189. 
                   
                 GUCUAUA 
                 1180 
                 1067744. 
                   
                 UCACC 
                 1180 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 880 
                 CGUCGCACUGAAAC 
                  645- 
                 A- 
                 1010 
                 UCGAAAAGUUUCAGUGCG 
                  643- 
               
               
                 953297. 
                 1701175. 
                   
                 UUUUCGA 
                  665 
                 1067242. 
                   
                 ACGCC 
                  665 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 881 
                 GAAAAAAAAUCAGU 
                 1456- 
                 A- 
                 1011 
                 UCCUCGAACUGAUUUUUU 
                 1454- 
               
               
                 953388. 
                 1701357. 
                   
                 UCGAGGA 
                 1476 
                 1700869. 
                   
                 UUCUU 
                 1476 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 882 
                 AUUGGUGUCUUCAC 
                 2193- 
                 A- 
                 1012 
                 UCAUCCAGUGAAGACACC 
                 2191- 
               
               
                 953407. 
                 1701395. 
                   
                 UGGAUGA 
                 2213 
                 1069372. 
                   
                 AAUAA 
                 2213 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 883 
                 AGAUCCGCAGACGU 
                 1629- 
                 A- 
                 1013 
                 UAUUUACACGUCUGCGGA 
                 1627- 
               
               
                 953397. 
                 1701375. 
                   
                 GUAAAUA 
                 1649 
                 1068484. 
                   
                 UCUUG 
                 1649 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 884 
                 GAUCCGCAGACGUG 
                 1630- 
                 A- 
                 1014 
                 UCAUUUACACGUCUGCGG 
                 1628- 
               
               
                 953398. 
                 1701377. 
                   
                 UAAAUGA 
                 1650 
                 1068486. 
                   
                 AUCUU 
                 1650 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 885 
                 UUGUUUGUACAAGA 
                 1618- 
                 A- 
                 1015 
                 UUGCGGAUCUUGUACAAA 
                 1616- 
               
               
                 953396. 
                 1701373. 
                   
                 UCCGCAA 
                 1638 
                 1068462. 
                   
                 CAAAU 
                 1638 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 886 
                 UGCUGUGGACUUGA 
                 2221- 
                 A- 
                 1016 
                 UCCCAACUCAAGUCCACA 
                 2219- 
               
               
                 953356. 
                 1701293. 
                   
                 GUUGGGA 
                 2241 
                 1069428. 
                   
                 GCAGU 
                 2241 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 887 
                 CACGUCUUUGUCUC 
                 3527- 
                 A- 
                 1017 
                 UGCACUAGAGACAAAGAC 
                 3525- 
               
               
                 953422. 
                 1701425. 
                   
                 UAGUGCA 
                 3547 
                 1070932. 
                   
                 GUGAU 
                 3547 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 888 
                 UUUUUUUCAGUAUU 
                 3028- 
                 A- 
                 1018 
                 UACCAAGAAUACUGAAAA 
                 3026- 
               
               
                 953413. 
                 1701407. 
                   
                 CUUGGUA 
                 3048 
                 1700899. 
                   
                 AAAAC 
                 3048 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 889 
                 GUGCUGGAAUUUGA 
                  125- 
                 A- 
                 1019 
                 UUGAAUAUCAAAUUCCAG 
                  123- 
               
               
                 953294. 
                 1701169. 
                   
                 UAUUCAA 
                  145 
                 1066884. 
                   
                 CACCG 
                  145 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 890 
                 UUAACAUCACGUCU 
                 3520- 
                 A- 
                 1020 
                 UAGACAAAGACGUGAUGU 
                 3518- 
               
               
                 953421. 
                 1701423. 
                   
                 UUGUCUA 
                 3540 
                 1070918. 
                   
                 UAAUA 
                 3540 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 891 
                 AGGGGCAAAAACGA 
                 1484- 
                 A- 
                 1021 
                 UGCGCUUUCGUUUUUGCC 
                 1482- 
               
               
                 953310. 
                 1701201. 
                   
                 AAGCGCA 
                 1504 
                 1700793. 
                   
                 CCUUU 
                 1504 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 892 
                 AAAGUGAGUGACCU 
                  415- 
                 A- 
                 1022 
                 UAAAAGCAGGUCACUCAC 
                  413- 
               
               
                 953296. 
                 1701173. 
                   
                 GCUUUUA 
                  435 
                 1067146. 
                   
                 UUUGC 
                  435 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 893 
                 AAAAACACAGACUC 
                 1657- 
                 A- 
                 1023 
                 UCAACGCGAGUCUGUGUU 
                 1655- 
               
               
                 953402. 
                 1701385. 
                   
                 GCGUUGA 
                 1677 
                 1068540. 
                   
                 UUUGC 
                 1677 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 894 
                 AUUUGUUUGUACAA 
                 1616- 
                 A- 
                 1024 
                 UCGGAUCUUGUACAAACA 
                 1614- 
               
               
                 953312. 
                 1701205. 
                   
                 GAUCCGA 
                 1636 
                 1068458. 
                   
                 AAUGC 
                 1636 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 895 
                 UUCCCCAAAUCACU 
                  278- 
                 A- 
                 1025 
                 UAUCCACAGUGAUUUGGG 
                  276- 
               
               
                 953295. 
                 1701171. 
                   
                 GUGGAUA 
                  298 
                 1700778. 
                   
                 GAAGU 
                  298 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 896 
                 AUUAACAUCACGUC 
                 3519- 
                 A- 
                 1026 
                 UGACAAAGACGUGAUGUU 
                 3517- 
               
               
                 953420. 
                 1701421. 
                   
                 UUUGUCA 
                 3539 
                 1070916. 
                   
                 AAUAU 
                 3539 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 897 
                 CGUCUUUGUCUCUA 
                 3529- 
                 A- 
                 1027 
                 UCUGCACUAGAGACAAAG 
                 3527- 
               
               
                 953423. 
                 1701427. 
                   
                 GUGCAGA 
                 3549 
                 1070936. 
                   
                 ACGUG 
                 3549 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 898 
                 AAAACACAGACUCG 
                 1658- 
                 A- 
                 1028 
                 UGCAACGCGAGUCUGUGU 
                 1656- 
               
               
                 953403. 
                 1701387. 
                   
                 CGUUGCA 
                 1678 
                 1068542. 
                   
                 UUUUG 
                 1678 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 899 
                 UGCAAAAACACAGA 
                 1654- 
                 A- 
                 1029 
                 UCGCGAGUCUGUGUUUUU 
                 1652- 
               
               
                 953400. 
                 1701381. 
                   
                 CUCGCGA 
                 1674 
                 1068534. 
                   
                 GCAGG 
                 1674 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 900 
                 AACACAGACUCGCG 
                 1660- 
                 A- 
                 1030 
                 UUUGCAACGCGAGUCUGU 
                 1658- 
               
               
                 953404. 
                 1701389. 
                   
                 UUGCAAA 
                 1680 
                 1068546. 
                   
                 GUUUU 
                 1680 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 901 
                 CUUGCAGAUGUGAC 
                 1709- 
                 A- 
                 1031 
                 UCGGCUUGUCACAUCUGC 
                 1707- 
               
               
                 953334. 
                 1701249. 
                   
                 AAGCCGA 
                 1729 
                 1068644. 
                   
                 AAGUA 
                 1729 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 902 
                 UUUAUCCGUAAUAA 
                 3490- 
                 A- 
                 1032 
                 UCCACAAUUAUUACGGAU 
                 3488- 
               
               
                 953418. 
                 1701417. 
                   
                 UUGUGGA 
                 3510 
                 1070894. 
                   
                 AAACA 
                 3510 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 903 
                 GCAAAAACACAGAC 
                 1655- 
                 A- 
                 1033 
                 UACGCGAGUCUGUGUUUU 
                 1653- 
               
               
                 953401. 
                 1701383. 
                   
                 UCGCGUA 
                 1675 
                 1068536. 
                   
                 UGCAG 
                 1675 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 904 
                 GUUUAUCCGUAAUA 
                 3489- 
                 A- 
                 1034 
                 UCACAAUUAUUACGGAUA 
                 3487- 
               
               
                 953417. 
                 1701415. 
                   
                 AUUGUGA 
                 3509 
                 1070892. 
                   
                 AACAG 
                 3509 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 905 
                 GGGCAAAAACGAAA 
                 1486- 
                 A- 
                 1035 
                 UUUGCGCUUUCGUUUUUG 
                 1484- 
               
               
                 953311. 
                 1701203. 
                   
                 GCGCAAA 
                 1506 
                 1068252. 
                   
                 CCCCU 
                 1506 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 906 
                 UUAUCCGUAAUAAU 
                 3491- 
                 A- 
                 1036 
                 UCCCACAAUUAUUACGGA 
                 3489- 
               
               
                 953419. 
                 1701419. 
                   
                 UGUGGGA 
                 3511 
                 1700905. 
                   
                 UAAAC 
                 3511 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4A 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Modified Single Strandsand Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 SEQ ID 
                   
                   
                 SEQ ID 
               
               
                   
                 Sense 
                 SEQ ID 
                   
                 Antisense 
                 NO: 
                   
                   
                 NO: 
               
               
                 Duplex 
                 Oligo 
                 NO: 
                   
                 Oligo 
                 (Anti- 
                   
                 mRNA target 
                 (mRNA 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Name 
                 sense) 
                 Antisense Sequence 
                 sequence 
                 target) 
               
               
                   
               
               
                 AD- 
                 A- 
                 1037 
                 asasaau(Ahd)gad 
                 A- 
                 1167 
                 VPusdAsgadAudAgc 
                 AUAAAAUAGACAU 
                 4483 
               
               
                 953504. 
                 1701069. 
                   
                 CadTugcuauucua 
                 1800407.1 
                   
                 aadTgdTcdTauuuusas 
                 UGCUAUUCUG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1038 
                 asgsugc(Uhd)aad 
                 A- 
                 1168 
                 VPusdAscadCcdAau 
                 ACAGUGCUAAUGU 
                 4484 
               
               
                 953481. 
                 1701023. 
                   
                 TgdTuauuggugu 
                 1800384.1 
                   
                 aadCadTudAgcacusg 
                 UAUUGGUGUC 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1039 
                 asusaca(Ghd)aad 
                 A- 
                 1169 
                 VPusdCsugdTadTcga 
                 UGAUACAGAACGA 
                 4485 
               
               
                 953472. 
                 1701005. 
                   
                 CgdAucgauacaga 
                 1800375.1 
                   
                 udCgdTudCuguauscs 
                 UCGAUACAGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1040 
                 ascsagc(Ahd)cad 
                 A- 
                 1170 
                 VPusdAsuudCadCau 
                 CUACAGCACAACA 
                 4486 
               
               
                 953517. 
                 1701095. 
                   
                 AcdAaaugugaaua 
                 1800420.1 
                   
                 uudGudTgdTgcugusa 
                 AAUGUGAAUG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1041 
                 csusgau(Ahd)cad 
                 A- 
                 1171 
                 VPusdTsaudCgdAuc 
                 GACUGAUACAGAA 
                 4487 
               
               
                 953471. 
                 1701003. 
                   
                 GadAcgaucgauaa 
                 1800374.1 
                   
                 gudTcdTgdTaucagsu 
                 CGAUCGAUAC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1042 
                 gsasgaa(Ahd)gud 
                 A- 
                 1172 
                 VPusdCsgudAudAua 
                 AAGAGAAAGUGUU 
                 4488 
               
               
                 953493. 
                 1701047. 
                   
                 GudTuuauauacga 
                 1800396.1 
                   
                 aadAcdAcdTuucucsu 
                 UUAUAUACGG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1043 
                 asascua(Uhd)uud 
                 A- 
                 1173 
                 VPusdGsaudAcdAuc 
                 UCAACUAUUUAUG 
                 4489 
               
               
                 953498. 
                 1701057. 
                   
                 AudGagauguauc 
                 1800401.1 
                   
                 ucdAudAadAuaguus 
                 AGAUGUAUCU 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 gsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1044 
                 asasgac(Uhd)gad 
                 A- 
                 1174 
                 VPusdGsaudCgdTuc 
                 GAAAGACUGAUAC 
                 4490 
               
               
                 953467. 
                 1700995. 
                   
                 TadCagaacgauca 
                 1800370.1 
                   
                 ugdTadTcdAgucuusu 
                 AGAACGAUCG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1045 
                 gsasgaa(Uhd)ucd 
                 A- 
                 1175 
                 VPusdAsuudTadGua 
                 UAGAGAAUUCUAC 
                 4491 
               
               
                 953545. 
                 1701151. 
                   
                 TadCauacuaaaua 
                 1800448.1 
                   
                 ugdTadGadAuucucsu 
                 AUACUAAAUC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1046 
                 asasaga(Chd)ugd 
                 A- 
                 1176 
                 VPusdAsucdGudTcu 
                 GGAAAGACUGAUA 
                 4492 
               
               
                 953466. 
                 1700993. 
                   
                 AudAcagaacgaua 
                 1800369.1 
                   
                 gudAudCadGucuuusc 
                 CAGAACGAUC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1047 
                 ascsggu(Ahd)cud 
                 A- 
                 1177 
                 VPusdGsgadTadTuaa 
                 AUACGGUACUUAU 
                 4493 
               
               
                 953494. 
                 1701049. 
                   
                 TadTuuaauaucca 
                 1800397.1 
                   
                 adTadAgdTaccgusas 
                 UUAAUAUCCC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1048 
                 ascsuga(Uhd) acd 
                 A- 
                 1178 
                 VPusdAsucdGadTcg 
                 AGACUGAUACAGA 
                 4494 
               
               
                 953470. 
                 1701001. 
                   
                 AgdAacgaucgaua 
                 1800373.1 
                   
                 uudCudGudAucagusc 
                 ACGAUCGAUA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 SU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1049 
                 csgsaca(Ghd)aad 
                 A- 
                 1179 
                 VPusdGsaudTadAgg 
                 AUCGACAGAACAG 
                 4495 
               
               
                 953473. 
                 1701007. 
                   
                 CadGuccuuaauca 
                 1800376.1 
                   
                 acdTgdTudCugucgsa 
                 UCCUUAAUCC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 SU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1050 
                 csasgaa(Chd)agd 
                 A- 
                 1180 
                 VPusdCsugdGadTua 
                 GACAGAACAGUCC 
                 4496 
               
               
                 953474. 
                 1701009. 
                   
                 TcdCuuaauccaga 
                 1800377.1 
                   
                 agdGadCudGuucugsu 
                 UUAAUCCAGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1051 
                 asascag(Uhd)gcd 
                 A- 
                 1181 
                 VPusdCscadAudAac 
                 UUAACAGUGCUAA 
                 4497 
               
               
                 953480. 
                 1701021. 
                   
                 TadAuguuauugg 
                 1800383.1 
                   
                 audTadGcdAcuguusa 
                 UGUUAUUGGU 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1052 
                 ascsagu(Chd)acd 
                 A- 
                 1182 
                 VPusdCsaadGadTaag 
                 UGACAGUCACUAG 
                 4498 
               
               
                 953503. 
                 1701067. 
                   
                 TadGcuuaucuuga 
                 1800406.1 
                   
                 cdTadGudGacuguscs 
                 CUUAUCUUGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1053 
                 csusugc(Uhd)gcd 
                 A- 
                 1183 
                 VPusdCsucdGgdTga 
                 UUCUUGCUGCUAA 
                 4499 
               
               
                 953478. 
                 1701017. 
                   
                 TadAaucaccgaga 
                 1800381.1 
                   
                 uudTadGcdAgcaagsa 
                 AUCACCGAGC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1054 
                 gsasaag(Uhd)gud 
                 A- 
                 1184 
                 VPusdAsccdGudAua 
                 GAGAAAGUGUUUU 
                 4500 
               
               
                 953540. 
                 1701141. 
                   
                 TudTauauacggua 
                 1800443.1 
                   
                 uadAadAcdAcuuucsu 
                 AUAUACGGUA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1055 
                 gscsucu(Chd)uud 
                 A- 
                 1185 
                 VPusdAsccdGgdTaca 
                 UUGCUCUCUUAUU 
                 4501 
               
               
                 953500. 
                 1701061. 
                   
                 AudTuguaccggua 
                 1800403.1 
                   
                 adAudAadGagagcsas 
                 UGUACCGGUU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1056 
                 ususcuu(Ghd)cud 
                 A- 
                 1186 
                 VPusdCsggdTgdAuu 
                 UUUUCUUGCUGCU 
                 4502 
               
               
                 953476. 
                 1701013. 
                   
                 GcdTaaaucaccga 
                 1800379.1 
                   
                 uadGcdAgdCaagaasa 
                 AAAUCACCGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1057 
                 csascca(Uhd)ugd 
                 A- 
                 1187 
                 VPusdAsacdTadGug 
                 CACACCAUUGAAA 
                 4503 
               
               
                 953492. 
                 1701045. 
                   
                 AadAccacuaguua 
                 1800395.1 
                   
                 gudTudCadAuggugsu 
                 CCACUAGUUC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1058 
                 csgsgua(Chd)uud 
                 A- 
                 1188 
                 VPusdGsggdAudAuu 
                 UACGGUACUUAUU 
                 4504 
               
               
                 953495. 
                 1701051. 
                   
                 AudTuaauauccca 
                 1800398.1 
                   
                 aadAudAadGuaccgsu 
                 UAAUAUCCCU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1059 
                 csasacu(Ahd)uud 
                 A- 
                 1189 
                 VPusdAsuadCadTCUC 
                 UUCAACUAUUUAU 
                 4505 
               
               
                 953497. 
                 1701055. 
                   
                 TadTgagauguaua 
                 1800400.1 
                   
                 adTadAadTaguugsas 
                 GAGAUGUAUC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1060 
                 usasauc(Chd)agd 
                 A- 
                 1190 
                 VPusdCsaudTudCag 
                 CUUAAUCCAGAAA 
                 4506 
               
               
                 953535. 
                 1701131. 
                   
                 AadAccugaaauga 
                 1800438.1 
                   
                 gudTudCudGgauuasa 
                 CCUGAAAUGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1061 
                 asasaua(Ghd)acd 
                 A- 
                 1191 
                 VPusdCsagdAadTagc 
                 UAAAAUAGACAUU 
                 4507 
               
               
                 953505. 
                 1701071. 
                   
                 AudTgcuauucuga 
                 1800408.1 
                   
                 adAudGudCuauuusus 
                 GCUAUUCUGU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1062 
                 asasagc(Ahd)uud 
                 A- 
                 1192 
                 VPusdCsuudGudAca 
                 AGAAAGCAUUUGU 
                 4508 
               
               
                 953524. 
                 1701109. 
                   
                 TgdTuuguacaaga 
                 1800427.1 
                   
                 aadCadAadTgcuuusc 
                 UUGUACAAGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1063 
                 csusugg(Ahd)aud 
                 A- 
                 1193 
                 VPusdAsugdGcdGaa 
                 CUCUUGGAAUUGG 
                 4509 
               
               
                 953475. 
                 1701011. 
                   
                 TgdGauucgccaua 
                 1800378.1 
                   
                 ucdCadAudTccaagsa 
                 AUUCGCCAUU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1064 
                 ascsacc(Ahd)uud 
                 A- 
                 1194 
                 VPusdAscudAgdTgg 
                 UCACACCAUUGAA 
                 4510 
               
               
                 953491. 
                 1701043. 
                   
                 GadAaccacuagua 
                 1800394.1 
                   
                 uudTcdAadTggugusg 
                 ACCACUAGUU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1065 
                 asascau(Chd)acd 
                 A- 
                 1195 
                 VPusdAsuadAudCug 
                 CCAACAUCACCAU 
                 4511 
               
               
                 953436. 
                 1700933. 
                   
                 CadTgcagauuaua 
                 1800339.1 
                   
                 cadTgdGudGauguusg 
                 GCAGAUUAUG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1066 
                 usgsaca(Ghd)ucd 
                 A- 
                 1196 
                 VPusdAsgadTadAgc 
                 GGUGACAGUCACU 
                 4512 
               
               
                 953502. 
                 1701065. 
                   
                 AcdTagcuuaucua 
                 1800405.1 
                   
                 uadGudGadCugucasc 
                 AGCUUAUCUU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1067 
                 asgsuua(Ahd)acd 
                 A- 
                 1197 
                 VPusdGscadAgdTac 
                 UGAGUUAAACGAA 
                 4513 
               
               
                 953461. 
                 1700983. 
                   
                 GadAcguacuugca 
                 1800364.1 
                   
                 gudTcdGudTuaacusc 
                 CGUACUUGCA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1068 
                 ascsuau(Uhd)uad 
                 A- 
                 1198 
                 VPusdAsgadTadCauc 
                 CAACUAUUUAUGA 
                 4514 
               
               
                 953544. 
                 1701149. 
                   
                 TgdAgauguaucua 
                 1800447.1 
                   
                 udCadTadAauagusus 
                 GAUGUAUCUU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1069 
                 ususaaa(Chd)gad 
                 A- 
                 1199 
                 VPusdCsugdCadAgu 
                 AGUUAAACGAACG 
                 4515 
               
               
                 953462. 
                 1700985. 
                   
                 AcdGuacuugcaga 
                 1800365.1 
                   
                 acdGudTcdGuuuaasc 
                 UACUUGCAGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1070 
                 gsgsuac(Uhd)uad 
                 A- 
                 1200 
                 VPusdAsggdGadTau 
                 ACGGUACUUAUUU 
                 4516 
               
               
                 953496. 
                 1701053. 
                   
                 TudTaauaucccua 
                 1800399.1 
                   
                 uadAadTadAguaccsg 
                 AAUAUCCCUU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1071 
                 csgsaag(Uhd)ggd 
                 A- 
                 1201 
                 VPusdCscadTgdAacu 
                 CACGAAGUGGUGA 
                 4517 
               
               
                 953516. 
                 1701093. 
                   
                 TgdAaguucaugga 
                 1800419.1 
                   
                 udCadCcdAcuucgsus 
                 AGUUCAUGGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1072 
                 usgsuua(Uhd)ug 
                 A- 
                 1202 
                 VPusdCsagdTgdAag 
                 AAUGUUAUUGGUG 
                 4518 
               
               
                 953483. 
                 1701027. 
                   
                 dGudGucuucacu 
                 1800386.1 
                   
                 acdAcdCadAuaacasu 
                 UCUUCACUGG 
                   
               
               
                 1 
                 1 
                   
                 gaL96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1073 
                 ususgcu(Chd)ucd 
                 A- 
                 1203 
                 VPusdCsggdTadCaaa 
                 UCUUGCUCUCUUA 
                 4519 
               
               
                 953499. 
                 1701059. 
                   
                 TudAuuuguaccga 
                 1800402.1 
                   
                 udAadGadGagcaasgs 
                 UUUGUACCGG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1074 
                 gsusuuu(Ahd)ua 
                 A- 
                 1204 
                 VPusdAsuadAgdTac 
                 GUGUUUUAUAUAC 
                 4520 
               
               
                 953541. 
                 1701143. 
                   
                 dTadCgguacuuau 
                 1800444.1 
                   
                 cgdTadTadTaaaacsas 
                 GGUACUUAUU 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1075 
                 uscsacu(Ghd)gad 
                 A- 
                 1205 
                 VPusdCsagdTcdAaau 
                 CUUCACUGGAUGU 
                 4521 
               
               
                 953538. 
                 1701137. 
                   
                 TgdTauuugacuga 
                 1800441.1 
                   
                 adCadTcdCagugasas 
                 AUUUGACUGC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1076 
                 cscsucc(Ghd)aad 
                 A- 
                 1206 
                 VPusdAsaadGudTca 
                 GGCCUCCGAAACC 
                 4522 
               
               
                 953430. 
                 1700921. 
                   
                 AcdCaugaacuuua 
                 1800333.1 
                   
                 ugdGudTudCggaggsc 
                 AUGAACUUUC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1077 
                 usasuug(Ghd)ug 
                 A- 
                 1207 
                 VPusdAsucdCadGug 
                 GUUAUUGGUGUCU 
                 4523 
               
               
                 953485. 
                 1701031. 
                   
                 dTcdTucacuggau 
                 1800388.1 
                   
                 aadGadCadCcaauasas 
                 UCACUGGAUG 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1078 
                 asgsacu(Ghd)aud 
                 A- 
                 1208 
                 VPusdCsgadTcdGuu 
                 AAAGACUGAUACA 
                 4524 
               
               
                 953468. 
                 1700997. 
                   
                 AcdAgaacgaucga 
                 1800371.1 
                   
                 cudGudAudCagucusu 
                 GAACGAUCGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1079 
                 uscscgc(Ahd)gad 
                 A- 
                 1209 
                 VPusdAsacdAudTua 
                 GAUCCGCAGACGU 
                 4525 
               
               
                 953444. 
                 1700949. 
                   
                 CgdTguaaauguua 
                 1800347.1 
                   
                 cadCgdTcdTgcggasu 
                 GUAAAUGUUC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1080 
                 gsasguu(Ahd)aad 
                 A- 
                 1210 
                 VPusdCsaadGudAcg 
                 UUGAGUUAAACGA 
                 4526 
               
               
                 953460. 
                 1700981. 
                   
                 CgdAacguacuuga 
                 1800363.1 
                   
                 uudCgdTudTaacucsa 
                 ACGUACUUGC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1081 
                 asgsaaa(Ghd)ugd 
                 A- 
                 1211 
                 VPusdCscgdTadTaua 
                 AGAGAAAGUGUUU 
                 4527 
               
               
                 953539. 
                 1701139. 
                   
                 TudTuauauacgga 
                 1800442.1 
                   
                 adAadCadCuuucuscs 
                 UAUAUACGGU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1082 
                 gsusuau(Uhd)gg 
                 A- 
                 1212 
                 VPusdCscadGudGaa 
                 AUGUUAUUGGUGU 
                 4528 
               
               
                 953484. 
                 1701029. 
                   
                 dTgdTcuucacugg 
                 1800387.1 
                   
                 gadCadCcdAauaacsa 
                 CUUCACUGGA 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1083 
                 csusuga(Ghd)uud 
                 A- 
                 1213 
                 VPusdGsuadCgdTuc 
                 AGCUUGAGUUAAA 
                 4529 
               
               
                 953457. 
                 1700975. 
                   
                 AadAcgaacguaca 
                 1800360.1 
                   
                 gudTudAadCucaagsc 
                 CGAACGUACU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1084 
                 usgsagu(Uhd)aad 
                 A- 
                 1214 
                 VPusdAsagdTadCgu 
                 CUUGAGUUAAACG 
                 4530 
               
               
                 953459. 
                 1700979. 
                   
                 AcdGaacguacuua 
                 1800362.1 
                   
                 ucdGudTudAacucasa 
                 AACGUACUUG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1085 
                 asuscac(Chd)aud 
                 A- 
                 1215 
                 VPusdCsgcdAudAau 
                 ACAUCACCAUGCA 
                 4531 
               
               
                 953437. 
                 1700935. 
                   
                 GcdAgauuaugcg 
                 1800340.1 
                   
                 cudGcdAudGgugaus 
                 GAUUAUGCGG 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 gsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1086 
                 ususgag(Uhd)uad 
                 A- 
                 1216 
                 VPusdAsgudAcdGuu 
                 GCUUGAGUUAAAC 
                 4532 
               
               
                 953458. 
                 1700977. 
                   
                 AadCgaacguacua 
                 1800361.1 
                   
                 cgdTudTadAcucaasg 
                 GAACGUACUU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1087 
                 gscsagc(Uhd)ugd 
                 A- 
                 1217 
                 VPusdGsuudCgdTuu 
                 AGGCAGCUUGAGU 
                 4533 
               
               
                 953453. 
                 1700967. 
                   
                 AgdTuaaacgaaca 
                 1800356.1 
                   
                 aadCudCadAgcugcsc 
                 UAAACGAACG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1088 
                 csgscac(Uhd)gad 
                 A- 
                 1218 
                 VPusdGsgadCgdAaa 
                 GUCGCACUGAAAC 
                 4534 
               
               
                 953428. 
                 1700917. 
                   
                 AadCuuuucgucca 
                 1800331.1 
                   
                 agdTudTcdAgugcgsa 
                 UUUUCGUCCA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1089 
                 uscsggu(Ghd)acd 
                 A- 
                 1219 
                 VPusdAsagdCudAgu 
                 GAUCGGUGACAGU 
                 4535 
               
               
                 953501. 
                 1701063. 
                   
                 AgdTcacuagcuua 
                 1800404.1 
                   
                 gadCudGudCaccgasu 
                 CACUAGCUUA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1090 
                 gsusgcu(Ahd)aud 
                 A- 
                 1220 
                 VPusdGsacdAcdCaa 
                 CAGUGCUAAUGUU 
                 4536 
               
               
                 953482. 
                 1701025. 
                   
                 GudTauugguguc 
                 1800385.1 
                   
                 uadAcdAudTagcacsu 
                 AUUGGUGUCU 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1091 
                 csgscag(Ahd)cgd 
                 A- 
                 1221 
                 VPusdGsgadAcdAuu 
                 UCCGCAGACGUGU 
                 4537 
               
               
                 953446. 
                 1700953. 
                   
                 TgdTaaauguucca 
                 1800349.1 
                   
                 uadCadCgdTcugcgsg 
                 AAAUGUUCCU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1092 
                 asgsaga(Ahd)gad 
                 A- 
                 1222 
                 VPusdCsaadCadAug 
                 GAAGAGAAGAGAC 
                 4538 
               
               
                 953488. 
                 1701037. 
                   
                 GadCacauuguuga 
                 1800391.1 
                   
                 ugdTcdTcdTucucusu 
                 ACAUUGUUGG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1093 
                 usgsaag(Uhd)ucd 
                 A- 
                 1223 
                 VPusdAsuadGadCau 
                 GGUGAAGUUCAUG 
                 4539 
               
               
                 953434. 
                 1700929. 
                   
                 AudGgaugucuau 
                 1800337.1 
                   
                 ccdAudGadAcuucasc 
                 GAUGUCUAUC 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1094 
                 asasuuc(Uhd)acd 
                 A- 
                 1224 
                 VPusdGsagdAudTua 
                 AGAAUUCUACAUA 
                 4540 
               
               
                 953546. 
                 1701153. 
                   
                 AudAcuaaaucuca 
                 1800449.1 
                   
                 gudAudGudAgaauus 
                 CUAAAUCUCU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 csu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1095 
                 csasgac(Ghd)ugd 
                 A- 
                 1225 
                 VPusdCsagdGadAca 
                 CGCAGACGUGUAA 
                 4541 
               
               
                 953529. 
                 1701119. 
                   
                 TadAauguuccuga 
                 1800432.1 
                   
                 uudTadCadCgucugsc 
                 AUGUUCCUGC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1096 
                 csascga(Ahd)gud 
                 A- 
                 1226 
                 VPusdAsugdAadCuu 
                 AUCACGAAGUGGU 
                 4542 
               
               
                 953433. 
                 1700927. 
                   
                 GgdTgaaguucaua 
                 1800336.1 
                   
                 cadCcdAcdTucgugsa 
                 GAAGUUCAUG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1097 
                 gscsuug(Ahd)gu 
                 A- 
                 1227 
                 VPusdTsacdGudTcgu 
                 CAGCUUGAGUUAA 
                 4543 
               
               
                 953456. 
                 1700973. 
                   
                 dTadAacgaacgua 
                 1800359.1 
                   
                 udTadAcdTcaagcsus 
                 ACGAACGUAC 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1098 
                 csasucu(Uhd)cad 
                 A- 
                 1228 
                 VPusdCsacdAgdGau 
                 UACAUCUUCAAGC 
                 4544 
               
               
                 953435. 
                 1700931. 
                   
                 AgdCcauccuguga 
                 1800338.1 
                   
                 ggdCudTgdAagaugsu 
                 CAUCCUGUGU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1099 
                 csascca(Uhd)gcd 
                 A- 
                 1229 
                 VPusdTsccdGcdAuaa 
                 AUCACCAUGCAGA 
                 4545 
               
               
                 953438. 
                 1700937. 
                   
                 AgdAuuaugcgga 
                 1800341.1 
                   
                 udCudGcdAuggugsas 
                 UUAUGCGGAU 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1100 
                 gsgscag(Chd)uud 
                 A- 
                 1230 
                 VPusdTsucdGudTuaa 
                 GAGGCAGCUUGAG 
                 4546 
               
               
                 953452. 
                 1700965. 
                   
                 GadGuuaaacgaaa 
                 1800355.1 
                   
                 cdTcdAadGcugccsus 
                 UUAAACGAAC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1101 
                 asusguc(Chd)ucd 
                 A- 
                 1231 
                 VPusdTsuudCadAug 
                 CUAUGUCCUCACA 
                 4547 
               
               
                 953489. 
                 1701039. 
                   
                 AcdAccauugaaaa 
                 1800392.1 
                   
                 gudGudGadGgacausa 
                 CCAUUGAAAC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1102 
                 cscsgca(Ghd)acd 
                 A- 
                 1232 
                 VPusdGsaadCadTuua 
                 AUCCGCAGACGUG 
                 4548 
               
               
                 953445. 
                 1700951. 
                   
                 GudGuaaauguuc 
                 1800348.1 
                   
                 cdAcdGudCugcggsas 
                 UAAAUGUUCC 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1103 
                 csasgaa(Uhd)cad 
                 A- 
                 1233 
                 VPusdAsccdAcdTuc 
                 GGCAGAAUCAUCA 
                 4549 
               
               
                 953432. 
                 1700925. 
                   
                 TcdAcgaaguggua 
                 1800335.1 
                   
                 gudGadTgdAuucugsc 
                 CGAAGUGGUG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1104 
                 gsusgcu(Ahd)cud 
                 A- 
                 1234 
                 VPusdTsuadCgdGau 
                 UGGUGCUACUGUU 
                 4550 
               
               
                 953509. 
                 1701079. 
                   
                 GudTuauccguaaa 
                 1800412.1 
                   
                 aadAcdAgdTagcacsc 
                 UAUCCGUAAU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1105 
                 usgsucc(Uhd)cad 
                 A- 
                 1235 
                 VPusdGsuudTcdAau 
                 UAUGUCCUCACAC 
                 4551 
               
               
                 953490. 
                 1701041. 
                   
                 CadCcauugaaaca 
                 1800393.1 
                   
                 ggdTgdTgdAggacasu 
                 CAUUGAAACC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1106 
                 csusgca(Ahd)aad 
                 A- 
                 1236 
                 VPusdGscgdAgdTcu 
                 UCCUGCAAAAACA 
                 4552 
               
               
                 953448. 
                 1700957. 
                   
                 AcdAcagacucgca 
                 1800351.1 
                   
                 gudGudTudTugcagsg 
                 CAGACUCGCG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1107 
                 gsasggc(Ahd)gcd 
                 A- 
                 1237 
                 VPusdCsgudTudAac 
                 GCGAGGCAGCUUG 
                 4553 
               
               
                 953450. 
                 1700961. 
                   
                 TudGaguuaaacga 
                 1800353.1 
                   
                 ucdAadGcdTgccucsg 
                 AGUUAAACGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1108 
                 asusccg(Chd)agd 
                 A- 
                 1238 
                 VPusdAscadTudTaca 
                 AGAUCCGCAGACG 
                 4554 
               
               
                 953443. 
                 1700947. 
                   
                 AcdGuguaaaugu 
                 1800346.1 
                   
                 cdGudCudGcggauscs 
                 UGUAAAUGUU 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1109 
                 gscsauu(Uhd)gud 
                 A- 
                 1239 
                 VPusdGsaudCudTgu 
                 AAGCAUUUGUUUG 
                 4555 
               
               
                 953525. 
                 1701111. 
                   
                 TudGuacaagauca 
                 1800428.1 
                   
                 acdAadAcdAaaugcsu 
                 UACAAGAUCC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1110 
                 gsasaag(Chd)aud 
                 A- 
                 1240 
                 VPusdTsugdTadCaaa 
                 GAGAAAGCAUUUG 
                 4556 
               
               
                 953523. 
                 1701107. 
                   
                 TudGuuuguacaaa 
                 1800426.1 
                   
                 cdAadAudGcuuucsus 
                 UUUGUACAAG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1111 
                 usgsgug(Chd)uad 
                 A- 
                 1241 
                 VPusdAscgdGadTaaa 
                 AUUGGUGCUACUG 
                 4557 
               
               
                 953507. 
                 1701075. 
                   
                 CudGuuuauccgu 
                 1800410.1 
                   
                 cdAgdTadGcaccasas 
                 UUUAUCCGUA 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1112 
                 asgsgca(Ghd)cud 
                 A- 
                 1242 
                 VPusdTscgdTudTaac 
                 CGAGGCAGCUUGA 
                 4558 
               
               
                 953451. 
                 1700963. 
                   
                 TgdAguuaaacgaa 
                 1800354.1 
                   
                 udCadAgdCugccuscs 
                 GUUAAACGAA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1113 
                 gscsacu(Ghd)aad 
                 A- 
                 1243 
                 VPusdTsggdAcdGaa 
                 UCGCACUGAAACU 
                 4559 
               
               
                 953429. 
                 1700919. 
                   
                 AcdTuuucguccaa 
                 1800332.1 
                   
                 aadGudTudCagugcsg 
                 UUUCGUCCAA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1114 
                 gsascug(Ahd)uad 
                 A- 
                 1244 
                 VPusdTscgdAudCgu 
                 AAGACUGAUACAG 
                 4560 
               
               
                 953469. 
                 1700999. 
                   
                 CadGaacgaucgaa 
                 1800372.1 
                   
                 ucdTgdTadTcagucsus 
                 AACGAUCGAU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1115 
                 ascsgaa(Chd)gud 
                 A- 
                 1245 
                 VPusdAscadTcdTgca 
                 AAACGAACGUACU 
                 4561 
               
               
                 953463. 
                 1700987. 
                   
                 AcdTugcagaugua 
                 1800366.1 
                   
                 adGudAcdGuucgusus 
                 UGCAGAUGUG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1116 
                 csasgcu(Uhd)gad 
                 A- 
                 1246 
                 VPusdCsgudTcdGuu 
                 GGCAGCUUGAGUU 
                 4562 
               
               
                 953454. 
                 1700969. 
                   
                 GudTaaacgaacga 
                 1800357.1 
                   
                 uadAcdTcdAagcugsc 
                 AAACGAACGU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1117 
                 asgscuu(Ghd)agd 
                 A- 
                 1247 
                 VPusdAscgdTudCgu 
                 GCAGCUUGAGUUA 
                 4563 
               
               
                 953455. 
                 1700971. 
                   
                 TudAaacgaacgua 
                 1800358.1 
                   
                 uudAadCudCaagcusg 
                 AACGAACGUA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1118 
                 gsasuau(Uhd)aad 
                 A- 
                 1248 
                 VPusdAsaadGadCgu 
                 AAGAUAUUAACAU 
                 4564 
               
               
                 953511. 
                 1701083. 
                   
                 CadTcacgucuuua 
                 1800414.1 
                   
                 gadTgdTudAauaucsu 
                 CACGUCUUUG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1119 
                 cscsugc(Ahd)aad 
                 A- 
                 1249 
                 VPusdCsgadGudCug 
                 UUCCUGCAAAAAC 
                 4565 
               
               
                 953447. 
                 1700955. 
                   
                 AadCacagacucga 
                 1800350.1 
                   
                 ugdTudTudTgcaggsa 
                 ACAGACUCGC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1120 
                 gsusgcu(Ghd)gad 
                 A- 
                 1250 
                 VPusdTsgadAudAuc 
                 CGGUGCUGGAAUU 
                 4566 
               
               
                 953424. 
                 1700909. 
                   
                 AudTugauauucaa 
                 1800327.1 
                   
                 aadAudTcdCagcacscs 
                 UGAUAUUCAU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1121 
                 ususggu(Ghd)cu 
                 A- 
                 1251 
                 VPusdCsggdAudAaa 
                 UAUUGGUGCUACU 
                 4567 
               
               
                 953506. 
                 1701073. 
                   
                 dAcdTguuuauccg 
                 1800409.1 
                   
                 cadGudAgdCaccaasu 
                 GUUUAUCCGU 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1122 
                 asusugg(Uhd)gu 
                 A- 
                 1252 
                 VPusdCsaudCcdAgu 
                 UUAUUGGUGUCUU 
                 4568 
               
               
                 953537. 
                 1701135. 
                   
                 dCudTcacuggaug 
                 1800440.1 
                   
                 gadAgdAcdAccaausa 
                 CACUGGAUGU 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1123 
                 uscsuug(Chd)ugd 
                 A- 
                 1253 
                 VPusdTscgdGudGau 
                 UUUCUUGCUGCUA 
                 4569 
               
               
                 953477. 
                 1701015. 
                   
                 CudAaaucaccgaa 
                 1800380.1 
                   
                 uudAgdCadGcaagasa 
                 AAUCACCGAG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1124 
                 ususgcu(Ghd)cud 
                 A- 
                 1254 
                 VPusdGscudCgdGug 
                 UCUUGCUGCUAAA 
                 4570 
               
               
                 953479. 
                 1701019. 
                   
                 AadAucaccgagca 
                 1800382.1 
                   
                 audTudAgdCagcaasg 
                 UCACCGAGCC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1125 
                 asgsauu(Ahd)ugd 
                 A- 
                 1255 
                 VPusdAsggdTudTga 
                 GCAGAUUAUGCGG 
                 4571 
               
               
                 953439. 
                 1700939. 
                   
                 CgdGaucaaaccua 
                 1800342.1 
                   
                 ucdCgdCadTaaucusg 
                 AUCAAACCUC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1126 
                 gsgsgca(Ghd)aad 
                 A- 
                 1256 
                 VPusdAscudTcdGug 
                 GAGGGCAGAAUCA 
                 4572 
               
               
                 953431. 
                 1700923. 
                   
                 TcdAucacgaagua 
                 1800334.1 
                   
                 audGadTudCugcccsu 
                 UCACGAAGUG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1127 
                 asusuug(Uhd)uu 
                 A- 
                 1257 
                 VPusdCsggdAudCuu 
                 GCAUUUGUUUGUA 
                 4573 
               
               
                 953442. 
                 1700945. 
                   
                 dGudAcaagauccg 
                 1800345.1 
                   
                 gudAcdAadAcaaausg 
                 CAAGAUCCGC 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1128 
                 csasaaa(Ahd)cad 
                 A- 
                 1258 
                 VPusdAsacdGcdGag 
                 UGCAAAAACACAG 
                 4574 
               
               
                 953449. 
                 1700959. 
                   
                 CadGacucgcguua 
                 1800352.1 
                   
                 ucdTgdTgdTuuuugsc 
                 ACUCGCGUUG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1129 
                 usgscua(Chd)ugd 
                 A- 
                 1259 
                 VPusdAsuudAcdGga 
                 GGUGCUACUGUUU 
                 4575 
               
               
                 953510. 
                 1701081. 
                   
                 TudTauccguaaua 
                 1800413.1 
                   
                 uadAadCadGuagcasc 
                 AUCCGUAAUA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1130 
                 ascsuuu(Uhd)cgd 
                 A- 
                 1260 
                 VPusdCscadGadAgu 
                 AAACUUUUCGUCC 
                 4576 
               
               
                 953514. 
                 1701089. 
                   
                 TcdCaacuucugga 
                 1800417.1 
                   
                 ugdGadCgdAaaagusu 
                 AACUUCUGGG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1131 
                 gsgsugc(Uhd)acd 
                 A- 
                 1261 
                 VPusdTsacdGgdAua 
                 UUGGUGCUACUGU 
                 4577 
               
               
                 953508. 
                 1701077. 
                   
                 TgdTuuauccguaa 
                 1800411.1 
                   
                 aadCadGudAgcaccsa 
                 UUAUCCGUAA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1132 
                 gscsaaa(Ahd)acd 
                 A- 
                 1262 
                 VPusdAscgdCgdAgu 
                 CUGCAAAAACACA 
                 4578 
               
               
                 953531. 
                 1701123. 
                   
                 AcdAgacucgcgua 
                 1800434.1 
                   
                 cudGudGudTuuugcsa 
                 GACUCGCGUU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1133 
                 csgsucg(Chd)acd 
                 A- 
                 1263 
                 VPusdCsgadAadAgu 
                 GGCGUCGCACUGA 
                 4579 
               
               
                 953427. 
                 1700915. 
                   
                 TgdAaacuuuucga 
                 1800330.1 
                   
                 uudCadGudGcgacgsc 
                 AACUUUUCGU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1134 
                 asusauu(Ahd)acd 
                 A- 
                 1264 
                 VPusdCsaadAgdAcg 
                 AGAUAUUAACAUC 
                 4580 
               
               
                 953512. 
                 1701085. 
                   
                 AudCacgucuuug 
                 1800415.1 
                   
                 ugdAudGudTaauausc 
                 ACGUCUUUGU 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1135 
                 asasaac(Ahd)cad 
                 A- 
                 1265 
                 VPusdGscadAcdGcg 
                 CAAAAACACAGAC 
                 4581 
               
               
                 953533. 
                 1701127. 
                   
                 GadCucgcguugca 
                 1800436.1 
                   
                 agdTcdTgdTguuuusu 
                 UCGCGUUGCA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1136 
                 csusugc(Ahd)gad 
                 A- 
                 1266 
                 VPusdCsggdCudTgu 
                 UACUUGCAGAUGU 
                 4582 
               
               
                 953464. 
                 1700989. 
                   
                 TgdTgacaagccga 
                 1800367.1 
                   
                 cadCadTcdTgcaagsus 
                 GACAAGCCGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1137 
                 ususuuu(Uhd)uu 
                 A- 
                 1267 
                 VPusdCscadAgdAau 
                 GGUUUUUUUUCAG 
                 4583 
               
               
                 953542. 
                 1701145. 
                   
                 dCadGuauucuug 
                 1800445.1 
                   
                 acdTgdAadAaaaaascs 
                 UAUUCUUGGU 
                   
               
               
                 1 
                 1 
                   
                 gaL96 
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1138 
                 asasagu(Ghd)agd 
                 A- 
                 1268 
                 VPusdAsaadAgdCag 
                 GCAAAGUGAGUGA 
                 4584 
               
               
                 953426. 
                 1700913. 
                   
                 TgdAccugcuuuua 
                 1800329.1 
                   
                 gudCadCudCacuuusg 
                 CCUGCUUUUG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1139 
                 ususcgu(Chd)cad 
                 A- 
                 1269 
                 VPusdCsagdCcdCaga 
                 UUUUCGUCCAACU 
                 4585 
               
               
                 953515. 
                 1701091. 
                   
                 AcdTucugggcuga 
                 1800418.1 
                   
                 adGudTgdGacgaasas 
                 UCUGGGCUGU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1140 
                 asgsgac(Ahd)uud 
                 A- 
                 1270 
                 VPusdCscadAadGcac 
                 UCAGGACAUUGCU 
                 4586 
               
               
                 953487. 
                 1701035. 
                   
                 GcdTgugcuuugg 
                 1800390.1 
                   
                 adGcdAadTguccusgs 
                 GUGCUUUGGG 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1141 
                 asasauc(Ahd)gud 
                 A- 
                 1271 
                 VPusdCsccdTudTccu 
                 AAAAAUCAGUUCG 
                 4587 
               
               
                 953521. 
                 1701103. 
                   
                 TcdGaggaaaggga 
                 1800424.1 
                   
                 cdGadAcdTgauuusus 
                 AGGAAAGGGA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1142 
                 ususccc(Chd)aad 
                 A- 
                 1272 
                 VPusdAsucdCadCag 
                 ACUUCCCCAAAUC 
                 4588 
               
               
                 953425. 
                 1700911. 
                   
                 AudCacuguggau 
                 1800328.1 
                   
                 ugdAudTudGgggaasg 
                 ACUGUGGAUU 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1143 
                 cscscuc(Uhd)ugd 
                 A- 
                 1273 
                 VPusdCsgadAudCca 
                 GUCCCUCUUGGAA 
                 4589 
               
               
                 953536. 
                 1701133. 
                   
                 GadAuuggauucg 
                 1800439.1 
                   
                 audTcdCadAgagggsa 
                 UUGGAUUCGC 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1144 
                 ususgca(Ghd)aud 
                 A- 
                 1274 
                 VPusdTscgdGcdTug 
                 ACUUGCAGAUGUG 
                 4590 
               
               
                 953465. 
                 1700991. 
                   
                 GudGacaagccgaa 
                 1800368.1 
                   
                 ucdAcdAudCugcaasg 
                 ACAAGCCGAG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1145 
                 csascgu(Chd)uud 
                 A- 
                 1275 
                 VPusdGscadCudAga 
                 AUCACGUCUUUGU 
                 4591 
               
               
                 953552. 
                 1701165. 
                   
                 TgdTcucuagugca 
                 1800455.1 
                   
                 gadCadAadGacgugsa 
                 CUCUAGUGCA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1146 
                 gsasucc(Ghd)cad 
                 A- 
                 1276 
                 VPusdCsaudTudAcac 
                 AAGAUCCGCAGAC 
                 4592 
               
               
                 953528. 
                 1701117. 
                   
                 GadCguguaaauga 
                 1800431.1 
                   
                 gdTcdTgdCggaucsus 
                 GUGUAAAUGU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1147 
                 asasaaa(Uhd)cad 
                 A- 
                 1277 
                 VPusdCsuudTcdCuc 
                 AAAAAAAUCAGUU 
                 4593 
               
               
                 953519. 
                 1701099. 
                   
                 GudTcgaggaaaga 
                 1800422.1 
                   
                 gadAcdTgdAuuuuusu 
                 CGAGGAAAGG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1148 
                 usgscug(Uhd)gg 
                 A- 
                 1278 
                 VPusdCsccdAadCuca 
                 ACUGCUGUGGACU 
                 4594 
               
               
                 953486. 
                 1701033. 
                   
                 dAcdTugaguugg 
                 1800389.1 
                   
                 adGudCcdAcagcasgs 
                 UGAGUUGGGA 
                   
               
               
                 1 
                 1 
                   
                 gaL96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1149 
                 asasggg(Ghd)cad 
                 A- 
                 1279 
                 VPusdCsgcdTudTcgu 
                 GAAAGGGGCAAAA 
                 4595 
               
               
                 953522. 
                 1701105. 
                   
                 AadAacgaaagcga 
                 1800425.1 
                   
                 udTudTgdCcccuusus 
                 ACGAAAGCGC 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1150 
                 usgscaa(Ahd)aad 
                 A- 
                 1280 
                 VPusdCsgcdGadGuc 
                 CCUGCAAAAACAC 
                 4596 
               
               
                 953530. 
                 1701121. 
                   
                 CadCagacucgcga 
                 1800433.1 
                   
                 ugdTgdTudTuugcasg 
                 AGACUCGCGU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1151 
                 ascsguc(Uhd)uud 
                 A- 
                 1281 
                 VPusdTsgcdAcdTaga 
                 UCACGUCUUUGUC 
                 4597 
               
               
                 953513. 
                 1701087. 
                   
                 GudCucuagugcaa 
                 1800416.1 
                   
                 gdAcdAadAgacgusgs 
                 UCUAGUGCAG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1152 
                 gsgsgca(Ahd)aad 
                 A- 
                 1282 
                 VPusdTsugdCgdCuu 
                 AGGGGCAAAAACG 
                 4598 
               
               
                 953441. 
                 1700943. 
                   
                 AcdGaaagcgcaaa 
                 1800344.1 
                   
                 ucdGudTudTugcccsc 
                 AAAGCGCAAG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1153 
                 asgsggg(Chd)aad 
                 A- 
                 1283 
                 VPusdGscgdCudTuc 
                 AAAGGGGCAAAAA 
                 4599 
               
               
                 953440. 
                 1700941. 
                   
                 AadAcgaaagcgca 
                 1800343.1 
                   
                 gudTudTudGccccusu 
                 CGAAAGCGCA 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1154 
                 gsasaaa(Ahd)aad 
                 A- 
                 1284 
                 VPusdCscudCgdAac 
                 AAGAAAAAAAAUC 
                 4600 
               
               
                 953518. 
                 1701097. 
                   
                 AudCaguucgagg 
                 1800421.1 
                   
                 ugdAudTudTuuuucsu 
                 AGUUCGAGGA 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1155 
                 asasaau(Chd)agd 
                 A- 
                 1285 
                 VPusdCscudTudCcuc 
                 AAAAAAUCAGUUC 
                 4601 
               
               
                 953520. 
                 1701101. 
                   
                 TudCgaggaaagga 
                 1800423.1 
                   
                 gdAadCudGauuuusus 
                 GAGGAAAGGG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1156 
                 asasaaa(Chd)acd 
                 A- 
                 1286 
                 VPusdCsaadCgdCga 
                 GCAAAAACACAGA 
                 4602 
               
               
                 953532. 
                 1701125. 
                   
                 AgdAcucgcguug 
                 1800435.1 
                   
                 gudCudGudGuuuuus 
                 CUCGCGUUGC 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 gsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1157 
                 ususuau(Chd)cgd 
                 A- 
                 1287 
                 VPusdCscadCadAuu 
                 UGUUUAUCCGUAA 
                 4603 
               
               
                 953548. 
                 1701157. 
                   
                 TadAuaauugugga 
                 1800451.1 
                   
                 audTadCgdGauaaasc 
                 UAAUUGUGGG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1158 
                 asgsauc(Chd)gcd 
                 A- 
                 1288 
                 VPusdAsuudTadCac 
                 CAAGAUCCGCAGA 
                 4604 
               
               
                 953527. 
                 1701115. 
                   
                 AgdAcguguaaau 
                 1800430.1 
                   
                 gudCudGcdGgaucusu 
                 CGUGUAAAUG 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1159 
                 ususaac(Ahd)ucd 
                 A- 
                 1289 
                 VPusdAsgadCadAag 
                 UAUUAACAUCACG 
                 4605 
               
               
                 953551. 
                 1701163. 
                   
                 AcdGucuuugucu 
                 1800454.1 
                   
                 acdGudGadTguuaasu 
                 UCUUUGUCUC 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1160 
                 csgsucu(Uhd)ugd 
                 A- 
                 1290 
                 VPusdCsugdCadCua 
                 CACGUCUUUGUCU 
                 4606 
               
               
                 953553. 
                 1701167. 
                   
                 TcdTcuagugcaga 
                 1800456.1 
                   
                 gadGadCadAagacgsu 
                 CUAGUGCAGU 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1161 
                 gsusuua(Uhd)ccd 
                 A- 
                 1291 
                 VPusdCsacdAadTuau 
                 CUGUUUAUCCGUA 
                 4607 
               
               
                 953547. 
                 1701155. 
                   
                 GudAauaauugug 
                 1800450.1 
                   
                 udAcdGgdAuaaacsas 
                 AUAAUUGUGG 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1162 
                 ususguu(Uhd)gu 
                 A- 
                 1292 
                 VPusdTsgcdGgdAuc 
                 AUUUGUUUGUACA 
                 4608 
               
               
                 953526. 
                 1701113. 
                   
                 dAcdAagauccgca 
                 1800429.1 
                   
                 uudGudAcdAaacaasa 
                 AGAUCCGCAG 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1163 
                 ususauc(Chd)gud 
                 A- 
                 1293 
                 VPusdCsccdAcdAau 
                 GUUUAUCCGUAAU 
                 4609 
               
               
                 953549. 
                 1701159. 
                   
                 AadTaauuguggga 
                 1800452.1 
                   
                 uadTudAcdGgauaasa 
                 AAUUGUGGGG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1164 
                 asascac(Ahd)gad 
                 A- 
                 1294 
                 VPusdTsugdCadAcg 
                 AAAACACAGACUC 
                 4610 
               
               
                 953534. 
                 1701129. 
                   
                 CudCgcguugcaaa 
                 1800437.1 
                   
                 cgdAgdTcdTguguusu 
                 GCGUUGCAAG 
                   
               
               
                 1 
                 1 
                   
                 L96 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1165 
                 ususuuu(Uhd)uc 
                 A- 
                 1295 
                 VPusdAsccdAadGaa 
                 GUUUUUUUUCAGU 
                 4611 
               
               
                 953543. 
                 1701147. 
                   
                 dAgdTauucuugg 
                 1800446.1 
                   
                 uadCudGadAaaaaasa 
                 AUUCUUGGUU 
                   
               
               
                 1 
                 1 
                   
                 uaL96 
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1166 
                 asusuaa(Chd)aud 
                 A- 
                 1296 
                 VPusdGsacdAadAga 
                 AUAUUAACAUCAC 
                 4612 
               
               
                 953550. 
                 1701161. 
                   
                 CadCgucuuuguc 
                 1800453.1 
                   
                 cgdTgdAudGuuaausa 
                 GUCUUUGUCU 
                   
               
               
                 1 
                 1 
                   
                 aL96 
                   
                   
                 su 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4B 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Unmodified Single Strands and Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                 SEQ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                 ID 
                   
                   
               
               
                   
                 Sense 
                 SEQ ID 
                   
                 mRNA 
                 Antisense 
                 NO: 
                   
                 mRNA 
               
               
                 Duplex 
                 Oligo 
                 NO: 
                   
                 Target 
                 Oligo 
                 (Anti- 
                   
                 Target 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Range 
                 Name 
                 sense) 
                 Antisense Sequence 
                 Range 
               
               
                   
               
               
                 AD- 
                 A- 
                 1297 
                 AAAAUAGACATUGCU 
                 3361- 
                 A- 
                 1427 
                 UAGAAUAGCAATGTCTA 
                 3359- 
               
               
                 953504. 
                 1701069. 
                   
                 AUUCUA 
                 3381 
                 1800407. 
                   
                 UUUUAU 
                 3381 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1298 
                 AGUGCUAATGTUAUU 
                 2181- 
                 A- 
                 1428 
                 UACACCAAUAACATUAG 
                 2179- 
               
               
                 953481. 
                 1701023. 
                   
                 GGUGUA 
                 2201 
                 1800384. 
                   
                 CACUGU 
                 2201 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1299 
                 AUACAGAACGAUCGA 
                 1803- 
                 A- 
                 1429 
                 UCUGTATCGAUCGTUCU 
                 1801- 
               
               
                 953472. 
                 1701005. 
                   
                 UACAGA 
                 1823 
                 1800375. 
                   
                 GUAUCA 
                 1823 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1300 
                 ACAGCACAACAAAUG 
                 1407- 
                 A- 
                 1430 
                 UAUUCACAUUUGUTGTG 
                 1405- 
               
               
                 953517. 
                 1701095. 
                   
                 UGAAUA 
                 1427 
                 1800420. 
                   
                 CUGUAG 
                 1427 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1301 
                 CUGAUACAGAACGAU 
                 1800- 
                 A- 
                 1431 
                 UTAUCGAUCGUTCTGTA 
                 1798- 
               
               
                 953471. 
                 1701003. 
                   
                 CGAUAA 
                 1820 
                 1800374. 
                   
                 UCAGUC 
                 1820 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1302 
                 GAGAAAGUGUTUUA 
                 2944- 
                 A- 
                 1432 
                 UCGUAUAUAAAACACTU 
                 2942- 
               
               
                 953493. 
                 1701047. 
                   
                 UAUACGA 
                 2964 
                 1800396. 
                   
                 UCUCUU 
                 2964 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1303 
                 AACUAUUUAUGAGA 
                 3062- 
                 A- 
                 1433 
                 UGAUACAUCUCAUAAA 
                 3060- 
               
               
                 953498. 
                 1701057. 
                   
                 UGUAUCA 
                 3082 
                 1800401. 
                   
                 UAGUUGA 
                 3082 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1304 
                 AAGACUGATACAGAA 
                 1796- 
                 A- 
                 1434 
                 UGAUCGTUCUGTATCAG 
                 1794- 
               
               
                 953467. 
                 1700995. 
                   
                 CGAUCA 
                 1816 
                 1800370. 
                   
                 UCUUUC 
                 1816 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1305 
                 GAGAAUUCTACAUAC 
                 3416- 
                 A- 
                 1435 
                 UAUUTAGUAUGTAGAA 
                 3414- 
               
               
                 953545. 
                 1701151. 
                   
                 UAAAUA 
                 3436 
                 1800448. 
                   
                 UUCUCUA 
                 3436 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1306 
                 AAAGACUGAUACAG 
                 1795- 
                 A- 
                 1436 
                 UAUCGUTCUGUAUCAGU 
                 1793- 
               
               
                 953466. 
                 1700993. 
                   
                 AACGAUA 
                 1815 
                 1800369. 
                   
                 CUUUCC 
                 1815 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1307 
                 ACGGUACUTATUUAA 
                 2961- 
                 A- 
                 1437 
                 UGGATATUAAATAAGTA 
                 2959- 
               
               
                 953494. 
                 1701049. 
                   
                 UAUCCA 
                 2981 
                 1800397. 
                   
                 CCGUAU 
                 2981 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1308 
                 ACUGAUACAGAACGA 
                 1799- 
                 A- 
                 1438 
                 UAUCGATCGUUCUGUAU 
                 1797- 
               
               
                 953470. 
                 1701001. 
                   
                 UCGAUA 
                 1819 
                 1800373. 
                   
                 CAGUCU 
                 1819 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1309 
                 CGACAGAACAGUCCU 
                 1855- 
                 A- 
                 1439 
                 UGAUTAAGGACTGTUCU 
                 1853- 
               
               
                 953473. 
                 1701007. 
                   
                 UAAUCA 
                 1875 
                 1800376. 
                   
                 GUCGAU 
                 1875 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1310 
                 CAGAACAGTCCUUAA 
                 1858- 
                 A- 
                 1440 
                 UCUGGATUAAGGACUG 
                 1856- 
               
               
                 953474. 
                 1701009. 
                   
                 UCCAGA 
                 1878 
                 1800377. 
                   
                 UUCUGUC 
                 1878 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1311 
                 AACAGUGCTAAUGUU 
                 2178- 
                 A- 
                 1441 
                 UCCAAUAACAUTAGCAC 
                 2176- 
               
               
                 953480. 
                 1701021. 
                   
                 AUUGGA 
                 2198 
                 1800383. 
                   
                 UGUUAA 
                 2198 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1312 
                 ACAGUCACTAGCUUA 
                 3164- 
                 A- 
                 1442 
                 UCAAGATAAGCTAGUGA 
                 3162- 
               
               
                 953503. 
                 1701067. 
                   
                 UCUUGA 
                 3184 
                 1800406. 
                   
                 CUGUCA 
                 3184 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1313 
                 CUUGCUGCTAAAUCA 
                 2011- 
                 A- 
                 1443 
                 UCUCGGTGAUUTAGCAG 
                 2009- 
               
               
                 953478. 
                 1701017. 
                   
                 CCGAGA 
                 2031 
                 1800381. 
                   
                 CAAGAA 
                 2031 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1314 
                 GAAAGUGUTUTAUAU 
                 2946- 
                 A- 
                 1444 
                 UACCGUAUAUAAAACA 
                 2944- 
               
               
                 953540. 
                 1701141. 
                   
                 ACGGUA 
                 2966 
                 1800443. 
                   
                 CUUUCUC 
                 2966 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1315 
                 GCUCUCUUAUTUGUA 
                 3096- 
                 A- 
                 1445 
                 UACCGGTACAAAUAAGA 
                 3094- 
               
               
                 953500. 
                 1701061. 
                   
                 CCGGUA 
                 3116 
                 1800403. 
                   
                 GAGCAA 
                 3116 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1316 
                 UUCUUGCUGCTAAAU 
                 2009- 
                 A- 
                 1446 
                 UCGGTGAUUUAGCAGCA 
                 2007- 
               
               
                 953476. 
                 1701013. 
                   
                 CACCGA 
                 2029 
                 1800379. 
                   
                 AGAAAA 
                 2029 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1317 
                 CACCAUUGAAACCAC 
                 2791- 
                 A- 
                 1447 
                 UAACTAGUGGUTUCAAU 
                 2789- 
               
               
                 953492. 
                 1701045. 
                   
                 UAGUUA 
                 2811 
                 1800395. 
                   
                 GGUGUG 
                 2811 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1318 
                 CGGUACUUAUTUAAU 
                 2962- 
                 A- 
                 1448 
                 UGGGAUAUUAAAUAAG 
                 2960- 
               
               
                 953495. 
                 1701051. 
                   
                 AUCCCA 
                 2982 
                 1800398. 
                   
                 UACCGUA 
                 2982 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1319 
                 CAACUAUUTATGAGA 
                 3061- 
                 A- 
                 1449 
                 UAUACATCUCATAAATA 
                 3059- 
               
               
                 953497. 
                 1701055. 
                   
                 UGUAUA 
                 3081 
                 1800400. 
                   
                 GUUGAA 
                 3081 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1320 
                 UAAUCCAGAAACCUG 
                 1870- 
                 A- 
                 1450 
                 UCAUTUCAGGUTUCUGG 
                 1868- 
               
               
                 953535. 
                 1701131. 
                   
                 AAAUGA 
                 1890 
                 1800438. 
                   
                 AUUAAG 
                 1890 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1321 
                 AAAUAGACAUTGCUA 
                 3362- 
                 A- 
                 1451 
                 UCAGAATAGCAAUGUCU 
                 3360- 
               
               
                 953505. 
                 1701071. 
                   
                 UUCUGA 
                 3382 
                 1800408. 
                   
                 AUUUUA 
                 3382 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1322 
                 AAAGCAUUTGTUUGU 
                 1611- 
                 A- 
                 1452 
                 UCUUGUACAAACAAATG 
                 1609- 
               
               
                 953524. 
                 1701109. 
                   
                 ACAAGA 
                 1631 
                 1800427. 
                   
                 CUUUCU 
                 1631 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1323 
                 CUUGGAAUTGGAUUC 
                 1982- 
                 A- 
                 1453 
                 UAUGGCGAAUCCAAUTC 
                 1980- 
               
               
                 953475. 
                 1701011. 
                   
                 GCCAUA 
                 2002 
                 1800378. 
                   
                 CAAGAG 
                 2002 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1324 
                 ACACCAUUGAAACCA 
                 2790- 
                 A- 
                 1454 
                 UACUAGTGGUUTCAATG 
                 2788- 
               
               
                 953491. 
                 1701043. 
                   
                 CUAGUA 
                 2810 
                 1800394. 
                   
                 GUGUGA 
                 2810 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1325 
                 AACAUCACCATGCAG 
                 1339- 
                 A- 
                 1455 
                 UAUAAUCUGCATGGUG 
                 1337- 
               
               
                 953436. 
                 1700933. 
                   
                 AUUAUA 
                 1359 
                 1800339. 
                   
                 AUGUUGG 
                 1359 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1326 
                 UGACAGUCACTAGCU 
                 3162- 
                 A- 
                 1456 
                 UAGATAAGCUAGUGAC 
                 3160- 
               
               
                 953502. 
                 1701065. 
                   
                 UAUCUA 
                 3182 
                 1800405. 
                   
                 UGUCACC 
                 3182 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1327 
                 AGUUAAACGAACGU 
                 1694- 
                 A- 
                 1457 
                 UGCAAGTACGUTCGUTU 
                 1692- 
               
               
                 953461. 
                 1700983. 
                   
                 ACUUGCA 
                 1714 
                 1800364. 
                   
                 AACUCA 
                 1714 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1328 
                 ACUAUUUATGAGAUG 
                 3063- 
                 A- 
                 1458 
                 UAGATACAUCUCATAAA 
                 3061- 
               
               
                 953544. 
                 1701149. 
                   
                 UAUCUA 
                 3083 
                 1800447. 
                   
                 UAGUUG 
                 3083 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1329 
                 UUAAACGAACGUACU 
                 1696- 
                 A- 
                 1459 
                 UCUGCAAGUACGUTCGU 
                 1694- 
               
               
                 953462. 
                 1700985. 
                   
                 UGCAGA 
                 1716 
                 1800365. 
                   
                 UUAACU 
                 1716 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1330 
                 GGUACUUATUTAAUA 
                 2963- 
                 A- 
                 1460 
                 UAGGGATAUUAAATAA 
                 2961- 
               
               
                 953496. 
                 1701053. 
                   
                 UCCCUA 
                 2983 
                 1800399. 
                   
                 GUACCGU 
                 2983 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1331 
                 CGAAGUGGTGAAGUU 
                 1152- 
                 A- 
                 1461 
                 UCCATGAACUUCACCAC 
                 1150- 
               
               
                 953516. 
                 1701093. 
                   
                 CAUGGA 
                 1172 
                 1800419. 
                   
                 UUCGUG 
                 1172 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1332 
                 UGUUAUUGGUGUCU 
                 2189- 
                 A- 
                 1462 
                 UCAGTGAAGACACCAAU 
                 2187- 
               
               
                 953483. 
                 1701027. 
                   
                 UCACUGA 
                 2209 
                 1800386. 
                   
                 AACAUU 
                 2209 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1333 
                 UUGCUCUCTUAUUUG 
                 3094- 
                 A- 
                 1463 
                 UCGGTACAAAUAAGAG 
                 3092- 
               
               
                 953499. 
                 1701059. 
                   
                 UACCGA 
                 3114 
                 1800402. 
                   
                 AGCAAGA 
                 3114 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1334 
                 GUUUUAUATACGGUA 
                 2952- 
                 A- 
                 1464 
                 UAUAAGTACCGTATATA 
                 2950- 
               
               
                 953541. 
                 1701143. 
                   
                 CUUAUA 
                 2972 
                 1800444. 
                   
                 AAACAC 
                 2972 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1335 
                 UCACUGGATGTAUUU 
                 2203- 
                 A- 
                 1465 
                 UCAGTCAAAUACATCCA 
                 2201- 
               
               
                 953538. 
                 1701137. 
                   
                 GACUGA 
                 2223 
                 1800441. 
                   
                 GUGAAG 
                 2223 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1336 
                 CCUCCGAAACCAUGA 
                 1028- 
                 A- 
                 1466 
                 UAAAGUTCAUGGUTUCG 
                 1026- 
               
               
                 953430. 
                 1700921. 
                   
                 ACUUUA 
                 1048 
                 1800333. 
                   
                 GAGGCC 
                 1048 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1337 
                 UAUUGGUGTCTUCAC 
                 2192- 
                 A- 
                 1467 
                 UAUCCAGUGAAGACACC 
                 2190- 
               
               
                 953485. 
                 1701031. 
                   
                 UGGAUA 
                 2212 
                 1800388. 
                   
                 AAUAAC 
                 2212 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1338 
                 AGACUGAUACAGAAC 
                 1797- 
                 A- 
                 1468 
                 UCGATCGUUCUGUAUCA 
                 1795- 
               
               
                 953468. 
                 1700997. 
                   
                 GAUCGA 
                 1817 
                 1800371. 
                   
                 GUCUUU 
                 1817 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1339 
                 UCCGCAGACGTGUAA 
                 1632- 
                 A- 
                 1469 
                 UAACAUTUACACGTCTG 
                 1630- 
               
               
                 953444. 
                 1700949. 
                   
                 AUGUUA 
                 1652 
                 1800347. 
                   
                 CGGAUC 
                 1652 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1340 
                 GAGUUAAACGAACG 
                 1693- 
                 A- 
                 1470 
                 UCAAGUACGUUCGTUTA 
                 1691- 
               
               
                 953460. 
                 1700981. 
                   
                 UACUUGA 
                 1713 
                 1800363. 
                   
                 ACUCAA 
                 1713 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1341 
                 AGAAAGUGTUTUAUA 
                 2945- 
                 A- 
                 1471 
                 UCCGTATAUAAAACACU 
                 2943- 
               
               
                 953539. 
                 1701139. 
                   
                 UACGGA 
                 2965 
                 1800442. 
                   
                 UUCUCU 
                 2965 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1342 
                 GUUAUUGGTGTCUUC 
                 2190- 
                 A- 
                 1472 
                 UCCAGUGAAGACACCAA 
                 2188- 
               
               
                 953484. 
                 1701029. 
                   
                 ACUGGA 
                 2210 
                 1800387. 
                   
                 UAACAU 
                 2210 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1343 
                 CUUGAGUUAAACGA 
                 1690- 
                 A- 
                 1473 
                 UGUACGTUCGUTUAACU 
                 1688- 
               
               
                 953457. 
                 1700975. 
                   
                 ACGUACA 
                 1710 
                 1800360. 
                   
                 CAAGCU 
                 1710 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1344 
                 UGAGUUAAACGAAC 
                 1692- 
                 A- 
                 1474 
                 UAAGTACGUUCGUTUAA 
                 1690- 
               
               
                 953459. 
                 1700979. 
                   
                 GUACUUA 
                 1712 
                 1800362. 
                   
                 CUCAAG 
                 1712 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1345 
                 AUCACCAUGCAGAUU 
                 1342- 
                 A- 
                 1475 
                 UCGCAUAAUCUGCAUG 
                 1340- 
               
               
                 953437. 
                 1700935. 
                   
                 AUGCGA 
                 1362 
                 1800340. 
                   
                 GUGAUGU 
                 1362 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1346 
                 UUGAGUUAAACGAA 
                 1691- 
                 A- 
                 1476 
                 UAGUACGUUCGTUTAAC 
                 1689- 
               
               
                 953458. 
                 1700977. 
                   
                 CGUACUA 
                 1711 
                 1800361. 
                   
                 UCAAGC 
                 1711 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1347 
                 GCAGCUUGAGTUAAA 
                 1686- 
                 A- 
                 1477 
                 UGUUCGTUUAACUCAAG 
                 1684- 
               
               
                 953453. 
                 1700967. 
                   
                 CGAACA 
                 1706 
                 1800356. 
                   
                 CUGCCU 
                 1706 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1348 
                 CGCACUGAAACUUUU 
                  648- 
                 A- 
                 1478 
                 UGGACGAAAAGTUTCAG 
                  646- 
               
               
                 953428. 
                 1700917. 
                   
                 CGUCCA 
                  668 
                 1800331. 
                   
                 UGCGAC 
                  668 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1349 
                 UCGGUGACAGTCACU 
                 3158- 
                 A- 
                 1479 
                 UAAGCUAGUGACUGUC 
                 3156- 
               
               
                 953501. 
                 1701063. 
                   
                 AGCUUA 
                 3178 
                 1800404. 
                   
                 ACCGAUC 
                 3178 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1350 
                 GUGCUAAUGUTAUUG 
                 2182- 
                 A- 
                 1480 
                 UGACACCAAUAACAUTA 
                 2180- 
               
               
                 953482. 
                 1701025. 
                   
                 GUGUCA 
                 2202 
                 1800385. 
                   
                 GCACUG 
                 2202 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1351 
                 CGCAGACGTGTAAAU 
                 1634- 
                 A- 
                 1481 
                 UGGAACAUUUACACGTC 
                 1632- 
               
               
                 953446. 
                 1700953. 
                   
                 GUUCCA 
                 1654 
                 1800349. 
                   
                 UGCGGA 
                 1654 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1352 
                 AGAGAAGAGACACA 
                 2673- 
                 A- 
                 1482 
                 UCAACAAUGUGTCTCTU 
                 2671- 
               
               
                 953488. 
                 1701037. 
                   
                 UUGUUGA 
                 2693 
                 1800391. 
                   
                 CUCUUC 
                 2693 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1353 
                 UGAAGUUCAUGGAU 
                 1160- 
                 A- 
                 1483 
                 UAUAGACAUCCAUGAA 
                 1158- 
               
               
                 953434. 
                 1700929. 
                   
                 GUCUAUA 
                 1180 
                 1800337. 
                   
                 CUUCACC 
                 1180 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1354 
                 AAUUCUACAUACUAA 
                 3419- 
                 A- 
                 1484 
                 UGAGAUTUAGUAUGUA 
                 3417- 
               
               
                 953546. 
                 1701153. 
                   
                 AUCUCA 
                 3439 
                 1800449. 
                   
                 GAAUUCU 
                 3439 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1355 
                 CAGACGUGTAAAUGU 
                 1636- 
                 A- 
                 1485 
                 UCAGGAACAUUTACACG 
                 1634- 
               
               
                 953529. 
                 1701119. 
                   
                 UCCUGA 
                 1656 
                 1800432. 
                   
                 UCUGCG 
                 1656 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1356 
                 CACGAAGUGGTGAAG 
                 1150- 
                 A- 
                 1486 
                 UAUGAACUUCACCACTU 
                 1148- 
               
               
                 953433. 
                 1700927. 
                   
                 UUCAUA 
                 1170 
                 1800336. 
                   
                 CGUGAU 
                 1170 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1357 
                 GCUUGAGUTAAACGA 
                 1689- 
                 A- 
                 1487 
                 UTACGUTCGUUTAACTC 
                 1687- 
               
               
                 953456. 
                 1700973. 
                   
                 ACGUAA 
                 1709 
                 1800359. 
                   
                 AAGCUG 
                 1709 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1358 
                 CAUCUUCAAGCCAUC 
                 1251- 
                 A- 
                 1488 
                 UCACAGGAUGGCUTGAA 
                 1249- 
               
               
                 953435. 
                 1700931. 
                   
                 CUGUGA 
                 1271 
                 1800338. 
                   
                 GAUGUA 
                 1271 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1359 
                 CACCAUGCAGAUUAU 
                 1344- 
                 A- 
                 1489 
                 UTCCGCAUAAUCUGCAU 
                 1342- 
               
               
                 953438. 
                 1700937. 
                   
                 GCGGAA 
                 1364 
                 1800341. 
                   
                 GGUGAU 
                 1364 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1360 
                 GGCAGCUUGAGUUA 
                 1685- 
                 A- 
                 1490 
                 UTUCGUTUAACTCAAGC 
                 1683- 
               
               
                 953452. 
                 1700965. 
                   
                 AACGAAA 
                 1705 
                 1800355. 
                   
                 UGCCUC 
                 1705 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1361 
                 AUGUCCUCACACCAU 
                 2782- 
                 A- 
                 1491 
                 UTUUCAAUGGUGUGAG 
                 2780- 
               
               
                 953489. 
                 1701039. 
                   
                 UGAAAA 
                 2802 
                 1800392. 
                   
                 GACAUAG 
                 2802 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1362 
                 CCGCAGACGUGUAAA 
                 1633- 
                 A- 
                 1492 
                 UGAACATUUACACGUCU 
                 1631- 
               
               
                 953445. 
                 1700951. 
                   
                 UGUUCA 
                 1653 
                 1800348. 
                   
                 GCGGAU 
                 1653 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1363 
                 CAGAAUCATCACGAA 
                 1141- 
                 A- 
                 1493 
                 UACCACTUCGUGATGAU 
                 1139- 
               
               
                 953432. 
                 1700925. 
                   
                 GUGGUA 
                 1161 
                 1800335. 
                   
                 UCUGCC 
                 1161 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1364 
                 GUGCUACUGUTUAUC 
                 3481- 
                 A- 
                 1494 
                 UTUACGGAUAAACAGTA 
                 3479- 
               
               
                 953509. 
                 1701079. 
                   
                 CGUAAA 
                 3501 
                 1800412. 
                   
                 GCACCA 
                 3501 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1365 
                 UGUCCUCACACCAUU 
                 2783- 
                 A- 
                 1495 
                 UGUUTCAAUGGTGTGAG 
                 2781- 
               
               
                 953490. 
                 1701041. 
                   
                 GAAACA 
                 2803 
                 1800393. 
                   
                 GACAUA 
                 2803 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1366 
                 CUGCAAAAACACAGA 
                 1653- 
                 A- 
                 1496 
                 UGCGAGTCUGUGUTUTU 
                 1651- 
               
               
                 953448. 
                 1700957. 
                   
                 CUCGCA 
                 1673 
                 1800351. 
                   
                 GCAGGA 
                 1673 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1367 
                 GAGGCAGCTUGAGUU 
                 1683- 
                 A- 
                 1497 
                 UCGUTUAACUCAAGCTG 
                 1681- 
               
               
                 953450. 
                 1700961. 
                   
                 AAACGA 
                 1703 
                 1800353. 
                   
                 CCUCGC 
                 1703 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1368 
                 AUCCGCAGACGUGUA 
                 1631- 
                 A- 
                 1498 
                 UACATUTACACGUCUGC 
                 1629- 
               
               
                 953443. 
                 1700947. 
                   
                 AAUGUA 
                 1651 
                 1800346. 
                   
                 GGAUCU 
                 1651 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1369 
                 GCAUUUGUTUGUACA 
                 1614- 
                 A- 
                 1499 
                 UGAUCUTGUACAAACAA 
                 1612- 
               
               
                 953525. 
                 1701111. 
                   
                 AGAUCA 
                 1634 
                 1800428. 
                   
                 AUGCUU 
                 1634 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1370 
                 GAAAGCAUTUGUUUG 
                 1610- 
                 A- 
                 1500 
                 UTUGTACAAACAAAUGC 
                 1608- 
               
               
                 953523. 
                 1701107. 
                   
                 UACAAA 
                 1630 
                 1800426. 
                   
                 UUUCUC 
                 1630 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1371 
                 UGGUGCUACUGUUU 
                 3479- 
                 A- 
                 1501 
                 UACGGATAAACAGTAGC 
                 3477- 
               
               
                 953507. 
                 1701075. 
                   
                 AUCCGUA 
                 3499 
                 1800410. 
                   
                 ACCAAU 
                 3499 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1372 
                 AGGCAGCUTGAGUUA 
                 1684- 
                 A- 
                 1502 
                 UTCGTUTAACUCAAGCU 
                 1682- 
               
               
                 953451. 
                 1700963. 
                   
                 AACGAA 
                 1704 
                 1800354. 
                   
                 GCCUCG 
                 1704 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1373 
                 GCACUGAAACTUUUC 
                  649- 
                 A- 
                 1503 
                 UTGGACGAAAAGUTUCA 
                  647- 
               
               
                 953429. 
                 1700919. 
                   
                 GUCCAA 
                  669 
                 1800332. 
                   
                 GUGCGA 
                  669 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1374 
                 GACUGAUACAGAACG 
                 1798- 
                 A- 
                 1504 
                 UTCGAUCGUUCTGTATC 
                 1796- 
               
               
                 953469. 
                 1700999. 
                   
                 AUCGAA 
                 1818 
                 1800372. 
                   
                 AGUCUU 
                 1818 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1375 
                 ACGAACGUACTUGCA 
                 1700- 
                 A- 
                 1505 
                 UACATCTGCAAGUACGU 
                 1698- 
               
               
                 953463. 
                 1700987. 
                   
                 GAUGUA 
                 1720 
                 1800366. 
                   
                 UCGUUU 
                 1720 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1376 
                 CAGCUUGAGUTAAAC 
                 1687- 
                 A- 
                 1506 
                 UCGUTCGUUUAACTCAA 
                 1685- 
               
               
                 953454. 
                 1700969. 
                   
                 GAACGA 
                 1707 
                 1800357. 
                   
                 GCUGCC 
                 1707 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1377 
                 AGCUUGAGTUAAACG 
                 1688- 
                 A- 
                 1507 
                 UACGTUCGUUUAACUCA 
                 1686- 
               
               
                 953455. 
                 1700971. 
                   
                 AACGUA 
                 1708 
                 1800358. 
                   
                 AGCUGC 
                 1708 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1378 
                 GAUAUUAACATCACG 
                 3516- 
                 A- 
                 1508 
                 UAAAGACGUGATGTUAA 
                 3514- 
               
               
                 953511. 
                 1701083. 
                   
                 UCUUUA 
                 3536 
                 1800414. 
                   
                 UAUCUU 
                 3536 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1379 
                 CCUGCAAAAACACAG 
                 1652- 
                 A- 
                 1509 
                 UCGAGUCUGUGTUTUTG 
                 1650- 
               
               
                 953447. 
                 1700955. 
                   
                 ACUCGA 
                 1672 
                 1800350. 
                   
                 CAGGAA 
                 1672 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1380 
                 GUGCUGGAAUTUGAU 
                  125- 
                 A- 
                 1510 
                 UTGAAUAUCAAAUTCCA 
                  123- 
               
               
                 953424. 
                 1700909. 
                   
                 AUUCAA 
                  145 
                 1800327. 
                   
                 GCACCG 
                  145 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1381 
                 UUGGUGCUACTGUUU 
                 3478- 
                 A- 
                 1511 
                 UCGGAUAAACAGUAGC 
                 3476- 
               
               
                 953506. 
                 1701073. 
                   
                 AUCCGA 
                 3498 
                 1800409. 
                   
                 ACCAAUA 
                 3498 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1382 
                 AUUGGUGUCUTCACU 
                 2193- 
                 A- 
                 1512 
                 UCAUCCAGUGAAGACAC 
                 2191- 
               
               
                 953537. 
                 1701135. 
                   
                 GGAUGA 
                 2213 
                 1800440. 
                   
                 CAAUAA 
                 2213 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1383 
                 UCUUGCUGCUAAAUC 
                 2010- 
                 A- 
                 1513 
                 UTCGGUGAUUUAGCAGC 
                 2008- 
               
               
                 953477. 
                 1701015. 
                   
                 ACCGAA 
                 2030 
                 1800380. 
                   
                 AAGAAA 
                 2030 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1384 
                 UUGCUGCUAAAUCAC 
                 2012- 
                 A- 
                 1514 
                 UGCUCGGUGAUTUAGCA 
                 2010- 
               
               
                 953479. 
                 1701019. 
                   
                 CGAGCA 
                 2032 
                 1800382. 
                   
                 GCAAGA 
                 2032 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1385 
                 AGAUUAUGCGGAUC 
                 1352- 
                 A- 
                 1515 
                 UAGGTUTGAUCCGCATA 
                 1350- 
               
               
                 953439. 
                 1700939. 
                   
                 AAACCUA 
                 1372 
                 1800342. 
                   
                 AUCUGC 
                 1372 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1386 
                 GGGCAGAATCAUCAC 
                 1138- 
                 A- 
                 1516 
                 UACUTCGUGAUGATUCU 
                 1136- 
               
               
                 953431. 
                 1700923. 
                   
                 GAAGUA 
                 1158 
                 1800334. 
                   
                 GCCCUC 
                 1158 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1387 
                 AUUUGUUUGUACAA 
                 1616- 
                 A- 
                 1517 
                 UCGGAUCUUGUACAAA 
                 1614- 
               
               
                 953442. 
                 1700945. 
                   
                 GAUCCGA 
                 1636 
                 1800345. 
                   
                 CAAAUGC 
                 1636 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1388 
                 CAAAAACACAGACUC 
                 1656- 
                 A- 
                 1518 
                 UAACGCGAGUCTGTGTU 
                 1654- 
               
               
                 953449. 
                 1700959. 
                   
                 GCGUUA 
                 1676 
                 1800352. 
                   
                 UUUGCA 
                 1676 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1389 
                 UGCUACUGTUTAUCC 
                 3482- 
                 A- 
                 1519 
                 UAUUACGGAUAAACAG 
                 3480- 
               
               
                 953510. 
                 1701081. 
                   
                 GUAAUA 
                 3502 
                 1800413. 
                   
                 UAGCACC 
                 3502 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1390 
                 ACUUUUCGTCCAACU 
                  657- 
                 A- 
                 1520 
                 UCCAGAAGUUGGACGA 
                  655- 
               
               
                 953514. 
                 1701089. 
                   
                 UCUGGA 
                  677 
                 1800417. 
                   
                 AAAGUUU 
                  677 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1391 
                 GGUGCUACTGTUUAU 
                 3480- 
                 A- 
                 1521 
                 UTACGGAUAAACAGUA 
                 3478- 
               
               
                 953508. 
                 1701077. 
                   
                 CCGUAA 
                 3500 
                 1800411. 
                   
                 GCACCAA 
                 3500 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1392 
                 GCAAAAACACAGACU 
                 1655- 
                 A- 
                 1522 
                 UACGCGAGUCUGUGUTU 
                 1653- 
               
               
                 953531. 
                 1701123. 
                   
                 CGCGUA 
                 1675 
                 1800434. 
                   
                 UUGCAG 
                 1675 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1393 
                 CGUCGCACTGAAACU 
                  645- 
                 A- 
                 1523 
                 UCGAAAAGUUUCAGUG 
                  643- 
               
               
                 953427. 
                 1700915. 
                   
                 UUUCGA 
                  665 
                 1800330. 
                   
                 CGACGCC 
                  665 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1394 
                 AUAUUAACAUCACGU 
                 3517- 
                 A- 
                 1524 
                 UCAAAGACGUGAUGUT 
                 3515- 
               
               
                 953512. 
                 1701085. 
                   
                 CUUUGA 
                 3537 
                 1800415. 
                   
                 AAUAUCU 
                 3537 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1395 
                 AAAACACAGACUCGC 
                 1658- 
                 A- 
                 1525 
                 UGCAACGCGAGTCTGTG 
                 1656- 
               
               
                 953533. 
                 1701127. 
                   
                 GUUGCA 
                 1678 
                 1800436. 
                   
                 UUUUUG 
                 1678 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1396 
                 CUUGCAGATGTGACA 
                 1709- 
                 A- 
                 1526 
                 UCGGCUTGUCACATCTG 
                 1707- 
               
               
                 953464. 
                 1700989. 
                   
                 AGCCGA 
                 1729 
                 1800367. 
                   
                 CAAGUA 
                 1729 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1397 
                 UUUUUUUUCAGUAU 
                 3027- 
                 A- 
                 1527 
                 UCCAAGAAUACTGAAAA 
                 3025- 
               
               
                 953542. 
                 1701145. 
                   
                 UCUUGGA 
                 3047 
                 1800445. 
                   
                 AAAACC 
                 3047 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1398 
                 AAAGUGAGTGACCUG 
                  415- 
                 A- 
                 1528 
                 UAAAAGCAGGUCACUC 
                  413- 
               
               
                 953426. 
                 1700913. 
                   
                 CUUUUA 
                  435 
                 1800329. 
                   
                 ACUUUGC 
                  435 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1399 
                 UUCGUCCAACTUCUG 
                  661- 
                 A- 
                 1529 
                 UCAGCCCAGAAGUTGGA 
                  659- 
               
               
                 953515. 
                 1701091. 
                   
                 GGCUGA 
                  681 
                 1800418. 
                   
                 CGAAAA 
                  681 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1400 
                 AGGACAUUGCTGUGC 
                 2518- 
                 A- 
                 1530 
                 UCCAAAGCACAGCAATG 
                 2516- 
               
               
                 953487. 
                 1701035. 
                   
                 UUUGGA 
                 2538 
                 1800390. 
                   
                 UCCUGA 
                 2538 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1401 
                 AAAUCAGUTCGAGGA 
                 1462- 
                 A- 
                 1531 
                 UCCCTUTCCUCGAACTG 
                 1460- 
               
               
                 953521. 
                 1701103. 
                   
                 AAGGGA 
                 1482 
                 1800424. 
                   
                 AUUUUU 
                 1482 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1402 
                 UUCCCCAAAUCACUG 
                  278- 
                 A- 
                 1532 
                 UAUCCACAGUGAUTUGG 
                  276- 
               
               
                 953425. 
                 1700911. 
                   
                 UGGAUA 
                  298 
                 1800328. 
                   
                 GGAAGU 
                  298 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1403 
                 CCCUCUUGGAAUUGG 
                 1978- 
                 A- 
                 1533 
                 UCGAAUCCAAUTCCAAG 
                 1976- 
               
               
                 953536. 
                 1701133. 
                   
                 AUUCGA 
                 1998 
                 1800439. 
                   
                 AGGGAC 
                 1998 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1404 
                 UUGCAGAUGUGACA 
                 1710- 
                 A- 
                 1534 
                 UTCGGCTUGUCACAUCU 
                 1708- 
               
               
                 953465. 
                 1700991. 
                   
                 AGCCGAA 
                 1730 
                 1800368. 
                   
                 GCAAGU 
                 1730 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1405 
                 CACGUCUUTGTCUCU 
                 3527- 
                 A- 
                 1535 
                 UGCACUAGAGACAAAG 
                 3525- 
               
               
                 953552. 
                 1701165. 
                   
                 AGUGCA 
                 3547 
                 1800455. 
                   
                 ACGUGAU 
                 3547 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1406 
                 GAUCCGCAGACGUGU 
                 1630- 
                 A- 
                 1536 
                 UCAUTUACACGTCTGCG 
                 1628- 
               
               
                 953528. 
                 1701117. 
                   
                 AAAUGA 
                 1650 
                 1800431. 
                   
                 GAUCUU 
                 1650 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1407 
                 AAAAAUCAGUTCGAG 
                 1460- 
                 A- 
                 1537 
                 UCUUTCCUCGAACTGAU 
                 1458- 
               
               
                 953519. 
                 1701099. 
                   
                 GAAAGA 
                 1480 
                 1800422. 
                   
                 UUUUUU 
                 1480 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1408 
                 UGCUGUGGACTUGAG 
                 2221- 
                 A- 
                 1538 
                 UCCCAACUCAAGUCCAC 
                 2219- 
               
               
                 953486. 
                 1701033. 
                   
                 UUGGGA 
                 2241 
                 1800389. 
                   
                 AGCAGU 
                 2241 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1409 
                 AAGGGGCAAAAACG 
                 1483- 
                 A- 
                 1539 
                 UCGCTUTCGUUTUTGCC 
                 1481- 
               
               
                 953522. 
                 1701105. 
                   
                 AAAGCGA 
                 1503 
                 1800425. 
                   
                 CCUUUC 
                 1503 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1410 
                 UGCAAAAACACAGAC 
                 1654- 
                 A- 
                 1540 
                 UCGCGAGUCUGTGTUTU 
                 1652- 
               
               
                 953530. 
                 1701121. 
                   
                 UCGCGA 
                 1674 
                 1800433. 
                   
                 UGCAGG 
                 1674 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1411 
                 ACGUCUUUGUCUCUA 
                 3528- 
                 A- 
                 1541 
                 UTGCACTAGAGACAAAG 
                 3526- 
               
               
                 953513. 
                 1701087. 
                   
                 GUGCAA 
                 3548 
                 1800416. 
                   
                 ACGUGA 
                 3548 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1412 
                 GGGCAAAAACGAAA 
                 1486- 
                 A- 
                 1542 
                 UTUGCGCUUUCGUTUTU 
                 1484- 
               
               
                 953441. 
                 1700943. 
                   
                 GCGCAAA 
                 1506 
                 1800344. 
                   
                 GCCCCU 
                 1506 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1413 
                 AGGGGCAAAAACGA 
                 1484- 
                 A- 
                 1543 
                 UGCGCUTUCGUTUTUGC 
                 1482- 
               
               
                 953440. 
                 1700941. 
                   
                 AAGCGCA 
                 1504 
                 1800343. 
                   
                 CCCUUU 
                 1504 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1414 
                 GAAAAAAAAUCAGU 
                 1456- 
                 A- 
                 1544 
                 UCCUCGAACUGAUTUTU 
                 1454- 
               
               
                 953518. 
                 1701097. 
                   
                 UCGAGGA 
                 1476 
                 1800421. 
                   
                 UUUCUU 
                 1476 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1415 
                 AAAAUCAGTUCGAGG 
                 1461- 
                 A- 
                 1545 
                 UCCUTUCCUCGAACUGA 
                 1459- 
               
               
                 953520. 
                 1701101. 
                   
                 AAAGGA 
                 1481 
                 1800423. 
                   
                 UUUUUU 
                 1481 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1416 
                 AAAAACACAGACUCG 
                 1657- 
                 A- 
                 1546 
                 UCAACGCGAGUCUGUG 
                 1655- 
               
               
                 953532. 
                 1701125. 
                   
                 CGUUGA 
                 1677 
                 1800435. 
                   
                 UUUUUGC 
                 1677 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1417 
                 UUUAUCCGTAAUAAU 
                 3490- 
                 A- 
                 1547 
                 UCCACAAUUAUTACGGA 
                 3488- 
               
               
                 953548. 
                 1701157. 
                   
                 UGUGGA 
                 3510 
                 1800451. 
                   
                 UAAACA 
                 3510 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1418 
                 AGAUCCGCAGACGUG 
                 1629- 
                 A- 
                 1548 
                 UAUUTACACGUCUGCGG 
                 1627- 
               
               
                 953527. 
                 1701115. 
                   
                 UAAAUA 
                 1649 
                 1800430. 
                   
                 AUCUUG 
                 1649 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1419 
                 UUAACAUCACGUCUU 
                 3520- 
                 A- 
                 1549 
                 UAGACAAAGACGUGAT 
                 3518- 
               
               
                 953551. 
                 1701163. 
                   
                 UGUCUA 
                 3540 
                 1800454. 
                   
                 GUUAAUA 
                 3540 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1420 
                 CGUCUUUGTCTCUAG 
                 3529- 
                 A- 
                 1550 
                 UCUGCACUAGAGACAA 
                 3527- 
               
               
                 953553. 
                 1701167. 
                   
                 UGCAGA 
                 3549 
                 1800456. 
                   
                 AGACGUG 
                 3549 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1421 
                 GUUUAUCCGUAAUA 
                 3489- 
                 A- 
                 1551 
                 UCACAATUAUUACGGAU 
                 3487- 
               
               
                 953547. 
                 1701155. 
                   
                 AUUGUGA 
                 3509 
                 1800450. 
                   
                 AAACAG 
                 3509 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1422 
                 UUGUUUGUACAAGA 
                 1618- 
                 A- 
                 1552 
                 UTGCGGAUCUUGUACAA 
                 1616- 
               
               
                 953526. 
                 1701113. 
                   
                 UCCGCAA 
                 1638 
                 1800429. 
                   
                 ACAAAU 
                 1638 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1423 
                 UUAUCCGUAATAAUU 
                 3491- 
                 A- 
                 1553 
                 UCCCACAAUUATUACGG 
                 3489- 
               
               
                 953549. 
                 1701159. 
                   
                 GUGGGA 
                 3511 
                 1800452. 
                   
                 AUAAAC 
                 3511 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1424 
                 AACACAGACUCGCGU 
                 1660- 
                 A- 
                 1554 
                 UTUGCAACGCGAGTCTG 
                 1658- 
               
               
                 953534. 
                 1701129. 
                   
                 UGCAAA 
                 1680 
                 1800437. 
                   
                 UGUUUU 
                 1680 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1425 
                 UUUUUUUCAGTAUUC 
                 3028- 
                 A- 
                 1555 
                 UACCAAGAAUACUGAA 
                 3026- 
               
               
                 953543. 
                 1701147. 
                   
                 UUGGUA 
                 3048 
                 1800446. 
                   
                 AAAAAAC 
                 3048 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1426 
                 AUUAACAUCACGUCU 
                 3519- 
                 A- 
                 1556 
                 UGACAAAGACGTGAUG 
                 3517- 
               
               
                 953550. 
                 1701161. 
                   
                 UUGUCA 
                 3539 
                 1800453. 
                   
                 UUAAUAU 
                 3539 
               
               
                 1 
                 1 
                   
                   
                   
                 1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5A 
               
             
            
               
                   
               
               
                 Exemplary Rat VEGF-A siRNA Modified Single Strands and Duplex Sequences. The mRNA target sequence refers to the target sequence in rat;  the 
               
               
                 corresponding human target sequence may differ. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                   
                   
                 SEQ ID 
               
               
                   
                 Sense 
                 SEQ ID 
                   
                 Antisense 
                 SEQ ID 
                   
                   
                 NO: 
               
               
                 Duplex 
                 Oligo 
                 NO: 
                   
                 Oligo 
                 NO: 
                   
                 mRNA target 
                 (mRNA 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Name 
                 (Antisense) 
                 Antisense Sequence 
                 sequence 
                 target) 
               
               
                   
               
               
                 AD- 
                 A- 
                 1557 
                 csgsgaa(Ahd)CfuUf 
                 A- 
                 1644 
                 VPusAfsguuGfgAfCf 
                 CACGGAAACUU 
                 4613 
               
               
                 579911. 
                 1110768 
                   
                 UfUfcguccaacsusa 
                 1100967.1 
                   
                 gaaaAfgUfuuccgsusg 
                 UUCGUCCAACU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1558 
                 gsgsaaa(Chd)UfuUf 
                 A- 
                 1645 
                 VPusAfsaguUfgGfAf 
                 ACGGAAACUUU 
                 4614 
               
               
                 579912. 
                 1110769 
                   
                 UfCfguccaacususa 
                 1100969.1 
                   
                 cgaaAfaGfuuuccsgsu 
                 UCGUCCAACUU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1559 
                 csgsaca(Ghd)AfaCfA 
                 A- 
                 1646 
                 VPusGfsauuAfaGfGf 
                 GUCGACAGAAC 
                 4615 
               
               
                 579913. 
                 1110770 
                   
                 fGfuccuuaauscsa 
                 1102172.1 
                   
                 acugUfuCfugucgsasc 
                 AGUCCUUAAUC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1560 
                 csusgcu(Ahd)AfuGf 
                 A- 
                 1647 
                 VPusGfsacaCfcAfAf 
                 CUCUGCUAAUG 
                 4616 
               
               
                 579914. 
                 1110771 
                   
                 UfUfauugguguscsa 
                 1102638.1 
                   
                 uaacAfuUfagcagsasg 
                 UUAUUGGUGUC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1561 
                 uscscga(Ghd)AfuAf 
                 A- 
                 1648 
                 VPusGfsuacUfaCfGf 
                 UUUCCGAGAUA 
                 4617 
               
               
                 579915. 
                 1110772 
                   
                 UfUfccguaguascsa 
                 1103944.1 
                   
                 gaauAfuCfucggasasa 
                 UUCCGUAGUAC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1562 
                 csgsaga(Uhd)AfuUf 
                 A- 
                 1649 
                 VPusAfsuguAfcUfAf 
                 UCCGAGAUAUU 
                 4618 
               
               
                 579916. 
                 1110773 
                   
                 CfCfguaguacasusa 
                 1103888.1 
                   
                 cggaAfuAfucucgsgsa 
                 CCGUAGUACAU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1563 
                 gscsacg(Ghd)AfaAf 
                 A- 
                 1650 
                 VPusUfsggaCfgAfAf 
                 UUGCACGGAAA 
                 4619 
               
               
                 579917. 
                 1110774 
                   
                 CfUfuuucguccsasa 
                 1100961.1 
                   
                 aaguUfuCfcgugcsasa 
                 CUUUUCGUCCA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1564 
                 csascgg(Ahd)AfaCf 
                 A- 
                 1651 
                 VPusUfsuggAfcGfAf 
                 UGCACGGAAAC 
                 4620 
               
               
                 579918. 
                 1110775 
                   
                 UfUfuucguccasasa 
                 1100963.1 
                   
                 aaagUfuUfccgugscsa 
                 UUUUCGUCCAA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1565 
                 gsasgau(Ahd)UfuCf 
                 A- 
                 1652 
                 VPusUfsaugUfaCfUf 
                 CCGAGAUAUUC 
                 4621 
               
               
                 579919. 
                 1110776 
                   
                 CfGfuaguacausasa 
                 1103889.1 
                   
                 acggAfaUfaucucsgsg 
                 CGUAGUACAUA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1566 
                 ususguu(Uhd)GfuCf 
                 A- 
                 1653 
                 VPusUfsgcgGfaUfCf 
                 AUUUGUUUGUC 
                 4622 
               
               
                 579921. 
                 1110778 
                   
                 CfAfagauccgcsasa 
                 1101976.1 
                   
                 uuggAfcAfaacaasasu 
                 CAAGAUCCGCA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 G 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1567 
                 ascsgga(Ahd)AfcUf 
                 A- 
                 1654 
                 VPusGfsuugGfaCfGf 
                 GCACGGAAACU 
                 4623 
               
               
                 579922. 
                 1110779 
                   
                 UfUfucguccaascsa 
                 1100965.1 
                   
                 aaaaGfuUfuccgusgsc 
                 UUUCGUCCAAC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1568 
                 asuscau(Ghd)CfgGf 
                 A- 
                 1655 
                 VPusUfsgagGfuUfUf 
                 AGAUCAUGCGG 
                 4624 
               
               
                 579923. 
                 1110780 
                   
                 AfUfcaaaccucsasa 
                 1101742.1 
                   
                 gaucCfgCfaugauscsu 
                 AUCAAACCUCA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1569 
                 asusgcg(Ghd)AfuCf 
                 A- 
                 1656 
                 VPusUfsgguGfaGfGf 
                 UCAUGCGGAUC 
                 4625 
               
               
                 579924. 
                 1110781 
                   
                 AfAfaccucaccsasa 
                 1101659.1 
                   
                 uuugAfuCfcgcausgsa 
                 AAACCUCACCA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1570 
                 gsasuca(Uhd)GfcGf 
                 A- 
                 1657 
                 VPusGfsaggUfuUfGf 
                 CAGAUCAUGCG 
                 4626 
               
               
                 579925. 
                 1110782 
                   
                 GfAfucaaaccuscsa 
                 1101740.1 
                   
                 auccGfcAfugaucsusg 
                 GAUCAAACCUC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1571 
                 ususugu(Uhd)UfgUf 
                 A- 
                 1658 
                 VPusGfscggAfuCfUf 
                 CAUUUGUUUGU 
                 4627 
               
               
                 579926. 
                 1110783 
                   
                 CfCfaagauccgscsa 
                 1101974.1 
                   
                 uggaCfaAfacaaasusg 
                 CCAAGAUCCGC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1572 
                 gsasucg(Ghd)UfgAf 
                 A- 
                 1659 
                 VPusGfscuaGfuGfAf 
                 CAGAUCGGUGA 
                 4628 
               
               
                 579927. 
                 1110784 
                   
                 CfAfgucacuagscsa 
                 1103783.1 
                   
                 cuguCfaCfcgaucsusg 
                 CAGUCACUAGC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1573 
                 asasgau(Chd)CfgCfA 
                 A- 
                 1660 
                 VPusUfsuuaCfaCfGf 
                 CCAAGAUCCGC 
                 4629 
               
               
                 579929. 
                 1110786 
                   
                 fGfacguguaasasa 
                 1101968.1 
                   
                 ucugCfgGfaucuusgsg 
                 AGACGUGUAAA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1574 
                 usgsucc(Ahd)AfgAf 
                 A- 
                 1661 
                 VPusAfscguCfuGfCf 
                 UUUGUCCAAGA 
                 4630 
               
               
                 579930. 
                 1110787 
                   
                 UfCfcgcagacgsusa 
                 1101986.1 
                   
                 ggauCfuUfggacasasa 
                 UCCGCAGACGU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 G 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1575 
                 asuscac(Ghd)UfcUf 
                 A- 
                 1662 
                 VPusUfscuaGfaGfAf 
                 ACAUCACGUCU 
                 4631 
               
               
                 579931. 
                 1110788 
                   
                 UfUfgucucuagsasa 
                 1103887.1 
                   
                 caaaGfaCfgugausgsu 
                 UUGUCUCUAGA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 G 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1576 
                 usgsaaa(Chd)CfaUfG 
                 A- 
                 1663 
                 VPusGfscagAfaAfGf 
                 UCUGAAACCAU 
                 4632 
               
               
                 579932. 
                 1110789 
                   
                 fAfacuuucugscsa 
                 1101283.1 
                   
                 uucaUfgGfuuucasgsa 
                 GAACUUUCUGC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1577 
                 ususguc(Uhd)CfuAf 
                 A- 
                 1664 
                 VPusGfsaaaAfcUfGf 
                 CUUUGUCUCUA 
                 4633 
               
               
                 579933. 
                 1110790 
                   
                 GfAfgcaguuuuscsa 
                 1103908.1 
                   
                 cucuAfgAfgacaasasg 
                 GAGCAGUUUUC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1578 
                 csascuu(Chd)CfaGfA 
                 A- 
                 1665 
                 VPusUfsuguCfgUfGf 
                 CUCACUUCCAG 
                 4634 
               
               
                 579934. 
                 1110791 
                   
                 fAfacacgacasasa 
                 1102962.1 
                   
                 uuucUfgGfaagugsasg 
                 AAACACGACAA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1579 
                 usgsaaa(Uhd)CfuGf 
                 A- 
                 1666 
                 VPusGfsauuGfgAfAf 
                 UAUGAAAUCUG 
                 4635 
               
               
                 579935. 
                 1110792 
                   
                 UfGfuuuccaauscsa 
                 1103728.1 
                   
                 acacAfgAfuuucasusa 
                 UGUUUCCAAUC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1580 
                 gsasaau(Chd)UfgUf 
                 A- 
                 1667 
                 VPusAfsgauUfgGfAf 
                 AUGAAAUCUGU 
                 4636 
               
               
                 579936. 
                 1110793 
                   
                 GfUfuuccaaucsusa 
                 1103730.1 
                   
                 aacaCfaGfauuucsasu 
                 GUUUCCAAUCU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1581 
                 ususugu(Chd)UfcUf 
                 A- 
                 1668 
                 VPusAfsaaaCfuGfCf 
                 UCUUUGUCUCU 
                 4637 
               
               
                 579937. 
                 1110794 
                   
                 AfGfagcaguuususa 
                 1103906.1 
                   
                 ucuaGfaGfacaaasgsa 
                 AGAGCAGUUUU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1582 
                 usgsucu(Chd)UfaGf 
                 A- 
                 1669 
                 VPusGfsgaaAfaCfUf 
                 UUUGUCUCUAG 
                 4638 
               
               
                 579938. 
                 1110795 
                   
                 AfGfcaguuuucscsa 
                 1103910.1 
                   
                 gcucUfaGfagacasasa 
                 AGCAGUUUUCC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 G 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1583 
                 asascug(Uhd)AfuUf 
                 A- 
                 1670 
                 VPusAfsagcGfuAfAf 
                 UAAACUGUAUU 
                 4639 
               
               
                 579939. 
                 1110796 
                   
                 GfUfuuuacgcususa 
                 1100541.1 
                   
                 aacaAfuAfcaguususa 
                 GUUUUACGCUU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1584 
                 ascsugu(Ahd)UfuGf 
                 A- 
                 1671 
                 VPusAfsaagCfgUfAf 
                 AAACUGUAUUG 
                 4640 
               
               
                 579940. 
                 1110797 
                   
                 UfUfuuacgcuususa 
                 1100543.1 
                   
                 aaacAfaUfacagususu 
                 UUUUACGCUUU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1585 
                 csusgua(Uhd)UfgUf 
                 A- 
                 1672 
                 VPusUfsaaaGfcGfUf 
                 AACUGUAUUGU 
                 4641 
               
               
                 579941. 
                 1110798 
                   
                 UfUfuacgcuuusasa 
                 1100545.1 
                   
                 aaaaCfaAfuacagsusu 
                 UUUACGCUUUA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1586 
                 usgsuau(Uhd)GfuUf 
                 A- 
                 1673 
                 VPusUfsuaaAfgCfGf 
                 ACUGUAUUGUU 
                 4642 
               
               
                 579942. 
                 1110799 
                   
                 UfUfacgcuuuasasa 
                 1100547.1 
                   
                 uaaaAfcAfauacasgsu 
                 UUACGCUUUAA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1587 
                 asusuga(Ahd)AfcCf 
                 A- 
                 1674 
                 VPusAfscagAfaUfUf 
                 CCAUUGAAACC 
                 4643 
               
               
                 579943. 
                 1110800 
                   
                 AfCfuaauucugsusa 
                 1103504.1 
                   
                 agugGfuUfucaausgsg 
                 ACUAAUUCUGU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1588 
                 ascsuua(Uhd)UfuAf 
                 A- 
                 1675 
                 VPusAfsaaaGfgGfCf 
                 GUACUUAUUUA 
                 4644 
               
               
                 579944. 
                 1110801 
                   
                 AfUfagcccuuususa 
                 1103594.1 
                   
                 uauuAfaAfuaagusasc 
                 AUAGCCCUUUU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1589 
                 uscsucu(Ahd)GfaGf 
                 A- 
                 1676 
                 VPusUfscggAfaAfAf 
                 UGUCUCUAGAG 
                 4645 
               
               
                 579945. 
                 1110802 
                   
                 CfAfguuuuccgsasa 
                 1103914.1 
                   
                 cugcUfcUfagagascsa 
                 CAGUUUUCCGA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 G 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1590 
                 cscsgag(Ahd)UfaUf 
                 A- 
                 1677 
                 VPusUfsguaCfuAfCf 
                 UUCCGAGAUAU 
                 4646 
               
               
                 579946. 
                 1110803 
                   
                 UfCfcguaguacsasa 
                 1103946.1 
                   
                 ggaaUfaUfcucggsasa 
                 UCCGUAGUACA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1591 
                 uscsugg(Ghd)AfuUf 
                 A- 
                 1678 
                 VPusUfsuugAfaUfAf 
                 GCUCUGGGAUU 
                 4647 
               
               
                 579947. 
                 1110804 
                   
                 UfGfauauucaasasa 
                 1100511.1 
                   
                 ucaaAfuCfccagasgsc 
                 UGAUAUUCAAA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1592 
                 ususcac(Uhd)GfgAf 
                 A- 
                 1679 
                 VPusAfsgucAfaAfCf 
                 UCUUCACUGGA 
                 4648 
               
               
                 579948. 
                 1110805 
                   
                 UfAfuguuugacsusa 
                 1102658.1 
                   
                 auauCfcAfgugaasgsa 
                 UAUGUUUGACU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 G 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1593 
                 gsgscuc(Ahd)CfuUf 
                 A- 
                 1680 
                 VPusCfsgugUfuUfCf 
                 UUGGCUCACUU 
                 4649 
               
               
                 579949. 
                 1110806 
                   
                 CfCfagaaacacsgsa 
                 1102954.1 
                   
                 uggaAfgUfgagccsasa 
                 CCAGAAACACG 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1594 
                 csusucc(Ahd)GfaAf 
                 A- 
                 1681 
                 VPusGfsuuuGfuCfGf 
                 CACUUCCAGAA 
                 4650 
               
               
                 579950. 
                 1110807 
                   
                 AfCfacgacaaascsa 
                 1102966.1 
                   
                 uguuUfcUfggaagsusg 
                 ACACGACAAAC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1595 
                 gsascca(Uhd)UfgAf 
                 A- 
                 1682 
                 VPusAfsauuAfgUfGf 
                 CAGACCAUUGA 
                 4651 
               
               
                 579951. 
                 1110808 
                   
                 AfAfccacuaaususa 
                 1103496.1 
                   
                 guuuCfaAfuggucsusg 
                 AACCACUAAUU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1596 
                 asgsuca(Chd)UfaGfC 
                 A- 
                 1683 
                 VPusCfsucaGfgAfCf 
                 ACAGUCACUAG 
                 4652 
               
               
                 579953. 
                 1110810 
                   
                 fUfuguccugasgsa 
                 1103805.1 
                   
                 aagcUfaGfugacusgsu 
                 CUUGUCCUGAG 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1597 
                 ascscac(Ahd)CfaUfU 
                 A- 
                 1684 
                 VPusAfsuuuCfaAfAf 
                 CCACCACACAU 
                 4653 
               
               
                 579954. 
                 1110811 
                   
                 fCfcuuugaaasusa 
                 1103837.1 
                   
                 ggaaUfgUfguggusgsg 
                 UCCUUUGAAAU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1598 
                 ascscgg(Ahd)AfaGf 
                 A- 
                 1685 
                 VPusGfsguuAfaUfCf 
                 UCACCGGAAAG 
                 4654 
               
               
                 579955. 
                 1110812 
                   
                 AfCfcgauuaacscsa 
                 1102128.1 
                   
                 ggucUfuUfccggusgsa 
                 ACCGAUUAACC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1599 
                 asgsacc(Ghd)AfuUf 
                 A- 
                 1686 
                 VPusGfsugaCfaUfGf 
                 AAAGACCGAUU 
                 4655 
               
               
                 579956. 
                 1110813 
                   
                 AfAfccaugucascsa 
                 1102142.1 
                   
                 guuaAfuCfggucususu 
                 AACCAUGUCAC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1600 
                 csusuca(Chd)UfgGf 
                 A- 
                 1687 
                 VPusGfsucaAfaCfAf 
                 GUCUUCACUGG 
                 4656 
               
               
                 579957. 
                 1110814 
                   
                 AfUfauguuugascsa 
                 1102656.1 
                   
                 uaucCfaGfugaagsasc 
                 AUAUGUUUGAC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1601 
                 ususggc(Uhd)CfaCf 
                 A- 
                 1688 
                 VPusUfsguuUfcUfGf 
                 CGUUGGCUCAC 
                 4657 
               
               
                 579958. 
                 1110815 
                   
                 UfUfccagaaacsasa 
                 1102950.1 
                   
                 gaagUfgAfgccaascsg 
                 UUCCAGAAACA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1602 
                 csuscac(Uhd)UfcCfA 
                 A- 
                 1689 
                 VPusGfsucgUfgUfUf 
                 GGCUCACUUCC 
                 4658 
               
               
                 579959. 
                 1110816 
                   
                 fGfaaacacgascsa 
                 1102958.1 
                   
                 ucugGfaAfgugagscsc 
                 AGAAACACGAC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1603 
                 gsusgac(Ahd)GfuCf 
                 A- 
                 1690 
                 VPusGfsacaAfgCfUf 
                 CGGUGACAGUC 
                 4659 
               
               
                 579960. 
                 1110817 
                   
                 AfCfuagcuuguscsa 
                 1103795.1 
                   
                 agugAfcUfgucacscsg 
                 ACUAGCUUGUC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1604 
                 gsuscuc(Uhd)AfgAf 
                 A- 
                 1691 
                 VPusCfsggaAfaAfCf 
                 UUGUCUCUAGA 
                 4660 
               
               
                 579961. 
                 1110818 
                   
                 GfCfaguuuuccsgsa 
                 1103912.1 
                   
                 ugcuCfuAfgagacsasa 
                 GCAGUUUUCCG 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1605 
                 csuscua(Ghd)AfgCf 
                 A- 
                 1692 
                 VPusCfsucgGfaAfAf 
                 GUCUCUAGAGC 
                 4661 
               
               
                 579962. 
                 1110819 
                   
                 AfGfuuuuccgasgsa 
                 1103916.1 
                   
                 acugCfuCfuagagsasc 
                 AGUUUUCCGAG 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1606 
                 gsusuuu(Chd)CfgAf 
                 A- 
                 1693 
                 VPusUfsacgGfaAfUf 
                 CAGUUUUCCGA 
                 4662 
               
               
                 579963. 
                 1110820 
                   
                 GfAfuauuccgusasa 
                 1103936.1 
                   
                 aucuCfgGfaaaacsusg 
                 GAUAUUCCGUA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 G 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1607 
                 ususccg(Ahd)GfaUf 
                 A- 
                 1694 
                 VPusUfsacuAfcGfGf 
                 UUUUCCGAGAU 
                 4663 
               
               
                 579964. 
                 1110821 
                   
                 AfUfuccguagusasa 
                 1103942.1 
                   
                 aauaUfcUfcggaasasa 
                 AUUCCGUAGUA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1608 
                 ususaaa(Chd)UfgUf 
                 A- 
                 1695 
                 VPusCfsguaAfaAfCf 
                 UCUUAAACUGU 
                 4664 
               
               
                 579965. 
                 1110822 
                   
                 AfUfuguuuuacsgsa 
                 1100535.1 
                   
                 aauaCfaGfuuuaasgsa 
                 AUUGUUUUACG 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1609 
                 asasacu(Ghd)UfaUf 
                 A- 
                 1696 
                 VPusAfsgcgUfaAfAf 
                 UUAAACUGUAU 
                 4665 
               
               
                 579966. 
                 1110823 
                   
                 UfGfuuuuacgcsusa 
                 1100539.1 
                   
                 acaaUfaCfaguuusasa 
                 UGUUUUACGCU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1610 
                 gsasuuc(Ghd)CfcAf 
                 A- 
                 1697 
                 VPusAfsuauAfaGfAf 
                 UGGAUUCGCCA 
                 4666 
               
               
                 579967. 
                 1110824 
                   
                 UfUfuucuuauasusa 
                 1102468.1 
                   
                 aaauGfgCfgaaucscsa 
                 UUUUCUUAUAU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1611 
                 uscsacu(Ghd)GfaUf 
                 A- 
                 1698 
                 VPusCfsaguCfaAfAf 
                 CUUCACUGGAU 
                 4667 
               
               
                 579968. 
                 1110825 
                   
                 AfUfguuugacusgsa 
                 1102660.1 
                   
                 cauaUfcCfagugasasg 
                 AUGUUUGACUG 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1612 
                 gsusugg(Chd)UfcAf 
                 A- 
                 1699 
                 VPusGfsuuuCfuGfGf 
                 ACGUUGGCUCA 
                 4668 
               
               
                 579969. 
                 1110826 
                   
                 CfUfuccagaaascsa 
                 1102948.1 
                   
                 aaguGfaGfccaacsgsu 
                 CUUCCAGAAAC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1613 
                 ascsuuc(Chd)AfgAf 
                 A- 
                 1700 
                 VPusUfsuugUfcGfUf 
                 UCACUUCCAGA 
                 4669 
               
               
                 579970. 
                 1110827 
                   
                 AfAfcacgacaasasa 
                 1102964.1 
                   
                 guuuCfuGfgaagusgsa 
                 AACACGACAAA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1614 
                 usascuu(Ahd)UfuUf 
                 A- 
                 1701 
                 VPusAfsaagGfgCfUf 
                 GGUACUUAUUU 
                 4670 
               
               
                 579971. 
                 1110828 
                   
                 AfAfuagcccuususa 
                 1103592.1 
                   
                 auuaAfaUfaaguascsc 
                 AAUAGCCCUUU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1615 
                 asgsagc(Ahd)GfuUf 
                 A- 
                 1702 
                 VPusAfsuauCfuCfGf 
                 CUAGAGCAGUU 
                 4671 
               
               
                 579972. 
                 1110829 
                   
                 UfUfccgagauasusa 
                 1103924.1 
                   
                 gaaaAfcUfgcucusasg 
                 UUCCGAGAUAU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1616 
                 usgsgga(Uhd)UfuGf 
                 A- 
                 1703 
                 VPusGfsguuUfgAfAf 
                 UCUGGGAUUUG 
                 4672 
               
               
                 579973. 
                 1110830 
                   
                 AfUfauucaaacscsa 
                 1100515.1 
                   
                 uaucAfaAfucccasgsa 
                 AUAUUCAAACC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1617 
                 gsgsgau(Uhd)UfgAf 
                 A- 
                 1704 
                 VPusAfsgguUfuGfAf 
                 CUGGGAUUUGA 
                 4673 
               
               
                 579974. 
                 1110831 
                   
                 UfAfuucaaaccsusa 
                 1100517.1 
                   
                 auauCfaAfaucccsasg 
                 UAUUCAAACCU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1618 
                 gsasuuu(Ghd)AfuAf 
                 A- 
                 1705 
                 VPusAfsgagGfuUfUf 
                 GGGAUUUGAUA 
                 4674 
               
               
                 579975. 
                 1110832 
                   
                 UfUfcaaaccucsusa 
                 1100521.1 
                   
                 gaauAfuCfaaaucscsc 
                 UUCAAACCUCU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1619 
                 usasaac(Uhd)GfuAf 
                 A- 
                 1706 
                 VPusGfscguAfaAfAf 
                 CUUAAACUGUA 
                 4675 
               
               
                 579976. 
                 1110833 
                   
                 UfUfguuuuacgscsa 
                 1100537.1 
                   
                 caauAfcAfguuuasasg 
                 UUGUUUUACGC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1620 
                 uscsacc(Ghd)GfaAf 
                 A- 
                 1707 
                 VPusUfsuaaUfcGfGf 
                 UCUCACCGGAA 
                 4676 
               
               
                 579977. 
                 1110834 
                   
                 AfGfaccgauuasasa 
                 1102124.1 
                   
                 ucuuUfcCfggugasgsa 
                 AGACCGAUUAA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1621 
                 csasccg(Ghd)AfaAf 
                 A- 
                 1708 
                 VPusGfsuuaAfuCfGf 
                 CUCACCGGAAA 
                 4677 
               
               
                 579978. 
                 1110835 
                   
                 GfAfccgauuaascsa 
                 1102126.1 
                   
                 gucuUfuCfcggugsasg 
                 GACCGAUUAAC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1622 
                 cscsgga(Ahd)AfgAf 
                 A- 
                 1709 
                 VPusUfsgguUfaAfUf 
                 CACCGGAAAGA 
                 4678 
               
               
                 579979. 
                 1110836 
                   
                 CfCfgauuaaccsasa 
                 1102130.1 
                   
                 cgguCfuUfuccggsusg 
                 CCGAUUAACCA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1623 
                 gsasacu(Ghd)GfaUf 
                 A- 
                 1710 
                 VPusGfsaaaAfuGfGf 
                 UGGAACUGGAU 
                 4679 
               
               
                 579980. 
                 1110837 
                   
                 UfCfgccauuuuscsa 
                 1102456.1 
                   
                 cgaaUfcCfaguucscsa 
                 UCGCCAUUUUC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1624 
                 csascug(Ghd)AfuAf 
                 A- 
                 1711 
                 VPusGfscagUfcAfAf 
                 UUCACUGGAUA 
                 4680 
               
               
                 579981. 
                 1110838 
                   
                 UfGfuuugacugscsa 
                 1102662.1 
                   
                 acauAfuCfcagugsasa 
                 UGUUUGACUGC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1625 
                 gsgsacc(Uhd)UfgUf 
                 A- 
                 1712 
                 VPusGfsgucUfgAfUf 
                 GAGGACCUUGU 
                 4681 
               
               
                 579982. 
                 1110839 
                   
                 GfUfgaucagacscsa 
                 1103464.1 
                   
                 cacaCfaAfgguccsusc 
                 GUGAUCAGACC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1626 
                 uscsaga(Chd)CfaUfU 
                 A- 
                 1713 
                 VPusUfsaguGfgUfUf 
                 GAUCAGACCAU 
                 4682 
               
               
                 579983. 
                 1110840 
                   
                 fGfaaaccacusasa 
                 1103490.1 
                   
                 ucaaUfgGfucugasusc 
                 UGAAACCACUA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1627 
                 csasuug(Ahd)AfaCf 
                 A- 
                 1714 
                 VPusCfsagaAfuUfAf 
                 ACCAUUGAAAC 
                 4683 
               
               
                 579984. 
                 1110841 
                   
                 CfAfcuaauucusgsa 
                 1103502.1 
                   
                 guggUfuUfcaaugsgsu 
                 CACUAAUUCUG 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1628 
                 csusaga(Ghd)CfaGf 
                 A- 
                 1715 
                 VPusAfsucuCfgGfAf 
                 CUCUAGAGCAG 
                 4684 
               
               
                 579985. 
                 1110842 
                   
                 UfUfuuccgagasusa 
                 1103920.1 
                   
                 aaacUfgCfucuagsasg 
                 UUUUCCGAGAU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1629 
                 usasgag(Chd)AfgUf 
                 A- 
                 1716 
                 VPusUfsaucUfcGfGf 
                 UCUAGAGCAGU 
                 4685 
               
               
                 579986. 
                 1110843 
                   
                 UfUfuccgagausasa 
                 1103922.1 
                   
                 aaaaCfuGfcucuasgsa 
                 UUUCCGAGAUA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1630 
                 asgsuuu(Uhd)CfcGf 
                 A- 
                 1717 
                 VPusAfscggAfaUfAf 
                 GCAGUUUUCCG 
                 4686 
               
               
                 579987. 
                 1110844 
                   
                 AfGfauauuccgsusa 
                 1103934.1 
                   
                 ucucGfgAfaaacusgsc 
                 AGAUAUUCCGU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1631 
                 gscsgga(Uhd)CfaAf 
                 A- 
                 1718 
                 VPusUfsuugGfuGfAf 
                 AUGCGGAUCAA 
                 4687 
               
               
                 579988. 
                 1110845 
                   
                 AfCfcucaccaasasa 
                 1101748.1 
                   
                 gguuUfgAfuccgcsasu 
                 ACCUCACCAAA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 G 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1632 
                 asgscau(Uhd)UfgUf 
                 A- 
                 1719 
                 VPusAfsucuUfgGfAf 
                 AAAGCAUUUGU 
                 4688 
               
               
                 579989. 
                 1110846 
                   
                 UfUfguccaagasusa 
                 1101962.1 
                   
                 caaaCfaAfaugcususu 
                 UUGUCCAAGAU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1633 
                 uscsuca(Chd)CfgGf 
                 A- 
                 1720 
                 VPusAfsaucGfgUfCf 
                 CCUCUCACCGG 
                 4689 
               
               
                 579990. 
                 1110847 
                   
                 AfAfagaccgaususa 
                 1102120.1 
                   
                 uuucCfgGfugagasgsg 
                 AAAGACCGAUU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1634 
                 uscsuag(Ahd)GfcAf 
                 A- 
                 1721 
                 VPusUfscucGfgAfAf 
                 UCUCUAGAGCA 
                 4690 
               
               
                 579992. 
                 1110849 
                   
                 GfUfuuuccgagsasa 
                 1103918.1 
                   
                 aacuGfcUfcuagasgsa 
                 GUUUUCCGAGA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1635 
                 asusugc(Ahd)CfgGf 
                 A- 
                 1722 
                 VPusAfscgaAfaAfGf 
                 GGAUUGCACGG 
                 4691 
               
               
                 579993. 
                 1110850 
                   
                 AfAfacuuuucgsusa 
                 1100955.1 
                   
                 uuucCfgUfgcaauscsc 
                 AAACUUUUCGU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1636 
                 gscsucu(Ghd)GfgAf 
                 A- 
                 1723 
                 VPusUfsgaaUfaUfCf 
                 GUGCUCUGGGA 
                 4692 
               
               
                 579995. 
                 1110852 
                   
                 UfUfugauauucsasa 
                 1100507.1 
                   
                 aaauCfcCfagagcsasc 
                 UUUGAUAUUCA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1637 
                 usgsagc(Chd)UfuGf 
                 A- 
                 1724 
                 VPusUfsccgCfuCfUf 
                 UGUGAGCCUUG 
                 4693 
               
               
                 579996. 
                 1110853 
                   
                 UfUfcagagcggsasa 
                 1101930.1 
                   
                 gaacAfaGfgcucascsa 
                 UUCAGAGCGGA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 G 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1638 
                 asgsccu(Uhd)GfuUf 
                 A- 
                 1725 
                 VPusUfscucCfgCfUf 
                 UGAGCCUUGUU 
                 4694 
               
               
                 579997. 
                 1110854 
                   
                 CfAfgagcggagsasa 
                 1101934.1 
                   
                 cugaAfcAfaggcuscsa 
                 CAGAGCGGAGA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1639 
                 csasuuu(Ghd)UfuUf 
                 A- 
                 1726 
                 VPusGfsgauCfuUfGf 
                 AGCAUUUGUUU 
                 4695 
               
               
                 579998. 
                 1110855 
                   
                 GfUfccaagaucscsa 
                 1101966.1 
                   
                 gacaAfaCfaaaugscsu 
                 GUCCAAGAUCC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 G 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1640 
                 gsgsaaa(Ghd)AfcCf 
                 A- 
                 1727 
                 VPusCfsaugGfuUfAf 
                 CCGGAAAGACC 
                 4696 
               
               
                 579999. 
                 1110856 
                   
                 GfAfuuaaccausgsa 
                 1102134.1 
                   
                 aucgGfuCfuuuccsgsg 
                 GAUUAACCAUG 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 U 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1641 
                 gsasaag(Ahd)CfcGf 
                 A- 
                 1728 
                 VPusAfscauGfgUfUf 
                 CGGAAAGACCG 
                 4697 
               
               
                 580000. 
                 1110857 
                   
                 AfUfuaaccaugsusa 
                 1102136.1 
                   
                 aaucGfgUfcuuucscsg 
                 AUUAACCAUGU 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1642 
                 asasgac(Chd)GfaUfU 
                 A- 
                 1729 
                 VPusUfsgacAfuGfGf 
                 GAAAGACCGAU 
                 4698 
               
               
                 580001. 
                 1110858 
                   
                 fAfaccaugucsasa 
                 1102140.1 
                   
                 uuaaUfcGfgucuususc 
                 UAACCAUGUCA 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1643 
                 gsasccg(Ahd)UfuAf 
                 A- 
                 1730 
                 VPusGfsgugAfcAfUf 
                 AAGACCGAUUA 
                 4699 
               
               
                 580002. 
                 1110859 
                   
                 AfCfcaugucacscsa 
                 1102144.1 
                   
                 gguuAfaUfcggucsusu 
                 ACCAUGUCACC 
                   
               
               
                 1 
                 .1 
                   
                   
                   
                   
                   
                 A 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5B 
               
             
            
               
                   
               
               
                 Exemplary Rat VEGF-A siRNA Unmodified Single Strands and Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 Sense 
                 SEQ 
                   
                 mRNA 
                 Antisense 
                 SEQ ID 
                   
                 mRNA 
               
               
                 Duplex 
                 Oligo 
                 ID NO: 
                   
                 Target 
                 Oligo 
                 NO: 
                 Antisense 
                 Target 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Range 
                 Name 
                 (Antisense) 
                 Sequence 
                 Range 
               
               
                   
               
               
                 AD- 
                 A- 
                 1731 
                 CGGAAACUUUUCGUC 
                  631- 
                 A- 
                 1818 
                 UAGUUGGACGAAA 
                  629- 
               
               
                 57991 
                 11107 
                   
                 CAACUA 
                  651 
                 1100967.1 
                   
                 AGUUUCCGUG 
                  651 
               
               
                 1.1 
                 68.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1732 
                 GGAAACUUUUCGUCC 
                  632- 
                 A- 
                 1819 
                 UAAGUUGGACGAA 
                  630- 
               
               
                 57991 
                 11107 
                   
                 AACUUA 
                  652 
                 1100969.1 
                   
                 AAGUUUCCGU 
                  652 
               
               
                 2.1 
                 69.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1733 
                 CGACAGAACAGUCCU 
                 1689- 
                 A- 
                 1820 
                 UGAUUAAGGACUG 
                 1687- 
               
               
                 57991 
                 11107 
                   
                 UAAUCA 
                 1709 
                 1102172.1 
                   
                 UUCUGUCGAC 
                 1709 
               
               
                 3.1 
                 70.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1734 
                 CUGCUAAUGUUAUUG 
                 2020- 
                 A- 
                 1821 
                 UGACACCAAUAAC 
                 2018- 
               
               
                 57991 
                 11107 
                   
                 GUGUCA 
                 2040 
                 1102638.1 
                   
                 AUUAGCAGAG 
                 2040 
               
               
                 4.1 
                 71.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1735 
                 UCCGAGAUAUUCCGU 
                 3364- 
                 A- 
                 1822 
                 UGUACUACGGAAU 
                 3362- 
               
               
                 57991 
                 11107 
                   
                 AGUACA 
                 3384 
                 1103944.1 
                   
                 AUCUCGGAAA 
                 3384 
               
               
                 5.1 
                 72.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1736 
                 CGAGAUAUUCCGUAG 
                 3366- 
                 A- 
                 1823 
                 UAUGUACUACGGA 
                 3364- 
               
               
                 57991 
                 11107 
                   
                 UACAUA 
                 3386 
                 1103888.1 
                   
                 AUAUCUCGGA 
                 3386 
               
               
                 6.1 
                 73.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1737 
                 GCACGGAAACUUUUC 
                  628- 
                 A- 
                 1824 
                 UUGGACGAAAAGU 
                  626- 
               
               
                 57991 
                 11107 
                   
                 GUCCAA 
                  648 
                 1100961.1 
                   
                 UUCCGUGCAA 
                  648 
               
               
                 7.1 
                 74.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1738 
                 CACGGAAACUUUUCG 
                  629- 
                 A- 
                 1825 
                 UUUGGACGAAAAG 
                  627- 
               
               
                 57991 
                 11107 
                   
                 UCCAAA 
                  649 
                 1100963.1 
                   
                 UUUCCGUGCA 
                  649 
               
               
                 8.1 
                 75.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1739 
                 GAGAUAUUCCGUAGU 
                 3367- 
                 A- 
                 1826 
                 UUAUGUACUACGG 
                 3365- 
               
               
                 57991 
                 11107 
                   
                 ACAUAA 
                 3387 
                 1103889.1 
                   
                 AAUAUCUCGG 
                 3387 
               
               
                 9.1 
                 76.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1740 
                 UUGUUUGUCCAAGAU 
                 1468- 
                 A- 
                 1827 
                 UUGCGGAUCUUGG 
                 1466- 
               
               
                 57992 
                 11107 
                   
                 CCGCAA 
                 1488 
                 1101976.1 
                   
                 ACAAACAAAU 
                 1488 
               
               
                 1.1 
                 78.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1741 
                 ACGGAAACUUUUCGU 
                  630- 
                 A- 
                 1828 
                 UGUUGGACGAAAA 
                  628- 
               
               
                 57992 
                 11107 
                   
                 CCAACA 
                  650 
                 1100965.1 
                   
                 GUUUCCGUGC 
                  650 
               
               
                 2.1 
                 79.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1742 
                 AUCAUGCGGAUCAAA 
                 1327- 
                 A- 
                 1829 
                 UUGAGGUUUGAUC 
                 1325- 
               
               
                 57992 
                 11107 
                   
                 CCUCAA 
                 1347 
                 1101742.1 
                   
                 CGCAUGAUCU 
                 1347 
               
               
                 3.1 
                 80.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1743 
                 AUGCGGAUCAAACCU 
                 1330- 
                 A- 
                 1830 
                 UUGGUGAGGUUUG 
                 1328- 
               
               
                 57992 
                 11107 
                   
                 CACCAA 
                 1350 
                 1101659.1 
                   
                 AUCCGCAUGA 
                 1350 
               
               
                 4.1 
                 81.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1744 
                 GAUCAUGCGGAUCAA 
                 1326- 
                 A- 
                 1831 
                 UGAGGUUUGAUCC 
                 1324- 
               
               
                 57992 
                 11107 
                   
                 ACCUCA 
                 1346 
                 1101740.1 
                   
                 GCAUGAUCUG 
                 1346 
               
               
                 5.1 
                 82.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1745 
                 UUUGUUUGUCCAAGA 
                 1467- 
                 A- 
                 1832 
                 UGCGGAUCUUGGA 
                 1465- 
               
               
                 57992 
                 11107 
                   
                 UCCGCA 
                 1487 
                 1101974.1 
                   
                 CAAACAAAUG 
                 1487 
               
               
                 6.1 
                 83.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1746 
                 GAUCGGUGACAGUCA 
                 2972- 
                 A- 
                 1833 
                 UGCUAGUGACUGU 
                 2970- 
               
               
                 57992 
                 11107 
                   
                 CUAGCA 
                 2992 
                 1103783.1 
                   
                 CACCGAUCUG 
                 2992 
               
               
                 7.1 
                 84.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1747 
                 AAGAUCCGCAGACGU 
                 1478- 
                 A- 
                 1834 
                 UUUUACACGUCUG 
                 1476- 
               
               
                 57992 
                 11107 
                   
                 GUAAAA 
                 1498 
                 1101968.1 
                   
                 CGGAUCUUGG 
                 1498 
               
               
                 9.1 
                 86.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1748 
                 UGUCCAAGAUCCGCA 
                 1473- 
                 A- 
                 1835 
                 UACGUCUGCGGAU 
                 1471- 
               
               
                 57993 
                 11107 
                   
                 GACGUA 
                 1493 
                 1101986.1 
                   
                 CUUGGACAAA 
                 1493 
               
               
                 0.1 
                 87.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1749 
                 AUCACGUCUUUGUCU 
                 3337- 
                 A- 
                 1836 
                 UUCUAGAGACAAA 
                 3335- 
               
               
                 57993 
                 11107 
                   
                 CUAGAA 
                 3357 
                 1103887.1 
                   
                 GACGUGAUGU 
                 3357 
               
               
                 1.1 
                 88.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1750 
                 UGAAACCAUGAACUU 
                 1008- 
                 A- 
                 1837 
                 UGCAGAAAGUUCA 
                 1006- 
               
               
                 57993 
                 11107 
                   
                 UCUGCA 
                 1028 
                 1101283.1 
                   
                 UGGUUUCAGA 
                 1028 
               
               
                 2.1 
                 89.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1751 
                 UUGUCUCUAGAGCAG 
                 3346- 
                 A- 
                 1838 
                 UGAAAACUGCUCU 
                 3344- 
               
               
                 57993 
                 11107 
                   
                 UUUUCA 
                 3366 
                 1103908.1 
                   
                 AGAGACAAAG 
                 3366 
               
               
                 3.1 
                 90.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1752 
                 CACUUCCAGAAACACG 
                 2222- 
                 A- 
                 1839 
                 UUUGUCGUGUUUC 
                 2220- 
               
               
                 57993 
                 11107 
                   
                 ACAAA 
                 2242 
                 1102962.1 
                   
                 UGGAAGUGAG 
                 2242 
               
               
                 4.1 
                 91.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1753 
                 UGAAAUCUGUGUUUC 
                 2941- 
                 A- 
                 1840 
                 UGAUUGGAAACAC 
                 2939- 
               
               
                 57993 
                 11107 
                   
                 CAAUCA 
                 2961 
                 1103728.1 
                   
                 AGAUUUCAUA 
                 2961 
               
               
                 5.1 
                 92.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1754 
                 GAAAUCUGUGUUUCC 
                 2942- 
                 A- 
                 1841 
                 UAGAUUGGAAACA 
                 2940- 
               
               
                 57993 
                 11107 
                   
                 AAUCUA 
                 2962 
                 1103730.1 
                   
                 CAGAUUUCAU 
                 2962 
               
               
                 6.1 
                 93.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1755 
                 UUUGUCUCUAGAGCA 
                 3345- 
                 A- 
                 1842 
                 UAAAACUGCUCUA 
                 3343- 
               
               
                 57993 
                 11107 
                   
                 GUUUUA 
                 3365 
                 1103906.1 
                   
                 GAGACAAAGA 
                 3365 
               
               
                 7.1 
                 94.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1756 
                 UGUCUCUAGAGCAGU 
                 3347- 
                 A- 
                 1843 
                 UGGAAAACUGCUC 
                 3345- 
               
               
                 57993 
                 11107 
                   
                 UUUCCA 
                 3367 
                 1103910.1 
                   
                 UAGAGACAAA 
                 3367 
               
               
                 8.1 
                 95.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1757 
                 AACUGUAUUGUUUUA 
                  167- 
                 A- 
                 1844 
                 UAAGCGUAAAACA 
                  165- 
               
               
                 57993 
                 11107 
                   
                 CGCUUA 
                  187 
                 1100541.1 
                   
                 AUACAGUUUA 
                  187 
               
               
                 9.1 
                 96.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1758 
                 ACUGUAUUGUUUUAC 
                  168- 
                 A- 
                 1845 
                 UAAAGCGUAAAAC 
                  166- 
               
               
                 57994 
                 11107 
                   
                 GCUUUA 
                  188 
                 1100543.1 
                   
                 AAUACAGUUU 
                  188 
               
               
                 0.1 
                 97.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1759 
                 CUGUAUUGUUUUACG 
                  169- 
                 A- 
                 1846 
                 UUAAAGCGUAAAA 
                  167- 
               
               
                 57994 
                 11107 
                   
                 CUUUAA 
                  189 
                 1100545.1 
                   
                 CAAUACAGUU 
                  189 
               
               
                 1.1 
                 98.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1760 
                 UGUAUUGUUUUACGC 
                  170- 
                 A- 
                 1847 
                 UUUAAAGCGUAAA 
                  168- 
               
               
                 57994 
                 11107 
                   
                 UUUAAA 
                  190 
                 1100547.1 
                   
                 ACAAUACAGU 
                  190 
               
               
                 2.1 
                 99.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1761 
                 AUUGAAACCACUAAU 
                 2611- 
                 A- 
                 1848 
                 UACAGAAUUAGUG 
                 2609- 
               
               
                 57994 
                 11108 
                   
                 UCUGUA 
                 2631 
                 1103504.1 
                   
                 GUUUCAAUGG 
                 2631 
               
               
                 3.1 
                 00.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1762 
                 ACUUAUUUAAUAGCC 
                 2764- 
                 A- 
                 1849 
                 UAAAAGGGCUAUU 
                 2762- 
               
               
                 57994 
                 11108 
                   
                 CUUUUA 
                 2784 
                 1103594.1 
                   
                 AAAUAAGUAC 
                 2784 
               
               
                 4.1 
                 01.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1763 
                 UCUCUAGAGCAGUUU 
                 3349- 
                 A- 
                 1850 
                 UUCGGAAAACUGC 
                 3347- 
               
               
                 57994 
                 11108 
                   
                 UCCGAA 
                 3369 
                 1103914.1 
                   
                 UCUAGAGACA 
                 3369 
               
               
                 5.1 
                 02.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1764 
                 CCGAGAUAUUCCGUA 
                 3365- 
                 A- 
                 1851 
                 UUGUACUACGGAA 
                 3363- 
               
               
                 57994 
                 11108 
                   
                 GUACAA 
                 3385 
                 1103946.1 
                   
                 UAUCUCGGAA 
                 3385 
               
               
                 6.1 
                 03.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1765 
                 UCUGGGAUUUGAUAU 
                  129- 
                 A- 
                 1852 
                 UUUUGAAUAUCAA 
                  127- 
               
               
                 57994 
                 11108 
                   
                 UCAAAA 
                  149 
                 1100511.1 
                   
                 AUCCCAGAGC 
                  149 
               
               
                 7.1 
                 04.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1766 
                 UUCACUGGAUAUGUU 
                 2040- 
                 A- 
                 1853 
                 UAGUCAAACAUAU 
                 2038- 
               
               
                 57994 
                 11108 
                   
                 UGACUA 
                 2060 
                 1102658.1 
                   
                 CCAGUGAAGA 
                 2060 
               
               
                 8.1 
                 05.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1767 
                 GGCUCACUUCCAGAA 
                 2218- 
                 A- 
                 1854 
                 UCGUGUUUCUGGA 
                 2216- 
               
               
                 57994 
                 11108 
                   
                 ACACGA 
                 2238 
                 1102954.1 
                   
                 AGUGAGCCAA 
                 2238 
               
               
                 9.1 
                 06.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1768 
                 CUUCCAGAAACACGAC 
                 2224- 
                 A- 
                 1855 
                 UGUUUGUCGUGUU 
                 2222- 
               
               
                 57995 
                 11108 
                   
                 AAACA 
                 2244 
                 1102966.1 
                   
                 UCUGGAAGUG 
                 2244 
               
               
                 0.1 
                 07.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1769 
                 GACCAUUGAAACCAC 
                 2607- 
                 A- 
                 1856 
                 UAAUUAGUGGUUU 
                 2605- 
               
               
                 57995 
                 11108 
                   
                 UAAUUA 
                 2627 
                 1103496.1 
                   
                 CAAUGGUCUG 
                 2627 
               
               
                 1.1 
                 08.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1770 
                 AGUCACUAGCUUGUC 
                 2982- 
                 A- 
                 1857 
                 UCUCAGGACAAGC 
                 2980- 
               
               
                 57995 
                 11108 
                   
                 CUGAGA 
                 3002 
                 1103805.1 
                   
                 UAGUGACUGU 
                 3002 
               
               
                 3.1 
                 10.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1771 
                 ACCACACAUUCCUUUG 
                 3049- 
                 A- 
                 1858 
                 UAUUUCAAAGGAA 
                 3047- 
               
               
                 57995 
                 11108 
                   
                 AAAUA 
                 3069 
                 1103837.1 
                   
                 UGUGUGGUGG 
                 3069 
               
               
                 4.1 
                 11.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1772 
                 ACCGGAAAGACCGAU 
                 1639- 
                 A- 
                 1859 
                 UGGUUAAUCGGUC 
                 1637- 
               
               
                 57995 
                 11108 
                   
                 UAACCA 
                 1659 
                 1102128.1 
                   
                 UUUCCGGUGA 
                 1659 
               
               
                 5.1 
                 12.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1773 
                 AGACCGAUUAACCAU 
                 1646- 
                 A- 
                 1860 
                 UGUGACAUGGUUA 
                 1644- 
               
               
                 57995 
                 11108 
                   
                 GUCACA 
                 1666 
                 1102142.1 
                   
                 AUCGGUCUUU 
                 1666 
               
               
                 6.1 
                 13.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1774 
                 CUUCACUGGAUAUGU 
                 2039- 
                 A- 
                 1861 
                 UGUCAAACAUAUC 
                 2037- 
               
               
                 57995 
                 11108 
                   
                 UUGACA 
                 2059 
                 1102656.1 
                   
                 CAGUGAAGAC 
                 2059 
               
               
                 7.1 
                 14.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1775 
                 UUGGCUCACUUCCAG 
                 2216- 
                 A- 
                 1862 
                 UUGUUUCUGGAAG 
                 2214- 
               
               
                 57995 
                 11108 
                   
                 AAACAA 
                 2236 
                 1102950.1 
                   
                 UGAGCCAACG 
                 2236 
               
               
                 8.1 
                 15.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1776 
                 CUCACUUCCAGAAACA 
                 2220- 
                 A- 
                 1863 
                 UGUCGUGUUUCUG 
                 2218- 
               
               
                 57995 
                 11108 
                   
                 CGACA 
                 2240 
                 1102958.1 
                   
                 GAAGUGAGCC 
                 2240 
               
               
                 9.1 
                 16.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1777 
                 GUGACAGUCACUAGC 
                 2977- 
                 A- 
                 1864 
                 UGACAAGCUAGUG 
                 2975- 
               
               
                 57996 
                 11108 
                   
                 UUGUCA 
                 2997 
                 1103795.1 
                   
                 ACUGUCACCG 
                 2997 
               
               
                 0.1 
                 17.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1778 
                 GUCUCUAGAGCAGUU 
                 3348- 
                 A- 
                 1865 
                 UCGGAAAACUGCU 
                 3346- 
               
               
                 57996 
                 11108 
                   
                 UUCCGA 
                 3368 
                 1103912.1 
                   
                 CUAGAGACAA 
                 3368 
               
               
                 1.1 
                 18.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1779 
                 CUCUAGAGCAGUUUU 
                 3350- 
                 A- 
                 1866 
                 UCUCGGAAAACUG 
                 3348- 
               
               
                 57996 
                 11108 
                   
                 CCGAGA 
                 3370 
                 1103916.1 
                   
                 CUCUAGAGAC 
                 3370 
               
               
                 2.1 
                 19.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1780 
                 GUUUUCCGAGAUAUU 
                 3360- 
                 A- 
                 1867 
                 UUACGGAAUAUCU 
                 3358- 
               
               
                 57996 
                 11108 
                   
                 CCGUAA 
                 3380 
                 1103936.1 
                   
                 CGGAAAACUG 
                 3380 
               
               
                 3.1 
                 20.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1781 
                 UUCCGAGAUAUUCCG 
                 3363- 
                 A- 
                 1868 
                 UUACUACGGAAUA 
                 3361- 
               
               
                 57996 
                 11108 
                   
                 UAGUAA 
                 3383 
                 1103942.1 
                   
                 UCUCGGAAAA 
                 3383 
               
               
                 4.1 
                 21.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1782 
                 UUAAACUGUAUUGUU 
                  164- 
                 A- 
                 1869 
                 UCGUAAAACAAUA 
                  162- 
               
               
                 57996 
                 11108 
                   
                 UUACGA 
                  184 
                 1100535.1 
                   
                 CAGUUUAAGA 
                  184 
               
               
                 5.1 
                 22.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1783 
                 AAACUGUAUUGUUUU 
                  166- 
                 A- 
                 1870 
                 UAGCGUAAAACAA 
                  164- 
               
               
                 57996 
                 11108 
                   
                 ACGCUA 
                  186 
                 1100539.1 
                   
                 UACAGUUUAA 
                  186 
               
               
                 6.1 
                 23.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1784 
                 GAUUCGCCAUUUUCU 
                 1830- 
                 A- 
                 1871 
                 UAUAUAAGAAAAU 
                 1828- 
               
               
                 57996 
                 11108 
                   
                 UAUAUA 
                 1850 
                 1102468.1 
                   
                 GGCGAAUCCA 
                 1850 
               
               
                 7.1 
                 24.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1785 
                 UCACUGGAUAUGUUU 
                 2041- 
                 A- 
                 1872 
                 UCAGUCAAACAUA 
                 2039- 
               
               
                 57996 
                 11108 
                   
                 GACUGA 
                 2061 
                 1102660.1 
                   
                 UCCAGUGAAG 
                 2061 
               
               
                 8.1 
                 25.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1786 
                 GUUGGCUCACUUCCA 
                 2215- 
                 A- 
                 1873 
                 UGUUUCUGGAAGU 
                 2213- 
               
               
                 57996 
                 11108 
                   
                 GAAACA 
                 2235 
                 1102948.1 
                   
                 GAGCCAACGU 
                 2235 
               
               
                 9.1 
                 26.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1787 
                 ACUUCCAGAAACACG 
                 2223- 
                 A- 
                 1874 
                 UUUUGUCGUGUUU 
                 2221- 
               
               
                 57997 
                 11108 
                   
                 ACAAAA 
                 2243 
                 1102964.1 
                   
                 CUGGAAGUGA 
                 2243 
               
               
                 0.1 
                 27.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1788 
                 UACUUAUUUAAUAGC 
                 2763- 
                 A- 
                 1875 
                 UAAAGGGCUAUUA 
                 2761- 
               
               
                 57997 
                 11108 
                   
                 CCUUUA 
                 2783 
                 1103592.1 
                   
                 AAUAAGUACC 
                 2783 
               
               
                 1.1 
                 28.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1789 
                 AGAGCAGUUUUCCGA 
                 3354- 
                 A- 
                 1876 
                 UAUAUCUCGGAAA 
                 3352- 
               
               
                 57997 
                 11108 
                   
                 GAUAUA 
                 3374 
                 1103924.1 
                   
                 ACUGCUCUAG 
                 3374 
               
               
                 2.1 
                 29.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1790 
                 UGGGAUUUGAUAUUC 
                  131- 
                 A- 
                 1877 
                 UGGUUUGAAUAUC 
                  129- 
               
               
                 57997 
                 11108 
                   
                 AAACCA 
                  151 
                 1100515.1 
                   
                 AAAUCCCAGA 
                  151 
               
               
                 3.1 
                 30.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1791 
                 GGGAUUUGAUAUUCA 
                  132- 
                 A- 
                 1878 
                 UAGGUUUGAAUAU 
                  130- 
               
               
                 57997 
                 11108 
                   
                 AACCUA 
                  152 
                 1100517.1 
                   
                 CAAAUCCCAG 
                  152 
               
               
                 4.1 
                 31.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1792 
                 GAUUUGAUAUUCAAA 
                  134- 
                 A- 
                 1879 
                 UAGAGGUUUGAAU 
                  132- 
               
               
                 57997 
                 11108 
                   
                 CCUCUA 
                  154 
                 1100521.1 
                   
                 AUCAAAUCCC 
                  154 
               
               
                 5.1 
                 32.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1793 
                 UAAACUGUAUUGUUU 
                  165- 
                 A- 
                 1880 
                 UGCGUAAAACAAU 
                  163- 
               
               
                 57997 
                 11108 
                   
                 UACGCA 
                  185 
                 1100537.1 
                   
                 ACAGUUUAAG 
                  185 
               
               
                 6.1 
                 33.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1794 
                 UCACCGGAAAGACCG 
                 1637- 
                 A- 
                 1881 
                 UUUAAUCGGUCUU 
                 1635- 
               
               
                 57997 
                 11108 
                   
                 AUUAAA 
                 1657 
                 1102124.1 
                   
                 UCCGGUGAGA 
                 1657 
               
               
                 7.1 
                 34.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1795 
                 CACCGGAAAGACCGA 
                 1638- 
                 A- 
                 1882 
                 UGUUAAUCGGUCU 
                 1636- 
               
               
                 57997 
                 11108 
                   
                 UUAACA 
                 1658 
                 1102126.1 
                   
                 UUCCGGUGAG 
                 1658 
               
               
                 8.1 
                 35.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1796 
                 CCGGAAAGACCGAUU 
                 1640- 
                 A- 
                 1883 
                 UUGGUUAAUCGGU 
                 1638- 
               
               
                 57997 
                 11108 
                   
                 AACCAA 
                 1660 
                 1102130.1 
                   
                 CUUUCCGGUG 
                 1660 
               
               
                 9.1 
                 36.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1797 
                 GAACUGGAUUCGCCA 
                 1824- 
                 A- 
                 1884 
                 UGAAAAUGGCGAA 
                 1822- 
               
               
                 57998 
                 11108 
                   
                 UUUUCA 
                 1844 
                 1102456.1 
                   
                 UCCAGUUCCA 
                 1844 
               
               
                 0.1 
                 37.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1798 
                 CACUGGAUAUGUUUG 
                 2042- 
                 A- 
                 1885 
                 UGCAGUCAAACAU 
                 2040- 
               
               
                 57998 
                 11108 
                   
                 ACUGCA 
                 2062 
                 1102662.1 
                   
                 AUCCAGUGAA 
                 2062 
               
               
                 1.1 
                 38.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1799 
                 GGACCUUGUGUGAUC 
                 2591- 
                 A- 
                 1886 
                 UGGUCUGAUCACA 
                 2589- 
               
               
                 57998 
                 11108 
                   
                 AGACCA 
                 2611 
                 1103464.1 
                   
                 CAAGGUCCUC 
                 2611 
               
               
                 2.1 
                 39.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1800 
                 UCAGACCAUUGAAAC 
                 2604- 
                 A- 
                 1887 
                 UUAGUGGUUUCAA 
                 2602- 
               
               
                 57998 
                 11108 
                   
                 CACUAA 
                 2624 
                 1103490.1 
                   
                 UGGUCUGAUC 
                 2624 
               
               
                 3.1 
                 40.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1801 
                 CAUUGAAACCACUAA 
                 2610- 
                 A- 
                 1888 
                 UCAGAAUUAGUGG 
                 2608- 
               
               
                 57998 
                 11108 
                   
                 UUCUGA 
                 2630 
                 1103502.1 
                   
                 UUUCAAUGGU 
                 2630 
               
               
                 4.1 
                 41.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1802 
                 CUAGAGCAGUUUUCC 
                 3352- 
                 A- 
                 1889 
                 UAUCUCGGAAAAC 
                 3350- 
               
               
                 57998 
                 11108 
                   
                 GAGAUA 
                 3372 
                 1103920.1 
                   
                 UGCUCUAGAG 
                 3372 
               
               
                 5.1 
                 42.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1803 
                 UAGAGCAGUUUUCCG 
                 3353- 
                 A- 
                 1890 
                 UUAUCUCGGAAAA 
                 3351- 
               
               
                 57998 
                 11108 
                   
                 AGAUAA 
                 3373 
                 1103922.1 
                   
                 CUGCUCUAGA 
                 3373 
               
               
                 6.1 
                 43.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1804 
                 AGUUUUCCGAGAUAU 
                 3359- 
                 A- 
                 1891 
                 UACGGAAUAUCUC 
                 3357- 
               
               
                 57998 
                 11108 
                   
                 UCCGUA 
                 3379 
                 1103934.1 
                   
                 GGAAAACUGC 
                 3379 
               
               
                 7.1 
                 44.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1805 
                 GCGGAUCAAACCUCAC 
                 1332- 
                 A- 
                 1892 
                 UUUUGGUGAGGUU 
                 1330- 
               
               
                 57998 
                 11108 
                   
                 CAAAA 
                 1352 
                 1101748.1 
                   
                 UGAUCCGCAU 
                 1352 
               
               
                 8.1 
                 45.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1806 
                 AGCAUUUGUUUGUCC 
                 1463- 
                 A- 
                 1893 
                 UAUCUUGGACAAA 
                 1461- 
               
               
                 57998 
                 11108 
                   
                 AAGAUA 
                 1483 
                 1101962.1 
                   
                 CAAAUGCUUU 
                 1483 
               
               
                 9.1 
                 46.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1807 
                 UCUCACCGGAAAGACC 
                 1635- 
                 A- 
                 1894 
                 UAAUCGGUCUUUC 
                 1633- 
               
               
                 57999 
                 11108 
                   
                 GAUUA 
                 1655 
                 1102120.1 
                   
                 CGGUGAGAGG 
                 1655 
               
               
                 0.1 
                 47.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1808 
                 UCUAGAGCAGUUUUC 
                 3351- 
                 A- 
                 1895 
                 UUCUCGGAAAACU 
                 3349- 
               
               
                 57999 
                 11108 
                   
                 CGAGAA 
                 3371 
                 1103918.1 
                   
                 GCUCUAGAGA 
                 3371 
               
               
                 2.1 
                 49.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1809 
                 AUUGCACGGAAACUU 
                  625- 
                 A- 
                 1896 
                 UACGAAAAGUUUC 
                  623- 
               
               
                 57999 
                 11108 
                   
                 UUCGUA 
                  645 
                 1100955.1 
                   
                 CGUGCAAUCC 
                  645 
               
               
                 3.1 
                 50.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1810 
                 GCUCUGGGAUUUGAU 
                  127- 
                 A- 
                 1897 
                 UUGAAUAUCAAAU 
                  125- 
               
               
                 57999 
                 11108 
                   
                 AUUCAA 
                  147 
                 1100507.1 
                   
                 CCCAGAGCAC 
                  147 
               
               
                 5.1 
                 52.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1811 
                 UGAGCCUUGUUCAGA 
                 1440- 
                 A- 
                 1898 
                 UUCCGCUCUGAAC 
                 1438- 
               
               
                 57999 
                 11108 
                   
                 GCGGAA 
                 1460 
                 1101930.1 
                   
                 AAGGCUCACA 
                 1460 
               
               
                 6.1 
                 53.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1812 
                 AGCCUUGUUCAGAGC 
                 1442- 
                 A- 
                 1899 
                 UUCUCCGCUCUGA 
                 1440- 
               
               
                 57999 
                 11108 
                   
                 GGAGAA 
                 1462 
                 1101934.1 
                   
                 ACAAGGCUCA 
                 1462 
               
               
                 7.1 
                 54.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1813 
                 CAUUUGUUUGUCCAA 
                 1465- 
                 A- 
                 1900 
                 UGGAUCUUGGACA 
                 1463- 
               
               
                 57999 
                 11108 
                   
                 GAUCCA 
                 1485 
                 1101966.1 
                   
                 AACAAAUGCU 
                 1485 
               
               
                 8.1 
                 55.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1814 
                 GGAAAGACCGAUUAA 
                 1642- 
                 A- 
                 1901 
                 UCAUGGUUAAUCG 
                 1640- 
               
               
                 57999 
                 11108 
                   
                 CCAUGA 
                 1662 
                 1102134.1 
                   
                 GUCUUUCCGG 
                 1662 
               
               
                 9.1 
                 56.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1815 
                 GAAAGACCGAUUAAC 
                 1643- 
                 A- 
                 1902 
                 UACAUGGUUAAUC 
                 1641- 
               
               
                 58000 
                 11108 
                   
                 CAUGUA 
                 1663 
                 1102136.1 
                   
                 GGUCUUUCCG 
                 1663 
               
               
                 0.1 
                 57.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1816 
                 AAGACCGAUUAACCA 
                 1645- 
                 A- 
                 1903 
                 UUGACAUGGUUAA 
                 1643- 
               
               
                 58000 
                 11108 
                   
                 UGUCAA 
                 1665 
                 1102140.1 
                   
                 UCGGUCUUUC 
                 1665 
               
               
                 1.1 
                 58.1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1817 
                 GACCGAUUAACCAUG 
                 1647- 
                 A- 
                 1904 
                 UGGUGACAUGGUU 
                 1645- 
               
               
                 58000 
                 11108 
                   
                 UCACCA 
                 1667 
                 1102144.1 
                   
                 AAUCGGUCUU 
                 1667 
               
               
                 2.1 
                 59.1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8A 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Modified Single Strands and Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                 Anti- 
                 SEQ ID 
                   
                   
                 SEQ ID 
               
               
                   
                   
                 SEQ 
                   
                 sense 
                 NO: 
                   
                   
                 NO: 
               
               
                 Duplex 
                 Sense Oligo 
                 ID NO: 
                   
                 Oligo 
                 (Anti- 
                   
                 mRNA Target 
                 (mRNA 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Name 
                 sense) 
                 Antisense Sequence 
                 Sequence 
                 target) 
               
               
                   
               
               
                 AD- 
                 A- 
                 2000 
                 csgsgugcUfgGfAfAfuuuga 
                 A- 
                 2449 
                 VPusAfsauaUfcaaauucC 
                 CUCGGUGCUGGAAU 
                 4700 
               
               
                 12228 
                 22821 
                   
                 uauuaL96 
                 228211 
                   
                 faGfcaccgsasg 
                 UUGAUAUUC 
                   
               
               
                 66.1 
                 11.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2001 
                 gsgsugcuGfgAfAfUfuugau 
                 A- 
                 2450 
                 VPusGfsaauAfucaaauuC 
                 UCGGUGCUGGAAUU 
                 4701 
               
               
                 12228 
                 22821 
                   
                 auucaL96 
                 228211 
                   
                 fcAfgcaccsgsa 
                 UGAUAUUCA 
                   
               
               
                 67.1 
                 13.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2002 
                 usgscuggAfaUfUfUfgauauu 
                 A- 
                 2451 
                 VPusAfsugaAfuaucaaaU 
                 GGUGCUGGAAUUUG 
                 4702 
               
               
                 12228 
                 22821 
                   
                 cauaL96 
                 228211 
                   
                 fuCfcagcascsc 
                 AUAUUCAUU 
                   
               
               
                 68.1 
                 15.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2003 
                 gscsuggaAfuUfUfGfauauuc 
                 A- 
                 2452 
                 VPusAfsaugAfauaucaaA 
                 GUGCUGGAAUUUGA 
                 4703 
               
               
                 12228 
                 22821 
                   
                 auuaL96 
                 228211 
                   
                 fuUfccagcsasc 
                 UAUUCAUUG 
                   
               
               
                 69.1 
                 17.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2004 
                 usgsgaauUfuGfAfUfauucau 
                 A- 
                 2453 
                 VPusUfscaaUfgaauaucA 
                 GCUGGAAUUUGAUA 
                 4704 
               
               
                 12228 
                 22821 
                   
                 ugaaL96 
                 228212 
                   
                 faAfuuccasgsc 
                 UUCAUUGAU 
                   
               
               
                 70.1 
                 19.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2005 
                 gsgsaauuUfgAfUfAfuucauu 
                 A- 
                 2454 
                 VPusAfsucaAfugaauauC 
                 CUGGAAUUUGAUAU 
                 4705 
               
               
                 12228 
                 22821 
                   
                 gauaL96 
                 228212 
                   
                 faAfauuccsasg 
                 UCAUUGAUC 
                   
               
               
                 71.1 
                 21.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2006 
                 gsasauuuGfaUfAfUfucauug 
                 A- 
                 2455 
                 VPusGfsaucAfaugaauaU 
                 UGGAAUUUGAUAU 
                 4706 
               
               
                 12228 
                 22821 
                   
                 aucaL96 
                 228212 
                   
                 fcAfaauucscsa 
                 UCAUUGAUCC 
                   
               
               
                 72.1 
                 23.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2007 
                 asasuuugAfuAfUfUfcauuga 
                 A- 
                 2456 
                 VPusGfsgauCfaaugaauA 
                 GGAAUUUGAUAUUC 
                 4707 
               
               
                 12228 
                 22821 
                   
                 uccaL96 
                 228212 
                   
                 fuCfaaauuscsc 
                 AUUGAUCCG 
                   
               
               
                 73.1 
                 25.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2008 
                 asusuugaUfaUfUfCfauugau 
                 A- 
                 2457 
                 VPusCfsggaUfcaaugaaU 
                 GAAUUUGAUAUUCA 
                 4708 
               
               
                 12228 
                 22821 
                   
                 ccgaL96 
                 228212 
                   
                 faUfcaaaususc 
                 UUGAUCCGG 
                   
               
               
                 74.1 
                 27.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2009 
                 ususugauAfuUfCfAfuugauc 
                 A- 
                 2458 
                 VPusCfscggAfucaaugaA 
                 AAUUUGAUAUUCAU 
                 4709 
               
               
                 12228 
                 22821 
                   
                 cggaL96 
                 228213 
                   
                 fuAfucaaasusu 
                 UGAUCCGGG 
                   
               
               
                 75.1 
                 29.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2010 
                 ususuauuUfuUfGfCfuugcca 
                 A- 
                 2459 
                 VPusGfsaauGfgcaagcaA 
                 AAUUUAUUUUUGCU 
                 4710 
               
               
                 12228 
                 22821 
                   
                 uucaL96 
                 228213 
                   
                 faAfauaaasusu 
                 UGCCAUUCC 
                   
               
               
                 76.1 
                 31.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2011 
                 ususauuuUfuGfCfUfugccau 
                 A- 
                 2460 
                 VPusGfsgaaUfggcaagcA 
                 AUUUAUUUUUGCUU 
                 4711 
               
               
                 12228 
                 22821 
                   
                 uccaL96 
                 228213 
                   
                 faAfaauaasasu 
                 GCCAUUCCC 
                   
               
               
                 77.1 
                 33.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2012 
                 csasaaucAfcUfGfUfggauuu 
                 A- 
                 2461 
                 VPusCfscaaAfauccacaG 
                 CCCAAAUCACUGUG 
                 4712 
               
               
                 12228 
                 22821 
                   
                 uggaL96 
                 228213 
                   
                 fuGfauuugsgsg 
                 GAUUUUGGA 
                   
               
               
                 78.1 
                 35.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2013 
                 asasaucaCfuGfUfGfgauuuu 
                 A- 
                 2462 
                 VPusUfsccaAfaauccacA 
                 CCAAAUCACUGUGG 
                 4713 
               
               
                 12228 
                 22821 
                   
                 ggaaL96 
                 228213 
                   
                 fgUfgauuusgsg 
                 AUUUUGGAA 
                   
               
               
                 79.1 
                 37.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2014 
                 asasucacUfgUfGfGfauuuug 
                 A- 
                 2463 
                 VPusUfsuccAfaaauccaC 
                 CAAAUCACUGUGGA 
                 4714 
               
               
                 12228 
                 22821 
                   
                 gaaaL96 
                 228214 
                   
                 faGfugauususg 
                 UUUUGGAAA 
                   
               
               
                 80.1 
                 39.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2015 
                 asuscacuGfuGfGfAfuuuugg 
                 A- 
                 2464 
                 VPusUfsuucCfaaaauccA 
                 AAAUCACUGUGGAU 
                 4715 
               
               
                 12228 
                 22821 
                   
                 aaaaL96 
                 228214 
                   
                 fcAfgugaususu 
                 UUUGGAAAC 
                   
               
               
                 81.1 
                 41.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2016 
                 uscsacugUfgGfAfUfuuugga 
                 A- 
                 2465 
                 VPusGfsuuuCfcaaaaucC 
                 AAUCACUGUGGAUU 
                 4716 
               
               
                 12228 
                 22821 
                   
                 aacaL96 
                 228214 
                   
                 faCfagugasusu 
                 UUGGAAACC 
                   
               
               
                 82.1 
                 43.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2017 
                 csascuguGfgAfUfUfuuggaa 
                 A- 
                 2466 
                 VPusGfsguuUfccaaaauC 
                 AUCACUGUGGAUUU 
                 4717 
               
               
                 12228 
                 22821 
                   
                 accaL96 
                 228214 
                   
                 fcAfcagugsasu 
                 UGGAAACCA 
                   
               
               
                 83.1 
                 45.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2018 
                 ascsugugGfaUfUfUfuggaaa 
                 A- 
                 2467 
                 VPusUfsgguUfuccaaaaU 
                 UCACUGUGGAUUUU 
                 4718 
               
               
                 12228 
                 22821 
                   
                 ccaaL96 
                 228214 
                   
                 fcCfacagusgsa 
                 GGAAACCAG 
                   
               
               
                 84.1 
                 47.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2019 
                 csusguggAfuUfUfUfggaaac 
                 A- 
                 2468 
                 VPusCfsuggUfuuccaaaA 
                 CACUGUGGAUUUUG 
                 4719 
               
               
                 12228 
                 22821 
                   
                 cagaL96 
                 228215 
                   
                 fuCfcacagsusg 
                 GAAACCAGC 
                   
               
               
                 85.1 
                 49.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2020 
                 usgsuggaUfuUfUfGfgaaacc 
                 A- 
                 2469 
                 VPusGfscugGfuuuccaa 
                 ACUGUGGAUUUUGG 
                 4720 
               
               
                 12228 
                 22821 
                   
                 agcaL96 
                 228215 
                   
                 AfaUfccacasgsu 
                 AAACCAGCA 
                   
               
               
                 86.1 
                 51.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2021 
                 gsusggauUfuUfGfGfaaacca 
                 A- 
                 2470 
                 VPusUfsgcuGfguuucca 
                 CUGUGGAUUUUGGA 
                 4721 
               
               
                 12228 
                 22821 
                   
                 gcaaL96 
                 228215 
                   
                 AfaAfuccacsasg 
                 AACCAGCAG 
                   
               
               
                 87.1 
                 53.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2022 
                 gsasuuuuGfgAfAfAfccagca 
                 A- 
                 2471 
                 VPusUfsucuGfcugguuu 
                 UGGAUUUUGGAAAC 
                 4722 
               
               
                 12228 
                 22821 
                   
                 gaaaL96 
                 228215 
                   
                 CfcAfaaaucscsa 
                 CAGCAGAAA 
                   
               
               
                 88.1 
                 55.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2023 
                 asusuuugGfaAfAfCfcagcag 
                 A- 
                 2472 
                 VPusUfsuucUfgcugguu 
                 GGAUUUUGGAAACC 
                 4723 
               
               
                 12228 
                 22821 
                   
                 aaaaL96 
                 228215 
                   
                 UfcCfaaaauscsc 
                 AGCAGAAAG 
                   
               
               
                 89.1 
                 57.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2024 
                 ususuuggAfaAfCfCfagcaga 
                 A- 
                 2473 
                 VPusCfsuuuCfugcuggu 
                 GAUUUUGGAAACCA 
                 4724 
               
               
                 12228 
                 22821 
                   
                 aagaL96 
                 228216 
                   
                 UfuCfcaaaasusc 
                 GCAGAAAGA 
                   
               
               
                 90.1 
                 59.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2025 
                 ususuggaAfaCfCfAfgcagaa 
                 A- 
                 2474 
                 VPusUfscuuUfcugcugg 
                 AUUUUGGAAACCAG 
                 4725 
               
               
                 12228 
                 22821 
                   
                 agaaL96 
                 228216 
                   
                 UfuUfccaaasasu 
                 CAGAAAGAG 
                   
               
               
                 91.1 
                 61.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2026 
                 gsgsaaacCfaGfCfAfgaaaga 
                 A- 
                 2475 
                 VPusUfsccuCfuuucugc 
                 UUGGAAACCAGCAG 
                 4726 
               
               
                 12228 
                 22821 
                   
                 ggaaL96 
                 228216 
                   
                 UfgGfuuuccsasa 
                 AAAGAGGAA 
                   
               
               
                 92.1 
                 63.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2027 
                 asasaccaGfcAfGfAfaagagg 
                 A- 
                 2476 
                 VPusUfsuucCfucuuucu 
                 GGAAACCAGCAGAA 
                 4727 
               
               
                 12228 
                 22821 
                   
                 aaaaL96 
                 228216 
                   
                 GfcUfgguuuscsc 
                 AGAGGAAAG 
                   
               
               
                 93.1 
                 65.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2028 
                 asasccagCfaGfAfAfagagga 
                 A- 
                 2477 
                 VPusCfsuuuCfcucuuuc 
                 GAAACCAGCAGAAA 
                 4728 
               
               
                 12228 
                 22821 
                   
                 aagaL96 
                 228216 
                   
                 UfgCfugguususc 
                 GAGGAAAGA 
                   
               
               
                 94.1 
                 67.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2029 
                 ascscagcAfgAfAfAfgaggaa 
                 A- 
                 2478 
                 VPusUfscuuUfccucuuu 
                 AAACCAGCAGAAAG 
                 4729 
               
               
                 12228 
                 22821 
                   
                 agaaL96 
                 228217 
                   
                 CfuGfcuggususu 
                 AGGAAAGAG 
                   
               
               
                 95.1 
                 69.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2030 
                 cscsagcaGfaAfAfGfaggaaa 
                 A- 
                 2479 
                 VPusCfsucuUfuccucuu 
                 AACCAGCAGAAAGA 
                 4730 
               
               
                 12228 
                 22821 
                   
                 gagaL96 
                 228217 
                   
                 UfcUfgcuggsusu 
                 GGAAAGAGG 
                   
               
               
                 96.1 
                 71.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2031 
                 csasgcagAfaAfGfAfggaaag 
                 A- 
                 2480 
                 VPusCfscucUfuuccucuU 
                 ACCAGCAGAAAGAG 
                 4731 
               
               
                 12228 
                 22821 
                   
                 aggaL96 
                 228217 
                   
                 fuCfugcugsgsu 
                 GAAAGAGGU 
                   
               
               
                 97.1 
                 73.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2032 
                 asgscagaAfaGfAfGfgaaaga 
                 A- 
                 2481 
                 VPusAfsccuCfuuuccucU 
                 CCAGCAGAAAGAGG 
                 4732 
               
               
                 12228 
                 22821 
                   
                 gguaL96 
                 228217 
                   
                 fuUfcugcusgsg 
                 AAAGAGGUA 
                   
               
               
                 98.1 
                 75.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2033 
                 gscsagaaAfgAfGfGfaaagag 
                 A- 
                 2482 
                 VPusUfsaccUfcuuuccuC 
                 CAGCAGAAAGAGGA 
                 4733 
               
               
                 12228 
                 22821 
                   
                 guaaL96 
                 228217 
                   
                 fuUfucugcsusg 
                 AAGAGGUAG 
                   
               
               
                 99.1 
                 77.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2034 
                 csasgaaaGfaGfGfAfaagagg 
                 A- 
                 2483 
                 VPusCfsuacCfucuuuccU 
                 AGCAGAAAGAGGAA 
                 4734 
               
               
                 12229 
                 22821 
                   
                 uagaL96 
                 228218 
                   
                 fcUfuucugscsu 
                 AGAGGUAGC 
                   
               
               
                 00.1 
                 79.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2035 
                 asasagagGfaAfAfGfagguag 
                 A- 
                 2484 
                 VPusUfsugcUfaccucuu 
                 AGAAAGAGGAAAG 
                 4735 
               
               
                 12229 
                 22821 
                   
                 caaaL96 
                 228218 
                   
                 UfcCfucuuuscsu 
                 AGGUAGCAAG 
                   
               
               
                 01.1 
                 81.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2036 
                 asasgaggAfaAfGfAfgguagc 
                 A- 
                 2485 
                 VPusCfsuugCfuaccucuU 
                 GAAAGAGGAAAGA 
                 4736 
               
               
                 12229 
                 22821 
                   
                 aagaL96 
                 228218 
                   
                 fuCfcucuususc 
                 GGUAGCAAGA 
                   
               
               
                 02.1 
                 83.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2037 
                 asgsaggaAfaGfAfGfguagca 
                 A- 
                 2486 
                 VPusUfscuuGfcuaccucU 
                 AAAGAGGAAAGAG 
                 4737 
               
               
                 12229 
                 22821 
                   
                 agaaL96 
                 228218 
                   
                 fuUfccucususu 
                 GUAGCAAGAG 
                   
               
               
                 03.1 
                 85.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2038 
                 gsasggaaAfgAfGfGfuagcaa 
                 A- 
                 2487 
                 VPusCfsucuUfgcuaccuC 
                 AAGAGGAAAGAGG 
                 4738 
               
               
                 12229 
                 22821 
                   
                 gagaL96 
                 228218 
                   
                 fuUfuccucsusu 
                 UAGCAAGAGC 
                   
               
               
                 04.1 
                 87.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2039 
                 gsgsaaagAfgGfUfAfgcaaga 
                 A- 
                 2488 
                 VPusAfsgcuCfuugcuacC 
                 GAGGAAAGAGGUA 
                 4739 
               
               
                 12229 
                 22821 
                   
                 gcuaL96 
                 228219 
                   
                 fuCfuuuccsusc 
                 GCAAGAGCUC 
                   
               
               
                 05.1 
                 89.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2040 
                 asgsguagCfaAfGfAfgcucca 
                 A- 
                 2489 
                 VPusCfsucuGfgagcucu 
                 AGAGGUAGCAAGAG 
                 4740 
               
               
                 12229 
                 22821 
                   
                 gagaL96 
                 228219 
                   
                 UfgCfuaccuscsu 
                 CUCCAGAGA 
                   
               
               
                 06.1 
                 91.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2041 
                 uscscagaGfaGfAfAfgucgag 
                 A- 
                 2490 
                 VPusUfsuccUfcgacuucU 
                 GCUCCAGAGAGAAG 
                 4741 
               
               
                 12229 
                 22821 
                   
                 gaaaL96 
                 228219 
                   
                 fcUfcuggasgsc 
                 UCGAGGAAG 
                   
               
               
                 07.1 
                 93.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2042 
                 cscsagagAfgAfAfGfucgagg 
                 A- 
                 2491 
                 VPusCfsuucCfucgacuuC 
                 CUCCAGAGAGAAGU 
                 4742 
               
               
                 12229 
                 22821 
                   
                 aagaL96 
                 228219 
                   
                 fuCfucuggsasg 
                 CGAGGAAGA 
                   
               
               
                 08.1 
                 95.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2043 
                 csasgagaGfaAfGfUfcgagga 
                 A- 
                 2492 
                 VPusUfscuuCfcucgacuU 
                 UCCAGAGAGAAGUC 
                 4743 
               
               
                 12229 
                 22821 
                   
                 agaaL96 
                 228219 
                   
                 fcUfcucugsgsa 
                 GAGGAAGAG 
                   
               
               
                 09.1 
                 97.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2044 
                 asgsagaaGfuCfGfAfggaaga 
                 A- 
                 2493 
                 VPusCfsucuCfuuccucgA 
                 AGAGAGAAGUCGAG 
                 4744 
               
               
                 12229 
                 22821 
                   
                 gagaL96 
                 228220 
                   
                 fcUfucucuscsu 
                 GAAGAGAGA 
                   
               
               
                 10.1 
                 99.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2045 
                 gsasgaagUfcGfAfGfgaagag 
                 A- 
                 2494 
                 VPusUfscucUfcuuccucG 
                 GAGAGAAGUCGAGG 
                 4745 
               
               
                 12229 
                 22822 
                   
                 agaaL96 
                 228220 
                   
                 faCfuucucsusc 
                 AAGAGAGAG 
                   
               
               
                 11.1 
                 01.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2046 
                 gsasagucGfaGfGfAfagagag 
                 A- 
                 2495 
                 VPusUfscucUfcucuuccU 
                 GAGAAGUCGAGGAA 
                 4746 
               
               
                 12229 
                 22822 
                   
                 agaaL96 
                 228220 
                   
                 fcGfacuucsusc 
                 GAGAGAGAC 
                   
               
               
                 12.1 
                 03.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2047 
                 asgsugagUfgAfCfCfugcuuu 
                 A- 
                 2496 
                 VPusCfscaaAfagcagguC 
                 AAAGUGAGUGACCU 
                 4747 
               
               
                 12229 
                 22822 
                   
                 uggaL96 
                 228220 
                   
                 faCfucacususu 
                 GCUUUUGGG 
                   
               
               
                 13.1 
                 05.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2048 
                 gsgscgucGfcAfCfUfgaaacu 
                 A- 
                 2497 
                 VPusAfsaaaGfuuucagu 
                 GCGGCGUCGCACUG 
                 4748 
               
               
                 12229 
                 22822 
                   
                 uuuaL96 
                 228220 
                   
                 GfcGfacgccsgsc 
                 AAACUUUUC 
                   
               
               
                 14.1 
                 07.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2049 
                 gsuscgcaCfuGfAfAfacuuuu 
                 A- 
                 2498 
                 VPusAfscgaAfaaguuuc 
                 GCGUCGCACUGAAA 
                 4749 
               
               
                 12229 
                 22822 
                   
                 cguaL96 
                 228221 
                   
                 AfgUfgcgacsgsc 
                 CUUUUCGUC 
                   
               
               
                 15.1 
                 09.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2050 
                 uscsgcacUfgAfAfAfcuuuuc 
                 A- 
                 2499 
                 VPusGfsacgAfaaaguuuC 
                 CGUCGCACUGAAAC 
                 4750 
               
               
                 12229 
                 22822 
                   
                 gucaL96 
                 228221 
                   
                 faGfugcgascsg 
                 UUUUCGUCC 
                   
               
               
                 16.1 
                 11.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2051 
                 csascugaAfaCfUfUfuucguc 
                 A- 
                 2500 
                 VPusUfsuggAfcgaaaag 
                 CGCACUGAAACUUU 
                 4751 
               
               
                 12229 
                 22822 
                   
                 caaaL96 
                 228221 
                   
                 UfuUfcagugscsg 
                 UCGUCCAAC 
                   
               
               
                 17.1 
                 13.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2052 
                 ascsugaaAfcUfUfUfucgucc 
                 A- 
                 2501 
                 VPusGfsuugGfacgaaaaG 
                 GCACUGAAACUUUU 
                 4752 
               
               
                 12229 
                 22822 
                   
                 aacaL96 
                 228221 
                   
                 fuUfucagusgsc 
                 CGUCCAACU 
                   
               
               
                 18.1 
                 15.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2053 
                 usgsaaacUfuUfUfCfguccaa 
                 A- 
                 2502 
                 VPusAfsaguUfggacgaa 
                 ACUGAAACUUUUCG 
                 4753 
               
               
                 12229 
                 22822 
                   
                 cuuaL96 
                 228222 
                   
                 AfaGfuuucasgsu 
                 UCCAACUUC 
                   
               
               
                 20.1 
                 19.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2054 
                 asascuuuUfcGfUfCfcaacuu 
                 A- 
                 2503 
                 VPusCfsagaAfguuggac 
                 GAAACUUUUCGUCC 
                 4754 
               
               
                 12229 
                 22822 
                   
                 cugaL96 
                 228222 
                   
                 GfaAfaaguususc 
                 AACUUCUGG 
                   
               
               
                 21.1 
                 21.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2055 
                 csusgggcUfgUfUfCfucgcuu 
                 A- 
                 2504 
                 VPusCfscgaAfgcgagaaC 
                 UUCUGGGCUGUUCU 
                 4755 
               
               
                 12229 
                 22822 
                   
                 cggaL96 
                 228222 
                   
                 faGfcccagsasa 
                 CGCUUCGGA 
                   
               
               
                 22.1 
                 23.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2056 
                 usgsggcuGfuUfCfUfcgcuuc 
                 A- 
                 2505 
                 VPusUfsccgAfagcgagaA 
                 UCUGGGCUGUUCUC 
                 4756 
               
               
                 12229 
                 22822 
                   
                 ggaaL96 
                 228222 
                   
                 fcAfgcccasgsa 
                 GCUUCGGAG 
                   
               
               
                 23.1 
                 25.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2057 
                 gsgsgcugUfuCfUfCfgcuucg 
                 A- 
                 2506 
                 VPusCfsuccGfaagcgagA 
                 CUGGGCUGUUCUCG 
                 4757 
               
               
                 12229 
                 22822 
                   
                 gagaL96 
                 228222 
                   
                 faCfagcccsasg 
                 CUUCGGAGG 
                   
               
               
                 24.1 
                 27.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2058 
                 gscsuguuCfuCfGfCfuucgga 
                 A- 
                 2507 
                 VPusUfsccuCfcgaagcgA 
                 GGGCUGUUCUCGCU 
                 4758 
               
               
                 12229 
                 22822 
                   
                 ggaaL96 
                 228223 
                   
                 fgAfacagcscsc 
                 UCGGAGGAG 
                   
               
               
                 25.1 
                 29.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2059 
                 gscscgcgAfgAfAfGfugcuag 
                 A- 
                 2508 
                 VPusGfsagcUfagcacuuC 
                 GAGCCGCGAGAAGU 
                 4759 
               
               
                 12229 
                 22822 
                   
                 cucaL96 
                 228223 
                   
                 fuCfgcggcsusc 
                 GCUAGCUCG 
                   
               
               
                 26.1 
                 31.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2060 
                 cscsgcgaGfaAfGfUfgcuagc 
                 A- 
                 2509 
                 VPusCfsgagCfuagcacuU 
                 AGCCGCGAGAAGUG 
                 4760 
               
               
                 12229 
                 22822 
                   
                 ucgaL96 
                 228223 
                   
                 fcUfcgcggscsu 
                 CUAGCUCGG 
                   
               
               
                 27.1 
                 33.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2061 
                 gscscuccGfaAfAfCfcaugaa 
                 A- 
                 2510 
                 VPusAfsaguUfcaugguu 
                 GGGCCUCCGAAACC 
                 4761 
               
               
                 12229 
                 22822 
                   
                 cuuaL96 
                 228223 
                   
                 UfcGfgaggcscsc 
                 AUGAACUUU 
                   
               
               
                 28.1 
                 35.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2062 
                 asasggagGfaGfGfGfcagaau 
                 A- 
                 2511 
                 VPusAfsugaUfucugccc 
                 AGAAGGAGGAGGGC 
                 4762 
               
               
                 12229 
                 22822 
                   
                 cauaL96 
                 228223 
                   
                 UfcCfuccuuscsu 
                 AGAAUCAUC 
                   
               
               
                 29.1 
                 37.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2063 
                 gsgscagaAfuCfAfUfcacgaa 
                 A- 
                 2512 
                 VPusCfsacuUfcgugaug 
                 AGGGCAGAAUCAUC 
                 4763 
               
               
                 12229 
                 22822 
                   
                 gugaL96 
                 228224 
                   
                 AfuUfcugccscsu 
                 ACGAAGUGG 
                   
               
               
                 30.1 
                 39.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2064 
                 asasucauCfaCfGfAfaguggu 
                 A- 
                 2513 
                 VPusUfsucaCfcacuucgU 
                 AGAAUCAUCACGAA 
                 4764 
               
               
                 12229 
                 22822 
                   
                 gaaaL96 
                 228224 
                   
                 fgAfugauuscsu 
                 GUGGUGAAG 
                   
               
               
                 31.1 
                 41.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2065 
                 asuscaucAfcGfAfAfguggug 
                 A- 
                 2514 
                 VPusCfsuucAfccacuucG 
                 GAAUCAUCACGAAG 
                 4765 
               
               
                 12229 
                 22822 
                   
                 aagaL96 
                 228224 
                   
                 fuGfaugaususc 
                 UGGUGAAGU 
                   
               
               
                 32.1 
                 43.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2066 
                 uscsaucaCfgAfAfGfugguga 
                 A- 
                 2515 
                 VPusAfscuuCfaccacuuC 
                 AAUCAUCACGAAGU 
                 4766 
               
               
                 12229 
                 22822 
                   
                 aguaL96 
                 228224 
                   
                 fgUfgaugasusu 
                 GGUGAAGUU 
                   
               
               
                 33.1 
                 45.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2067 
                 csasucacGfaAfGfUfggugaa 
                 A- 
                 2516 
                 VPusAfsacuUfcaccacuU 
                 AUCAUCACGAAGUG 
                 4767 
               
               
                 12229 
                 22822 
                   
                 guuaL96 
                 228224 
                   
                 fcGfugaugsasu 
                 GUGAAGUUC 
                   
               
               
                 34.1 
                 47.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2068 
                 uscsacgaAfgUfGfGfugaagu 
                 A- 
                 2517 
                 VPusUfsgaaCfuucaccaC 
                 CAUCACGAAGUGGU 
                 4768 
               
               
                 12229 
                 22822 
                   
                 ucaaL96 
                 228225 
                   
                 fuUfcgugasusg 
                 GAAGUUCAU 
                   
               
               
                 35.1 
                 49.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2069 
                 asasguggUfgAfAfGfuucaug 
                 A- 
                 2518 
                 VPusAfsuccAfugaacuuC 
                 CGAAGUGGUGAAGU 
                 4769 
               
               
                 12229 
                 22822 
                   
                 gauaL96 
                 228225 
                   
                 faCfcacuuscsg 
                 UCAUGGAUG 
                   
               
               
                 36.1 
                 51.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2070 
                 asgsugguGfaAfGfUfucaugg 
                 A- 
                 2519 
                 VPusCfsaucCfaugaacuU 
                 GAAGUGGUGAAGU 
                 4770 
               
               
                 12229 
                 22822 
                   
                 augaL96 
                 228225 
                   
                 fcAfccacususc 
                 UCAUGGAUGU 
                   
               
               
                 37.1 
                 53.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2071 
                 gsusggugAfaGfUfUfcaugga 
                 A- 
                 2520 
                 VPusAfscauCfcaugaacU 
                 AAGUGGUGAAGUUC 
                 4771 
               
               
                 12229 
                 22822 
                   
                 uguaL96 
                 228225 
                   
                 fuCfaccacsusu 
                 AUGGAUGUC 
                   
               
               
                 38.1 
                 55.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2072 
                 gsgsugaaGfuUfCfAfuggaug 
                 A- 
                 2521 
                 VPusAfsgacAfuccaugaA 
                 GUGGUGAAGUUCAU 
                 4772 
               
               
                 12229 
                 22822 
                   
                 ucuaL96 
                 228225 
                   
                 fcUfucaccsasc 
                 GGAUGUCUA 
                   
               
               
                 39.1 
                 57.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2073 
                 gsusgaagUfuCfAfUfggaugu 
                 A- 
                 2522 
                 VPusUfsagaCfauccaugA 
                 UGGUGAAGUUCAUG 
                 4773 
               
               
                 12229 
                 22822 
                   
                 cuaaL96 
                 228226 
                   
                 faCfuucacscsa 
                 GAUGUCUAU 
                   
               
               
                 40.1 
                 59.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2074 
                 usgsaaguUfcAfUfGfgauguc 
                 A- 
                 2523 
                 VPusAfsuagAfcauccauG 
                 GGUGAAGUUCAUGG 
                 4774 
               
               
                 12229 
                 22822 
                   
                 uauaL96 
                 228226 
                   
                 faAfcuucascsc 
                 AUGUCUAUC 
                   
               
               
                 41.1 
                 61.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2075 
                 asasguucAfuGfGfAfugucua 
                 A- 
                 2524 
                 VPusUfsgauAfgacauccA 
                 UGAAGUUCAUGGAU 
                 4775 
               
               
                 12229 
                 22822 
                   
                 ucaaL96 
                 228226 
                   
                 fuGfaacuuscsa 
                 GUCUAUCAG 
                   
               
               
                 42.1 
                 63.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2076 
                 asgsuucaUfgGfAfUfgucuau 
                 A- 
                 2525 
                 VPusCfsugaUfagacaucC 
                 GAAGUUCAUGGAUG 
                 4776 
               
               
                 12229 
                 22822 
                   
                 cagaL96 
                 228226 
                   
                 faUfgaacususc 
                 UCUAUCAGC 
                   
               
               
                 43.1 
                 65.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2077 
                 ususcaugGfaUfGfUfcuauca 
                 A- 
                 2526 
                 VPusCfsgcuGfauagacaU 
                 AGUUCAUGGAUGUC 
                 4777 
               
               
                 12229 
                 22822 
                   
                 gcgaL96 
                 228226 
                   
                 fcCfaugaascsu 
                 UAUCAGCGC 
                   
               
               
                 44.1 
                 67.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2078 
                 gsusggacAfuCfUfUfccagga 
                 A- 
                 2527 
                 VPusUfsacuCfcuggaagA 
                 UGGUGGACAUCUUC 
                 4778 
               
               
                 12229 
                 22822 
                   
                 guaaL96 
                 228227 
                   
                 fuGfuccacscsa 
                 CAGGAGUAC 
                   
               
               
                 45.1 
                 69.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2079 
                 uscsgaguAfcAfUfCfuucaag 
                 A- 
                 2528 
                 VPusUfsggcUfugaagau 
                 GAUCGAGUACAUCU 
                 4779 
               
               
                 12229 
                 22822 
                   
                 ccaaL96 
                 228227 
                   
                 GfuAfcucgasusc 
                 UCAAGCCAU 
                   
               
               
                 46.1 
                 71.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2080 
                 csgsaguaCfaUfCfUfucaagc 
                 A- 
                 2529 
                 VPusAfsuggCfuugaaga 
                 AUCGAGUACAUCUU 
                 4780 
               
               
                 12229 
                 22822 
                   
                 cauaL96 
                 228227 
                   
                 UfgUfacucgsasu 
                 CAAGCCAUC 
                   
               
               
                 47.1 
                 73.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2081 
                 gsasguacAfuCfUfUfcaagcc 
                 A- 
                 2530 
                 VPusGfsaugGfcuugaag 
                 UCGAGUACAUCUUC 
                 4781 
               
               
                 12229 
                 22822 
                   
                 aucaL96 
                 228227 
                   
                 AfuGfuacucsgsa 
                 AAGCCAUCC 
                   
               
               
                 48.1 
                 75.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2082 
                 gsusacauCfuUfCfAfagccau 
                 A- 
                 2531 
                 VPusAfsggaUfggcuuga 
                 GAGUACAUCUUCAA 
                 4782 
               
               
                 12229 
                 22822 
                   
                 ccuaL96 
                 228227 
                   
                 AfgAfuguacsusc 
                 GCCAUCCUG 
                   
               
               
                 49.1 
                 77.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2083 
                 cscsaacaUfcAfCfCfaugcaga 
                 A- 
                 2532 
                 VPusAfsaucUfgcauggu 
                 GUCCAACAUCACCA 
                 4783 
               
               
                 12229 
                 22822 
                   
                 uuaL96 
                 228228 
                   
                 GfaUfguuggsasc 
                 UGCAGAUUA 
                   
               
               
                 50.1 
                 79.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2084 
                 csasacauCfaCfCfAfugcaga 
                 A- 
                 2533 
                 VPusUfsaauCfugcaugg 
                 UCCAACAUCACCAU 
                 4784 
               
               
                 12229 
                 22822 
                   
                 uuaaL96 
                 228228 
                   
                 UfgAfuguugsgsa 
                 GCAGAUUAU 
                   
               
               
                 51.1 
                 81.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2085 
                 ascsaucaCfAfUfGfcagauu 
                 A- 
                 2534 
                 VPusCfsauaAfucugcauG 
                 CAACAUCACCAUGC 
                 4785 
               
               
                 12229 
                 22822 
                   
                 augaL96 
                 228228 
                   
                 fgUfgaugususg 
                 AGAUUAUGC 
                   
               
               
                 52.1 
                 83.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2086 
                 csasucacCfaUfGfCfagauua 
                 A- 
                 2535 
                 VPusGfscauAfaucugcaU 
                 AACAUCACCAUGCA 
                 4786 
               
               
                 12229 
                 22822 
                   
                 ugcaL96 
                 228228 
                   
                 fgGfugaugsusu 
                 GAUUAUGCG 
                   
               
               
                 53.1 
                 85.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2087 
                 ascscaugCfaGfAfUfuaugcg 
                 A- 
                 2536 
                 VPusAfsuccGfcauaaucU 
                 UCACCAUGCAGAUU 
                 4787 
               
               
                 12229 
                 22822 
                   
                 gauaL96 
                 228228 
                   
                 fgCfauggusgsa 
                 AUGCGGAUC 
                   
               
               
                 54.1 
                 87.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2088 
                 asusgcagAfuUfAfUfgcggau 
                 A- 
                 2537 
                 VPusUfsugaUfccgcauaA 
                 CCAUGCAGAUUAUG 
                 4788 
               
               
                 12229 
                 22822 
                   
                 caaaL96 
                 228229 
                   
                 fuCfugcausgsg 
                 CGGAUCAAA 
                   
               
               
                 55.1 
                 89.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2089 
                 usgscagaUfuAfUfGfcggauc 
                 A- 
                 2538 
                 VPusUfsuugAfuccgcau 
                 CAUGCAGAUUAUGC 
                 4789 
               
               
                 12229 
                 22822 
                   
                 aaaaL96 
                 228229 
                   
                 AfaUfcugcasusg 
                 GGAUCAAAC 
                   
               
               
                 56.1 
                 91.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2090 
                 gscsagauUfaUfGfCfggauca 
                 A- 
                 2539 
                 VPusGfsuuuGfauccgca 
                 AUGCAGAUUAUGCG 
                 4790 
               
               
                 12229 
                 22822 
                   
                 aacaL96 
                 228229 
                   
                 UfaAfucugcsasu 
                 GAUCAAACC 
                   
               
               
                 57.1 
                 93.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2091 
                 gsasuuauGfcGfGfAfucaaac 
                 A- 
                 2540 
                 VPusGfsaggUfuugaucc 
                 CAGAUUAUGCGGAU 
                 4791 
               
               
                 12229 
                 22822 
                   
                 cucaL96 
                 228229 
                   
                 GfcAfuaaucsusg 
                 CAAACCUCA 
                   
               
               
                 58.1 
                 95.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2092 
                 asusuaugCfgGfAfUfcaaacc 
                 A- 
                 2541 
                 VPusUfsgagGfuuugauc 
                 AGAUUAUGCGGAUC 
                 4792 
               
               
                 12229 
                 22822 
                   
                 ucaaL96 
                 228229 
                   
                 CfgCfauaauscsu 
                 AAACCUCAC 
                   
               
               
                 59.1 
                 97.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2093 
                 csgsgaucAfaAfCfCfucacca 
                 A- 
                 2542 
                 VPusCfscuuGfgugaggu 
                 UGCGGAUCAAACCU 
                 4793 
               
               
                 12229 
                 22822 
                   
                 aggaL96 
                 228230 
                   
                 UfuGfauccgscsa 
                 CACCAAGGC 
                   
               
               
                 60.1 
                 99.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2094 
                 gsgsagagAfuGfAfGfcuuccu 
                 A- 
                 2543 
                 VPusUfsguaGfgaagcuc 
                 UAGGAGAGAUGAGC 
                 4794 
               
               
                 12229 
                 22823 
                   
                 acaaL96 
                 228230 
                   
                 AfuCfucuccsusa 
                 UUCCUACAG 
                   
               
               
                 61.1 
                 01.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2095 
                 gsasgaugAfgCfUfUfccuaca 
                 A- 
                 2544 
                 VPusUfsgcuGfuaggaag 
                 GAGAGAUGAGCUUC 
                 4795 
               
               
                 12229 
                 22823 
                   
                 gcaaL96 
                 228230 
                   
                 CfuCfaucucsusc 
                 CUACAGCAC 
                   
               
               
                 62.1 
                 03.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2096 
                 gsasugagCfuUfCfCfuacagc 
                 A- 
                 2545 
                 VPusUfsgugCfuguagga 
                 GAGAUGAGCUUCCU 
                 4796 
               
               
                 12229 
                 22823 
                   
                 acaaL96 
                 228230 
                   
                 AfgCfucaucsusc 
                 ACAGCACAA 
                   
               
               
                 63.1 
                 05.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2097 
                 asusgagcUfuCfCfUfacagca 
                 A- 
                 2546 
                 VPusUfsuguGfcuguagg 
                 AGAUGAGCUUCCUA 
                 4797 
               
               
                 12229 
                 22823 
                   
                 caaaL96 
                 228230 
                   
                 AfaGfcucauscsu 
                 CAGCACAAC 
                   
               
               
                 64.1 
                 07.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2098 
                 gsasgcuuCfcUfAfCfagcaca 
                 A- 
                 2547 
                 VPusUfsguuGfugcugua 
                 AUGAGCUUCCUACA 
                 4798 
               
               
                 12229 
                 22823 
                   
                 acaaL96 
                 228231 
                   
                 GfgAfagcucsasu 
                 GCACAACAA 
                   
               
               
                 65.1 
                 09.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2099 
                 asgscuucCfuAfCfAfgcacaa 
                 A- 
                 2548 
                 VPusUfsuguUfgugcugu 
                 UGAGCUUCCUACAG 
                 4799 
               
               
                 12229 
                 22823 
                   
                 caaaL96 
                 228231 
                   
                 AfgGfaagcuscsa 
                 CACAACAAA 
                   
               
               
                 66.1 
                 11.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2100 
                 gscsuuccUfaCfAfGfcacaac 
                 A- 
                 2549 
                 VPusUfsuugUfugugcug 
                 GAGCUUCCUACAGC 
                 4800 
               
               
                 12229 
                 22823 
                   
                 aaaaL96 
                 228231 
                   
                 UfaGfgaagcsusc 
                 ACAACAAAU 
                   
               
               
                 67.1 
                 13.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2101 
                 csusuccuAfcAfGfCfacaaca 
                 A- 
                 2550 
                 VPusAfsuuuGfuugugcu 
                 AGCUUCCUACAGCA 
                 4801 
               
               
                 12229 
                 22823 
                   
                 aauaL96 
                 228231 
                   
                 GfuAfggaagscsu 
                 CAACAAAUG 
                   
               
               
                 68.1 
                 15.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2102 
                 uscscuacAfgCfAfCfaacaaa 
                 A- 
                 2551 
                 VPusAfscauUfuguugug 
                 CUUCCUACAGCACA 
                 4802 
               
               
                 12229 
                 22823 
                   
                 uguaL96 
                 228231 
                   
                 CfuGfuaggasasg 
                 ACAAAUGUG 
                   
               
               
                 69.1 
                 17.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2103 
                 csusacagCfaCfAfAfcaaaug 
                 A- 
                 2552 
                 VPusUfscacAfuuuguug 
                 UCCUACAGCACAAC 
                 4803 
               
               
                 12229 
                 22823 
                   
                 ugaaL96 
                 228232 
                   
                 UfgCfuguagsgsa 
                 AAAUGUGAA 
                   
               
               
                 70.1 
                 19.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2104 
                 usascagcAfcAfAfCfaaaugu 
                 A- 
                 2553 
                 VPusUfsucaCfauuuguu 
                 CCUACAGCACAACA 
                 4804 
               
               
                 12229 
                 22823 
                   
                 gaaaL96 
                 228232 
                   
                 GfuGfcuguasgsg 
                 AAUGUGAAU 
                   
               
               
                 71.1 
                 21.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2105 
                 asgscacaAfcAfAfAfugugaa 
                 A- 
                 2554 
                 VPusGfscauUfcacauuuG 
                 ACAGCACAACAAAU 
                 4805 
               
               
                 12229 
                 22823 
                   
                 ugcaL96 
                 228232 
                   
                 fuUfgugcusgsu 
                 GUGAAUGCA 
                   
               
               
                 72.1 
                 23.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2106 
                 gscsacaaCfaAfAfUfgugaau 
                 A- 
                 2555 
                 VPusUfsgcaUfucacauuU 
                 CAGCACAACAAAUG 
                 4806 
               
               
                 12229 
                 22823 
                   
                 gcaaL96 
                 228232 
                   
                 fgUfugugcsusg 
                 UGAAUGCAG 
                   
               
               
                 73.1 
                 25.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2107 
                 csuscaccAfgGfAfAfagacug 
                 A- 
                 2556 
                 VPusUfsaucAfgucuuuc 
                 CUCUCACCAGGAAA 
                 4807 
               
               
                 12229 
                 22823 
                   
                 auaaL96 
                 228232 
                   
                 CfuGfgugagsasg 
                 GACUGAUAC 
                   
               
               
                 74.1 
                 27.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2108 
                 uscsaccaGfgAfAfAfgacuga 
                 A- 
                 2557 
                 VPusGfsuauCfagucuuu 
                 UCUCACCAGGAAAG 
                 4808 
               
               
                 12229 
                 22823 
                   
                 uacaL96 
                 228233 
                   
                 CfcUfggugasgsa 
                 ACUGAUACA 
                   
               
               
                 75.1 
                 29.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2109 
                 csasccagGfaAfAfGfacugau 
                 A- 
                 2558 
                 VPusUfsguaUfcagucuu 
                 CUCACCAGGAAAGA 
                 4809 
               
               
                 12229 
                 22823 
                   
                 acaaL96 
                 228233 
                   
                 UfcCfuggugsasg 
                 CUGAUACAG 
                   
               
               
                 76.1 
                 31.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2110 
                 ascscaggAfaAfGfAfcugaua 
                 A- 
                 2559 
                 VPusCfsuguAfucagucu 
                 UCACCAGGAAAGAC 
                 4810 
               
               
                 12229 
                 22823 
                   
                 cagaL96 
                 228233 
                   
                 UfuCfcuggusgsa 
                 UGAUACAGA 
                   
               
               
                 77.1 
                 33.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2111 
                 cscsaggaAfaGfAfCfugauac 
                 A- 
                 2560 
                 VPusUfscugUfaucaguc 
                 CACCAGGAAAGACU 
                 4811 
               
               
                 12229 
                 22823 
                   
                 agaaL96 
                 228233 
                   
                 UfuUfccuggsusg 
                 GAUACAGAA 
                   
               
               
                 78.1 
                 35.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2112 
                 csasggaaAfgAfCfUfgauaca 
                 A- 
                 2561 
                 VPusUfsucuGfuaucagu 
                 ACCAGGAAAGACUG 
                 4812 
               
               
                 12229 
                 22823 
                   
                 gaaaL96 
                 228233 
                   
                 CfuUfuccugsgsu 
                 AUACAGAAC 
                   
               
               
                 79.1 
                 37.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2113 
                 asgsgaaaGfaCfUfGfauacag 
                 A- 
                 2562 
                 VPusGfsuucUfguaucag 
                 CCAGGAAAGACUGA 
                 4813 
               
               
                 12229 
                 22823 
                   
                 aacaL96 
                 228234 
                   
                 UfcUfuuccusgsg 
                 UACAGAACG 
                   
               
               
                 80.1 
                 39.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2114 
                 gsgsaaagAfcUfGfAfuacaga 
                 A- 
                 2563 
                 VPusCfsguuCfuguauca 
                 CAGGAAAGACUGAU 
                 4814 
               
               
                 12229 
                 22823 
                   
                 acgaL96 
                 228234 
                   
                 GfuCfuuuccsusg 
                 ACAGAACGA 
                   
               
               
                 81.1 
                 41.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2115 
                 gsasaagaCfuGfAfUfacagaa 
                 A- 
                 2564 
                 VPusUfscguUfcuguauc 
                 AGGAAAGACUGAUA 
                 4815 
               
               
                 12229 
                 22823 
                   
                 cgaaL96 
                 228234 
                   
                 AfgUfcuuucscsu 
                 CAGAACGAU 
                   
               
               
                 82.1 
                 43.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2116 
                 asasagacUfgAfUfAfcagaac 
                 A- 
                 2565 
                 VPusAfsucgUfucuguau 
                 GGAAAGACUGAUAC 
                 4816 
               
               
                 12229 
                 22823 
                   
                 gauaL96 
                 228234 
                   
                 CfaGfucuuuscsc 
                 AGAACGAUC 
                   
               
               
                 83.1 
                 45.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2117 
                 asasgacuGfaUfAfCfagaacg 
                 A- 
                 2566 
                 VPusGfsaucGfuucugua 
                 GAAAGACUGAUACA 
                 4817 
               
               
                 12229 
                 22823 
                   
                 aucaL96 
                 228234 
                   
                 UfcAfgucuususc 
                 GAACGAUCG 
                   
               
               
                 84.1 
                 47.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2118 
                 asgsacugAfuAfCfAfgaacga 
                 A- 
                 2567 
                 VPusCfsgauCfguucugu 
                 AAAGACUGAUACAG 
                 4818 
               
               
                 12229 
                 22823 
                   
                 ucgaL96 
                 228235 
                   
                 AfuCfagucususu 
                 AACGAUCGA 
                   
               
               
                 85.1 
                 49.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2119 
                 gsascugaUfaCfAfGfaacgau 
                 A- 
                 2568 
                 VPusUfscgaUfcguucug 
                 AAGACUGAUACAGA 
                 4819 
               
               
                 12229 
                 22823 
                   
                 cgaaL96 
                 228235 
                   
                 UfaUfcagucsusu 
                 ACGAUCGAU 
                   
               
               
                 86.1 
                 51.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2120 
                 ascsugauAfcAfGfAfacgauc 
                 A- 
                 2569 
                 VPusAfsucgAfucguucu 
                 AGACUGAUACAGAA 
                 4820 
               
               
                 12229 
                 22823 
                   
                 gauaL96 
                 228235 
                   
                 GfuAfucaguscsu 
                 CGAUCGAUA 
                   
               
               
                 87.1 
                 53.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2121 
                 csusgauaCfaGfAfAfcgaucg 
                 A- 
                 2570 
                 VPusUfsaucGfaucguuc 
                 GACUGAUACAGAAC 
                 4821 
               
               
                 12229 
                 22823 
                   
                 auaaL96 
                 228235 
                   
                 UfgUfaucagsusc 
                 GAUCGAUAC 
                   
               
               
                 88.1 
                 55.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2122 
                 usgsauacAfgAfAfCfgaucga 
                 A- 
                 2571 
                 VPusGfsuauCfgaucguu 
                 ACUGAUACAGAACG 
                 4822 
               
               
                 12229 
                 22823 
                   
                 uacaL96 
                 228235 
                   
                 CfuGfuaucasgsu 
                 AUCGAUACA 
                   
               
               
                 89.1 
                 57.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2123 
                 gsasuacaGfaAfCfGfaucgau 
                 A- 
                 2572 
                 VPusUfsguaUfcgaucgu 
                 CUGAUACAGAACGA 
                 4823 
               
               
                 12229 
                 22823 
                   
                 acaaL96 
                 228236 
                   
                 UfcUfguaucsasg 
                 UCGAUACAG 
                   
               
               
                 90.1 
                 59.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2124 
                 asusacagAfaCfGfAfucgaua 
                 A- 
                 2573 
                 VPusCfsuguAfucgaucg 
                 UGAUACAGAACGAU 
                 4824 
               
               
                 12229 
                 22823 
                   
                 cagaL96 
                 228236 
                   
                 UfuCfuguauscsa 
                 CGAUACAGA 
                   
               
               
                 91.1 
                 61.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2125 
                 usascagaAfcGfAfUfcgauac 
                 A- 
                 2574 
                 VPusUfscugUfaucgauc 
                 GAUACAGAACGAUC 
                 4825 
               
               
                 12229 
                 22823 
                   
                 agaaL96 
                 228236 
                   
                 GfuUfcuguasusc 
                 GAUACAGAA 
                   
               
               
                 92.1 
                 63.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2126 
                 ascsagaaCfgAfUfCfgauaca 
                 A- 
                 2575 
                 VPusUfsucuGfuaucgau 
                 AUACAGAACGAUCG 
                 4826 
               
               
                 12229 
                 22823 
                   
                 gaaaL96 
                 228236 
                   
                 CfgUfucugusasu 
                 AUACAGAAA 
                   
               
               
                 93.1 
                 65.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2127 
                 csasgaacGfaUfCfGfauacag 
                 A- 
                 2576 
                 VPusUfsuucUfguaucga 
                 UACAGAACGAUCGA 
                 4827 
               
               
                 12229 
                 22823 
                   
                 aaaaL96 
                 228236 
                   
                 UfcGfuucugsusa 
                 UACAGAAAC 
                   
               
               
                 94.1 
                 67.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2128 
                 asgsaacgAfuCfGfAfuacaga 
                 A- 
                 2577 
                 VPusGfsuuuCfuguaucg 
                 ACAGAACGAUCGAU 
                 4828 
               
               
                 12229 
                 22823 
                   
                 aacaL96 
                 228237 
                   
                 AfuCfguucusgsu 
                 ACAGAAACC 
                   
               
               
                 95.1 
                 69.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2129 
                 gsasacgaUfcGfAfUfacagaa 
                 A- 
                 2578 
                 VPusGfsguuUfcuguauc 
                 CAGAACGAUCGAUA 
                 4829 
               
               
                 12229 
                 22823 
                   
                 accaL96 
                 228237 
                   
                 GfaUfcguucsusg 
                 CAGAAACCA 
                   
               
               
                 96.1 
                 71.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2130 
                 asascgauCfgAfUfAfcagaaa 
                 A- 
                 2579 
                 VPusUfsgguUfucuguau 
                 AGAACGAUCGAUAC 
                 4830 
               
               
                 12229 
                 22823 
                   
                 ccaaL96 
                 228237 
                   
                 CfgAfucguuscsu 
                 AGAAACCAC 
                   
               
               
                 97.1 
                 73.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2131 
                 ascsgaucGfaUfAfCfagaaac 
                 A- 
                 2580 
                 VPusGfsuggUfuucugua 
                 GAACGAUCGAUACA 
                 4831 
               
               
                 12229 
                 22823 
                   
                 cacaL96 
                 228237 
                   
                 UfcGfaucgususc 
                 GAAACCACG 
                   
               
               
                 98.1 
                 75.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2132 
                 csgsaucgAfuAfCfAfgaaacc 
                 A- 
                 2581 
                 VPusCfsgugGfuuucugu 
                 AACGAUCGAUACAG 
                 4832 
               
               
                 12229 
                 22823 
                   
                 acgaL96 
                 228237 
                   
                 AfuCfgaucgsusu 
                 AAACCACGC 
                   
               
               
                 99.1 
                 77.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2133 
                 csasccauCfaCfCfAfucgacag 
                 A- 
                 2582 
                 VPusUfsucuGfucgaugg 
                 CACACCAUCACCAU 
                 4833 
               
               
                 12230 
                 22823 
                   
                 aaaL96 
                 228238 
                   
                 UfgAfuggugsusg 
                 CGACAGAAC 
                   
               
               
                 00.1 
                 79.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2134 
                 csasucacCfaUfCfGfacagaac 
                 A- 
                 2583 
                 VPusCfsuguUfcugucga 
                 ACCAUCACCAUCGA 
                 4834 
               
               
                 12230 
                 22823 
                   
                 agaL96 
                 228238 
                   
                 UfgGfugaugsgsu 
                 CAGAACAGU 
                   
               
               
                 01.1 
                 81.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2135 
                 uscsaccaUfcGfAfCfagaaca 
                 A- 
                 2584 
                 VPusGfsacuGfuucuguc 
                 CAUCACCAUCGACA 
                 4835 
               
               
                 12230 
                 22823 
                   
                 gucaL96 
                 228238 
                   
                 GfaUfggugasusg 
                 GAACAGUCC 
                   
               
               
                 02.1 
                 83.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2136 
                 csasccauCfgAfCfAfgaacag 
                 A- 
                 2585 
                 VPusGfsgacUfguucugu 
                 AUCACCAUCGACAG 
                 4836 
               
               
                 12230 
                 22823 
                   
                 uccaL96 
                 228238 
                   
                 CfgAfuggugsasu 
                 AACAGUCCU 
                   
               
               
                 03.1 
                 85.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2137 
                 ascscaucGfaCfAfGfaacagu 
                 A- 
                 2586 
                 VPusAfsggaCfuguucug 
                 UCACCAUCGACAGA 
                 4837 
               
               
                 12230 
                 22823 
                   
                 ccuaL96 
                 228238 
                   
                 UfcGfauggusgsa 
                 ACAGUCCUU 
                   
               
               
                 04.1 
                 87.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2138 
                 cscsaucgAfcAfGfAfacaguc 
                 A- 
                 2587 
                 VPusAfsaggAfcuguucu 
                 CACCAUCGACAGAA 
                 4838 
               
               
                 12230 
                 22823 
                   
                 cuuaL96 
                 228239 
                   
                 GfuCfgauggsusg 
                 CAGUCCUUA 
                   
               
               
                 05.1 
                 89.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2139 
                 csasucgaCfaGfAfAfcagucc 
                 A- 
                 2588 
                 VPusUfsaagGfacuguuc 
                 ACCAUCGACAGAAC 
                 4839 
               
               
                 12230 
                 22823 
                   
                 uuaaL96 
                 228239 
                   
                 UfgUfcgaugsgsu 
                 AGUCCUUAA 
                   
               
               
                 06.1 
                 91.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2140 
                 asuscgacAfgAfAfCfaguccu 
                 A- 
                 2589 
                 VPusUfsuaaGfgacuguu 
                 CCAUCGACAGAACA 
                 4840 
               
               
                 12230 
                 22823 
                   
                 uaaaL96 
                 228239 
                   
                 CfuGfucgausgsg 
                 GUCCUUAAU 
                   
               
               
                 07.1 
                 93.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2141 
                 uscsgacaGfaAfCfAfguccuu 
                 A- 
                 2590 
                 VPusAfsuuaAfggacugu 
                 CAUCGACAGAACAG 
                 4841 
               
               
                 12230 
                 22823 
                   
                 aauaL96 
                 228239 
                   
                 UfcUfgucgasusg 
                 UCCUUAAUC 
                   
               
               
                 08.1 
                 95.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2142 
                 csgsacagAfaCfAfGfuccuua 
                 A- 
                 2591 
                 VPusGfsauuAfaggacug 
                 AUCGACAGAACAGU 
                 4842 
               
               
                 12230 
                 22823 
                   
                 aucaL96 
                 228239 
                   
                 UfuCfugucgsasu 
                 CCUUAAUCC 
                   
               
               
                 09.1 
                 97.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2143 
                 gsascagaAfcAfGfUfccuuaa 
                 A- 
                 2592 
                 VPusGfsgauUfaaggacu 
                 UCGACAGAACAGUC 
                 4843 
               
               
                 12230 
                 22823 
                   
                 uccaL96 
                 228240 
                   
                 GfuUfcugucsgsa 
                 CUUAAUCCA 
                   
               
               
                 10.1 
                 99.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2144 
                 ascsagaaCfaGfUfCfcuuaau 
                 A- 
                 2593 
                 VPusUfsggaUfuaaggac 
                 CGACAGAACAGUCC 
                 4844 
               
               
                 12230 
                 22824 
                   
                 ccaaL96 
                 228240 
                   
                 UfgUfucuguscsg 
                 UUAAUCCAG 
                   
               
               
                 11.1 
                 01.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2145 
                 asgsaacaGfuCfCfUfuaaucc 
                 A- 
                 2594 
                 VPusUfscugGfauuaagg 
                 ACAGAACAGUCCUU 
                 4845 
               
               
                 12230 
                 22824 
                   
                 agaaL96 
                 228240 
                   
                 AfcUfguucusgsu 
                 AAUCCAGAA 
                   
               
               
                 12.1 
                 03.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2146 
                 gsasacagUfcCfUfUfaaucca 
                 A- 
                 2595 
                 VPusUfsucuGfgauuaag 
                 CAGAACAGUCCUUA 
                 4846 
               
               
                 12230 
                 22824 
                   
                 gaaaL96 
                 228240 
                   
                 GfaCfuguucsusg 
                 AUCCAGAAA 
                   
               
               
                 13.1 
                 05.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2147 
                 asascaguCfcUfUfAfauccag 
                 A- 
                 2596 
                 VPusUfsuucUfggauuaa 
                 AGAACAGUCCUUAA 
                 4847 
               
               
                 12230 
                 22824 
                   
                 aaaaL96 
                 228240 
                   
                 GfgAfcuguuscsu 
                 UCCAGAAAC 
                   
               
               
                 14.1 
                 07.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2148 
                 ascsagucCfuUfAfAfuccaga 
                 A- 
                 2597 
                 VPusGfsuuuCfuggauua 
                 GAACAGUCCUUAAU 
                 4848 
               
               
                 12230 
                 22824 
                   
                 aacaL96 
                 228241 
                   
                 AfgGfacugususc 
                 CCAGAAACC 
                   
               
               
                 15.1 
                 09.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2149 
                 csasguccUfuAfAfUfccagaa 
                 A- 
                 2598 
                 VPusGfsguuUfcuggauu 
                 AACAGUCCUUAAUC 
                 4849 
               
               
                 12230 
                 22824 
                   
                 accaL96 
                 228241 
                   
                 AfaGfgacugsusu 
                 CAGAAACCU 
                   
               
               
                 16.1 
                 11.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2150 
                 asgsuccuUfaAfUfCfcagaaa 
                 A- 
                 2599 
                 VPusAfsgguUfucuggau 
                 ACAGUCCUUAAUCC 
                 4850 
               
               
                 12230 
                 22824 
                   
                 ccuaL96 
                 228241 
                   
                 UfaAfggacusgsu 
                 AGAAACCUG 
                   
               
               
                 17.1 
                 13.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2151 
                 gsusccuuAfaUfCfCfagaaac 
                 A- 
                 2600 
                 VPusCfsaggUfuucugga 
                 CAGUCCUUAAUCCA 
                 4851 
               
               
                 12230 
                 22824 
                   
                 cugaL96 
                 228241 
                   
                 UfuAfaggacsusg 
                 GAAACCUGA 
                   
               
               
                 18.1 
                 15.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2152 
                 uscscuuaAfuCfCfAfgaaacc 
                 A- 
                 2601 
                 VPusUfscagGfuuucugg 
                 AGUCCUUAAUCCAG 
                 4852 
               
               
                 12230 
                 22824 
                   
                 ugaaL96 
                 228241 
                   
                 AfuUfaaggascsu 
                 AAACCUGAA 
                   
               
               
                 19.1 
                 17.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2153 
                 cscsuuaaUfcCfAfGfaaaccu 
                 A- 
                 2602 
                 VPusUfsucaGfguuucug 
                 GUCCUUAAUCCAGA 
                 4853 
               
               
                 12230 
                 22824 
                   
                 gaaaL96 
                 228242 
                   
                 GfaUfuaaggsasc 
                 AACCUGAAA 
                   
               
               
                 20.1 
                 19.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2154 
                 csusuaauCfcAfGfAfaaccug 
                 A- 
                 2603 
                 VPusUfsuucAfgguuucu 
                 UCCUUAAUCCAGAA 
                 4854 
               
               
                 12230 
                 22824 
                   
                 aaaaL96 
                 228242 
                   
                 GfgAfuuaagsgsa 
                 ACCUGAAAU 
                   
               
               
                 21.1 
                 21.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2155 
                 ususaaucCfaGfAfAfaccuga 
                 A- 
                 2604 
                 VPusAfsuuuCfagguuuc 
                 CCUUAAUCCAGAAA 
                 4855 
               
               
                 12230 
                 22824 
                   
                 aauaL96 
                 228242 
                   
                 UfgGfauuaasgsg 
                 CCUGAAAUG 
                   
               
               
                 22.1 
                 23.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2156 
                 csasgaaaCfcUfGfAfaaugaa 
                 A- 
                 2605 
                 VPusUfsccuUfcauuucaG 
                 UCCAGAAACCUGAA 
                 4856 
               
               
                 12230 
                 22824 
                   
                 ggaaL96 
                 228242 
                   
                 fgUfuucugsgsa 
                 AUGAAGGAA 
                   
               
               
                 23.1 
                 25.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2157 
                 asgsaaacCfuGfAfAfaugaag 
                 A- 
                 2606 
                 VPusUfsuccUfucauuuc 
                 CCAGAAACCUGAAA 
                 4857 
               
               
                 12230 
                 22824 
                   
                 gaaaL96 
                 228242 
                   
                 AfgGfuuucusgsg 
                 UGAAGGAAG 
                   
               
               
                 24.1 
                 27.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2158 
                 gsasaaccUfgAfAfAfugaagg 
                 A- 
                 2607 
                 VPusCfsuucCfuucauuuC 
                 CAGAAACCUGAAAU 
                 4858 
               
               
                 12230 
                 22824 
                   
                 aagaL96 
                 228243 
                   
                 faGfguuucsusg 
                 GAAGGAAGA 
                   
               
               
                 25.1 
                 29.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2159 
                 asasaccuGfaAfAfUfgaagga 
                 A- 
                 2608 
                 VPusUfscuuCfcuucauu 
                 AGAAACCUGAAAUG 
                 4859 
               
               
                 12230 
                 22824 
                   
                 agaaL96 
                 228243 
                   
                 UfcAfgguuuscsu 
                 AAGGAAGAG 
                   
               
               
                 26.1 
                 31.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2160 
                 asasccugAfaAfUfGfaaggaa 
                 A- 
                 2609 
                 VPusCfsucuUfccuucauU 
                 GAAACCUGAAAUGA 
                 4860 
               
               
                 12230 
                 22824 
                   
                 gagaL96 
                 228243 
                   
                 fuCfagguususc 
                 AGGAAGAGG 
                   
               
               
                 27.1 
                 33.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2161 
                 cscsugaaAfuGfAfAfggaaga 
                 A- 
                 2610 
                 VPusUfsccuCfuuccuucA 
                 AACCUGAAAUGAAG 
                 4861 
               
               
                 12230 
                 22824 
                   
                 ggaaL96 
                 228243 
                   
                 fuUfucaggsusu 
                 GAAGAGGAG 
                   
               
               
                 28.1 
                 35.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2162 
                 asusgaagGfaAfGfAfggagac 
                 A- 
                 2611 
                 VPusAfsgagUfcuccucu 
                 AAAUGAAGGAAGA 
                 4862 
               
               
                 12230 
                 22824 
                   
                 ucuaL96 
                 228243 
                   
                 UfcCfuucaususu 
                 GGAGACUCUG 
                   
               
               
                 29.1 
                 37.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2163 
                 uscsccucUfuGfGfAfauugga 
                 A- 
                 2612 
                 VPusGfsaauCfcaauuccA 
                 GGUCCCUCUUGGAA 
                 4863 
               
               
                 12230 
                 22824 
                   
                 uucaL96 
                 228244 
                   
                 faGfagggascsc 
                 UUGGAUUCG 
                   
               
               
                 30.1 
                 39.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2164 
                 cscsucuuGfgAfAfUfuggauu 
                 A- 
                 2613 
                 VPusGfscgaAfuccaauuC 
                 UCCCUCUUGGAAUU 
                 4864 
               
               
                 12230 
                 22824 
                   
                 cgcaL96 
                 228244 
                   
                 fcAfagaggsgsa 
                 GGAUUCGCC 
                   
               
               
                 31.1 
                 41.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2165 
                 csuscuugGfaAfUfUfggauuc 
                 A- 
                 2614 
                 VPusGfsgcgAfauccaauU 
                 CCCUCUUGGAAUUG 
                 4865 
               
               
                 12230 
                 22824 
                   
                 gccaL96 
                 228244 
                   
                 fcCfaagagsgsg 
                 GAUUCGCCA 
                   
               
               
                 32.1 
                 43.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2166 
                 ususggaaUfuGfGfAfuucgcc 
                 A- 
                 2615 
                 VPusAfsaugGfcgaauccA 
                 UCUUGGAAUUGGAU 
                 4866 
               
               
                 12230 
                 22824 
                   
                 auuaL96 
                 228244 
                   
                 faUfuccaasgsa 
                 UCGCCAUUU 
                   
               
               
                 33.1 
                 45.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2167 
                 usgsgaauUfgGfAfUfucgcca 
                 A- 
                 2616 
                 VPusAfsaauGfgcgaaucC 
                 CUUGGAAUUGGAUU 
                 4867 
               
               
                 12230 
                 22824 
                   
                 uuuaL96 
                 228244 
                   
                 faAfuuccasasg 
                 CGCCAUUUU 
                   
               
               
                 34.1 
                 47.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2168 
                 gsgsaauuGfgAfUfUfcgccau 
                 A- 
                 2617 
                 VPusAfsaaaUfggcgaauC 
                 UUGGAAUUGGAUUC 
                 4868 
               
               
                 12230 
                 22824 
                   
                 uuuaL96 
                 228245 
                   
                 fcAfauuccsasa 
                 GCCAUUUUA 
                   
               
               
                 35.1 
                 49.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2169 
                 gsasauugGfaUfUfCfgccauu 
                 A- 
                 2618 
                 VPusUfsaaaAfuggcgaaU 
                 UGGAAUUGGAUUCG 
                 4869 
               
               
                 12230 
                 22824 
                   
                 uuaaL96 
                 228245 
                   
                 fcCfaauucscsa 
                 CCAUUUUAU 
                   
               
               
                 36.1 
                 51.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2170 
                 asasuuggAfuUfCfGfccauuu 
                 A- 
                 2619 
                 VPusAfsuaaAfauggcga 
                 GGAAUUGGAUUCGC 
                 4870 
               
               
                 12230 
                 22824 
                   
                 uauaL96 
                 228245 
                   
                 AfuCfcaauuscsc 
                 CAUUUUAUU 
                   
               
               
                 37.1 
                 53.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2171 
                 asusuggaUfuCfGfCfcauuuu 
                 A- 
                 2620 
                 VPusAfsauaAfaauggcg 
                 GAAUUGGAUUCGCC 
                 4871 
               
               
                 12230 
                 22824 
                   
                 auuaL96 
                 228245 
                   
                 AfaUfccaaususc 
                 AUUUUAUUU 
                   
               
               
                 38.1 
                 55.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2172 
                 ususggauUfcGfCfCfauuuua 
                 A- 
                 2621 
                 VPusAfsaauAfaaauggcG 
                 AAUUGGAUUCGCCA 
                 4872 
               
               
                 12230 
                 22824 
                   
                 uuuaL96 
                 228245 
                   
                 faAfuccaasusu 
                 UUUUAUUUU 
                   
               
               
                 39.1 
                 57.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2173 
                 usgsgauuCfgCfCfAfuuuuau 
                 A- 
                 2622 
                 VPusAfsaaaUfaaaauggC 
                 AUUGGAUUCGCCAU 
                 4873 
               
               
                 12230 
                 22824 
                   
                 uuuaL96 
                 228246 
                   
                 fgAfauccasasu 
                 UUUAUUUUU 
                   
               
               
                 40.1 
                 59.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2174 
                 gsgsauucGfcCfAfUfuuuauu 
                 A- 
                 2623 
                 VPusAfsaaaAfuaaaaugG 
                 UUGGAUUCGCCAUU 
                 4874 
               
               
                 12230 
                 22824 
                   
                 uuuaL96 
                 228246 
                   
                 fcGfaauccsasa 
                 UUAUUUUUC 
                   
               
               
                 41.1 
                 61.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2175 
                 gsasuucgCfcAfUfUfuuauuu 
                 A- 
                 2624 
                 VPusGfsaaaAfauaaaauG 
                 UGGAUUCGCCAUUU 
                 4875 
               
               
                 12230 
                 22824 
                   
                 uucaL96 
                 228246 
                   
                 fgCfgaaucscsa 
                 UAUUUUUCU 
                   
               
               
                 42.1 
                 63.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2176 
                 uscsgccaUfuUfUfAfuuuuuc 
                 A- 
                 2625 
                 VPusCfsaagAfaaaauaaA 
                 AUUCGCCAUUUUAU 
                 4876 
               
               
                 12230 
                 22824 
                   
                 uugaL96 
                 228246 
                   
                 faUfggcgasasu 
                 UUUUCUUGC 
                   
               
               
                 43.1 
                 65.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2177 
                 csgsccauUfuUfAfUfuuuucu 
                 A- 
                 2626 
                 VPusGfscaaGfaaaaauaA 
                 UUCGCCAUUUUAUU 
                 4877 
               
               
                 12230 
                 22824 
                   
                 ugcaL96 
                 228246 
                   
                 faAfuggcgsasa 
                 UUUCUUGCU 
                   
               
               
                 44.1 
                 67.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2178 
                 gscscauuUfuAfUfUfuuucuu 
                 A- 
                 2627 
                 VPusAfsgcaAfgaaaaauA 
                 UCGCCAUUUUAUUU 
                 4878 
               
               
                 12230 
                 22824 
                   
                 gcuaL96 
                 228247 
                   
                 faAfauggcsgsa 
                 UUCUUGCUG 
                   
               
               
                 45.1 
                 69.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2179 
                 cscsauuuUfaUfUfUfuucuug 
                 A- 
                 2628 
                 VPusCfsagcAfagaaaaaU 
                 CGCCAUUUUAUUUU 
                 4879 
               
               
                 12230 
                 22824 
                   
                 cugaL96 
                 228247 
                   
                 faAfaauggscsg 
                 UCUUGCUGC 
                   
               
               
                 46.1 
                 71.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2180 
                 csasuuuuAfuUfUfUfucuugc 
                 A- 
                 2629 
                 VPusGfscagCfaagaaaaA 
                 GCCAUUUUAUUUUU 
                 4880 
               
               
                 12230 
                 22824 
                   
                 ugcaL96 
                 228247 
                   
                 fuAfaaaugsgsc 
                 CUUGCUGCU 
                   
               
               
                 47.1 
                 73.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2181 
                 asusuuuaUfuUfUfUfcuugcu 
                 A- 
                 2630 
                 VPusAfsgcaGfcaagaaaA 
                 CCAUUUUAUUUUUC 
                 4881 
               
               
                 12230 
                 22824 
                   
                 gcuaL96 
                 228247 
                   
                 faUfaaaausgsg 
                 UUGCUGCUA 
                   
               
               
                 48.1 
                 75.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2182 
                 ususuuauUfuUfUfCfuugcu 
                 A- 
                 2631 
                 VPusUfsagcAfgcaagaaA 
                 CAUUUUAUUUUUCU 
                 4882 
               
               
                 12230 
                 22824 
                   
                 gcuaaL96 
                 228247 
                   
                 faAfuaaaasusg 
                 UGCUGCUAA 
                   
               
               
                 49.1 
                 77.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2183 
                 ususucuuGfcUfGfCfuaaauc 
                 A- 
                 2632 
                 VPusGfsgugAfuuuagca 
                 UUUUUCUUGCUGCU 
                 4883 
               
               
                 12230 
                 22824 
                   
                 accaL96 
                 228248 
                   
                 GfcAfagaaasasa 
                 AAAUCACCG 
                   
               
               
                 50.1 
                 79.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2184 
                 uscsaccgAfgCfCfCfggaaga 
                 A- 
                 2633 
                 VPusUfsaauCfuuccgggC 
                 AAUCACCGAGCCCG 
                 4884 
               
               
                 12230 
                 22824 
                   
                 uuaaL96 
                 228248 
                   
                 fuCfggugasusu 
                 GAAGAUUAG 
                   
               
               
                 51.1 
                 81.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2185 
                 gscsccggAfaGfAfUfuagaga 
                 A- 
                 2634 
                 VPusAfsacuCfucuaaucU 
                 GAGCCCGGAAGAUU 
                 4885 
               
               
                 12230 
                 22824 
                   
                 guuaL96 
                 228248 
                   
                 fuCfcgggcsusc 
                 AGAGAGUUU 
                   
               
               
                 52.1 
                 83.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2186 
                 cscscggaAfgAfUfUfagagag 
                 A- 
                 2635 
                 VPusAfsaacUfcucuaauC 
                 AGCCCGGAAGAUUA 
                 4886 
               
               
                 12230 
                 22824 
                   
                 uuuaL96 
                 228248 
                   
                 fuUfccgggscsu 
                 GAGAGUUUU 
                   
               
               
                 53.1 
                 85.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2187 
                 csgsgaagAfuUfAfGfagaguu 
                 A- 
                 2636 
                 VPusUfsaaaAfcucucuaA 
                 CCCGGAAGAUUAGA 
                 4887 
               
               
                 12230 
                 22824 
                   
                 uuaaL96 
                 228248 
                   
                 fuCfuuccgsgsg 
                 GAGUUUUAU 
                   
               
               
                 54.1 
                 87.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2188 
                 gsgsaagaUfuAfGfAfgaguuu 
                 A- 
                 2637 
                 VPusAfsuaaAfacucucuA 
                 CCGGAAGAUUAGAG 
                 4888 
               
               
                 12230 
                 22824 
                   
                 uauaL96 
                 228249 
                   
                 faUfcuuccsgsg 
                 AGUUUUAUU 
                   
               
               
                 55.1 
                 89.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2189 
                 gsasagauUfaGfAfGfaguuuu 
                 A- 
                 2638 
                 VPusAfsauaAfaacucucU 
                 CGGAAGAUUAGAGA 
                 4889 
               
               
                 12230 
                 22824 
                   
                 auuaL96 
                 228249 
                   
                 faAfucuucscsg 
                 GUUUUAUUU 
                   
               
               
                 56.1 
                 91.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2190 
                 asasgauuAfgAfGfAfguuuua 
                 A- 
                 2639 
                 VPusAfsaauAfaaacucuC 
                 GGAAGAUUAGAGA 
                 4890 
               
               
                 12230 
                 22824 
                   
                 uuuaL96 
                 228249 
                   
                 fuAfaucuuscsc 
                 GUUUUAUUUC 
                   
               
               
                 57.1 
                 93.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2191 
                 asgsauuaGfaGfAfGfuuuuau 
                 A- 
                 2640 
                 VPusGfsaaaUfaaaacucU 
                 GAAGAUUAGAGAG 
                 4891 
               
               
                 12230 
                 22824 
                   
                 uucaL96 
                 228249 
                   
                 fcUfaaucususc 
                 UUUUAUUUCU 
                   
               
               
                 58.1 
                 95.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2192 
                 asusuagaGfaGfUfUfuuauuu 
                 A- 
                 2641 
                 VPusCfsagaAfauaaaacU 
                 AGAUUAGAGAGUU 
                 4892 
               
               
                 12230 
                 22824 
                   
                 cugaL96 
                 228249 
                   
                 fcUfcuaauscsu 
                 UUAUUUCUGG 
                   
               
               
                 59.1 
                 97.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2193 
                 ususagagAfgUfUfUfuauuuc 
                 A- 
                 2642 
                 VPusCfscagAfaauaaaaC 
                 GAUUAGAGAGUUU 
                 4893 
               
               
                 12230 
                 22824 
                   
                 uggaL96 
                 228250 
                   
                 fuCfucuaasusc 
                 UAUUUCUGGG 
                   
               
               
                 60.1 
                 99.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2194 
                 usasgagaGfuUfUfUfauuucu 
                 A- 
                 2643 
                 VPusCfsccaGfaaauaaaA 
                 AUUAGAGAGUUUU 
                 4894 
               
               
                 12230 
                 22825 
                   
                 gggaL96 
                 228250 
                   
                 fcUfcucuasasu 
                 AUUUCUGGGA 
                   
               
               
                 61.1 
                 01.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2195 
                 asgsagagUfuUfUfAfuuucug 
                 A- 
                 2644 
                 VPusUfscccAfgaaauaaA 
                 UUAGAGAGUUUUA 
                 4895 
               
               
                 12230 
                 22825 
                   
                 ggaaL96 
                 228250 
                   
                 faCfucucusasa 
                 UUUCUGGGAU 
                   
               
               
                 62.1 
                 03.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2196 
                 gsasgaguUfuUfAfUfuucug 
                 A- 
                 2645 
                 VPusAfsuccCfagaaauaA 
                 UAGAGAGUUUUAU 
                 4896 
               
               
                 12230 
                 22825 
                   
                 ggauaL96 
                 228250 
                   
                 faAfcucucsusa 
                 UUCUGGGAUU 
                   
               
               
                 63.1 
                 05.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2197 
                 asgsaguuUfuAfUfUfucugg 
                 A- 
                 2646 
                 VPusAfsaucCfcagaaauA 
                 AGAGAGUUUUAUU 
                 4897 
               
               
                 12230 
                 22825 
                   
                 gauuaL96 
                 228250 
                   
                 faAfacucuscsu 
                 UCUGGGAUUC 
                   
               
               
                 64.1 
                 07.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2198 
                 gsasguuuUfaUfUfUfcuggga 
                 A- 
                 2647 
                 VPusGfsaauCfccagaaaU 
                 GAGAGUUUUAUUUC 
                 4898 
               
               
                 12230 
                 22825 
                   
                 uucaL96 
                 228251 
                   
                 faAfaacucsusc 
                 UGGGAUUCC 
                   
               
               
                 65.1 
                 09.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2199 
                 asgsuuuuAfuUfUfCfuggga 
                 A- 
                 2648 
                 VPusGfsgaaUfcccagaaA 
                 AGAGUUUUAUUUCU 
                 4899 
               
               
                 12230 
                 22825 
                   
                 uuccaL96 
                 228251 
                   
                 fuAfaaacuscsu 
                 GGGAUUCCU 
                   
               
               
                 66.1 
                 11.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2200 
                 gsusuuuaUfuUfCfUfgggau 
                 A- 
                 2649 
                 VPusAfsggaAfucccagaA 
                 GAGUUUUAUUUCUG 
                 4900 
               
               
                 12230 
                 22825 
                   
                 uccuaL96 
                 228251 
                   
                 faUfaaaacsusc 
                 GGAUUCCUG 
                   
               
               
                 67.1 
                 13.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2201 
                 ususuuauUfuCfUfGfggauuc 
                 A- 
                 2650 
                 VPusCfsaggAfaucccagA 
                 AGUUUUAUUUCUGG 
                 4901 
               
               
                 12230 
                 22825 
                   
                 cugaL96 
                 228251 
                   
                 faAfuaaaascsu 
                 GAUUCCUGU 
                   
               
               
                 68.1 
                 15.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2202 
                 ususuauuUfcUfGfGfgauucc 
                 A- 
                 2651 
                 VPusAfscagGfaaucccaG 
                 GUUUUAUUUCUGGG 
                 4902 
               
               
                 12230 
                 22825 
                   
                 uguaL96 
                 228251 
                   
                 faAfauaaasasc 
                 AUUCCUGUA 
                   
               
               
                 69.1 
                 17.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2203 
                 ususauuuCfuGfGfGfauuccu 
                 A- 
                 2652 
                 VPusUfsacaGfgaaucccA 
                 UUUUAUUUCUGGGA 
                 4903 
               
               
                 12230 
                 22825 
                   
                 guaaL96 
                 228252 
                   
                 fgAfaauaasasa 
                 UUCCUGUAG 
                   
               
               
                 70.1 
                 19.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2204 
                 usasuuucUfgGfGfAfuuccug 
                 A- 
                 2653 
                 VPusCfsuacAfggaauccC 
                 UUUAUUUCUGGGAU 
                 4904 
               
               
                 12230 
                 22825 
                   
                 uagaL96 
                 228252 
                   
                 faGfaaauasasa 
                 UCCUGUAGA 
                   
               
               
                 71.1 
                 21.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2205 
                 asusuucuGfgGfAfUfuccugu 
                 A- 
                 2654 
                 VPusUfscuaCfaggaaucC 
                 UUAUUUCUGGGAUU 
                 4905 
               
               
                 12230 
                 22825 
                   
                 agaaL96 
                 228252 
                   
                 fcAfgaaausasa 
                 CCUGUAGAC 
                   
               
               
                 72.1 
                 23.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2206 
                 ususucugGfgAfUfUfccugua 
                 A- 
                 2655 
                 VPusGfsucuAfcaggaauC 
                 UAUUUCUGGGAUUC 
                 4906 
               
               
                 12230 
                 22825 
                   
                 gacaL96 
                 228252 
                   
                 fcCfagaaasusa 
                 CUGUAGACA 
                   
               
               
                 73.1 
                 25.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2207 
                 uscsugggAfuUfCfCfuguaga 
                 A- 
                 2656 
                 VPusGfsuguCfuacagga 
                 UUUCUGGGAUUCCU 
                 4907 
               
               
                 12230 
                 22825 
                   
                 cacaL96 
                 228252 
                   
                 AfuCfccagasasa 
                 GUAGACACA 
                   
               
               
                 74.1 
                 27.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2208 
                 csusgggaUfuCfCfUfguagac 
                 A- 
                 2657 
                 VPusUfsgugUfcuacagg 
                 UUCUGGGAUUCCUG 
                 4908 
               
               
                 12230 
                 22825 
                   
                 acaaL96 
                 228253 
                   
                 AfaUfcccagsasa 
                 UAGACACAC 
                   
               
               
                 75.1 
                 29.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2209 
                 usgsggauUfcCfUfGfuagaca 
                 A- 
                 2658 
                 VPusGfsuguGfucuacag 
                 UCUGGGAUUCCUGU 
                 4909 
               
               
                 12230 
                 22825 
                   
                 cacaL96 
                 228253 
                   
                 GfaAfucccasgsa 
                 AGACACACC 
                   
               
               
                 76.1 
                 31.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2210 
                 gsgsgauuCfcUfGfUfagacac 
                 A- 
                 2659 
                 VPusGfsgugUfgucuaca 
                 CUGGGAUUCCUGUA 
                 4910 
               
               
                 12230 
                 22825 
                   
                 accaL96 
                 228253 
                   
                 GfgAfaucccsasg 
                 GACACACCC 
                   
               
               
                 77.1 
                 33.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2211 
                 ascsacacCfcAfCfCfcacauac 
                 A- 
                 2660 
                 VPusAfsuguAfugugggu 
                 AGACACACCCACCC 
                 4911 
               
               
                 12230 
                 22825 
                   
                 auaL96 
                 228253 
                   
                 GfgGfuguguscsu 
                 ACAUACAUA 
                   
               
               
                 78.1 
                 35.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2212 
                 ascsccacCfcAfCfAfuacauac 
                 A- 
                 2661 
                 VPusAfsuguAfuguaugu 
                 ACACCCACCCACAU 
                 4912 
               
               
                 12230 
                 22825 
                   
                 auaL96 
                 228253 
                   
                 GfgGfugggusgsu 
                 ACAUACAUU 
                   
               
               
                 79.1 
                 37.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2213 
                 cscscaccCfaCfAfUfacauaca 
                 A- 
                 2662 
                 VPusAfsaugUfauguaug 
                 CACCCACCCACAUA 
                 4913 
               
               
                 12230 
                 22825 
                   
                 uuaL96 
                 228254 
                   
                 UfgGfgugggsusg 
                 CAUACAUUU 
                   
               
               
                 80.1 
                 39.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2214 
                 cscsacccAfcAfUfAfcauaca 
                 A- 
                 2663 
                 VPusAfsaauGfuauguau 
                 ACCCACCCACAUAC 
                 4914 
               
               
                 12230 
                 22825 
                   
                 uuuaL96 
                 228254 
                   
                 GfuGfgguggsgsu 
                 AUACAUUUA 
                   
               
               
                 81.1 
                 41.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2215 
                 csascccaCfaUfAfCfauacauu 
                 A- 
                 2664 
                 VPusUfsaaaUfguaugua 
                 CCCACCCACAUACA 
                 4915 
               
               
                 12230 
                 22825 
                   
                 uaaL96 
                 228254 
                   
                 UfgUfgggugsgsg 
                 UACAUUUAU 
                   
               
               
                 82.1 
                 43.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2216 
                 cscsacauAfcAfUfAfcauuua 
                 A- 
                 2665 
                 VPusAfsuauAfaauguau 
                 ACCCACAUACAUAC 
                 4916 
               
               
                 12230 
                 22825 
                   
                 uauaL96 
                 228254 
                   
                 GfuAfuguggsgsu 
                 AUUUAUAUA 
                   
               
               
                 83.1 
                 45.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2217 
                 csascauaCfaUfAfCfauuuau 
                 A- 
                 2666 
                 VPusUfsauaUfaaauguaU 
                 CCCACAUACAUACA 
                 4917 
               
               
                 12230 
                 22825 
                   
                 auaaL96 
                 228254 
                   
                 fgUfaugugsgsg 
                 UUUAUAUAU 
                   
               
               
                 84.1 
                 47.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2218 
                 ususaaauUfaAfCfAfgugcua 
                 A- 
                 2667 
                 VPusCfsauuAfgcacugu 
                 UUUUAAAUUAACAG 
                 4918 
               
               
                 12230 
                 22825 
                   
                 augaL96 
                 228255 
                   
                 UfaAfuuuaasasa 
                 UGCUAAUGU 
                   
               
               
                 85.1 
                 49.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2219 
                 usasaauuAfaCfAfGfugcuaa 
                 A- 
                 2668 
                 VPusAfscauUfagcacugU 
                 UUUAAAUUAACAGU 
                 4919 
               
               
                 12230 
                 22825 
                   
                 uguaL96 
                 228255 
                   
                 fuAfauuuasasa 
                 GCUAAUGUU 
                   
               
               
                 86.1 
                 51.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2220 
                 asasauuaAfcAfGfUfgcuaau 
                 A- 
                 2669 
                 VPusAfsacaUfuagcacuG 
                 UUAAAUUAACAGUG 
                 4920 
               
               
                 12230 
                 22825 
                   
                 guuaL96 
                 228255 
                   
                 fuUfaauuusasa 
                 CUAAUGUUA 
                   
               
               
                 87.1 
                 53.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2221 
                 asasuuaaCfaGfUfGfcuaaug 
                 A- 
                 2670 
                 VPusUfsaacAfuuagcacU 
                 UAAAUUAACAGUGC 
                 4921 
               
               
                 12230 
                 22825 
                   
                 uuaaL96 
                 228255 
                   
                 fgUfuaauususa 
                 UAAUGUUAU 
                   
               
               
                 88.1 
                 55.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2222 
                 asusuaacAfgUfGfCfuaaugu 
                 A- 
                 2671 
                 VPusAfsuaaCfauuagcaC 
                 AAAUUAACAGUGCU 
                 4922 
               
               
                 12230 
                 22825 
                   
                 uauaL96 
                 228255 
                   
                 fuGfuuaaususu 
                 AAUGUUAUU 
                   
               
               
                 89.1 
                 57.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2223 
                 ususaacaGfuGfCfUfaauguu 
                 A- 
                 2672 
                 VPusAfsauaAfcauuagcA 
                 AAUUAACAGUGCUA 
                 4923 
               
               
                 12230 
                 22825 
                   
                 auuaL96 
                 228256 
                   
                 fcUfguuaasusu 
                 AUGUUAUUG 
                   
               
               
                 90.1 
                 59.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2224 
                 usasacagUfgCfUfAfauguua 
                 A- 
                 2673 
                 VPusCfsaauAfacauuagC 
                 AUUAACAGUGCUAA 
                 4924 
               
               
                 12230 
                 22825 
                   
                 uugaL96 
                 228256 
                   
                 faCfuguuasasu 
                 UGUUAUUGG 
                   
               
               
                 91.1 
                 61.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2225 
                 asascaguGfcUfAfAfuguuau 
                 A- 
                 2674 
                 VPusCfscaaUfaacauuaG 
                 UUAACAGUGCUAAU 
                 4925 
               
               
                 12230 
                 22825 
                   
                 uggaL96 
                 228256 
                   
                 fcAfcuguusasa 
                 GUUAUUGGU 
                   
               
               
                 92.1 
                 63.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2226 
                 ascsagugCfuAfAfUfguuauu 
                 A- 
                 2675 
                 VPusAfsccaAfuaacauuA 
                 UAACAGUGCUAAUG 
                 4926 
               
               
                 12230 
                 22825 
                   
                 gguaL96 
                 228256 
                   
                 fgCfacugususa 
                 UUAUUGGUG 
                   
               
               
                 93.1 
                 65.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2227 
                 csasgugcUfaAfUfGfuuauug 
                 A- 
                 2676 
                 VPusCfsaccAfauaacauU 
                 AACAGUGCUAAUGU 
                 4927 
               
               
                 12230 
                 22825 
                   
                 gugaL96 
                 228256 
                   
                 faGfcacugsusu 
                 UAUUGGUGU 
                   
               
               
                 94.1 
                 67.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2228 
                 gsusgcuaAfuGfUfUfauugg 
                 A- 
                 2677 
                 VPusGfsacaCfcaauaacA 
                 CAGUGCUAAUGUUA 
                 4928 
               
               
                 12230 
                 22825 
                   
                 ugucaL96 
                 228257 
                   
                 fuUfagcacsusg 
                 UUGGUGUCU 
                   
               
               
                 95.1 
                 69.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2229 
                 usgscuaaUfgUfUfAfuuggu 
                 A- 
                 2678 
                 VPusAfsgacAfccaauaaC 
                 AGUGCUAAUGUUAU 
                 4929 
               
               
                 12230 
                 22825 
                   
                 gucuaL96 
                 228257 
                   
                 faUfuagcascsu 
                 UGGUGUCUU 
                   
               
               
                 96.1 
                 71.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2230 
                 gscsuaauGfuUfAfUfuggug 
                 A- 
                 2679 
                 VPusAfsagaCfaccaauaA 
                 GUGCUAAUGUUAUU 
                 4930 
               
               
                 12230 
                 22825 
                   
                 ucuuaL96 
                 228257 
                   
                 fcAfuuagcsasc 
                 GGUGUCUUC 
                   
               
               
                 97.1 
                 73.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2231 
                 csusaaugUfuAfUfUfgguguc 
                 A- 
                 2680 
                 VPusGfsaagAfcaccaauA 
                 UGCUAAUGUUAUUG 
                 4931 
               
               
                 12230 
                 22825 
                   
                 uucaL96 
                 228257 
                   
                 faCfauuagscsa 
                 GUGUCUUCA 
                   
               
               
                 98.1 
                 75.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2232 
                 usasauguUfaUfUfGfgugucu 
                 A- 
                 2681 
                 VPusUfsgaaGfacaccaaU 
                 GCUAAUGUUAUUGG 
                 4932 
               
               
                 12230 
                 22825 
                   
                 ucaaL96 
                 228257 
                   
                 faAfcauuasgsc 
                 UGUCUUCAC 
                   
               
               
                 99.1 
                 77.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2233 
                 asasuguuAfuUfGfGfugucu 
                 A- 
                 2682 
                 VPusGfsugaAfgacaccaA 
                 CUAAUGUUAUUGGU 
                 4933 
               
               
                 12231 
                 22825 
                   
                 ucacaL96 
                 228258 
                   
                 fuAfacauusasg 
                 GUCUUCACU 
                   
               
               
                 00.1 
                 79.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2234 
                 asusguuaUfuGfGfUfgucuuc 
                 A- 
                 2683 
                 VPusAfsgugAfagacaccA 
                 UAAUGUUAUUGGU 
                 4934 
               
               
                 12231 
                 22825 
                   
                 acuaL96 
                 228258 
                   
                 faUfaacaususa 
                 GUCUUCACUG 
                   
               
               
                 01.1 
                 81.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2235 
                 usgsuuauUfgGfUfGfucuuca 
                 A- 
                 2684 
                 VPusCfsaguGfaagacacC 
                 AAUGUUAUUGGUG 
                 4935 
               
               
                 12231 
                 22825 
                   
                 cugaL96 
                 228258 
                   
                 faAfuaacasusu 
                 UCUUCACUGG 
                   
               
               
                 02.1 
                 83.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2236 
                 gsusuauuGfgUfGfUfcuucac 
                 A- 
                 2685 
                 VPusCfscagUfgaagacaC 
                 AUGUUAUUGGUGUC 
                 4936 
               
               
                 12231 
                 22825 
                   
                 uggaL96 
                 228258 
                   
                 fcAfauaacsasu 
                 UUCACUGGA 
                   
               
               
                 03.1 
                 85.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2237 
                 ususauugGfuGfUfCfuucacu 
                 A- 
                 2686 
                 VPusUfsccaGfugaagacA 
                 UGUUAUUGGUGUCU 
                 4937 
               
               
                 12231 
                 22825 
                   
                 ggaaL96 
                 228258 
                   
                 fcCfaauaascsa 
                 UCACUGGAU 
                   
               
               
                 04.1 
                 87.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2238 
                 usgsguguCfuUfCfAfcuggau 
                 A- 
                 2687 
                 VPusUfsacaUfccagugaA 
                 AUUGGUGUCUUCAC 
                 4938 
               
               
                 12231 
                 22825 
                   
                 guaaL96 
                 228259 
                   
                 fgAfcaccasasu 
                 UGGAUGUAU 
                   
               
               
                 05.1 
                 89.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2239 
                 usgsucuuCfaCfUfGfgaugua 
                 A- 
                 2688 
                 VPusAfsaauAfcauccagU 
                 GGUGUCUUCACUGG 
                 4939 
               
               
                 12231 
                 22825 
                   
                 uuuaL96 
                 228259 
                   
                 fgAfagacascsc 
                 AUGUAUUUG 
                   
               
               
                 06.1 
                 91.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2240 
                 csascuggAfuGfUfAfuuugac 
                 A- 
                 2689 
                 VPusGfscagUfcaaauacA 
                 UUCACUGGAUGUAU 
                 4940 
               
               
                 12231 
                 22825 
                   
                 ugcaL96 
                 228259 
                   
                 fuCfcagugsasa 
                 UUGACUGCU 
                   
               
               
                 07.1 
                 93.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2241 
                 ascsuggaUfgUfAfUfuugacu 
                 A- 
                 2690 
                 VPusAfsgcaGfucaaauaC 
                 UCACUGGAUGUAUU 
                 4941 
               
               
                 12231 
                 22825 
                   
                 gcuaL96 
                 228259 
                   
                 faUfccagusgsa 
                 UGACUGCUG 
                   
               
               
                 08.1 
                 95.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2242 
                 usgsgaugUfaUfUfUfgacugc 
                 A- 
                 2691 
                 VPusAfscagCfagucaaaU 
                 ACUGGAUGUAUUUG 
                 4942 
               
               
                 12231 
                 22825 
                   
                 uguaL96 
                 228259 
                   
                 faCfauccasgsu 
                 ACUGCUGUG 
                   
               
               
                 09.1 
                 97.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2243 
                 usasuuugAfcUfGfCfugugga 
                 A- 
                 2692 
                 VPusAfsaguCfcacagcaG 
                 UGUAUUUGACUGCU 
                 4943 
               
               
                 12231 
                 22825 
                   
                 cuuaL96 
                 228260 
                   
                 fuCfaaauascsa 
                 GUGGACUUG 
                   
               
               
                 10.1 
                 99.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2244 
                 ususugacUfgCfUfGfuggacu 
                 A- 
                 2693 
                 VPusUfscaaGfuccacagC 
                 UAUUUGACUGCUGU 
                 4944 
               
               
                 12231 
                 22826 
                   
                 ugaaL96 
                 228260 
                   
                 faGfucaaasusa 
                 GGACUUGAG 
                   
               
               
                 11.1 
                 01.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2245 
                 gscsugugGfaCfUfUfgaguug 
                 A- 
                 2694 
                 VPusUfscccAfacucaagU 
                 CUGCUGUGGACUUG 
                 4945 
               
               
                 12231 
                 22826 
                   
                 ggaaL96 
                 228260 
                   
                 fcCfacagcsasg 
                 AGUUGGGAG 
                   
               
               
                 12.1 
                 03.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2246 
                 uscsccacUfcAfGfAfuccuga 
                 A- 
                 2695 
                 VPusCfsuguCfaggaucu 
                 GUUCCCACUCAGAU 
                 4946 
               
               
                 12231 
                 22826 
                   
                 cagaL96 
                 228260 
                   
                 GfaGfugggasasc 
                 CCUGACAGG 
                   
               
               
                 13.1 
                 05.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2247 
                 cscscacuCfaGfAfUfccugac 
                 A- 
                 2696 
                 VPusCfscugUfcaggaucU 
                 UUCCCACUCAGAUC 
                 4947 
               
               
                 12231 
                 22826 
                   
                 aggaL96 
                 228260 
                   
                 fgAfgugggsasa 
                 CUGACAGGG 
                   
               
               
                 14.1 
                 07.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2248 
                 gsgsaggaGfaUfGfAfgagacu 
                 A- 
                 2697 
                 VPusCfsagaGfucucucaU 
                 GAGGAGGAGAUGA 
                 4948 
               
               
                 12231 
                 22826 
                   
                 cugaL96 
                 228261 
                   
                 fcUfccuccsusc 
                 GAGACUCUGG 
                   
               
               
                 15.1 
                 09.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2249 
                 gsasggagAfuGfAfGfagacuc 
                 A- 
                 2698 
                 VPusCfscagAfgucucucA 
                 AGGAGGAGAUGAG 
                 4949 
               
               
                 12231 
                 22826 
                   
                 uggaL96 
                 228261 
                   
                 fuCfuccucscsu 
                 AGACUCUGGC 
                   
               
               
                 16.1 
                 11.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2250 
                 gsgsagauGfaGfAfGfacucug 
                 A- 
                 2699 
                 VPusUfsgccAfgagucuc 
                 GAGGAGAUGAGAG 
                 4950 
               
               
                 12231 
                 22826 
                   
                 gcaaL96 
                 228261 
                   
                 UfcAfucuccsusc 
                 ACUCUGGCAU 
                   
               
               
                 17.1 
                 13.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2251 
                 gsasgacuCfuGfGfCfaugauc 
                 A- 
                 2700 
                 VPusAfsaagAfucaugccA 
                 GAGAGACUCUGGCA 
                 4951 
               
               
                 12231 
                 22826 
                   
                 uuuaL96 
                 228261 
                   
                 fgAfgucucsusc 
                 UGAUCUUUU 
                   
               
               
                 18.1 
                 15.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2252 
                 asgsacucUfgGfCfAfugaucu 
                 A- 
                 2701 
                 VPusAfsaaaGfaucaugcC 
                 AGAGACUCUGGCAU 
                 4952 
               
               
                 12231 
                 22826 
                   
                 uuuaL96 
                 228261 
                   
                 faGfagucuscsu 
                 GAUCUUUUU 
                   
               
               
                 19.1 
                 17.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2253 
                 ususuuggGfaAfCfAfccgaca 
                 A- 
                 2702 
                 VPusGfsuuuGfucggugu 
                 AGUUUUGGGAACAC 
                 4953 
               
               
                 12231 
                 22826 
                   
                 aacaL96 
                 228262 
                   
                 UfcCfcaaaascsu 
                 CGACAAACC 
                   
               
               
                 20.1 
                 19.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2254 
                 gsasgcuuCfaGfGfAfcauugc 
                 A- 
                 2703 
                 VPusAfscagCfaauguccU 
                 GGGAGCUUCAGGAC 
                 4954 
               
               
                 12231 
                 22826 
                   
                 uguaL96 
                 228262 
                   
                 fgAfagcucscsc 
                 AUUGCUGUG 
                   
               
               
                 21.1 
                 21.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2255 
                 gscsuucaGfgAfCfAfuugcug 
                 A- 
                 2704 
                 VPusGfscacAfgcaauguC 
                 GAGCUUCAGGACAU 
                 4955 
               
               
                 12231 
                 22826 
                   
                 ugcaL96 
                 228262 
                   
                 fcUfgaagcsusc 
                 UGCUGUGCU 
                   
               
               
                 22.1 
                 23.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2256 
                 csusucagGfaCfAfUfugcugu 
                 A- 
                 2705 
                 VPusAfsgcaCfagcaaugU 
                 AGCUUCAGGACAUU 
                 4956 
               
               
                 12231 
                 22826 
                   
                 gcuaL96 
                 228262 
                   
                 fcCfugaagscsu 
                 GCUGUGCUU 
                   
               
               
                 23.1 
                 25.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2257 
                 ususcaggAfcAfUfUfgcugug 
                 A- 
                 2706 
                 VPusAfsagcAfcagcaauG 
                 GCUUCAGGACAUUG 
                 4957 
               
               
                 12231 
                 22826 
                   
                 cuuaL96 
                 228262 
                   
                 fuCfcugaasgsc 
                 CUGUGCUUU 
                   
               
               
                 24.1 
                 27.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2258 
                 uscsaggaCfaUfUfGfcugugc 
                 A- 
                 2707 
                 VPusAfsaagCfacagcaaU 
                 CUUCAGGACAUUGC 
                 4958 
               
               
                 12231 
                 22826 
                   
                 uuuaL96 
                 228263 
                   
                 fgUfccugasasg 
                 UGUGCUUUG 
                   
               
               
                 25.1 
                 29.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2259 
                 csasggacAfuUfGfCfugugcu 
                 A- 
                 2708 
                 VPusCfsaaaGfcacagcaA 
                 UUCAGGACAUUGCU 
                 4959 
               
               
                 12231 
                 22826 
                   
                 uugaL96 
                 228263 
                   
                 fuGfuccugsasa 
                 GUGCUUUGG 
                   
               
               
                 26.1 
                 31.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2260 
                 csgscuuaCfuCfUfCfaccugc 
                 A- 
                 2709 
                 VPusGfsaagCfaggugag 
                 UUCGCUUACUCUCA 
                 4960 
               
               
                 12231 
                 22826 
                   
                 uucaL96 
                 228263 
                   
                 AfgUfaagcgsasa 
                 CCUGCUUCU 
                   
               
               
                 27.1 
                 33.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2261 
                 gscsuuacUfcUfCfAfccugcu 
                 A- 
                 2710 
                 VPusAfsgaaGfcagguga 
                 UCGCUUACUCUCAC 
                 4961 
               
               
                 12231 
                 22826 
                   
                 ucuaL96 
                 228263 
                   
                 GfaGfuaagcsgsa 
                 CUGCUUCUG 
                   
               
               
                 28.1 
                 35.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2262 
                 ususacucUfcAfCfCfugcuuc 
                 A- 
                 2711 
                 VPusUfscagAfagcaggu 
                 GCUUACUCUCACCU 
                 4962 
               
               
                 12231 
                 22826 
                   
                 ugaaL96 
                 228263 
                   
                 GfaGfaguaasgsc 
                 GCUUCUGAG 
                   
               
               
                 29.1 
                 37.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2263 
                 csuscucaCfcUfGfCfuucuga 
                 A- 
                 2712 
                 VPusAfsacuCfagaagcaG 
                 UACUCUCACCUGCU 
                 4963 
               
               
                 12231 
                 22826 
                   
                 guuaL96 
                 228264 
                   
                 fgUfgagagsusa 
                 UCUGAGUUG 
                   
               
               
                 30.1 
                 39.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2264 
                 uscsucacCfuGfCfUfucugag 
                 A- 
                 2713 
                 VPusCfsaacUfcagaagcA 
                 ACUCUCACCUGCUU 
                 4964 
               
               
                 12231 
                 22826 
                   
                 uugaL96 
                 228264 
                   
                 fgGfugagasgsu 
                 CUGAGUUGC 
                   
               
               
                 31.1 
                 41.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2265 
                 csuscaccUfgCfUfUfcugagu 
                 A- 
                 2714 
                 VPusGfscaaCfucagaagC 
                 CUCUCACCUGCUUC 
                 4965 
               
               
                 12231 
                 22826 
                   
                 ugcaL96 
                 228264 
                   
                 faGfgugagsasg 
                 UGAGUUGCC 
                   
               
               
                 32.1 
                 43.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2266 
                 uscsaccuGfcUfUfCfugaguu 
                 A- 
                 2715 
                 VPusGfsgcaAfcucagaaG 
                 UCUCACCUGCUUCU 
                 4966 
               
               
                 12231 
                 22826 
                   
                 gccaL96 
                 228264 
                   
                 fcAfggugasgsa 
                 GAGUUGCCC 
                   
               
               
                 33.1 
                 45.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2267 
                 csasccugCfuUfCfUfgaguug 
                 A- 
                 2716 
                 VPusGfsggcAfacucagaA 
                 CUCACCUGCUUCUG 
                 4967 
               
               
                 12231 
                 22826 
                   
                 cccaL96 
                 228264 
                   
                 fgCfaggugsasg 
                 AGUUGCCCA 
                   
               
               
                 34.1 
                 47.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2268 
                 ascscugcUfuCfUfGfaguugc 
                 A- 
                 2717 
                 VPusUfsgggCfaacucagA 
                 UCACCUGCUUCUGA 
                 4968 
               
               
                 12231 
                 22826 
                   
                 ccaaL96 
                 228265 
                   
                 faGfcaggusgsa 
                 GUUGCCCAG 
                   
               
               
                 35.1 
                 49.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2269 
                 cscsugcuUfcUfGfAfguugcc 
                 A- 
                 2718 
                 VPusCfsuggGfcaacucaG 
                 CACCUGCUUCUGAG 
                 4969 
               
               
                 12231 
                 22826 
                   
                 cagaL96 
                 228265 
                   
                 faAfgcaggsusg 
                 UUGCCCAGG 
                   
               
               
                 36.1 
                 51.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2270 
                 csgsgcgaAfgAfGfAfagagac 
                 A- 
                 2719 
                 VPusUfsgugUfcucuucu 
                 CCCGGCGAAGAGAA 
                 4970 
               
               
                 12231 
                 22826 
                   
                 acaaL96 
                 228265 
                   
                 CfuUfcgccgsgsg 
                 GAGACACAU 
                   
               
               
                 37.1 
                 53.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2271 
                 gsgscgaaGfaGfAfAfgagaca 
                 A- 
                 2720 
                 VPusAfsuguGfucucuuc 
                 CCGGCGAAGAGAAG 
                 4971 
               
               
                 12231 
                 22826 
                   
                 cauaL96 
                 228265 
                   
                 UfcUfucgccsgsg 
                 AGACACAUU 
                   
               
               
                 38.1 
                 55.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2272 
                 gscsgaagAfgAfAfGfagacac 
                 A- 
                 2721 
                 VPusAfsaugUfgucucuu 
                 CGGCGAAGAGAAGA 
                 4972 
               
               
                 12231 
                 22826 
                   
                 auuaL96 
                 228265 
                   
                 CfuCfuucgcscsg 
                 GACACAUUG 
                   
               
               
                 39.1 
                 57.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2273 
                 csgsaagaGfaAfGfAfgacaca 
                 A- 
                 2722 
                 VPusCfsaauGfugucucu 
                 GGCGAAGAGAAGAG 
                 4973 
               
               
                 12231 
                 22826 
                   
                 uugaL96 
                 228266 
                   
                 UfcUfcuucgscsc 
                 ACACAUUGU 
                   
               
               
                 40.1 
                 59.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2274 
                 gsasagagAfaGfAfGfacacau 
                 A- 
                 2723 
                 VPusAfscaaUfgugucuc 
                 GCGAAGAGAAGAGA 
                 4974 
               
               
                 12231 
                 22826 
                   
                 uguaL96 
                 228266 
                   
                 UfuCfucuucsgsc 
                 CACAUUGUU 
                   
               
               
                 41.1 
                 61.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2275 
                 asasgagaAfgAfGfAfcacauu 
                 A- 
                 2724 
                 VPusAfsacaAfugugucu 
                 CGAAGAGAAGAGAC 
                 4975 
               
               
                 12231 
                 22826 
                   
                 guuaL96 
                 228266 
                   
                 CfuUfcucuuscsg 
                 ACAUUGUUG 
                   
               
               
                 42.1 
                 63.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2276 
                 asgsagaaGfaGfAfCfacauug 
                 A- 
                 2725 
                 VPusCfsaacAfaugugucU 
                 GAAGAGAAGAGACA 
                 4976 
               
               
                 12231 
                 22826 
                   
                 uugaL96 
                 228266 
                   
                 fcUfucucususc 
                 CAUUGUUGG 
                   
               
               
                 43.1 
                 65.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2277 
                 gsasgaagAfgAfCfAfcauugu 
                 A- 
                 2726 
                 VPusCfscaaCfaauguguC 
                 AAGAGAAGAGACAC 
                 4977 
               
               
                 12231 
                 22826 
                   
                 uggaL96 
                 228266 
                   
                 fuCfuucucsusu 
                 AUUGUUGGA 
                   
               
               
                 44.1 
                 67.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2278 
                 asgsaagaGfaCfAfCfauuguu 
                 A- 
                 2727 
                 VPusUfsccaAfcaaugugU 
                 AGAGAAGAGACACA 
                 4978 
               
               
                 12231 
                 22826 
                   
                 ggaaL96 
                 228267 
                   
                 fcUfcuucuscsu 
                 UUGUUGGAA 
                   
               
               
                 45.1 
                 69.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2279 
                 gsasagagAfcAfCfAfuuguug 
                 A- 
                 2728 
                 VPusUfsuccAfacaauguG 
                 GAGAAGAGACACAU 
                 4979 
               
               
                 12231 
                 22826 
                   
                 gaaaL96 
                 228267 
                   
                 fuCfucuucsusc 
                 UGUUGGAAG 
                   
               
               
                 46.1 
                 71.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2280 
                 asasgagaCfaCfAfUfuguugg 
                 A- 
                 2729 
                 VPusCfsuucCfaacaaugU 
                 AGAAGAGACACAUU 
                 4980 
               
               
                 12231 
                 22826 
                   
                 aagaL96 
                 228267 
                   
                 fgUfcucuuscsu 
                 GUUGGAAGA 
                   
               
               
                 47.1 
                 73.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2281 
                 asgsagacAfcAfUfUfguugga 
                 A- 
                 2730 
                 VPusUfscuuCfcaacaauG 
                 GAAGAGACACAUUG 
                 4981 
               
               
                 12231 
                 22826 
                   
                 agaaL96 
                 228267 
                   
                 fuGfucucususc 
                 UUGGAAGAA 
                   
               
               
                 48.1 
                 75.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2282 
                 gsasgacaCfaUfUfGfuuggaa 
                 A- 
                 2731 
                 VPusUfsucuUfccaacaaU 
                 AAGAGACACAUUGU 
                 4982 
               
               
                 12231 
                 22826 
                   
                 gaaaL96 
                 228267 
                   
                 fgUfgucucsusu 
                 UGGAAGAAG 
                   
               
               
                 49.1 
                 77.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2283 
                 asgsacacAfuUfGfUfuggaag 
                 A- 
                 2732 
                 VPusCfsuucUfuccaacaA 
                 AGAGACACAUUGUU 
                 4983 
               
               
                 12231 
                 22826 
                   
                 aagaL96 
                 228268 
                   
                 fuGfugucuscsu 
                 GGAAGAAGC 
                   
               
               
                 50.1 
                 79.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2284 
                 gsascacaUfuGfUfUfggaaga 
                 A- 
                 2733 
                 VPusGfscuuCfuuccaacA 
                 GAGACACAUUGUUG 
                 4984 
               
               
                 12231 
                 22826 
                   
                 agcaL96 
                 228268 
                   
                 faUfgugucsusc 
                 GAAGAAGCA 
                   
               
               
                 51.1 
                 81.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2285 
                 ascsacauUfgUfUfGfgaagaa 
                 A- 
                 2734 
                 VPusUfsgcuUfcuuccaaC 
                 AGACACAUUGUUGG 
                 4985 
               
               
                 12231 
                 22826 
                   
                 gcaaL96 
                 228268 
                   
                 faAfugugusesu 
                 AAGAAGCAG 
                   
               
               
                 52.1 
                 83.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2286 
                 csascauuGfuUfGfGfaagaag 
                 A- 
                 2735 
                 VPusCfsugcUfucuuccaA 
                 GACACAUUGUUGGA 
                 4986 
               
               
                 12231 
                 22826 
                   
                 cagaL96 
                 228268 
                   
                 fcAfaugugsusc 
                 AGAAGCAGC 
                   
               
               
                 53.1 
                 85.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2287 
                 usasugucCfuCfAfCfaccauu 
                 A- 
                 2736 
                 VPusUfsucaAfuggugug 
                 CCUAUGUCCUCACA 
                 4987 
               
               
                 12231 
                 22826 
                   
                 gaaaL96 
                 228268 
                   
                 AfgGfacauasgsg 
                 CCAUUGAAA 
                   
               
               
                 54.1 
                 87.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2288 
                 uscscucaCfaCfCfAfuugaaa 
                 A- 
                 2737 
                 VPusUfsgguUfucaaugg 
                 UGUCCUCACACCAU 
                 4988 
               
               
                 12231 
                 22826 
                   
                 ccaaL96 
                 228269 
                   
                 UfgUfgaggascsa 
                 UGAAACCAC 
                   
               
               
                 55.1 
                 89.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2289 
                 cscsucacAfcCfAfUfugaaac 
                 A- 
                 2738 
                 VPusGfsuggUfuucaaug 
                 GUCCUCACACCAUU 
                 4989 
               
               
                 12231 
                 22826 
                   
                 cacaL96 
                 228269 
                   
                 GfuGfugaggsasc 
                 GAAACCACU 
                   
               
               
                 56.1 
                 91.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2290 
                 csuscacaCfcAfUfUfgaaacca 
                 A- 
                 2739 
                 VPusAfsgugGfuuucaau 
                 UCCUCACACCAUUG 
                 4990 
               
               
                 12231 
                 22826 
                   
                 cuaL96 
                 228269 
                   
                 GfgUfgugagsgsa 
                 AAACCACUA 
                   
               
               
                 57.1 
                 93.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2291 
                 uscsacacCfaUfUfGfaaaccac 
                 A- 
                 2740 
                 VPusUfsaguGfguuucaa 
                 CCUCACACCAUUGA 
                 4991 
               
               
                 12231 
                 22826 
                   
                 uaaL96 
                 228269 
                   
                 UfgGfugugasgsg 
                 AACCACUAG 
                   
               
               
                 58.1 
                 95.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2292 
                 csascaccAfuUfGfAfaaccac 
                 A- 
                 2741 
                 VPusCfsuagUfgguuuca 
                 CUCACACCAUUGAA 
                 4992 
               
               
                 12231 
                 22826 
                   
                 uagaL96 
                 228269 
                   
                 AfuGfgugugsasg 
                 ACCACUAGU 
                   
               
               
                 59.1 
                 97.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2293 
                 cscsauugAfaAfCfCfacuagu 
                 A- 
                 2742 
                 VPusAfsgaaCfuaguggu 
                 CACCAUUGAAACCA 
                 4993 
               
               
                 12231 
                 22826 
                   
                 ucuaL96 
                 228270 
                   
                 UfuCfaauggsusg 
                 CUAGUUCUG 
                   
               
               
                 60.1 
                 99.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2294 
                 csasuugaAfaCfCfAfcuaguu 
                 A- 
                 2743 
                 VPusCfsagaAfcuagugg 
                 ACCAUUGAAACCAC 
                 4994 
               
               
                 12231 
                 22827 
                   
                 cugaL96 
                 228270 
                   
                 UfuUfcaaugsgsu 
                 UAGUUCUGU 
                   
               
               
                 61.1 
                 01.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2295 
                 asusugaaAfcCfAfCfuaguuc 
                 A- 
                 2744 
                 VPusAfscagAfacuagug 
                 CCAUUGAAACCACU 
                 4995 
               
               
                 12231 
                 22827 
                   
                 uguaL96 
                 228270 
                   
                 GfuUfucaausgsg 
                 AGUUCUGUC 
                   
               
               
                 62.1 
                 03.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2296 
                 ususgaaaCfAfCfUfaguucu 
                 A- 
                 2745 
                 VPusGfsacaGfaacuaguG 
                 CAUUGAAACCACUA 
                 4996 
               
               
                 12231 
                 22827 
                   
                 gucaL96 
                 228270 
                   
                 fgUfuucaasusg 
                 GUUCUGUCC 
                   
               
               
                 63.1 
                 05.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2297 
                 usgsaaacCfaCfUfAfguucug 
                 A- 
                 2746 
                 VPusGfsgacAfgaacuagU 
                 AUUGAAACCACUAG 
                 4997 
               
               
                 12231 
                 22827 
                   
                 uccaL96 
                 228270 
                   
                 fgGfuuucasasu 
                 UUCUGUCCC 
                   
               
               
                 64.1 
                 07.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2298 
                 gsasccugGfuUfGfUfgugug 
                 A- 
                 2747 
                 VPusCfsacaCfacacacaAf 
                 GAGACCUGGUUGUG 
                 4998 
               
               
                 12231 
                 22827 
                   
                 ugugaL96 
                 228271 
                   
                 cCfaggucsusc 
                 UGUGUGUGA 
                   
               
               
                 65.1 
                 09.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2299 
                 ascscuggUfuGfUfGfugugu 
                 A- 
                 2748 
                 VPusUfscacAfcacacacA 
                 AGACCUGGUUGUGU 
                 4999 
               
               
                 12231 
                 22827 
                   
                 gugaaL96 
                 228271 
                   
                 faCfcagguscsu 
                 GUGUGUGAG 
                   
               
               
                 66.1 
                 11.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2300 
                 cscsugguUfgUfGfUfgugug 
                 A- 
                 2749 
                 VPusCfsucaCfacacacaCf 
                 GACCUGGUUGUGUG 
                 5000 
               
               
                 12231 
                 22827 
                   
                 ugagaL96 
                 228271 
                   
                 aAfccaggsusc 
                 UGUGUGAGU 
                   
               
               
                 67.1 
                 13.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2301 
                 csusgguuGfuGfUfGfugugu 
                 A- 
                 2750 
                 VPusAfscucAfcacacacA 
                 ACCUGGUUGUGUGU 
                 5001 
               
               
                 12231 
                 22827 
                   
                 gaguaL96 
                 228271 
                   
                 fcAfaccagsgsu 
                 GUGUGAGUG 
                   
               
               
                 68.1 
                 15.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2302 
                 usgsguugUfgUfGfUfgugug 
                 A- 
                 2751 
                 VPusCfsacuCfacacacaCf 
                 CCUGGUUGUGUGUG 
                 5002 
               
               
                 12231 
                 22827 
                   
                 agugaL96 
                 228271 
                   
                 aCfaaccasgsg 
                 UGUGAGUGG 
                   
               
               
                 69.1 
                 17.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2303 
                 gsgsuuguGfuGfUfGfuguga 
                 A- 
                 2752 
                 VPusCfscacUfcacacacA 
                 CUGGUUGUGUGUGU 
                 1914 
               
               
                 12231 
                 22827 
                   
                 guggaL96 
                 228272 
                   
                 fcAfcaaccsasg 
                 GUGAGUGGU 
                   
               
               
                 70.1 
                 19.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2304 
                 gsusguguGfuGfUfGfagugg 
                 A- 
                 2753 
                 VPusUfscaaCfcacucacA 
                 UUGUGUGUGUGUG 
                 1915 
               
               
                 12231 
                 22827 
                   
                 uugaaL96 
                 228272 
                   
                 fcAfcacacsasa 
                 AGUGGUUGAC 
                   
               
               
                 71.1 
                 21.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2305 
                 usgsugugUfgUfGfAfguggu 
                 A- 
                 2754 
                 VPusGfsucaAfccacucaC 
                 UGUGUGUGUGUGA 
                 1916 
               
               
                 12231 
                 22827 
                   
                 ugacaL96 
                 228272 
                   
                 faCfacacascsa 
                 GUGGUUGACC 
                   
               
               
                 72.1 
                 23.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2306 
                 usgsugugUfgAfGfUfgguug 
                 A- 
                 2755 
                 VPusAfsgguCfaaccacuC 
                 UGUGUGUGUGAGU 
                 1917 
               
               
                 12231 
                 22827 
                   
                 accuaL96 
                 228272 
                   
                 faCfacacascsa 
                 GGUUGACCUU 
                   
               
               
                 73.1 
                 25.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2307 
                 usgsugugAfgUfGfGfuugac 
                 A- 
                 2756 
                 VPusGfsaagGfucaaccaC 
                 UGUGUGUGAGUGG 
                 1918 
               
               
                 12231 
                 22827 
                   
                 cuucaL96 
                 228272 
                   
                 fuCfacacascsa 
                 UUGACCUUCC 
                   
               
               
                 74.1 
                 27.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2308 
                 gsusgugaGfuGfGfUfugaccu 
                 A- 
                 2757 
                 VPusGfsgaaGfgucaaccA 
                 GUGUGUGAGUGGU 
                 1919 
               
               
                 12231 
                 22827 
                   
                 uccaL96 
                 228273 
                   
                 fcUfcacacsasc 
                 UGACCUUCCU 
                   
               
               
                 75.1 
                 29.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2309 
                 usgsugagUfgGfUfUfgaccuu 
                 A- 
                 2758 
                 VPusAfsggaAfggucaacC 
                 UGUGUGAGUGGUU 
                 1920 
               
               
                 12231 
                 22827 
                   
                 ccuaL96 
                 228273 
                   
                 faCfucacascsa 
                 GACCUUCCUC 
                   
               
               
                 76.1 
                 31.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2310 
                 usgsagugGfuUfGfAfccuucc 
                 A- 
                 2759 
                 VPusGfsgagGfaagguca 
                 UGUGAGUGGUUGAC 
                 1921 
               
               
                 12231 
                 22827 
                   
                 uccaL96 
                 228273 
                   
                 AfcCfacucascsa 
                 CUUCCUCCA 
                   
               
               
                 77.1 
                 33.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2311 
                 gsusgguuGfaCfCfUfuccucc 
                 A- 
                 2760 
                 VPusGfsaugGfaggaagg 
                 GAGUGGUUGACCUU 
                 1922 
               
               
                 12231 
                 22827 
                   
                 aucaL96 
                 228273 
                   
                 UfcAfaccacsusc 
                 CCUCCAUCC 
                   
               
               
                 78.1 
                 35.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2312 
                 ususguggAfgGfCfAfgagaaa 
                 A- 
                 2761 
                 VPusUfscuuUfucucugc 
                 CAUUGUGGAGGCAG 
                 1923 
               
               
                 12231 
                 22827 
                   
                 agaaL96 
                 228273 
                   
                 CfuCfcacaasusg 
                 AGAAAAGAG 
                   
               
               
                 79.1 
                 37.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2313 
                 usgsuggaGfgCfAfGfagaaaa 
                 A- 
                 2762 
                 VPusCfsucuUfuucucug 
                 AUUGUGGAGGCAGA 
                 1924 
               
               
                 12231 
                 22827 
                   
                 gagaL96 
                 228274 
                   
                 CfcUfccacasasu 
                 GAAAAGAGA 
                   
               
               
                 80.1 
                 39.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2314 
                 gsusggagGfcAfGfAfgaaaag 
                 A- 
                 2763 
                 VPusUfscucUfuuucucu 
                 UUGUGGAGGCAGAG 
                 1925 
               
               
                 12231 
                 22827 
                   
                 agaaL96 
                 228274 
                   
                 GfcCfuccacsasa 
                 AAAAGAGAA 
                   
               
               
                 81.1 
                 41.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2315 
                 usgsgaggCfaGfAfGfaaaaga 
                 A- 
                 2764 
                 VPusUfsucuCfuuuucuc 
                 UGUGGAGGCAGAGA 
                 1926 
               
               
                 12231 
                 22827 
                   
                 gaaaL96 
                 228274 
                   
                 UfgCfcuccascsa 
                 AAAGAGAAA 
                   
               
               
                 82.1 
                 43.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2316 
                 gsgsaggcAfgAfGfAfaaagag 
                 A- 
                 2765 
                 VPusUfsuucUfcuuuucu 
                 GUGGAGGCAGAGAA 
                 1927 
               
               
                 12231 
                 22827 
                   
                 aaaaL96 
                 228274 
                   
                 CfuGfccuccsasc 
                 AAGAGAAAG 
                   
               
               
                 83.1 
                 45.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2317 
                 gsasggcaGfaGfAfAfaagaga 
                 A- 
                 2766 
                 VPusCfsuuuCfucuuuuc 
                 UGGAGGCAGAGAAA 
                 1928 
               
               
                 12231 
                 22827 
                   
                 aagaL96 
                 228274 
                   
                 UfcUfgccucscsa 
                 AGAGAAAGU 
                   
               
               
                 84.1 
                 47.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2318 
                 asgsgcagAfgAfAfAfagagaa 
                 A- 
                 2767 
                 VPusAfscuuUfcucuuuu 
                 GGAGGCAGAGAAAA 
                 1929 
               
               
                 12231 
                 22827 
                   
                 aguaL96 
                 228275 
                   
                 CfuCfugccuscsc 
                 GAGAAAGUG 
                   
               
               
                 85.1 
                 49.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2319 
                 gsgscagaGfaAfAfAfgagaaa 
                 A- 
                 2768 
                 VPusCfsacuUfucucuuu 
                 GAGGCAGAGAAAAG 
                 1930 
               
               
                 12231 
                 22827 
                   
                 gugaL96 
                 228275 
                   
                 UfcUfcugccsusc 
                 AGAAAGUGU 
                   
               
               
                 86.1 
                 51.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2320 
                 gscsagagAfaAfAfGfagaaag 
                 A- 
                 2769 
                 VPusAfscacUfuucucuu 
                 AGGCAGAGAAAAGA 
                 1931 
               
               
                 12231 
                 22827 
                   
                 uguaL96 
                 228275 
                   
                 UfuCfucugcscsu 
                 GAAAGUGUU 
                   
               
               
                 87.1 
                 53.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2321 
                 csasgagaAfaAfGfAfgaaagu 
                 A- 
                 2770 
                 VPusAfsacaCfuuucucuU 
                 GGCAGAGAAAAGAG 
                 1932 
               
               
                 12231 
                 22827 
                   
                 guuaL96 
                 228275 
                   
                 fuUfcucugscsc 
                 AAAGUGUUU 
                   
               
               
                 88.1 
                 55.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2322 
                 asgsagaaAfaGfAfGfaaagug 
                 A- 
                 2771 
                 VPusAfsaacAfcuuucucU 
                 GCAGAGAAAAGAGA 
                 1933 
               
               
                 12231 
                 22827 
                   
                 uuuaL96 
                 228275 
                   
                 fuUfucucusgsc 
                 AAGUGUUUU 
                   
               
               
                 89.1 
                 57.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2323 
                 gsasgaaaAfgAfGfAfaagugu 
                 A- 
                 2772 
                 VPusAfsaaaCfacuuucuC 
                 CAGAGAAAAGAGAA 
                 1934 
               
               
                 12231 
                 22827 
                   
                 uuuaL96 
                 228276 
                   
                 fuUfuucucsusg 
                 AGUGUUUUA 
                   
               
               
                 90.1 
                 59.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2324 
                 asgsaaaaGfaGfAfAfaguguu 
                 A- 
                 2773 
                 VPusUfsaaaAfcacuuucU 
                 AGAGAAAAGAGAA 
                 1935 
               
               
                 12231 
                 22827 
                   
                 uuaaL96 
                 228276 
                   
                 fcUfuuucuscsu 
                 AGUGUUUUAU 
                   
               
               
                 91.1 
                 61.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2325 
                 gsasaaagAfgAfAfAfguguuu 
                 A- 
                 2774 
                 VPusAfsuaaAfacacuuuC 
                 GAGAAAAGAGAAA 
                 1936 
               
               
                 12231 
                 22827 
                   
                 uauaL96 
                 228276 
                   
                 fuCfuuuucsusc 
                 GUGUUUUAUA 
                   
               
               
                 92.1 
                 63.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2326 
                 asasaagaGfaAfAfGfuguuuu 
                 A- 
                 2775 
                 VPusUfsauaAfaacacuuU 
                 AGAAAAGAGAAAG 
                 1937 
               
               
                 12231 
                 22827 
                   
                 auaaL96 
                 228276 
                   
                 fcUfcuuuuscsu 
                 UGUUUUAUAU 
                   
               
               
                 93.1 
                 65.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2327 
                 asasagagAfaAfGfUfguuuua 
                 A- 
                 2776 
                 VPusAfsuauAfaaacacuU 
                 GAAAAGAGAAAGU 
                 1938 
               
               
                 12231 
                 22827 
                   
                 uauaL96 
                 228276 
                   
                 fuCfucuuususc 
                 GUUUUAUAUA 
                   
               
               
                 94.1 
                 67.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2328 
                 asasgagaAfaGfUfGfuuuuau 
                 A- 
                 2777 
                 VPusUfsauaUfaaaacacU 
                 AAAAGAGAAAGUG 
                 1939 
               
               
                 12231 
                 22827 
                   
                 auaaL96 
                 228277 
                   
                 fuUfcucuususu 
                 UUUUAUAUAC 
                   
               
               
                 95.1 
                 69.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2329 
                 asgsagaaAfgUfGfUfuuuaua 
                 A- 
                 2778 
                 VPusGfsuauAfuaaaacaC 
                 AAAGAGAAAGUGU 
                 1940 
               
               
                 12231 
                 22827 
                   
                 uacaL96 
                 228277 
                   
                 fuUfucucususu 
                 UUUAUAUACG 
                   
               
               
                 96.1 
                 71.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2330 
                 gsasgaaaGfuGfUfUfuuauau 
                 A- 
                 2779 
                 VPusCfsguaUfauaaaacA 
                 AAGAGAAAGUGUU 
                 1941 
               
               
                 12231 
                 22827 
                   
                 acgaL96 
                 228277 
                   
                 fcUfuucucsusu 
                 UUAUAUACGG 
                   
               
               
                 97.1 
                 73.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2331 
                 asgsaaagUfgUfUfUfuauaua 
                 A- 
                 2780 
                 VPusCfscguAfuauaaaaC 
                 AGAGAAAGUGUUU 
                 1942 
               
               
                 12231 
                 22827 
                   
                 cggaL96 
                 228277 
                   
                 faCfuuucuscsu 
                 UAUAUACGGU 
                   
               
               
                 98.1 
                 75.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2332 
                 asasagugUfuUfUfAfuauacg 
                 A- 
                 2781 
                 VPusUfsaccGfuauauaaA 
                 AGAAAGUGUUUUA 
                 1943 
               
               
                 12231 
                 22827 
                   
                 guaaL96 
                 228277 
                   
                 faCfacuuuscsu 
                 UAUACGGUAC 
                   
               
               
                 99.1 
                 77.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2333 
                 asasguguUfuUfAfUfauacgg 
                 A- 
                 2782 
                 VPusGfsuacCfguauauaA 
                 GAAAGUGUUUUAU 
                 1944 
               
               
                 12232 
                 22827 
                   
                 uacaL96 
                 228278 
                   
                 faAfcacuususc 
                 AUACGGUACU 
                   
               
               
                 00.1 
                 79.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2334 
                 asgsuguuUfuAfUfAfuacgg 
                 A- 
                 2783 
                 VPusAfsguaCfcguauau 
                 AAAGUGUUUUAUA 
                 1945 
               
               
                 12232 
                 22827 
                   
                 uacuaL96 
                 228278 
                   
                 AfaAfacacususu 
                 UACGGUACUU 
                   
               
               
                 01.1 
                 81.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2335 
                 gsusguuuUfaUfAfUfacggua 
                 A- 
                 2784 
                 VPusAfsaguAfccguaua 
                 AAGUGUUUUAUAU 
                 1946 
               
               
                 12232 
                 22827 
                   
                 cuuaL96 
                 228278 
                   
                 UfaAfaacacsusu 
                 ACGGUACUUA 
                   
               
               
                 02.1 
                 83.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2336 
                 usgsuuuuAfuAfUfAfcggua 
                 A- 
                 2785 
                 VPusUfsaagUfaccguauA 
                 AGUGUUUUAUAUAC 
                 1947 
               
               
                 12232 
                 22827 
                   
                 cuuaaL96 
                 228278 
                   
                 fuAfaaacascsu 
                 GGUACUUAU 
                   
               
               
                 03.1 
                 85.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2337 
                 gsusuuuaUfaUfAfCfgguacu 
                 A- 
                 2786 
                 VPusAfsuaaGfuaccguaU 
                 GUGUUUUAUAUACG 
                 1948 
               
               
                 12232 
                 22827 
                   
                 uauaL96 
                 228278 
                   
                 faUfaaaacsasc 
                 GUACUUAUU 
                   
               
               
                 04.1 
                 87.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2338 
                 ususuuauAfuAfCfGfguacuu 
                 A- 
                 2787 
                 VPusAfsauaAfguaccgu 
                 UGUUUUAUAUACGG 
                 1949 
               
               
                 12232 
                 22827 
                   
                 auuaL96 
                 228279 
                   
                 AfuAfuaaaascsa 
                 UACUUAUUU 
                   
               
               
                 05.1 
                 89.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2339 
                 ususuauaUfaCfGfGfuacuua 
                 A- 
                 2788 
                 VPusAfsaauAfaguaccgU 
                 GUUUUAUAUACGGU 
                 1950 
               
               
                 12232 
                 22827 
                   
                 uuuaL96 
                 228279 
                   
                 faUfauaaasasc 
                 ACUUAUUUA 
                   
               
               
                 06.1 
                 91.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2340 
                 ususauauAfcGfGfUfacuuau 
                 A- 
                 2789 
                 VPusUfsaaaUfaaguaccG 
                 UUUUAUAUACGGUA 
                 5040 
               
               
                 12232 
                 22827 
                   
                 uuaaL96 
                 228279 
                   
                 fuAfuauaasasa 
                 CUUAUUUAA 
                   
               
               
                 07.1 
                 93.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2341 
                 usasuauaCfgGfUfAfcuuauu 
                 A- 
                 2790 
                 VPusUfsuaaAfuaaguacC 
                 UUUAUAUACGGUAC 
                 5041 
               
               
                 12232 
                 22827 
                   
                 uaaaL96 
                 228279 
                   
                 fgUfauauasasa 
                 UUAUUUAAU 
                   
               
               
                 08.1 
                 95.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2342 
                 gsusacuuAfuUfUfAfauaucc 
                 A- 
                 2791 
                 VPusAfsaggGfauauuaa 
                 CGGUACUUAUUUAA 
                 5042 
               
               
                 12232 
                 22827 
                   
                 cuuaL96 
                 228279 
                   
                 AfuAfaguacscsg 
                 UAUCCCUUU 
                   
               
               
                 09.1 
                 97.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2343 
                 usascuuaUfuUfAfAfuauccc 
                 A- 
                 2792 
                 VPusAfsaagGfgauauua 
                 GGUACUUAUUUAAU 
                 5043 
               
               
                 12232 
                 22827 
                   
                 uuuaL96 
                 228280 
                   
                 AfaUfaaguascsc 
                 AUCCCUUUU 
                   
               
               
                 10.1 
                 99.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2344 
                 ususaugaGfaUfGfUfaucuuu 
                 A- 
                 2793 
                 VPusGfscaaAfagauacaU 
                 AUUUAUGAGAUGU 
                 5044 
               
               
                 12232 
                 22828 
                   
                 ugcaL96 
                 228280 
                   
                 fcUfcauaasasu 
                 AUCUUUUGCU 
                   
               
               
                 11.1 
                 01.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2345 
                 usasugagAfuGfUfAfucuuu 
                 A- 
                 2794 
                 VPusAfsgcaAfaagauacA 
                 UUUAUGAGAUGUA 
                 5045 
               
               
                 12232 
                 22828 
                   
                 ugcuaL96 
                 228280 
                   
                 fuCfucauasasa 
                 UCUUUUGCUC 
                   
               
               
                 12.1 
                 03.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2346 
                 asusgagaUfgUfAfUfcuuuug 
                 A- 
                 2795 
                 VPusGfsagcAfaaagauaC 
                 UUAUGAGAUGUAUC 
                 5046 
               
               
                 12232 
                 22828 
                   
                 cucaL96 
                 228280 
                   
                 faUfcucausasa 
                 UUUUGCUCU 
                   
               
               
                 13.1 
                 05.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2347 
                 usgsagauGfuAfUfCfuuuugc 
                 A- 
                 2796 
                 VPusAfsgagCfaaaagauA 
                 UAUGAGAUGUAUCU 
                 5047 
               
               
                 12232 
                 22828 
                   
                 ucuaL96 
                 228280 
                   
                 fcAfucucasusa 
                 UUUGCUCUC 
                   
               
               
                 14.1 
                 07.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2348 
                 gsasgaugUfaUfCfUfuuugcu 
                 A- 
                 2797 
                 VPusGfsagaGfcaaaagaU 
                 AUGAGAUGUAUCUU 
                 5048 
               
               
                 12232 
                 22828 
                   
                 cucaL96 
                 228281 
                   
                 faCfaucucsasu 
                 UUGCUCUCU 
                   
               
               
                 15.1 
                 09.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2349 
                 asgsauguAfuCfUfUfuugcuc 
                 A- 
                 2798 
                 VPusAfsgagAfgcaaaagA 
                 UGAGAUGUAUCUUU 
                 5049 
               
               
                 12232 
                 22828 
                   
                 ucuaL96 
                 228281 
                   
                 fuAfcaucuscsa 
                 UGCUCUCUC 
                   
               
               
                 16.1 
                 11.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2350 
                 gsasuguaUfcUfUfUfugcucu 
                 A- 
                 2799 
                 VPusGfsagaGfagcaaaaG 
                 GAGAUGUAUCUUUU 
                 5050 
               
               
                 12232 
                 22828 
                   
                 cucaL96 
                 228281 
                   
                 faUfacaucsusc 
                 GCUCUCUCU 
                   
               
               
                 17.1 
                 13.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2351 
                 asusguauCfuUfUfUfgcucuc 
                 A- 
                 2800 
                 VPusAfsgagAfgagcaaaA 
                 AGAUGUAUCUUUUG 
                 5051 
               
               
                 12232 
                 22828 
                   
                 ucuaL96 
                 228281 
                   
                 fgAfuacauscsu 
                 CUCUCUCUU 
                   
               
               
                 18.1 
                 15.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2352 
                 gscsucucUfcUfUfGfcucucu 
                 A- 
                 2801 
                 VPusAfsuaaGfagagcaaG 
                 UUGCUCUCUCUUGC 
                 5052 
               
               
                 12232 
                 22828 
                   
                 uauaL96 
                 228281 
                   
                 faGfagagcsasa 
                 UCUCUUAUU 
                   
               
               
                 19.1 
                 17.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2353 
                 csuscucuCfuUfGfCfucucuu 
                 A- 
                 2802 
                 VPusAfsauaAfgagagcaA 
                 UGCUCUCUCUUGCU 
                 5053 
               
               
                 12232 
                 22828 
                   
                 auuaL96 
                 228282 
                   
                 fgAfgagagscsa 
                 CUCUUAUUU 
                   
               
               
                 20.1 
                 19.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2354 
                 uscsucucUfuGfCfUfcucuua 
                 A- 
                 2803 
                 VPusAfsaauAfagagagcA 
                 GCUCUCUCUUGCUC 
                 5054 
               
               
                 12232 
                 22828 
                   
                 uuuaL96 
                 228282 
                   
                 faGfagagasgsc 
                 UCUUAUUUG 
                   
               
               
                 21.1 
                 21.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2355 
                 csuscucuUfgCfUfCfucuuau 
                 A- 
                 2804 
                 VPusCfsaaaUfaagagagC 
                 CUCUCUCUUGCUCU 
                 5055 
               
               
                 12232 
                 22828 
                   
                 uugaL96 
                 228282 
                   
                 faAfgagagsasg 
                 CUUAUUUGU 
                   
               
               
                 22.1 
                 23.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2356 
                 uscsucuuGfcUfCfUfcuuauu 
                 A- 
                 2805 
                 VPusAfscaaAfuaagagaG 
                 UCUCUCUUGCUCUC 
                 5056 
               
               
                 12232 
                 22828 
                   
                 uguaL96 
                 228282 
                   
                 fcAfagagasgsa 
                 UUAUUUGUA 
                   
               
               
                 23.1 
                 25.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2357 
                 csuscuugCfuCfUfCfuuauuu 
                 A- 
                 2806 
                 VPusUfsacaAfauaagagA 
                 CUCUCUUGCUCUCU 
                 5057 
               
               
                 12232 
                 22828 
                   
                 guaaL96 
                 228282 
                   
                 fgCfaagagsasg 
                 UAUUUGUAC 
                   
               
               
                 24.1 
                 27.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2358 
                 uscsuugcUfcUfCfUfuauuug 
                 A- 
                 2807 
                 VPusGfsuacAfaauaagaG 
                 UCUCUUGCUCUCUU 
                 5058 
               
               
                 12232 
                 22828 
                   
                 uacaL96 
                 228283 
                   
                 faGfcaagasgsa 
                 AUUUGUACC 
                   
               
               
                 25.1 
                 29.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2359 
                 csusugcuCfuCfUfUfauuugu 
                 A- 
                 2808 
                 VPusGfsguaCfaaauaagA 
                 CUCUUGCUCUCUUA 
                 5059 
               
               
                 12232 
                 22828 
                   
                 accaL96 
                 228283 
                   
                 fgAfgcaagsasg 
                 UUUGUACCG 
                   
               
               
                 26.1 
                 31.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2360 
                 ususgcucUfcUfUfAfuuugua 
                 A- 
                 2809 
                 VPusCfsgguAfcaaauaaG 
                 UCUUGCUCUCUUAU 
                 5060 
               
               
                 12232 
                 22828 
                   
                 ccgaL96 
                 228283 
                   
                 faGfagcaasgsa 
                 UUGUACCGG 
                   
               
               
                 27.1 
                 33.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2361 
                 usgscucuCfuUfAfUfuuguac 
                 A- 
                 2810 
                 VPusCfscggUfacaaauaA 
                 CUUGCUCUCUUAUU 
                 5061 
               
               
                 12232 
                 22828 
                   
                 cggaL96 
                 228283 
                   
                 fgAfgagcasasg 
                 UGUACCGGU 
                   
               
               
                 28.1 
                 35.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2362 
                 csuscucuUfaUfUfUfguaccg 
                 A- 
                 2811 
                 VPusAfsaccGfguacaaaU 
                 UGCUCUCUUAUUUG 
                 5062 
               
               
                 12232 
                 22828 
                   
                 guuaL96 
                 228283 
                   
                 faAfgagagscsa 
                 UACCGGUUU 
                   
               
               
                 29.1 
                 37.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2363 
                 uscsucuuAfuUfUfGfuaccgg 
                 A- 
                 2812 
                 VPusAfsaacCfgguacaaA 
                 GCUCUCUUAUUUGU 
                 5063 
               
               
                 12232 
                 22828 
                   
                 uuuaL96 
                 228284 
                   
                 fuAfagagasgsc 
                 ACCGGUUUU 
                   
               
               
                 30.1 
                 39.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2364 
                 csuscuuaUfuUfGfUfaccggu 
                 A- 
                 2813 
                 VPusAfsaaaCfcgguacaA 
                 CUCUCUUAUUUGUA 
                 5064 
               
               
                 12232 
                 22828 
                   
                 uuuaL96 
                 228284 
                   
                 faUfaagagsasg 
                 CCGGUUUUU 
                   
               
               
                 31.1 
                 41.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2365 
                 uscsuuauUfuGfUfAfccgguu 
                 A- 
                 2814 
                 VPusAfsaaaAfccgguacA 
                 UCUCUUAUUUGUAC 
                 5065 
               
               
                 12232 
                 22828 
                   
                 uuuaL96 
                 228284 
                   
                 faAfuaagasgsa 
                 CGGUUUUUG 
                   
               
               
                 32.1 
                 43.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2366 
                 csusuauuUfgUfAfCfcgguuu 
                 A- 
                 2815 
                 VPusCfsaaaAfaccgguaC 
                 CUCUUAUUUGUACC 
                 5066 
               
               
                 12232 
                 22828 
                   
                 uugaL96 
                 228284 
                   
                 faAfauaagsasg 
                 GGUUUUUGU 
                   
               
               
                 33.1 
                 45.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2367 
                 ususauuuGfuAfCfCfgguuu 
                 A- 
                 2816 
                 VPusAfscaaAfaaccgguA 
                 UCUUAUUUGUACCG 
                 5067 
               
               
                 12232 
                 22828 
                   
                 uuguaL96 
                 228284 
                   
                 fcAfaauaasgsa 
                 GUUUUUGUA 
                   
               
               
                 34.1 
                 47.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2368 
                 usasuuugUfaCfCfGfguuuuu 
                 A- 
                 2817 
                 VPusUfsacaAfaaaccggU 
                 CUUAUUUGUACCGG 
                 5068 
               
               
                 12232 
                 22828 
                   
                 guaaL96 
                 228285 
                   
                 faCfaaauasasg 
                 UUUUUGUAU 
                   
               
               
                 35.1 
                 49.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2369 
                 asusuuguAfcCfGfGfuuuuu 
                 A- 
                 2818 
                 VPusAfsuacAfaaaaccgG 
                 UUAUUUGUACCGGU 
                 5069 
               
               
                 12232 
                 22828 
                   
                 guauaL96 
                 228285 
                   
                 fuAfcaaausasa 
                 UUUUGUAUA 
                   
               
               
                 36.1 
                 51.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2370 
                 ususuguaCfcGfGfUfuuuug 
                 A- 
                 2819 
                 VPusUfsauaCfaaaaaccG 
                 UAUUUGUACCGGUU 
                 5070 
               
               
                 12232 
                 22828 
                   
                 uauaaL96 
                 228285 
                   
                 fgUfacaaasusa 
                 UUUGUAUAU 
                   
               
               
                 37.1 
                 53.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2371 
                 ususguacCfgGfUfUfuuugua 
                 A- 
                 2820 
                 VPusAfsuauAfcaaaaacC 
                 AUUUGUACCGGUUU 
                 5071 
               
               
                 12232 
                 22828 
                   
                 uauaL96 
                 228285 
                   
                 fgGfuacaasasu 
                 UUGUAUAUA 
                   
               
               
                 38.1 
                 55.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2372 
                 usgsuaccGfgUfUfUfuuguau 
                 A- 
                 2821 
                 VPusUfsauaUfacaaaaaC 
                 UUUGUACCGGUUUU 
                 5072 
               
               
                 12232 
                 22828 
                   
                 auaaL96 
                 228285 
                   
                 fcGfguacasasa 
                 UGUAUAUAA 
                   
               
               
                 39.1 
                 57.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2373 
                 gsusaccgGfuUfUfUfuguaua 
                 A- 
                 2822 
                 VPusUfsuauAfuacaaaaA 
                 UUGUACCGGUUUUU 
                 5073 
               
               
                 12232 
                 22828 
                   
                 uaaaL96 
                 228286 
                   
                 fcCfgguacsasa 
                 GUAUAUAAA 
                   
               
               
                 40.1 
                 59.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2374 
                 usasccggUfuUfUfUfguauau 
                 A- 
                 2823 
                 VPusUfsuuaUfauacaaaA 
                 UGUACCGGUUUUUG 
                 5074 
               
               
                 12232 
                 22828 
                   
                 aaaaL96 
                 228286 
                   
                 faCfcgguascsa 
                 UAUAUAAAA 
                   
               
               
                 41.1 
                 61.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2375 
                 ascscgguUfuUfUfGfuauaua 
                 A- 
                 2824 
                 VPusUfsuuuAfuauacaa 
                 GUACCGGUUUUUGU 
                 5075 
               
               
                 12232 
                 22828 
                   
                 aaaaL96 
                 228286 
                   
                 AfaAfccggusasc 
                 AUAUAAAAU 
                   
               
               
                 42.1 
                 63.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2376 
                 asusucauGfuUfUfCfcaaucu 
                 A- 
                 2825 
                 VPusGfsagaGfauuggaa 
                 AAAUUCAUGUUUCC 
                 5076 
               
               
                 12232 
                 22828 
                   
                 cucaL96 
                 228286 
                   
                 AfcAfugaaususu 
                 AAUCUCUCU 
                   
               
               
                 43.1 
                 65.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2377 
                 ususcaugUfuUfCfCfaaucuc 
                 A- 
                 2826 
                 VPusAfsgagAfgauugga 
                 AAUUCAUGUUUCCA 
                 5077 
               
               
                 12232 
                 22828 
                   
                 ucuaL96 
                 228286 
                   
                 AfaCfaugaasusu 
                 AUCUCUCUC 
                   
               
               
                 44.1 
                 67.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2378 
                 uscsauguUfuCfCfAfaucucu 
                 A- 
                 2827 
                 VPusGfsagaGfagauugg 
                 AUUCAUGUUUCCAA 
                 5078 
               
               
                 12232 
                 22828 
                   
                 cucaL96 
                 228287 
                   
                 AfaAfcaugasasu 
                 UCUCUCUCU 
                   
               
               
                 45.1 
                 69.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2379 
                 csasuguuUfcCfAfAfucucuc 
                 A- 
                 2828 
                 VPusAfsgagAfgagauug 
                 UUCAUGUUUCCAAU 
                 5079 
               
               
                 12232 
                 22828 
                   
                 ucuaL96 
                 228287 
                   
                 GfaAfacaugsasa 
                 CUCUCUCUC 
                   
               
               
                 46.1 
                 71.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2380 
                 asusguuuCfcAfAfUfcucucu 
                 A- 
                 2829 
                 VPusGfsagaGfagagauu 
                 UCAUGUUUCCAAUC 
                 5080 
               
               
                 12232 
                 22828 
                   
                 cucaL96 
                 228287 
                   
                 GfgAfaacausgsa 
                 UCUCUCUCC 
                   
               
               
                 47.1 
                 73.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2381 
                 usgsuuucCfaAfUfCfucucuc 
                 A- 
                 2830 
                 VPusGfsgagAfgagagau 
                 CAUGUUUCCAAUCU 
                 5081 
               
               
                 12232 
                 22828 
                   
                 uccaL96 
                 228287 
                   
                 UfgGfaaacasusg 
                 CUCUCUCCC 
                   
               
               
                 48.1 
                 75.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2382 
                 ususuccaAfuCfUfCfucucuc 
                 A- 
                 2831 
                 VPusAfsgggAfgagagag 
                 UGUUUCCAAUCUCU 
                 5082 
               
               
                 12232 
                 22828 
                   
                 ccuaL96 
                 228287 
                   
                 AfuUfggaaascsa 
                 CUCUCCCUG 
                   
               
               
                 49.1 
                 77.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2383 
                 uscscaauCfuCfUfCfucuccc 
                 A- 
                 2832 
                 VPusUfscagGfgagagag 
                 UUUCCAAUCUCUCU 
                 5083 
               
               
                 12232 
                 22828 
                   
                 ugaaL96 
                 228288 
                   
                 AfgAfuuggasasa 
                 CUCCCUGAU 
                   
               
               
                 50.1 
                 79.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2384 
                 csgsgugaCfaGfUfCfacuagc 
                 A- 
                 2833 
                 VPusUfsaagCfuagugacU 
                 AUCGGUGACAGUCA 
                 5084 
               
               
                 12232 
                 22828 
                   
                 uuaaL96 
                 228288 
                   
                 fgUfcaccgsasu 
                 CUAGCUUAU 
                   
               
               
                 51.1 
                 81.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2385 
                 gsgsugacAfgUfCfAfcuagcu 
                 A- 
                 2834 
                 VPusAfsuaaGfcuagugaC 
                 UCGGUGACAGUCAC 
                 5085 
               
               
                 12232 
                 22828 
                   
                 uauaL96 
                 228288 
                   
                 fuGfucaccsgsa 
                 UAGCUUAUC 
                   
               
               
                 52.1 
                 83.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2386 
                 asgsucacUfaGfCfUfuaucuu 
                 A- 
                 2835 
                 VPusUfsucaAfgauaagcU 
                 ACAGUCACUAGCUU 
                 5086 
               
               
                 12232 
                 22828 
                   
                 gaaaL96 
                 228288 
                   
                 faGfugacusgsu 
                 AUCUUGAAC 
                   
               
               
                 53.1 
                 85.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2387 
                 gsuscacuAfgCfUfUfaucuug 
                 A- 
                 2836 
                 VPusGfsuucAfagauaagC 
                 CAGUCACUAGCUUA 
                 5087 
               
               
                 12232 
                 22828 
                   
                 aacaL96 
                 228288 
                   
                 fuAfgugacsusg 
                 UCUUGAACA 
                   
               
               
                 54.1 
                 87.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2388 
                 uscsacuaGfcUfUfAfucuuga 
                 A- 
                 2837 
                 VPusUfsguuCfaagauaaG 
                 AGUCACUAGCUUAU 
                 5088 
               
               
                 12232 
                 22828 
                   
                 acaaL96 
                 228289 
                   
                 fcUfagugascsu 
                 CUUGAACAG 
                   
               
               
                 55.1 
                 89.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2389 
                 ascsuagcUfuAfUfCfuugaac 
                 A- 
                 2838 
                 VPusUfscugUfucaagau 
                 UCACUAGCUUAUCU 
                 5089 
               
               
                 12232 
                 22828 
                   
                 agaaL96 
                 228289 
                   
                 AfaGfcuagusgsa 
                 UGAACAGAU 
                   
               
               
                 56.1 
                 91.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2390 
                 csusagcuUfaUfCfUfugaaca 
                 A- 
                 2839 
                 VPusAfsucuGfuucaaga 
                 CACUAGCUUAUCUU 
                 5090 
               
               
                 12232 
                 22828 
                   
                 gauaL96 
                 228289 
                   
                 UfaAfgcuagsusg 
                 GAACAGAUA 
                   
               
               
                 57.1 
                 93.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2391 
                 usasgcuuAfuCfUfUfgaacag 
                 A- 
                 2840 
                 VPusUfsaucUfguucaag 
                 ACUAGCUUAUCUUG 
                 5091 
               
               
                 12232 
                 22828 
                   
                 auaaL96 
                 228289 
                   
                 AfuAfagcuasgsu 
                 AACAGAUAU 
                   
               
               
                 58.1 
                 95.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2392 
                 asgscuuaUfcUfUfGfaacaga 
                 A- 
                 2841 
                 VPusAfsuauCfuguucaa 
                 CUAGCUUAUCUUGA 
                 5092 
               
               
                 12232 
                 22828 
                   
                 uauaL96 
                 228289 
                   
                 GfaUfaagcusasg 
                 ACAGAUAUU 
                   
               
               
                 59.1 
                 97.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2393 
                 gscsuuauCfuUfGfAfacagau 
                 A- 
                 2842 
                 VPusAfsauaUfcuguuca 
                 UAGCUUAUCUUGAA 
                 5093 
               
               
                 12232 
                 22828 
                   
                 auuaL96 
                 228290 
                   
                 AfgAfuaagcsusa 
                 CAGAUAUUU 
                   
               
               
                 60.1 
                 99.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2394 
                 csasgcacAfcAfUfUfccuuug 
                 A- 
                 2843 
                 VPusUfsuucAfaaggaau 
                 CCCAGCACACAUUC 
                 5094 
               
               
                 12232 
                 22829 
                   
                 aaaaL96 
                 228290 
                   
                 GfuGfugcugsgsg 
                 CUUUGAAAU 
                   
               
               
                 61.1 
                 01.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2395 
                 asgscacaCfaUfUfCfcuuuga 
                 A- 
                 2844 
                 VPusAfsuuuCfaaaggaaU 
                 CCAGCACACAUUCC 
                 5095 
               
               
                 12232 
                 22829 
                   
                 aauaL96 
                 228290 
                   
                 fgUfgugcusgsg 
                 UUUGAAAUA 
                   
               
               
                 62.1 
                 03.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2396 
                 gscsacacAfuUfCfCfuuugaa 
                 A- 
                 2845 
                 VPusUfsauuUfcaaaggaA 
                 CAGCACACAUUCCU 
                 5096 
               
               
                 12232 
                 22829 
                   
                 auaaL96 
                 228290 
                   
                 fuGfugugcsusg 
                 UUGAAAUAA 
                   
               
               
                 63.1 
                 05.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2397 
                 csascacaUfuCfCfUfuugaaa 
                 A- 
                 2846 
                 VPusUfsuauUfucaaagg 
                 AGCACACAUUCCUU 
                 5097 
               
               
                 12232 
                 22829 
                   
                 uaaaL96 
                 228290 
                   
                 AfaUfgugugscsu 
                 UGAAAUAAG 
                   
               
               
                 64.1 
                 07.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2398 
                 csascauuCfcUfUfUfgaaaua 
                 A- 
                 2847 
                 VPusCfscuuAfuuucaaaG 
                 CACACAUUCCUUUG 
                 5098 
               
               
                 12232 
                 22829 
                   
                 aggaL96 
                 228291 
                   
                 fgAfaugugsusg 
                 AAAUAAGGU 
                   
               
               
                 65.1 
                 09.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2399 
                 uscscuuuGfaAfAfUfaagguu 
                 A- 
                 2848 
                 VPusUfsgaaAfccuuauu 
                 AUUCCUUUGAAAUA 
                 5099 
               
               
                 12232 
                 22829 
                   
                 ucaaL96 
                 228291 
                   
                 UfcAfaaggasasu 
                 AGGUUUCAA 
                   
               
               
                 66.1 
                 11.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2400 
                 csusuugaAfaUfAfAfgguuuc 
                 A- 
                 2849 
                 VPusAfsuugAfaaccuua 
                 UCCUUUGAAAUAAG 
                 5100 
               
               
                 12232 
                 22829 
                   
                 aauaL96 
                 228291 
                   
                 UfuUfcaaagsgsa 
                 GUUUCAAUA 
                   
               
               
                 67.1 
                 13.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2401 
                 ususugaaAfuAfAfGfguuuca 
                 A- 
                 2850 
                 VPusUfsauuGfaaaccuuA 
                 CCUUUGAAAUAAGG 
                 5101 
               
               
                 12232 
                 22829 
                   
                 auaaL96 
                 228291 
                   
                 fuUfucaaasgsg 
                 UUUCAAUAU 
                   
               
               
                 68.1 
                 15.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2402 
                 asgsguuuCfaAfUfAfuacauc 
                 A- 
                 2851 
                 VPusGfsuagAfuguauau 
                 UAAGGUUUCAAUAU 
                 5102 
               
               
                 12232 
                 22829 
                   
                 uacaL96 
                 228291 
                   
                 UfgAfaaccususa 
                 ACAUCUACA 
                   
               
               
                 69.1 
                 17.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2403 
                 gsgsuuucAfaUfAfUfacaucu 
                 A- 
                 2852 
                 VPusUfsguaGfauguaua 
                 AAGGUUUCAAUAUA 
                 5103 
               
               
                 12232 
                 22829 
                   
                 acaaL96 
                 228292 
                   
                 UfuGfaaaccsusu 
                 CAUCUACAU 
                   
               
               
                 70.1 
                 19.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2404 
                 gsusuucaAfuAfUfAfcaucua 
                 A- 
                 2853 
                 VPusAfsuguAfgauguau 
                 AGGUUUCAAUAUAC 
                 5104 
               
               
                 12232 
                 22829 
                   
                 cauaL96 
                 228292 
                   
                 AfuUfgaaacscsu 
                 AUCUACAUA 
                   
               
               
                 71.1 
                 21.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2405 
                 ususucaaUfaUfAfCfaucuac 
                 A- 
                 2854 
                 VPusUfsaugUfagaugua 
                 GGUUUCAAUAUACA 
                 5105 
               
               
                 12232 
                 22829 
                   
                 auaaL96 
                 228292 
                   
                 UfaUfugaaascsc 
                 UCUACAUAC 
                   
               
               
                 72.1 
                 23.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2406 
                 ususcaauAfuAfCfAfucuaca 
                 A- 
                 2855 
                 VPusGfsuauGfuagaugu 
                 GUUUCAAUAUACAU 
                 5106 
               
               
                 12232 
                 22829 
                   
                 uacaL96 
                 228292 
                   
                 AfuAfuugaasasc 
                 CUACAUACU 
                   
               
               
                 73.1 
                 25.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2407 
                 usasuuugGfcAfAfCfuuguau 
                 A- 
                 2856 
                 VPusCfsaaaUfacaaguuG 
                 UAUAUUUGGCAACU 
                 5107 
               
               
                 12232 
                 22829 
                   
                 uugaL96 
                 228292 
                   
                 fcCfaaauasusa 
                 UGUAUUUGU 
                   
               
               
                 74.1 
                 27.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2408 
                 ususuggcAfaCfUfUfguauuu 
                 A- 
                 2857 
                 VPusCfsacaAfauacaagU 
                 UAUUUGGCAACUUG 
                 5108 
               
               
                 12232 
                 22829 
                   
                 gugaL96 
                 228293 
                   
                 fuGfccaaasusa 
                 UAUUUGUGU 
                   
               
               
                 75.1 
                 29.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2409 
                 usgsgcaaCfuUfGfUfauuugu 
                 A- 
                 2858 
                 VPusCfsacaCfaaauacaA 
                 UUUGGCAACUUGUA 
                 5109 
               
               
                 12232 
                 22829 
                   
                 gugaL96 
                 228293 
                   
                 fgUfugccasasa 
                 UUUGUGUGU 
                   
               
               
                 76.1 
                 31.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2410 
                 gsgscaacUfuGfUfAfuuugug 
                 A- 
                 2859 
                 VPusAfscacAfcaaauacA 
                 UUGGCAACUUGUAU 
                 5110 
               
               
                 12232 
                 22829 
                   
                 uguaL96 
                 228293 
                   
                 faGfuugccsasa 
                 UUGUGUGUA 
                   
               
               
                 77.1 
                 33.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2411 
                 gscsaacuUfgUfAfUfuugugu 
                 A- 
                 2860 
                 VPusUfsacaCfacaaauaC 
                 UGGCAACUUGUAUU 
                 5111 
               
               
                 12232 
                 22829 
                   
                 guaaL96 
                 228293 
                   
                 faAfguugcscsa 
                 UGUGUGUAU 
                   
               
               
                 78.1 
                 35.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2412 
                 csasacuuGfuAfUfUfugugug 
                 A- 
                 2861 
                 VPusAfsuacAfcacaaauA 
                 GGCAACUUGUAUUU 
                 5112 
               
               
                 12232 
                 22829 
                   
                 uauaL96 
                 228293 
                   
                 fcAfaguugscsc 
                 GUGUGUAUA 
                   
               
               
                 79.1 
                 37.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2413 
                 asascuugUfaUfUfUfgugugu 
                 A- 
                 2862 
                 VPusUfsauaCfacacaaaU 
                 GCAACUUGUAUUUG 
                 5113 
               
               
                 12232 
                 22829 
                   
                 auaaL96 
                 228294 
                   
                 faCfaaguusgsc 
                 UGUGUAUAU 
                   
               
               
                 80.1 
                 39.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2414 
                 ascsuuguAfuUfUfGfugugu 
                 A- 
                 2863 
                 VPusAfsuauAfcacacaaA 
                 CAACUUGUAUUUGU 
                 5114 
               
               
                 12232 
                 22829 
                   
                 auauaL96 
                 228294 
                   
                 fuAfcaagususg 
                 GUGUAUAUA 
                   
               
               
                 81.1 
                 41.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2415 
                 ususcugaUfaAfAfAfuagaca 
                 A- 
                 2864 
                 VPusCfsaauGfucuauuu 
                 GAUUCUGAUAAAAU 
                 5115 
               
               
                 12232 
                 22829 
                   
                 uugaL96 
                 228294 
                   
                 UfaUfcagaasusc 
                 AGACAUUGC 
                   
               
               
                 82.1 
                 43.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2416 
                 usgsauaaAfaUfAfGfacauug 
                 A- 
                 2865 
                 VPusUfsagcAfaugucua 
                 UCUGAUAAAAUAGA 
                 5116 
               
               
                 12232 
                 22829 
                   
                 cuaaL96 
                 228294 
                   
                 UfuUfuaucasgsa 
                 CAUUGCUAU 
                   
               
               
                 83.1 
                 45.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2417 
                 gsasuaaaAfuAfGfAfcauugc 
                 A- 
                 2866 
                 VPusAfsuagCfaaugucu 
                 CUGAUAAAAUAGAC 
                 5117 
               
               
                 12232 
                 22829 
                   
                 uauaL96 
                 228294 
                   
                 AfuUfuuaucsasg 
                 AUUGCUAUU 
                   
               
               
                 84.1 
                 47.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2418 
                 usasaaauAfgAfCfAfuugcua 
                 A- 
                 2867 
                 VPusGfsaauAfgcaauguC 
                 GAUAAAAUAGACAU 
                 5118 
               
               
                 12232 
                 22829 
                   
                 uucaL96 
                 228295 
                   
                 fuAfuuuuasusc 
                 UGCUAUUCU 
                   
               
               
                 85.1 
                 49.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2419 
                 usasgacaUfuGfCfUfauucug 
                 A- 
                 2868 
                 VPusAfsaacAfgaauagcA 
                 AAUAGACAUUGCUA 
                 5119 
               
               
                 12232 
                 22829 
                   
                 uuuaL96 
                 228295 
                   
                 faUfgucuasusu 
                 UUCUGUUUU 
                   
               
               
                 86.1 
                 51.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2420 
                 asgsacauUfgCfUfAfuucugu 
                 A- 
                 2869 
                 VPusAfsaaaCfagaauagC 
                 AUAGACAUUGCUAU 
                 5120 
               
               
                 12232 
                 22829 
                   
                 uuuaL96 
                 228295 
                   
                 faAfugucusasu 
                 UCUGUUUUU 
                   
               
               
                 87.1 
                 53.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2421 
                 uscsuacaUfaCfUfAfaaucuc 
                 A- 
                 2870 
                 VPusAfsgagAfgauuuag 
                 AUUCUACAUACUAA 
                 5121 
               
               
                 12232 
                 22829 
                   
                 ucuaL96 
                 228295 
                   
                 UfaUfguagasasu 
                 AUCUCUCUC 
                   
               
               
                 88.1 
                 55.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2422 
                 csusacauAfcUfAfAfaucucu 
                 A- 
                 2871 
                 VPusGfsagaGfagauuua 
                 UUCUACAUACUAAA 
                 5122 
               
               
                 12232 
                 22829 
                   
                 cucaL96 
                 228295 
                   
                 GfuAfuguagsasa 
                 UCUCUCUCC 
                   
               
               
                 89.1 
                 57.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2423 
                 usascauaCfuAfAfAfucucuc 
                 A- 
                 2872 
                 VPusGfsgagAfgagauuu 
                 UCUACAUACUAAAU 
                 5123 
               
               
                 12232 
                 22829 
                   
                 uccaL96 
                 228296 
                   
                 AfgUfauguasgsa 
                 cucucuccu 
                   
               
               
                 90.1 
                 59.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2424 
                 ascsauacUfaAfAfUfcucucu 
                 A- 
                 2873 
                 VPusAfsggaGfagagauu 
                 CUACAUACUAAAUC 
                 5124 
               
               
                 12232 
                 22829 
                   
                 ccuaL96 
                 228296 
                   
                 UfaGfuaugusasg 
                 UCUCUCCUU 
                   
               
               
                 91.1 
                 61.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2425 
                 csasuacuAfaAfUfCfucucuc 
                 A- 
                 2874 
                 VPusAfsaggAfgagagau 
                 UACAUACUAAAUCU 
                 5125 
               
               
                 12232 
                 22829 
                   
                 cuuaL96 
                 228296 
                   
                 UfuAfguaugsusa 
                 CUCUCCUUU 
                   
               
               
                 92.1 
                 63.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2426 
                 asusacuaAfaUfCfUfcucucc 
                 A- 
                 2875 
                 VPusAfsaagGfagagagaU 
                 ACAUACUAAAUCUC 
                 5126 
               
               
                 12232 
                 22829 
                   
                 uuuaL96 
                 228296 
                   
                 fuUfaguausgsu 
                 UCUCCUUUU 
                   
               
               
                 93.1 
                 65.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2427 
                 usascuaaAfuCfUfCfucuccu 
                 A- 
                 2876 
                 VPusAfsaaaGfgagagagA 
                 CAUACUAAAUCUCU 
                 5127 
               
               
                 12232 
                 22829 
                   
                 uuuaL96 
                 228296 
                   
                 fuUfuaguasusg 
                 CUCCUUUUU 
                   
               
               
                 94.1 
                 67.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2428 
                 csasuuuaUfuUfAfUfuggugc 
                 A- 
                 2877 
                 VPusGfsuagCfaccaauaA 
                 AUCAUUUAUUUAUU 
                 5128 
               
               
                 12232 
                 22829 
                   
                 uacaL96 
                 228297 
                   
                 faUfaaaugsasu 
                 GGUGCUACU 
                   
               
               
                 95.1 
                 69.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2429 
                 asusuuauUfuAfUfUfggugc 
                 A- 
                 2878 
                 VPusAfsguaGfcaccaauA 
                 UCAUUUAUUUAUUG 
                 5129 
               
               
                 12232 
                 22829 
                   
                 uacuaL96 
                 228297 
                   
                 faAfuaaausgsa 
                 GUGCUACUG 
                   
               
               
                 96.1 
                 71.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2430 
                 ususuauuUfaUfUfGfgugcua 
                 A- 
                 2879 
                 VPusCfsaguAfgcaccaaU 
                 CAUUUAUUUAUUGG 
                 5130 
               
               
                 12232 
                 22829 
                   
                 cugaL96 
                 228297 
                   
                 faAfauaaasusg 
                 UGCUACUGU 
                   
               
               
                 97.1 
                 73.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2431 
                 ususauuuAfuUfGfGfugcuac 
                 A- 
                 2880 
                 VPusAfscagUfagcaccaA 
                 AUUUAUUUAUUGG 
                 5131 
               
               
                 12232 
                 22829 
                   
                 uguaL96 
                 228297 
                   
                 fuAfaauaasasu 
                 UGCUACUGUU 
                   
               
               
                 98.1 
                 75.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2432 
                 usasuuuaUfuGfGfUfgcuacu 
                 A- 
                 2881 
                 VPusAfsacaGfuagcaccA 
                 UUUAUUUAUUGGU 
                 5132 
               
               
                 12232 
                 22829 
                   
                 guuaL96 
                 228297 
                   
                 faUfaaauasasa 
                 GCUACUGUUU 
                   
               
               
                 99.1 
                 77.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2433 
                 asusuuauUfgGfUfGfcuacug 
                 A- 
                 2882 
                 VPusAfsaacAfguagcacC 
                 UUAUUUAUUGGUGC 
                 5133 
               
               
                 12233 
                 22829 
                   
                 uuuaL96 
                 228298 
                   
                 faAfuaaausasa 
                 UACUGUUUA 
                   
               
               
                 00.1 
                 79.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2434 
                 ususauugGfuGfCfUfacuguu 
                 A- 
                 2883 
                 VPusAfsuaaAfcaguagcA 
                 AUUUAUUGGUGCUA 
                 5134 
               
               
                 12233 
                 22829 
                   
                 uauaL96 
                 228298 
                   
                 fcCfaauaasasu 
                 CUGUUUAUC 
                   
               
               
                 01.1 
                 81.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2435 
                 asusugguGfcUfAfCfuguuua 
                 A- 
                 2884 
                 VPusGfsgauAfaacaguaG 
                 UUAUUGGUGCUACU 
                 5135 
               
               
                 12233 
                 22829 
                   
                 uccaL96 
                 228298 
                   
                 fcAfccaausasa 
                 GUUUAUCCG 
                   
               
               
                 02.1 
                 83.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2436 
                 gsasaaagAfuAfUfUfaacauc 
                 A- 
                 2885 
                 VPusCfsgugAfuguuaau 
                 GGGAAAAGAUAUU 
                 5136 
               
               
                 12233 
                 22829 
                   
                 acgaL96 
                 228298 
                   
                 AfuCfuuuucscsc 
                 AACAUCACGU 
                   
               
               
                 03.1 
                 85.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2437 
                 asascaucAfcGfUfCfuuuguc 
                 A- 
                 2886 
                 VPusAfsgagAfcaaagacG 
                 UUAACAUCACGUCU 
                 5137 
               
               
                 12233 
                 22829 
                   
                 ucuaL96 
                 228298 
                   
                 fuGfauguusasa 
                 UUGUCUCUA 
                   
               
               
                 04.1 
                 87.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2438 
                 ascsaucaCfgUfCfUfuugucu 
                 A- 
                 2887 
                 VPusUfsagaGfacaaagaC 
                 UAACAUCACGUCUU 
                 5138 
               
               
                 12233 
                 22829 
                   
                 cuaaL96 
                 228299 
                   
                 fgUfgaugususa 
                 UGUCUCUAG 
                   
               
               
                 05.1 
                 89.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2439 
                 gsuscuuuGfuCfUfCfuagugc 
                 A- 
                 2888 
                 VPusAfscugCfacuagagA 
                 ACGUCUUUGUCUCU 
                 5139 
               
               
                 12233 
                 22829 
                   
                 aguaL96 
                 228299 
                   
                 fcAfaagacsgsu 
                 AGUGCAGUU 
                   
               
               
                 06.1 
                 91.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2440 
                 uscsuuugUfcUfCfUfagugca 
                 A- 
                 2889 
                 VPusAfsacuGfcacuagaG 
                 CGUCUUUGUCUCUA 
                 5140 
               
               
                 12233 
                 22829 
                   
                 guuaL96 
                 228299 
                   
                 faCfaaagascsg 
                 GUGCAGUUU 
                   
               
               
                 07.1 
                 93.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2441 
                 csusuuguCfuCfUfAfgugcag 
                 A- 
                 2890 
                 VPusAfsaacUfgcacuagA 
                 GUCUUUGUCUCUAG 
                 5141 
               
               
                 12233 
                 22829 
                   
                 uuuaL96 
                 228299 
                   
                 fgAfcaaagsasc 
                 UGCAGUUUU 
                   
               
               
                 08.1 
                 95.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2442 
                 gsasgauaUfuCfCfGfuaguac 
                 A- 
                 2891 
                 VPusUfsaugUfacuacgg 
                 UCGAGAUAUUCCGU 
                 5142 
               
               
                 12233 
                 22829 
                   
                 auaaL96 
                 228299 
                   
                 AfaUfaucucsgsa 
                 AGUACAUAU 
                   
               
               
                 09.1 
                 97.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2443 
                 asgsauauUfcCfGfUfaguaca 
                 A- 
                 2892 
                 VPusAfsuauGfuacuacg 
                 CGAGAUAUUCCGUA 
                 5143 
               
               
                 12233 
                 22829 
                   
                 uauaL96 
                 228300 
                   
                 GfaAfuaucuscsg 
                 GUACAUAUU 
                   
               
               
                 10.1 
                 99.1 
                   
                   
                 0.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2444 
                 gsasuauuCfcGfUfAfguacau 
                 A- 
                 2893 
                 VPusAfsauaUfguacuacG 
                 GAGAUAUUCCGUAG 
                 5144 
               
               
                 12233 
                 22830 
                   
                 auuaL96 
                 228300 
                   
                 fgAfauaucsusc 
                 UACAUAUUU 
                   
               
               
                 11.1 
                 01.1 
                   
                   
                 2.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2445 
                 csgsacaaAfgAfAfAfuacaga 
                 A- 
                 2894 
                 VPusAfsuauCfuguauuu 
                 AACGACAAAGAAAU 
                 5145 
               
               
                 12233 
                 22830 
                   
                 uauaL96 
                 228300 
                   
                 CfuUfugucgsusu 
                 ACAGAUAUA 
                   
               
               
                 12.1 
                 03.1 
                   
                   
                 4.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2446 
                 gsascaaaGfaAfAfUfacagau 
                 A- 
                 2895 
                 VPusUfsauaUfcuguauu 
                 ACGACAAAGAAAUA 
                 5146 
               
               
                 12233 
                 22830 
                   
                 auaaL96 
                 228300 
                   
                 UfcUfuugucsgsu 
                 CAGAUAUAU 
                   
               
               
                 13.1 
                 05.1 
                   
                   
                 6.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2447 
                 ascsaaagAfaAfUfAfcagaua 
                 A- 
                 2896 
                 VPusAfsuauAfucuguau 
                 CGACAAAGAAAUAC 
                 5147 
               
               
                 12233 
                 22830 
                   
                 uauaL96 
                 228300 
                   
                 UfuCfuuuguscsg 
                 AGAUAUAUC 
                   
               
               
                 14.1 
                 07.1 
                   
                   
                 8.1 
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2448 
                 csasaagaAfaUfAfCfagauau 
                 A- 
                 2897 
                 VPusGfsauaUfaucugua 
                 GACAAAGAAAUACA 
                 5148 
               
               
                 12233 
                 22830 
                   
                 aucaL96 
                 228301 
                   
                 UfuUfcuuugsusc 
                 GAUAUAUCU 
                   
               
               
                 15.1 
                 09.1 
                   
                   
                 0.1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8B 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Unmodified Single Strands and Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 Anti- 
                 SEQ ID 
                   
                   
               
               
                   
                 Sense 
                 SEQ ID 
                   
                 mRNA 
                 sense 
                 NO: 
                   
                 mRNA 
               
               
                 Duplex 
                 Oligo 
                 NO: 
                   
                 Target 
                 Oligo 
                 (Anti- 
                   
                 Target 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Range 
                 Name 
                 sense) 
                 Antisense Sequence 
                 Range 
               
               
                   
               
               
                 AD- 
                 A- 
                 2898 
                 CGGUGCUGGAAUUU 
                  123- 
                 A- 
                 3347 
                 UAAUAUCAAAUUCCA 
                  121- 
               
               
                 122286 
                 228211 
                   
                 GAUAUUA 
                  143 
                 2282112. 
                   
                 GCACCGAG 
                  143 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2899 
                 GGUGCUGGAAUUUG 
                  124- 
                 A- 
                 3348 
                 UGAAUAUCAAAUUCC 
                  122- 
               
               
                 122286 
                 228211 
                   
                 AUAUUCA 
                  144 
                 2282114. 
                   
                 AGCACCGA 
                  144 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2900 
                 UGCUGGAAUUUGAU 
                  126- 
                 A- 
                 3349 
                 UAUGAAUAUCAAAUU 
                  124- 
               
               
                 122286 
                 228211 
                   
                 AUUCAUA 
                  146 
                 2282116. 
                   
                 CCAGCACC 
                  146 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2901 
                 GCUGGAAUUUGAUA 
                  127- 
                 A- 
                 3350 
                 UAAUGAAUAUCAAAU 
                  125- 
               
               
                 122286 
                 228211 
                   
                 UUCAUUA 
                  147 
                 2282118. 
                   
                 UCCAGCAC 
                  147 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2902 
                 UGGAAUUUGAUAUU 
                  129- 
                 A- 
                 3351 
                 UUCAAUGAAUAUCAA 
                  127- 
               
               
                 122287 
                 228211 
                   
                 CAUUGAA 
                  149 
                 2282120. 
                   
                 AUUCCAGC 
                  149 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2903 
                 GGAAUUUGAUAUUC 
                  130- 
                 A- 
                 3352 
                 UAUCAAUGAAUAUCA 
                  128- 
               
               
                 122287 
                 228212 
                   
                 AUUGAUA 
                  150 
                 2282122. 
                   
                 AAUUCCAG 
                  150 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2904 
                 GAAUUUGAUAUUCA 
                  131- 
                 A- 
                 3353 
                 UGAUCAAUGAAUAUC 
                  129- 
               
               
                 122287 
                 228212 
                   
                 UUGAUCA 
                  151 
                 2282124. 
                   
                 AAAUUCCA 
                  151 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2905 
                 AAUUUGAUAUUCAU 
                  132- 
                 A- 
                 3354 
                 UGGAUCAAUGAAUAU 
                  130- 
               
               
                 122287 
                 228212 
                   
                 UGAUCCA 
                  152 
                 2282126. 
                   
                 CAAAUUCC 
                  152 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2906 
                 AUUUGAUAUUCAUU 
                  133- 
                 A- 
                 3355 
                 UCGGAUCAAUGAAUA 
                  131- 
               
               
                 122287 
                 228212 
                   
                 GAUCCGA 
                  153 
                 2282128. 
                   
                 UCAAAUUC 
                  153 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2907 
                 UUUGAUAUUCAUUG 
                  134- 
                 A- 
                 3356 
                 UCCGGAUCAAUGAAU 
                  132- 
               
               
                 122287 
                 228212 
                   
                 AUCCGGA 
                  154 
                 2282130. 
                   
                 AUCAAAUU 
                  154 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2908 
                 UUUAUUUUUGCUUG 
                  217- 
                 A- 
                 3357 
                 UGAAUGGCAAGCAAA 
                  215- 
               
               
                 122287 
                 228213 
                   
                 CCAUUCA 
                  237 
                 2282132. 
                   
                 AAUAAAUU 
                  237 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2909 
                 UUAUUUUUGCUUGCC 
                  218- 
                 A- 
                 3358 
                 UGGAAUGGCAAGCAA 
                  216- 
               
               
                 122287 
                 228213 
                   
                 AUUCCA 
                  238 
                 2282134. 
                   
                 AAAUAAAU 
                  238 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2910 
                 CAAAUCACUGUGGAU 
                  283- 
                 A- 
                 3359 
                 UCCAAAAUCCACAGU 
                  281- 
               
               
                 122287 
                 228213 
                   
                 UUUGGA 
                  303 
                 2282136. 
                   
                 GAUUUGGG 
                  303 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2911 
                 AAAUCACUGUGGAU 
                  284- 
                 A- 
                 3360 
                 UUCCAAAAUCCACAG 
                  282- 
               
               
                 122287 
                 228213 
                   
                 UUUGGAA 
                  304 
                 2282138. 
                   
                 UGAUUUGG 
                  304 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2912 
                 AAUCACUGUGGAUU 
                  285- 
                 A- 
                 3361 
                 UUUCCAAAAUCCACA 
                  283- 
               
               
                 122288 
                 228213 
                   
                 UUGGAAA 
                  305 
                 2282140. 
                   
                 GUGAUUUG 
                  305 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2913 
                 AUCACUGUGGAUUU 
                  286- 
                 A- 
                 3362 
                 UUUUCCAAAAUCCAC 
                  284- 
               
               
                 122288 
                 228214 
                   
                 UGGAAAA 
                  306 
                 2282142. 
                   
                 AGUGAUUU 
                  306 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2914 
                 UCACUGUGGAUUUU 
                  287- 
                 A- 
                 3363 
                 UGUUUCCAAAAUCCA 
                  285- 
               
               
                 122288 
                 228214 
                   
                 GGAAACA 
                  307 
                 2282144. 
                   
                 CAGUGAUU 
                  307 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2915 
                 CACUGUGGAUUUUG 
                  288- 
                 A- 
                 3364 
                 UGGUUUCCAAAAUCC 
                  286- 
               
               
                 122288 
                 228214 
                   
                 GAAACCA 
                  308 
                 2282146. 
                   
                 ACAGUGAU 
                  308 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2916 
                 ACUGUGGAUUUUGG 
                  289- 
                 A- 
                 3365 
                 UUGGUUUCCAAAAUC 
                  287- 
               
               
                 122288 
                 228214 
                   
                 AAACCAA 
                  309 
                 2282148. 
                   
                 CACAGUGA 
                  309 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2917 
                 CUGUGGAUUUUGGA 
                  290- 
                 A- 
                 3366 
                 UCUGGUUUCCAAAAU 
                  288- 
               
               
                 122288 
                 228214 
                   
                 AACCAGA 
                  310 
                 2282150. 
                   
                 CCACAGUG 
                  310 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2918 
                 UGUGGAUUUUGGAA 
                  291- 
                 A- 
                 3367 
                 UGCUGGUUUCCAAAA 
                  289- 
               
               
                 122288 
                 228215 
                   
                 ACCAGCA 
                  311 
                 2282152. 
                   
                 UCCACAGU 
                  311 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2919 
                 GUGGAUUUUGGAAA 
                  292- 
                 A- 
                 3368 
                 UUGCUGGUUUCCAAA 
                  290- 
               
               
                 122288 
                 228215 
                   
                 CCAGCAA 
                  312 
                 2282154. 
                   
                 AUCCACAG 
                  312 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2920 
                 GAUUUUGGAAACCA 
                  295- 
                 A- 
                 3369 
                 UUUCUGCUGGUUUCC 
                  293- 
               
               
                 122288 
                 228215 
                   
                 GCAGAAA 
                  315 
                 2282156. 
                   
                 AAAAUCCA 
                  315 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2921 
                 AUUUUGGAAACCAGC 
                  296- 
                 A- 
                 3370 
                 UUUUCUGCUGGUUUC 
                  294- 
               
               
                 122288 
                 228215 
                   
                 AGAAAA 
                  316 
                 2282158. 
                   
                 CAAAAUCC 
                  316 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2922 
                 UUUUGGAAACCAGCA 
                  297- 
                 A- 
                 3371 
                 UCUUUCUGCUGGUUU 
                  295- 
               
               
                 122289 
                 228215 
                   
                 GAAAGA 
                  317 
                 2282160. 
                   
                 CCAAAAUC 
                  317 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2923 
                 UUUGGAAACCAGCAG 
                  298- 
                 A- 
                 3372 
                 UUCUUUCUGCUGGUU 
                  296- 
               
               
                 122289 
                 228216 
                   
                 AAAGAA 
                  318 
                 2282162. 
                   
                 UCCAAAAU 
                  318 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2924 
                 GGAAACCAGCAGAAA 
                  301- 
                 A- 
                 3373 
                 UUCCUCUUUCUGCUG 
                  299- 
               
               
                 122289 
                 228216 
                   
                 GAGGAA 
                  321 
                 2282164. 
                   
                 GUUUCCAA 
                  321 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2925 
                 AAACCAGCAGAAAGA 
                  303- 
                 A- 
                 3374 
                 UUUUCCUCUUUCUGC 
                  301- 
               
               
                 122289 
                 228216 
                   
                 GGAAAA 
                  323 
                 2282166. 
                   
                 UGGUUUCC 
                  323 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2926 
                 AACCAGCAGAAAGAG 
                  304- 
                 A- 
                 3375 
                 UCUUUCCUCUUUCUG 
                  302- 
               
               
                 122289 
                 228216 
                   
                 GAAAGA 
                  324 
                 2282168. 
                   
                 CUGGUUUC 
                  324 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2927 
                 ACCAGCAGAAAGAGG 
                  305- 
                 A- 
                 3376 
                 UUCUUUCCUCUUUCU 
                  303- 
               
               
                 122289 
                 228216 
                   
                 AAAGAA 
                  325 
                 2282170. 
                   
                 GCUGGUUU 
                  325 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2928 
                 CCAGCAGAAAGAGGA 
                  306- 
                 A- 
                 3377 
                 UCUCUUUCCUCUUUC 
                  304- 
               
               
                 122289 
                 228217 
                   
                 AAGAGA 
                  326 
                 2282172. 
                   
                 UGCUGGUU 
                  326 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2929 
                 CAGCAGAAAGAGGA 
                  307- 
                 A- 
                 3378 
                 uccucuuuccucuuuc 
                  305- 
               
               
                 122289 
                 228217 
                   
                 AAGAGGA 
                  327 
                 2282174. 
                   
                 UGCUGGU 
                  327 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2930 
                 AGCAGAAAGAGGAA 
                  308- 
                 A- 
                 3379 
                 UACCUCUUUCCUCUU 
                  306- 
               
               
                 122289 
                 228217 
                   
                 AGAGGUA 
                  328 
                 2282176. 
                   
                 UCUGCUGG 
                  328 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2931 
                 GCAGAAAGAGGAAA 
                  309- 
                 A- 
                 3380 
                 UUACCUCUUUCCUCU 
                  307- 
               
               
                 122289 
                 228217 
                   
                 GAGGUAA 
                  329 
                 2282178. 
                   
                 UUCUGCUG 
                  329 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2932 
                 CAGAAAGAGGAAAG 
                  310- 
                 A- 
                 3381 
                 UCUACCUCUUUCCUCU 
                  308- 
               
               
                 122290 
                 228217 
                   
                 AGGUAGA 
                  330 
                 2282180. 
                   
                 UUCUGCU 
                  330 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2933 
                 AAAGAGGAAAGAGG 
                  313- 
                 A- 
                 3382 
                 UUUGCUACCUCUUUC 
                  311- 
               
               
                 122290 
                 228218 
                   
                 UAGCAAA 
                  333 
                 2282182. 
                   
                 CUCUUUCU 
                  333 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2934 
                 AAGAGGAAAGAGGU 
                  314- 
                 A- 
                 3383 
                 UCUUGCUACCUCUUU 
                  312- 
               
               
                 122290 
                 228218 
                   
                 AGCAAGA 
                  334 
                 2282184. 
                   
                 ccucuuuc 
                  334 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2935 
                 AGAGGAAAGAGGUA 
                  315- 
                 A- 
                 3384 
                 UUCUUGCUACCUCUU 
                  313- 
               
               
                 122290 
                 228218 
                   
                 GCAAGAA 
                  335 
                 2282186. 
                   
                 uccucuuu 
                  335 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2936 
                 GAGGAAAGAGGUAG 
                  316- 
                 A- 
                 3385 
                 UCUCUUGCUACCUCU 
                  314- 
               
               
                 122290 
                 228218 
                   
                 CAAGAGA 
                  336 
                 2282188. 
                   
                 uuccucuu 
                  336 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2937 
                 GGAAAGAGGUAGCA 
                  318- 
                 A- 
                 3386 
                 UAGCUCUUGCUACCU 
                  316- 
               
               
                 122290 
                 228218 
                   
                 AGAGCUA 
                  338 
                 2282190. 
                   
                 cuuuccuc 
                  338 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2938 
                 AGGUAGCAAGAGCUC 
                  324- 
                 A- 
                 3387 
                 UCUCUGGAGCUCUUG 
                  322- 
               
               
                 122290 
                 228219 
                   
                 CAGAGA 
                  344 
                 2282192. 
                   
                 CUACCUCU 
                  344 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2939 
                 UCCAGAGAGAAGUCG 
                  337- 
                 A- 
                 3388 
                 UUUCCUCGACUUCUC 
                  335- 
               
               
                 122290 
                 228219 
                   
                 AGGAAA 
                  357 
                 2282194. 
                   
                 UCUGGAGC 
                  357 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2940 
                 CCAGAGAGAAGUCGA 
                  338- 
                 A- 
                 3389 
                 UCUUCCUCGACUUCUC 
                  336- 
               
               
                 122290 
                 228219 
                   
                 GGAAGA 
                  358 
                 2282196. 
                   
                 UCUGGAG 
                  358 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2941 
                 CAGAGAGAAGUCGA 
                  339- 
                 A- 
                 3390 
                 UUCUUCCUCGACUUC 
                  337- 
               
               
                 122290 
                 228219 
                   
                 GGAAGAA 
                  359 
                 2282198. 
                   
                 UCUCUGGA 
                  359 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2942 
                 AGAGAAGUCGAGGA 
                  342- 
                 A- 
                 3391 
                 UCUCUCUUCCUCGACU 
                  340- 
               
               
                 122291 
                 228219 
                   
                 AGAGAGA 
                  362 
                 2282200. 
                   
                 UCUCUCU 
                  362 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2943 
                 GAGAAGUCGAGGAA 
                  343- 
                 A- 
                 3392 
                 UUCUCUCUUCCUCGAC 
                  341- 
               
               
                 122291 
                 228220 
                   
                 GAGAGAA 
                  363 
                 2282202. 
                   
                 UUCUCUC 
                  363 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2944 
                 GAAGUCGAGGAAGA 
                  345- 
                 A- 
                 3393 
                 UUCUCUCUCUUCCUCG 
                  343- 
               
               
                 122291 
                 228220 
                   
                 GAGAGAA 
                  365 
                 2282204. 
                   
                 ACUUCUC 
                  365 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2945 
                 AGUGAGUGACCUGCU 
                  417- 
                 A- 
                 3394 
                 UCCAAAAGCAGGUCA 
                  415- 
               
               
                 122291 
                 228220 
                   
                 UUUGGA 
                  437 
                 2282206. 
                   
                 CUCACUUU 
                  437 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2946 
                 GGCGUCGCACUGAAA 
                  643- 
                 A- 
                 3395 
                 UAAAAGUUUCAGUGC 
                  641- 
               
               
                 122291 
                 228220 
                   
                 CUUUUA 
                  663 
                 2282208. 
                   
                 GACGCCGC 
                  663 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2947 
                 GUCGCACUGAAACUU 
                  646- 
                 A- 
                 3396 
                 UACGAAAAGUUUCAG 
                  644- 
               
               
                 122291 
                 228220 
                   
                 UUCGUA 
                  666 
                 2282210. 
                   
                 UGCGACGC 
                  666 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2948 
                 UCGCACUGAAACUUU 
                  647- 
                 A- 
                 3397 
                 UGACGAAAAGUUUCA 
                  645- 
               
               
                 122291 
                 228221 
                   
                 UCGUCA 
                  667 
                 2282212. 
                   
                 GUGCGACG 
                  667 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2949 
                 CACUGAAACUUUUCG 
                  650- 
                 A- 
                 3398 
                 UUUGGACGAAAAGUU 
                  648- 
               
               
                 122291 
                 228221 
                   
                 UCCAAA 
                  670 
                 2282214. 
                   
                 UCAGUGCG 
                  670 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2950 
                 ACUGAAACUUUUCGU 
                  651- 
                 A- 
                 3399 
                 UGUUGGACGAAAAGU 
                  649- 
               
               
                 122291 
                 228221 
                   
                 CCAACA 
                  671 
                 2282216. 
                   
                 UUCAGUGC 
                  671 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2951 
                 UGAAACUUUUCGUCC 
                  653- 
                 A- 
                 3400 
                 UAAGUUGGACGAAAA 
                  651- 
               
               
                 122292 
                 228221 
                   
                 AACUUA 
                  673 
                 2282220. 
                   
                 GUUUCAGU 
                  673 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2952 
                 AACUUUUCGUCCAAC 
                  656- 
                 A- 
                 3401 
                 UCAGAAGUUGGACGA 
                  654- 
               
               
                 122292 
                 228222 
                   
                 UUCUGA 
                  676 
                 2282222. 
                   
                 AAAGUUUC 
                  676 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2953 
                 CUGGGCUGUUCUCGC 
                  673- 
                 A- 
                 3402 
                 UCCGAAGCGAGAACA 
                  671- 
               
               
                 122292 
                 228222 
                   
                 UUCGGA 
                  693 
                 2282224. 
                   
                 GCCCAGAA 
                  693 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2954 
                 UGGGCUGUUCUCGCU 
                  674- 
                 A- 
                 3403 
                 UUCCGAAGCGAGAAC 
                  672- 
               
               
                 122292 
                 228222 
                   
                 UCGGAA 
                  694 
                 2282226. 
                   
                 AGCCCAGA 
                  694 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2955 
                 GGGCUGUUCUCGCUU 
                  675- 
                 A- 
                 3404 
                 UCUCCGAAGCGAGAA 
                  673- 
               
               
                 122292 
                 228222 
                   
                 CGGAGA 
                  695 
                 2282228. 
                   
                 CAGCCCAG 
                  695 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2956 
                 GCUGUUCUCGCUUCG 
                  677- 
                 A- 
                 3405 
                 UUCCUCCGAAGCGAG 
                  675- 
               
               
                 122292 
                 228222 
                   
                 GAGGAA 
                  697 
                 2282230. 
                   
                 AACAGCCC 
                  697 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2957 
                 GCCGCGAGAAGUGCU 
                  733- 
                 A- 
                 3406 
                 UGAGCUAGCACUUCU 
                  731- 
               
               
                 122292 
                 228223 
                   
                 AGCUCA 
                  753 
                 2282232. 
                   
                 CGCGGCUC 
                  753 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2958 
                 CCGCGAGAAGUGCUA 
                  734- 
                 A- 
                 3407 
                 UCGAGCUAGCACUUC 
                  732- 
               
               
                 122292 
                 228223 
                   
                 GCUCGA 
                  754 
                 2282234. 
                   
                 UCGCGGCU 
                  754 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2959 
                 GCCUCCGAAACCAUG 
                 1027- 
                 A- 
                 3408 
                 UAAGUUCAUGGUUUC 
                 1025- 
               
               
                 122292 
                 228223 
                   
                 AACUUA 
                 1047 
                 2282236. 
                   
                 GGAGGCCC 
                 1047 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2960 
                 AAGGAGGAGGGCAG 
                 1130- 
                 A- 
                 3409 
                 UAUGAUUCUGCCCUC 
                 1128- 
               
               
                 122292 
                 228223 
                   
                 AAUCAUA 
                 1150 
                 2282238. 
                   
                 CUCCUUCU 
                 1150 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2961 
                 GGCAGAAUCAUCACG 
                 1139- 
                 A- 
                 3410 
                 UCACUUCGUGAUGAU 
                 1137- 
               
               
                 122293 
                 228223 
                   
                 AAGUGA 
                 1159 
                 2282240. 
                   
                 UCUGCCCU 
                 1159 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2962 
                 AAUCAUCACGAAGUG 
                 1144- 
                 A- 
                 3411 
                 UUUCACCACUUCGUG 
                 1142- 
               
               
                 122293 
                 228224 
                   
                 GUGAAA 
                 1164 
                 2282242. 
                   
                 AUGAUUCU 
                 1164 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2963 
                 AUCAUCACGAAGUGG 
                 1145- 
                 A- 
                 3412 
                 UCUUCACCACUUCGU 
                 1143- 
               
               
                 122293 
                 228224 
                   
                 UGAAGA 
                 1165 
                 2282244. 
                   
                 GAUGAUUC 
                 1165 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2964 
                 UCAUCACGAAGUGGU 
                 1146- 
                 A- 
                 3413 
                 UACUUCACCACUUCG 
                 1144- 
               
               
                 122293 
                 228224 
                   
                 GAAGUA 
                 1166 
                 2282246. 
                   
                 UGAUGAUU 
                 1166 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2965 
                 CAUCACGAAGUGGUG 
                 1147- 
                 A- 
                 3414 
                 UAACUUCACCACUUC 
                 1145- 
               
               
                 122293 
                 228224 
                   
                 AAGUUA 
                 1167 
                 2282248. 
                   
                 GUGAUGAU 
                 1167 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2966 
                 UCACGAAGUGGUGA 
                 1149- 
                 A- 
                 3415 
                 UUGAACUUCACCACU 
                 1147- 
               
               
                 122293 
                 228224 
                   
                 AGUUCAA 
                 1169 
                 2282250. 
                   
                 UCGUGAUG 
                 1169 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2967 
                 AAGUGGUGAAGUUC 
                 1154- 
                 A- 
                 3416 
                 UAUCCAUGAACUUCA 
                 1152- 
               
               
                 122293 
                 228225 
                   
                 AUGGAUA 
                 1174 
                 2282252. 
                   
                 CCACUUCG 
                 1174 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2968 
                 AGUGGUGAAGUUCA 
                 1155- 
                 A- 
                 3417 
                 UCAUCCAUGAACUUC 
                 1153- 
               
               
                 122293 
                 228225 
                   
                 UGGAUGA 
                 1175 
                 2282254. 
                   
                 ACCACUUC 
                 1175 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2969 
                 GUGGUGAAGUUCAU 
                 1156- 
                 A- 
                 3418 
                 UACAUCCAUGAACUU 
                 1154- 
               
               
                 122293 
                 228225 
                   
                 GGAUGUA 
                 1176 
                 2282256. 
                   
                 CACCACUU 
                 1176 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2970 
                 GGUGAAGUUCAUGG 
                 1158- 
                 A- 
                 3419 
                 UAGACAUCCAUGAAC 
                 1156- 
               
               
                 122293 
                 228225 
                   
                 AUGUCUA 
                 1178 
                 2282258. 
                   
                 UUCACCAC 
                 1178 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2971 
                 GUGAAGUUCAUGGA 
                 1159- 
                 A- 
                 3420 
                 UUAGACAUCCAUGAA 
                 1157- 
               
               
                 122294 
                 228225 
                   
                 UGUCUAA 
                 1179 
                 2282260. 
                   
                 CUUCACCA 
                 1179 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2972 
                 UGAAGUUCAUGGAU 
                 1160- 
                 A- 
                 3421 
                 UAUAGACAUCCAUGA 
                 1158- 
               
               
                 122294 
                 228226 
                   
                 GUCUAUA 
                 1180 
                 2282262. 
                   
                 ACUUCACC 
                 1180 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2973 
                 AAGUUCAUGGAUGU 
                 1162- 
                 A- 
                 3422 
                 UUGAUAGACAUCCAU 
                 1160- 
               
               
                 122294 
                 228226 
                   
                 CUAUCAA 
                 1182 
                 2282264. 
                   
                 GAACUUCA 
                 1182 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2974 
                 AGUUCAUGGAUGUC 
                 1163- 
                 A- 
                 3423 
                 UCUGAUAGACAUCCA 
                 1161- 
               
               
                 122294 
                 228226 
                   
                 UAUCAGA 
                 1183 
                 2282266. 
                   
                 UGAACUUC 
                 1183 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2975 
                 UUCAUGGAUGUCUA 
                 1165- 
                 A- 
                 3424 
                 UCGCUGAUAGACAUC 
                 1163- 
               
               
                 122294 
                 228226 
                   
                 UCAGCGA 
                 1185 
                 2282268. 
                   
                 CAUGAACU 
                 1185 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2976 
                 GUGGACAUCUUCCAG 
                 1213- 
                 A- 
                 3425 
                 UUACUCCUGGAAGAU 
                 1211- 
               
               
                 122294 
                 228226 
                   
                 GAGUAA 
                 1233 
                 2282270. 
                   
                 GUCCACCA 
                 1233 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2977 
                 UCGAGUACAUCUUCA 
                 1244- 
                 A- 
                 3426 
                 UUGGCUUGAAGAUGU 
                 1242- 
               
               
                 122294 
                 228227 
                   
                 AGCCAA 
                 1264 
                 2282272. 
                   
                 ACUCGAUC 
                 1264 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2978 
                 CGAGUACAUCUUCAA 
                 1245- 
                 A- 
                 3427 
                 UAUGGCUUGAAGAUG 
                 1243- 
               
               
                 122294 
                 228227 
                   
                 GCCAUA 
                 1265 
                 2282274. 
                   
                 UACUCGAU 
                 1265 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2979 
                 GAGUACAUCUUCAAG 
                 1246- 
                 A- 
                 3428 
                 UGAUGGCUUGAAGAU 
                 1244- 
               
               
                 122294 
                 228227 
                   
                 CCAUCA 
                 1266 
                 2282276. 
                   
                 GUACUCGA 
                 1266 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2980 
                 GUACAUCUUCAAGCC 
                 1248- 
                 A- 
                 3429 
                 UAGGAUGGCUUGAAG 
                 1246- 
               
               
                 122294 
                 228227 
                   
                 AUCCUA 
                 1268 
                 2282278. 
                   
                 AUGUACUC 
                 1268 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2981 
                 CCAACAUCACCAUGC 
                 1337- 
                 A- 
                 3430 
                 UAAUCUGCAUGGUGA 
                 1335- 
               
               
                 122295 
                 228227 
                   
                 AGAUUA 
                 1357 
                 2282280. 
                   
                 UGUUGGAC 
                 1357 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2982 
                 CAACAUCACCAUGCA 
                 1338- 
                 A- 
                 3431 
                 UUAAUCUGCAUGGUG 
                 1336- 
               
               
                 122295 
                 228228 
                   
                 GAUUAA 
                 1358 
                 2282282. 
                   
                 AUGUUGGA 
                 1358 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2983 
                 ACAUCACCAUGCAGA 
                 1340- 
                 A- 
                 3432 
                 UCAUAAUCUGCAUGG 
                 1338- 
               
               
                 122295 
                 228228 
                   
                 UUAUGA 
                 1360 
                 2282284. 
                   
                 UGAUGUUG 
                 1360 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2984 
                 CAUCACCAUGCAGAU 
                 1341- 
                 A- 
                 3433 
                 UGCAUAAUCUGCAUG 
                 1339- 
               
               
                 122295 
                 228228 
                   
                 UAUGCA 
                 1361 
                 2282286. 
                   
                 GUGAUGUU 
                 1361 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2985 
                 ACCAUGCAGAUUAUG 
                 1345- 
                 A- 
                 3434 
                 UAUCCGCAUAAUCUG 
                 1343- 
               
               
                 122295 
                 228228 
                   
                 CGGAUA 
                 1365 
                 2282288. 
                   
                 CAUGGUGA 
                 1365 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2986 
                 AUGCAGAUUAUGCG 
                 1348- 
                 A- 
                 3435 
                 UUUGAUCCGCAUAAU 
                 1346- 
               
               
                 122295 
                 228228 
                   
                 GAUCAAA 
                 1368 
                 2282290. 
                   
                 CUGCAUGG 
                 1368 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2987 
                 UGCAGAUUAUGCGG 
                 1349- 
                 A- 
                 3436 
                 UUUUGAUCCGCAUAA 
                 1347- 
               
               
                 122295 
                 228229 
                   
                 AUCAAAA 
                 1369 
                 2282292. 
                   
                 UCUGCAUG 
                 1369 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2988 
                 GCAGAUUAUGCGGA 
                 1350- 
                 A- 
                 3437 
                 UGUUUGAUCCGCAUA 
                 1348- 
               
               
                 122295 
                 228229 
                   
                 UCAAACA 
                 1370 
                 2282294. 
                   
                 AUCUGCAU 
                 1370 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2989 
                 GAUUAUGCGGAUCA 
                 1353- 
                 A- 
                 3438 
                 UGAGGUUUGAUCCGC 
                 1351- 
               
               
                 122295 
                 228229 
                   
                 AACCUCA 
                 1373 
                 2282296. 
                   
                 AUAAUCUG 
                 1373 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2990 
                 AUUAUGCGGAUCAA 
                 1354- 
                 A- 
                 3439 
                 UUGAGGUUUGAUCCG 
                 1352- 
               
               
                 122295 
                 228229 
                   
                 ACCUCAA 
                 1374 
                 2282298. 
                   
                 CAUAAUCU 
                 1374 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2991 
                 CGGAUCAAACCUCAC 
                 1360- 
                 A- 
                 3440 
                 UCCUUGGUGAGGUUU 
                 1358- 
               
               
                 122296 
                 228229 
                   
                 CAAGGA 
                 1380 
                 2282300. 
                   
                 GAUCCGCA 
                 1380 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2992 
                 GGAGAGAUGAGCUU 
                 1390- 
                 A- 
                 3441 
                 UUGUAGGAAGCUCAU 
                 1388- 
               
               
                 122296 
                 228230 
                   
                 CCUACAA 
                 1410 
                 2282302. 
                   
                 CUCUCCUA 
                 1410 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2993 
                 GAGAUGAGCUUCCUA 
                 1393- 
                 A- 
                 3442 
                 UUGCUGUAGGAAGCU 
                 1391- 
               
               
                 122296 
                 228230 
                   
                 CAGCAA 
                 1413 
                 2282304. 
                   
                 CAUCUCUC 
                 1413 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2994 
                 GAUGAGCUUCCUACA 
                 1395- 
                 A- 
                 3443 
                 UUGUGCUGUAGGAAG 
                 1393- 
               
               
                 122296 
                 228230 
                   
                 GCACAA 
                 1415 
                 2282306. 
                   
                 CUCAUCUC 
                 1415 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2995 
                 AUGAGCUUCCUACAG 
                 1396- 
                 A- 
                 3444 
                 UUUGUGCUGUAGGAA 
                 1394- 
               
               
                 122296 
                 228230 
                   
                 CACAAA 
                 1416 
                 2282308. 
                   
                 GCUCAUCU 
                 1416 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2996 
                 GAGCUUCCUACAGCA 
                 1398- 
                 A- 
                 3445 
                 UUGUUGUGCUGUAGG 
                 1396- 
               
               
                 122296 
                 228230 
                   
                 CAACAA 
                 1418 
                 2282310. 
                   
                 AAGCUCAU 
                 1418 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2997 
                 AGCUUCCUACAGCAC 
                 1399- 
                 A- 
                 3446 
                 UUUGUUGUGCUGUAG 
                 1397- 
               
               
                 122296 
                 228231 
                   
                 AACAAA 
                 1419 
                 2282312. 
                   
                 GAAGCUCA 
                 1419 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2998 
                 GCUUCCUACAGCACA 
                 1400- 
                 A- 
                 3447 
                 UUUUGUUGUGCUGUA 
                 1398- 
               
               
                 122296 
                 228231 
                   
                 ACAAAA 
                 1420 
                 2282314. 
                   
                 GGAAGCUC 
                 1420 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2999 
                 CUUCCUACAGCACAA 
                 1401- 
                 A- 
                 3448 
                 UAUUUGUUGUGCUGU 
                 1399- 
               
               
                 122296 
                 228231 
                   
                 CAAAUA 
                 1421 
                 2282316. 
                   
                 AGGAAGCU 
                 1421 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3000 
                 UCCUACAGCACAACA 
                 1403- 
                 A- 
                 3449 
                 UACAUUUGUUGUGCU 
                 1401- 
               
               
                 122296 
                 228231 
                   
                 AAUGUA 
                 1423 
                 2282318. 
                   
                 GUAGGAAG 
                 1423 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3001 
                 CUACAGCACAACAAA 
                 1405- 
                 A- 
                 3450 
                 UUCACAUUUGUUGUG 
                 1403- 
               
               
                 122297 
                 228231 
                   
                 UGUGAA 
                 1425 
                 2282320. 
                   
                 CUGUAGGA 
                 1425 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3002 
                 UACAGCACAACAAAU 
                 1406- 
                 A- 
                 3451 
                 UUUCACAUUUGUUGU 
                 1404- 
               
               
                 122297 
                 228232 
                   
                 GUGAAA 
                 1426 
                 2282322. 
                   
                 GCUGUAGG 
                 1426 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3003 
                 AGCACAACAAAUGUG 
                 1409- 
                 A- 
                 3452 
                 UGCAUUCACAUUUGU 
                 1407- 
               
               
                 122297 
                 228232 
                   
                 AAUGCA 
                 1429 
                 2282324. 
                   
                 UGUGCUGU 
                 1429 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3004 
                 GCACAACAAAUGUGA 
                 1410- 
                 A- 
                 3453 
                 UUGCAUUCACAUUUG 
                 1408- 
               
               
                 122297 
                 228232 
                   
                 AUGCAA 
                 1430 
                 2282326. 
                   
                 UUGUGCUG 
                 1430 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3005 
                 CUCACCAGGAAAGAC 
                 1786- 
                 A- 
                 3454 
                 UUAUCAGUCUUUCCU 
                 1784- 
               
               
                 122297 
                 228232 
                   
                 UGAUAA 
                 1806 
                 2282328. 
                   
                 GGUGAGAG 
                 1806 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3006 
                 UCACCAGGAAAGACU 
                 1787- 
                 A- 
                 3455 
                 UGUAUCAGUCUUUCC 
                 1785- 
               
               
                 122297 
                 228232 
                   
                 GAUACA 
                 1807 
                 2282330. 
                   
                 UGGUGAGA 
                 1807 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3007 
                 CACCAGGAAAGACUG 
                 1788- 
                 A- 
                 3456 
                 UUGUAUCAGUCUUUC 
                 1786- 
               
               
                 122297 
                 228233 
                   
                 AUACAA 
                 1808 
                 2282332. 
                   
                 CUGGUGAG 
                 1808 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3008 
                 ACCAGGAAAGACUGA 
                 1789- 
                 A- 
                 3457 
                 UCUGUAUCAGUCUUU 
                 1787- 
               
               
                 122297 
                 228233 
                   
                 UACAGA 
                 1809 
                 2282334. 
                   
                 CCUGGUGA 
                 1809 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3009 
                 CCAGGAAAGACUGAU 
                 1790- 
                 A- 
                 3458 
                 UUCUGUAUCAGUCUU 
                 1788- 
               
               
                 122297 
                 228233 
                   
                 ACAGAA 
                 1810 
                 2282336. 
                   
                 UCCUGGUG 
                 1810 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3010 
                 CAGGAAAGACUGAU 
                 1791- 
                 A- 
                 3459 
                 UUUCUGUAUCAGUCU 
                 1789- 
               
               
                 122297 
                 228233 
                   
                 ACAGAAA 
                 1811 
                 2282338. 
                   
                 UUCCUGGU 
                 1811 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3011 
                 AGGAAAGACUGAUA 
                 1792- 
                 A- 
                 3460 
                 UGUUCUGUAUCAGUC 
                 1790- 
               
               
                 122298 
                 228233 
                   
                 CAGAACA 
                 1812 
                 2282340. 
                   
                 UUUCCUGG 
                 1812 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3012 
                 GGAAAGACUGAUAC 
                 1793- 
                 A- 
                 3461 
                 UCGUUCUGUAUCAGU 
                 1791- 
               
               
                 122298 
                 228234 
                   
                 AGAACGA 
                 1813 
                 2282342. 
                   
                 CUUUCCUG 
                 1813 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3013 
                 GAAAGACUGAUACA 
                 1794- 
                 A- 
                 3462 
                 UUCGUUCUGUAUCAG 
                 1792- 
               
               
                 122298 
                 228234 
                   
                 GAACGAA 
                 1814 
                 2282344. 
                   
                 UCUUUCCU 
                 1814 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3014 
                 AAAGACUGAUACAG 
                 1795- 
                 A- 
                 3463 
                 UAUCGUUCUGUAUCA 
                 1793- 
               
               
                 122298 
                 228234 
                   
                 AACGAUA 
                 1815 
                 2282346. 
                   
                 GUCUUUCC 
                 1815 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3015 
                 AAGACUGAUACAGA 
                 1796- 
                 A- 
                 3464 
                 UGAUCGUUCUGUAUC 
                 1794- 
               
               
                 122298 
                 228234 
                   
                 ACGAUCA 
                 1816 
                 2282348. 
                   
                 AGUCUUUC 
                 1816 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3016 
                 AGACUGAUACAGAAC 
                 1797- 
                 A- 
                 3465 
                 UCGAUCGUUCUGUAU 
                 1795- 
               
               
                 122298 
                 228234 
                   
                 GAUCGA 
                 1817 
                 2282350. 
                   
                 CAGUCUUU 
                 1817 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3017 
                 GACUGAUACAGAACG 
                 1798- 
                 A- 
                 3466 
                 UUCGAUCGUUCUGUA 
                 1796- 
               
               
                 122298 
                 228235 
                   
                 AUCGAA 
                 1818 
                 2282352. 
                   
                 UCAGUCUU 
                 1818 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3018 
                 ACUGAUACAGAACGA 
                 1799- 
                 A- 
                 3467 
                 UAUCGAUCGUUCUGU 
                 1797- 
               
               
                 122298 
                 228235 
                   
                 UCGAUA 
                 1819 
                 2282354. 
                   
                 AUCAGUCU 
                 1819 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3019 
                 CUGAUACAGAACGAU 
                 1800- 
                 A- 
                 3468 
                 UUAUCGAUCGUUCUG 
                 1798- 
               
               
                 122298 
                 228235 
                   
                 CGAUAA 
                 1820 
                 2282356. 
                   
                 UAUCAGUC 
                 1820 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3020 
                 UGAUACAGAACGAUC 
                 1801- 
                 A- 
                 3469 
                 UGUAUCGAUCGUUCU 
                 1799- 
               
               
                 122298 
                 228235 
                   
                 GAUACA 
                 1821 
                 2282358. 
                   
                 GUAUCAGU 
                 1821 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3021 
                 GAUACAGAACGAUCG 
                 1802- 
                 A- 
                 3470 
                 UUGUAUCGAUCGUUC 
                 1800- 
               
               
                 122299 
                 228235 
                   
                 AUACAA 
                 1822 
                 2282360. 
                   
                 UGUAUCAG 
                 1822 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3022 
                 AUACAGAACGAUCGA 
                 1803- 
                 A- 
                 3471 
                 UCUGUAUCGAUCGUU 
                 1801- 
               
               
                 122299 
                 228236 
                   
                 UACAGA 
                 1823 
                 2282362. 
                   
                 CUGUAUCA 
                 1823 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3023 
                 UACAGAACGAUCGAU 
                 1804- 
                 A- 
                 3472 
                 UUCUGUAUCGAUCGU 
                 1802- 
               
               
                 122299 
                 228236 
                   
                 ACAGAA 
                 1824 
                 2282364. 
                   
                 UCUGUAUC 
                 1824 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3024 
                 ACAGAACGAUCGAUA 
                 1805- 
                 A- 
                 3473 
                 UUUCUGUAUCGAUCG 
                 1803- 
               
               
                 122299 
                 228236 
                   
                 CAGAAA 
                 1825 
                 2282366. 
                   
                 UUCUGUAU 
                 1825 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3025 
                 CAGAACGAUCGAUAC 
                 1806- 
                 A- 
                 3474 
                 UUUUCUGUAUCGAUC 
                 1804- 
               
               
                 122299 
                 228236 
                   
                 AGAAAA 
                 1826 
                 2282368. 
                   
                 GUUCUGUA 
                 1826 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3026 
                 AGAACGAUCGAUACA 
                 1807- 
                 A- 
                 3475 
                 UGUUUCUGUAUCGAU 
                 1805- 
               
               
                 122299 
                 228236 
                   
                 GAAACA 
                 1827 
                 2282370. 
                   
                 CGUUCUGU 
                 1827 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3027 
                 GAACGAUCGAUACAG 
                 1808- 
                 A- 
                 3476 
                 UGGUUUCUGUAUCGA 
                 1806- 
               
               
                 122299 
                 228237 
                   
                 AAACCA 
                 1828 
                 2282372. 
                   
                 UCGUUCUG 
                 1828 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3028 
                 AACGAUCGAUACAGA 
                 1809- 
                 A- 
                 3477 
                 UUGGUUUCUGUAUCG 
                 1807- 
               
               
                 122299 
                 228237 
                   
                 AACCAA 
                 1829 
                 2282374. 
                   
                 AUCGUUCU 
                 1829 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3029 
                 ACGAUCGAUACAGAA 
                 1810- 
                 A- 
                 3478 
                 UGUGGUUUCUGUAUC 
                 1808- 
               
               
                 122299 
                 228237 
                   
                 ACCACA 
                 1830 
                 2282376. 
                   
                 GAUCGUUC 
                 1830 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3030 
                 CGAUCGAUACAGAAA 
                 1811- 
                 A- 
                 3479 
                 UCGUGGUUUCUGUAU 
                 1809- 
               
               
                 122299 
                 228237 
                   
                 CCACGA 
                 1831 
                 2282378. 
                   
                 CGAUCGUU 
                 1831 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3031 
                 CACCAUCACCAUCGA 
                 1843- 
                 A- 
                 3480 
                 UUUCUGUCGAUGGUG 
                 1841- 
               
               
                 122300 
                 228237 
                   
                 CAGAAA 
                 1863 
                 2282380. 
                   
                 AUGGUGUG 
                 1863 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3032 
                 CAUCACCAUCGACAG 
                 1846- 
                 A- 
                 3481 
                 UCUGUUCUGUCGAUG 
                 1844- 
               
               
                 122300 
                 228238 
                   
                 AACAGA 
                 1866 
                 2282382. 
                   
                 GUGAUGGU 
                 1866 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3033 
                 UCACCAUCGACAGAA 
                 1848- 
                 A- 
                 3482 
                 UGACUGUUCUGUCGA 
                 1846- 
               
               
                 122300 
                 228238 
                   
                 CAGUCA 
                 1868 
                 2282384. 
                   
                 UGGUGAUG 
                 1868 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3034 
                 CACCAUCGACAGAAC 
                 1849- 
                 A- 
                 3483 
                 UGGACUGUUCUGUCG 
                 1847- 
               
               
                 122300 
                 228238 
                   
                 AGUCCA 
                 1869 
                 2282386. 
                   
                 AUGGUGAU 
                 1869 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3035 
                 ACCAUCGACAGAACA 
                 1850- 
                 A- 
                 3484 
                 UAGGACUGUUCUGUC 
                 1848- 
               
               
                 122300 
                 228238 
                   
                 GUCCUA 
                 1870 
                 2282388. 
                   
                 GAUGGUGA 
                 1870 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3036 
                 CCAUCGACAGAACAG 
                 1851- 
                 A- 
                 3485 
                 UAAGGACUGUUCUGU 
                 1849- 
               
               
                 122300 
                 228238 
                   
                 UCCUUA 
                 1871 
                 2282390. 
                   
                 CGAUGGUG 
                 1871 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3037 
                 CAUCGACAGAACAGU 
                 1852- 
                 A- 
                 3486 
                 UUAAGGACUGUUCUG 
                 1850- 
               
               
                 122300 
                 228239 
                   
                 CCUUAA 
                 1872 
                 2282392. 
                   
                 UCGAUGGU 
                 1872 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3038 
                 AUCGACAGAACAGUC 
                 1853- 
                 A- 
                 3487 
                 UUUAAGGACUGUUCU 
                 1851- 
               
               
                 122300 
                 228239 
                   
                 CUUAAA 
                 1873 
                 2282394. 
                   
                 GUCGAUGG 
                 1873 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3039 
                 UCGACAGAACAGUCC 
                 1854- 
                 A- 
                 3488 
                 UAUUAAGGACUGUUC 
                 1852- 
               
               
                 122300 
                 228239 
                   
                 UUAAUA 
                 1874 
                 2282396. 
                   
                 UGUCGAUG 
                 1874 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3040 
                 CGACAGAACAGUCCU 
                 1855- 
                 A- 
                 3489 
                 UGAUUAAGGACUGUU 
                 1853- 
               
               
                 122300 
                 228239 
                   
                 UAAUCA 
                 1875 
                 2282398. 
                   
                 CUGUCGAU 
                 1875 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3041 
                 GACAGAACAGUCCUU 
                 1856- 
                 A- 
                 3490 
                 UGGAUUAAGGACUGU 
                 1854- 
               
               
                 122301 
                 228239 
                   
                 AAUCCA 
                 1876 
                 2282400. 
                   
                 UCUGUCGA 
                 1876 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3042 
                 ACAGAACAGUCCUUA 
                 1857- 
                 A- 
                 3491 
                 UUGGAUUAAGGACUG 
                 1855- 
               
               
                 122301 
                 228240 
                   
                 AUCCAA 
                 1877 
                 2282402. 
                   
                 UUCUGUCG 
                 1877 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3043 
                 AGAACAGUCCUUAAU 
                 1859- 
                 A- 
                 3492 
                 UUCUGGAUUAAGGAC 
                 1857- 
               
               
                 122301 
                 228240 
                   
                 CCAGAA 
                 1879 
                 2282404. 
                   
                 UGUUCUGU 
                 1879 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3044 
                 GAACAGUCCUUAAUC 
                 1860- 
                 A- 
                 3493 
                 UUUCUGGAUUAAGGA 
                 1858- 
               
               
                 122301 
                 228240 
                   
                 CAGAAA 
                 1880 
                 2282406. 
                   
                 CUGUUCUG 
                 1880 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3045 
                 AACAGUCCUUAAUCC 
                 1861- 
                 A- 
                 3494 
                 UUUUCUGGAUUAAGG 
                 1859- 
               
               
                 122301 
                 228240 
                   
                 AGAAAA 
                 1881 
                 2282408. 
                   
                 ACUGUUCU 
                 1881 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3046 
                 ACAGUCCUUAAUCCA 
                 1862- 
                 A- 
                 3495 
                 UGUUUCUGGAUUAAG 
                 1860- 
               
               
                 122301 
                 228240 
                   
                 GAAACA 
                 1882 
                 2282410. 
                   
                 GACUGUUC 
                 1882 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3047 
                 CAGUCCUUAAUCCAG 
                 1863- 
                 A- 
                 3496 
                 UGGUUUCUGGAUUAA 
                 1861- 
               
               
                 122301 
                 228241 
                   
                 AAACCA 
                 1883 
                 2282412. 
                   
                 GGACUGUU 
                 1883 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3048 
                 AGUCCUUAAUCCAGA 
                 1864- 
                 A- 
                 3497 
                 UAGGUUUCUGGAUUA 
                 1862- 
               
               
                 122301 
                 228241 
                   
                 AACCUA 
                 1884 
                 2282414. 
                   
                 AGGACUGU 
                 1884 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3049 
                 GUCCUUAAUCCAGAA 
                 1865- 
                 A- 
                 3498 
                 UCAGGUUUCUGGAUU 
                 1863- 
               
               
                 122301 
                 228241 
                   
                 ACCUGA 
                 1885 
                 2282416. 
                   
                 AAGGACUG 
                 1885 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3050 
                 UCCUUAAUCCAGAAA 
                 1866- 
                 A- 
                 3499 
                 UUCAGGUUUCUGGAU 
                 1864- 
               
               
                 122301 
                 228241 
                   
                 CCUGAA 
                 1886 
                 2282418. 
                   
                 UAAGGACU 
                 1886 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3051 
                 CCUUAAUCCAGAAAC 
                 1867- 
                 A- 
                 3500 
                 UUUCAGGUUUCUGGA 
                 1865- 
               
               
                 122302 
                 228241 
                   
                 CUGAAA 
                 1887 
                 2282420. 
                   
                 UUAAGGAC 
                 1887 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3052 
                 CUUAAUCCAGAAACC 
                 1868- 
                 A- 
                 3501 
                 UUUUCAGGUUUCUGG 
                 1866- 
               
               
                 122302 
                 228242 
                   
                 UGAAAA 
                 1888 
                 2282422. 
                   
                 AUUAAGGA 
                 1888 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3053 
                 UUAAUCCAGAAACCU 
                 1869- 
                 A- 
                 3502 
                 UAUUUCAGGUUUCUG 
                 1867- 
               
               
                 122302 
                 228242 
                   
                 GAAAUA 
                 1889 
                 2282424. 
                   
                 GAUUAAGG 
                 1889 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3054 
                 CAGAAACCUGAAAUG 
                 1875- 
                 A- 
                 3503 
                 UUCCUUCAUUUCAGG 
                 1873- 
               
               
                 122302 
                 228242 
                   
                 AAGGAA 
                 1895 
                 2282426. 
                   
                 UUUCUGGA 
                 1895 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3055 
                 AGAAACCUGAAAUG 
                 1876- 
                 A- 
                 3504 
                 UUUCCUUCAUUUCAG 
                 1874- 
               
               
                 122302 
                 228242 
                   
                 AAGGAAA 
                 1896 
                 2282428. 
                   
                 GUUUCUGG 
                 1896 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3056 
                 GAAACCUGAAAUGA 
                 1877- 
                 A- 
                 3505 
                 UCUUCCUUCAUUUCA 
                 1875- 
               
               
                 122302 
                 228242 
                   
                 AGGAAGA 
                 1897 
                 2282430. 
                   
                 GGUUUCUG 
                 1897 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3057 
                 AAACCUGAAAUGAA 
                 1878- 
                 A- 
                 3506 
                 UUCUUCCUUCAUUUC 
                 1876- 
               
               
                 122302 
                 228243 
                   
                 GGAAGAA 
                 1898 
                 2282432. 
                   
                 AGGUUUCU 
                 1898 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3058 
                 AACCUGAAAUGAAG 
                 1879- 
                 A- 
                 3507 
                 UCUCUUCCUUCAUUU 
                 1877- 
               
               
                 122302 
                 228243 
                   
                 GAAGAGA 
                 1899 
                 2282434. 
                   
                 CAGGUUUC 
                 1899 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3059 
                 CCUGAAAUGAAGGA 
                 1881- 
                 A- 
                 3508 
                 UUCCUCUUCCUUCAU 
                 1879- 
               
               
                 122302 
                 228243 
                   
                 AGAGGAA 
                 1901 
                 2282436. 
                   
                 UUCAGGUU 
                 1901 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3060 
                 AUGAAGGAAGAGGA 
                 1887- 
                 A- 
                 3509 
                 UAGAGUCUCCUCUUC 
                 1885- 
               
               
                 122302 
                 228243 
                   
                 GACUCUA 
                 1907 
                 2282438. 
                   
                 CUUCAUUU 
                 1907 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3061 
                 UCCCUCUUGGAAUUG 
                 1977- 
                 A- 
                 3510 
                 UGAAUCCAAUUCCAA 
                 1975- 
               
               
                 122303 
                 228243 
                   
                 GAUUCA 
                 1997 
                 2282440. 
                   
                 GAGGGACC 
                 1997 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3062 
                 CCUCUUGGAAUUGGA 
                 1979- 
                 A- 
                 3511 
                 UGCGAAUCCAAUUCC 
                 1977- 
               
               
                 122303 
                 228244 
                   
                 UUCGCA 
                 1999 
                 2282442. 
                   
                 AAGAGGGA 
                 1999 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3063 
                 CUCUUGGAAUUGGA 
                 1980- 
                 A- 
                 3512 
                 UGGCGAAUCCAAUUC 
                 1978- 
               
               
                 122303 
                 228244 
                   
                 UUCGCCA 
                 2000 
                 2282444. 
                   
                 CAAGAGGG 
                 2000 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3064 
                 UUGGAAUUGGAUUC 
                 1983- 
                 A- 
                 3513 
                 UAAUGGCGAAUCCAA 
                 1981- 
               
               
                 122303 
                 228244 
                   
                 GCCAUUA 
                 2003 
                 2282446. 
                   
                 UUCCAAGA 
                 2003 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3065 
                 UGGAAUUGGAUUCG 
                 1984- 
                 A- 
                 3514 
                 UAAAUGGCGAAUCCA 
                 1982- 
               
               
                 122303 
                 228244 
                   
                 CCAUUUA 
                 2004 
                 2282448. 
                   
                 AUUCCAAG 
                 2004 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3066 
                 GGAAUUGGAUUCGCC 
                 1985- 
                 A- 
                 3515 
                 UAAAAUGGCGAAUCC 
                 1983- 
               
               
                 122303 
                 228244 
                   
                 AUUUUA 
                 2005 
                 2282450. 
                   
                 AAUUCCAA 
                 2005 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3067 
                 GAAUUGGAUUCGCCA 
                 1986- 
                 A- 
                 3516 
                 UUAAAAUGGCGAAUC 
                 1984- 
               
               
                 122303 
                 228245 
                   
                 UUUUAA 
                 2006 
                 2282452. 
                   
                 CAAUUCCA 
                 2006 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3068 
                 AAUUGGAUUCGCCAU 
                 1987- 
                 A- 
                 3517 
                 UAUAAAAUGGCGAAU 
                 1985- 
               
               
                 122303 
                 228245 
                   
                 UUUAUA 
                 2007 
                 2282454. 
                   
                 CCAAUUCC 
                 2007 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3069 
                 AUUGGAUUCGCCAUU 
                 1988- 
                 A- 
                 3518 
                 UAAUAAAAUGGCGAA 
                 1986- 
               
               
                 122303 
                 228245 
                   
                 UUAUUA 
                 2008 
                 2282456. 
                   
                 UCCAAUUC 
                 2008 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3070 
                 UUGGAUUCGCCAUUU 
                 1989- 
                 A- 
                 3519 
                 UAAAUAAAAUGGCGA 
                 1987- 
               
               
                 122303 
                 228245 
                   
                 UAUUUA 
                 2009 
                 2282458. 
                   
                 AUCCAAUU 
                 2009 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3071 
                 UGGAUUCGCCAUUUU 
                 1990- 
                 A- 
                 3520 
                 UAAAAUAAAAUGGCG 
                 1988- 
               
               
                 122304 
                 228245 
                   
                 AUUUUA 
                 2010 
                 2282460. 
                   
                 AAUCCAAU 
                 2010 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3072 
                 GGAUUCGCCAUUUUA 
                 1991- 
                 A- 
                 3521 
                 UAAAAAUAAAAUGGC 
                 1989- 
               
               
                 122304 
                 228246 
                   
                 UUUUUA 
                 2011 
                 2282462. 
                   
                 GAAUCCAA 
                 2011 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3073 
                 GAUUCGCCAUUUUAU 
                 1992- 
                 A- 
                 3522 
                 UGAAAAAUAAAAUGG 
                 1990- 
               
               
                 122304 
                 228246 
                   
                 UUUUCA 
                 2012 
                 2282464. 
                   
                 CGAAUCCA 
                 2012 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3074 
                 UCGCCAUUUUAUUUU 
                 1995- 
                 A- 
                 3523 
                 UCAAGAAAAAUAAAA 
                 1993- 
               
               
                 122304 
                 228246 
                   
                 UCUUGA 
                 2015 
                 2282466. 
                   
                 UGGCGAAU 
                 2015 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3075 
                 CGCCAUUUUAUUUUU 
                 1996- 
                 A- 
                 3524 
                 UGCAAGAAAAAUAAA 
                 1994- 
               
               
                 122304 
                 228246 
                   
                 CUUGCA 
                 2016 
                 2282468. 
                   
                 AUGGCGAA 
                 2016 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3076 
                 GCCAUUUUAUUUUUC 
                 1997- 
                 A- 
                 3525 
                 UAGCAAGAAAAAUAA 
                 1995- 
               
               
                 122304 
                 228246 
                   
                 UUGCUA 
                 2017 
                 2282470. 
                   
                 AAUGGCGA 
                 2017 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3077 
                 CCAUUUUAUUUUUCU 
                 1998- 
                 A- 
                 3526 
                 UCAGCAAGAAAAAUA 
                 1996- 
               
               
                 122304 
                 228247 
                   
                 UGCUGA 
                 2018 
                 2282472. 
                   
                 AAAUGGCG 
                 2018 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3078 
                 CAUUUUAUUUUUCU 
                 1999- 
                 A- 
                 3527 
                 UGCAGCAAGAAAAAU 
                 1997- 
               
               
                 122304 
                 228247 
                   
                 UGCUGCA 
                 2019 
                 2282474. 
                   
                 AAAAUGGC 
                 2019 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3079 
                 AUUUUAUUUUUCUU 
                 2000- 
                 A- 
                 3528 
                 UAGCAGCAAGAAAAA 
                 1998- 
               
               
                 122304 
                 228247 
                   
                 GCUGCUA 
                 2020 
                 2282476. 
                   
                 UAAAAUGG 
                 2020 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3080 
                 UUUUAUUUUUCUUG 
                 2001- 
                 A- 
                 3529 
                 UUAGCAGCAAGAAAA 
                 1999- 
               
               
                 122304 
                 228247 
                   
                 CUGCUAA 
                 2021 
                 2282478. 
                   
                 AUAAAAUG 
                 2021 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3081 
                 UUUCUUGCUGCUAAA 
                 2008- 
                 A- 
                 3530 
                 UGGUGAUUUAGCAGC 
                 2006- 
               
               
                 122305 
                 228247 
                   
                 UCACCA 
                 2028 
                 2282480. 
                   
                 AAGAAAAA 
                 2028 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3082 
                 UCACCGAGCCCGGAA 
                 2023- 
                 A- 
                 3531 
                 UUAAUCUUCCGGGCU 
                 2021- 
               
               
                 122305 
                 228248 
                   
                 GAUUAA 
                 2043 
                 2282482. 
                   
                 CGGUGAUU 
                 2043 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3083 
                 GCCCGGAAGAUUAGA 
                 2030- 
                 A- 
                 3532 
                 UAACUCUCUAAUCUU 
                 2028- 
               
               
                 122305 
                 228248 
                   
                 GAGUUA 
                 2050 
                 2282484. 
                   
                 CCGGGCUC 
                 2050 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3084 
                 CCCGGAAGAUUAGAG 
                 2031- 
                 A- 
                 3533 
                 UAAACUCUCUAAUCU 
                 2029- 
               
               
                 122305 
                 228248 
                   
                 AGUUUA 
                 2051 
                 2282486. 
                   
                 UCCGGGCU 
                 2051 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3085 
                 CGGAAGAUUAGAGA 
                 2033- 
                 A- 
                 3534 
                 UUAAAACUCUCUAAU 
                 2031- 
               
               
                 122305 
                 228248 
                   
                 GUUUUAA 
                 2053 
                 2282488. 
                   
                 CUUCCGGG 
                 2053 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3086 
                 GGAAGAUUAGAGAG 
                 2034- 
                 A- 
                 3535 
                 UAUAAAACUCUCUAA 
                 2032- 
               
               
                 122305 
                 228248 
                   
                 UUUUAUA 
                 2054 
                 2282490. 
                   
                 UCUUCCGG 
                 2054 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3087 
                 GAAGAUUAGAGAGU 
                 2035- 
                 A- 
                 3536 
                 UAAUAAAACUCUCUA 
                 2033- 
               
               
                 122305 
                 228249 
                   
                 UUUAUUA 
                 2055 
                 2282492. 
                   
                 AUCUUCCG 
                 2055 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3088 
                 AAGAUUAGAGAGUU 
                 2036- 
                 A- 
                 3537 
                 UAAAUAAAACUCUCU 
                 2034- 
               
               
                 122305 
                 228249 
                   
                 UUAUUUA 
                 2056 
                 2282494. 
                   
                 AAUCUUCC 
                 2056 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3089 
                 AGAUUAGAGAGUUU 
                 2037- 
                 A- 
                 3538 
                 UGAAAUAAAACUCUC 
                 2035- 
               
               
                 122305 
                 228249 
                   
                 UAUUUCA 
                 2057 
                 2282496. 
                   
                 UAAUCUUC 
                 2057 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3090 
                 AUUAGAGAGUUUUA 
                 2039- 
                 A- 
                 3539 
                 UCAGAAAUAAAACUC 
                 2037- 
               
               
                 122305 
                 228249 
                   
                 UUUCUGA 
                 2059 
                 2282498. 
                   
                 UCUAAUCU 
                 2059 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3091 
                 UUAGAGAGUUUUAU 
                 2040- 
                 A- 
                 3540 
                 UCCAGAAAUAAAACU 
                 2038- 
               
               
                 122306 
                 228249 
                   
                 UUCUGGA 
                 2060 
                 2282500. 
                   
                 CUCUAAUC 
                 2060 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3092 
                 UAGAGAGUUUUAUU 
                 2041- 
                 A- 
                 3541 
                 UCCCAGAAAUAAAAC 
                 2039- 
               
               
                 122306 
                 228250 
                   
                 UCUGGGA 
                 2061 
                 2282502. 
                   
                 UCUCUAAU 
                 2061 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3093 
                 AGAGAGUUUUAUUU 
                 2042- 
                 A- 
                 3542 
                 UUCCCAGAAAUAAAA 
                 2040- 
               
               
                 122306 
                 228250 
                   
                 CUGGGAA 
                 2062 
                 2282504. 
                   
                 CUCUCUAA 
                 2062 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3094 
                 GAGAGUUUUAUUUC 
                 2043- 
                 A- 
                 3543 
                 UAUCCCAGAAAUAAA 
                 2041- 
               
               
                 122306 
                 228250 
                   
                 UGGGAUA 
                 2063 
                 2282506. 
                   
                 ACUCUCUA 
                 2063 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3095 
                 AGAGUUUUAUUUCU 
                 2044- 
                 A- 
                 3544 
                 UAAUCCCAGAAAUAA 
                 2042- 
               
               
                 122306 
                 228250 
                   
                 GGGAUUA 
                 2064 
                 2282508. 
                   
                 AACUCUCU 
                 2064 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3096 
                 GAGUUUUAUUUCUG 
                 2045- 
                 A- 
                 3545 
                 UGAAUCCCAGAAAUA 
                 2043- 
               
               
                 122306 
                 228250 
                   
                 GGAUUCA 
                 2065 
                 2282510. 
                   
                 AAACUCUC 
                 2065 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3097 
                 AGUUUUAUUUCUGG 
                 2046- 
                 A- 
                 3546 
                 UGGAAUCCCAGAAAU 
                 2044- 
               
               
                 122306 
                 228251 
                   
                 GAUUCCA 
                 2066 
                 2282512. 
                   
                 AAAACUCU 
                 2066 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3098 
                 GUUUUAUUUCUGGG 
                 2047- 
                 A- 
                 3547 
                 UAGGAAUCCCAGAAA 
                 2045- 
               
               
                 122306 
                 228251 
                   
                 AUUCCUA 
                 2067 
                 2282514. 
                   
                 UAAAACUC 
                 2067 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3099 
                 UUUUAUUUCUGGGA 
                 2048- 
                 A- 
                 3548 
                 UCAGGAAUCCCAGAA 
                 2046- 
               
               
                 122306 
                 228251 
                   
                 UUCCUGA 
                 2068 
                 2282516. 
                   
                 AUAAAACU 
                 2068 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3100 
                 UUUAUUUCUGGGAU 
                 2049- 
                 A- 
                 3549 
                 UACAGGAAUCCCAGA 
                 2047- 
               
               
                 122306 
                 228251 
                   
                 UCCUGUA 
                 2069 
                 2282518. 
                   
                 AAUAAAAC 
                 2069 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3101 
                 UUAUUUCUGGGAUU 
                 2050- 
                 A- 
                 3550 
                 UUACAGGAAUCCCAG 
                 2048- 
               
               
                 122307 
                 228251 
                   
                 CCUGUAA 
                 2070 
                 2282520. 
                   
                 AAAUAAAA 
                 2070 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3102 
                 UAUUUCUGGGAUUCC 
                 2051- 
                 A- 
                 3551 
                 UCUACAGGAAUCCCA 
                 2049- 
               
               
                 122307 
                 228252 
                   
                 UGUAGA 
                 2071 
                 2282522. 
                   
                 GAAAUAAA 
                 2071 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3103 
                 AUUUCUGGGAUUCCU 
                 2052- 
                 A- 
                 3552 
                 UUCUACAGGAAUCCC 
                 2050- 
               
               
                 122307 
                 228252 
                   
                 GUAGAA 
                 2072 
                 2282524. 
                   
                 AGAAAUAA 
                 2072 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3104 
                 UUUCUGGGAUUCCUG 
                 2053- 
                 A- 
                 3553 
                 UGUCUACAGGAAUCC 
                 2051- 
               
               
                 122307 
                 228252 
                   
                 UAGACA 
                 2073 
                 2282526. 
                   
                 CAGAAAUA 
                 2073 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3105 
                 UCUGGGAUUCCUGUA 
                 2055- 
                 A- 
                 3554 
                 UGUGUCUACAGGAAU 
                 2053- 
               
               
                 122307 
                 228252 
                   
                 GACACA 
                 2075 
                 2282528. 
                   
                 CCCAGAAA 
                 2075 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3106 
                 CUGGGAUUCCUGUAG 
                 2056- 
                 A- 
                 3555 
                 UUGUGUCUACAGGAA 
                 2054- 
               
               
                 122307 
                 228252 
                   
                 ACACAA 
                 2076 
                 2282530. 
                   
                 UCCCAGAA 
                 2076 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3107 
                 UGGGAUUCCUGUAG 
                 2057- 
                 A- 
                 3556 
                 UGUGUGUCUACAGGA 
                 2055- 
               
               
                 122307 
                 228253 
                   
                 ACACACA 
                 2077 
                 2282532. 
                   
                 AUCCCAGA 
                 2077 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3108 
                 GGGAUUCCUGUAGAC 
                 2058- 
                 A- 
                 3557 
                 UGGUGUGUCUACAGG 
                 2056- 
               
               
                 122307 
                 228253 
                   
                 ACACCA 
                 2078 
                 2282534. 
                   
                 AAUCCCAG 
                 2078 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3109 
                 ACACACCCACCCACA 
                 2071- 
                 A- 
                 3558 
                 UAUGUAUGUGGGUGG 
                 2069- 
               
               
                 122307 
                 228253 
                   
                 UACAUA 
                 2091 
                 2282536. 
                   
                 GUGUGUCU 
                 2091 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3110 
                 ACCCACCCACAUACA 
                 2075- 
                 A- 
                 3559 
                 UAUGUAUGUAUGUGG 
                 2073- 
               
               
                 122307 
                 228253 
                   
                 UACAUA 
                 2095 
                 2282538. 
                   
                 GUGGGUGU 
                 2095 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3111 
                 CCCACCCACAUACAU 
                 2076- 
                 A- 
                 3560 
                 UAAUGUAUGUAUGUG 
                 2074- 
               
               
                 122308 
                 228253 
                   
                 ACAUUA 
                 2096 
                 2282540. 
                   
                 GGUGGGUG 
                 2096 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3112 
                 CCACCCACAUACAUA 
                 2077- 
                 A- 
                 3561 
                 UAAAUGUAUGUAUGU 
                 2075- 
               
               
                 122308 
                 228254 
                   
                 CAUUUA 
                 2097 
                 2282542. 
                   
                 GGGUGGGU 
                 2097 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3113 
                 CACCCACAUACAUAC 
                 2078- 
                 A- 
                 3562 
                 UUAAAUGUAUGUAUG 
                 2076- 
               
               
                 122308 
                 228254 
                   
                 AUUUAA 
                 2098 
                 2282544. 
                   
                 UGGGUGGG 
                 2098 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3114 
                 CCACAUACAUACAUU 
                 2081- 
                 A- 
                 3563 
                 UAUAUAAAUGUAUGU 
                 2079- 
               
               
                 122308 
                 228254 
                   
                 UAUAUA 
                 2101 
                 2282546. 
                   
                 AUGUGGGU 
                 2101 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3115 
                 CACAUACAUACAUUU 
                 2082- 
                 A- 
                 3564 
                 UUAUAUAAAUGUAUG 
                 2080- 
               
               
                 122308 
                 228254 
                   
                 AUAUAA 
                 2102 
                 2282548. 
                   
                 UAUGUGGG 
                 2102 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3116 
                 UUAAAUUAACAGUG 
                 2171- 
                 A- 
                 3565 
                 UCAUUAGCACUGUUA 
                 2169- 
               
               
                 122308 
                 228254 
                   
                 CUAAUGA 
                 2191 
                 2282550. 
                   
                 AUUUAAAA 
                 2191 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3117 
                 UAAAUUAACAGUGC 
                 2172- 
                 A- 
                 3566 
                 UACAUUAGCACUGUU 
                 2 nO- 
               
               
                 122308 
                 228255 
                   
                 UAAUGUA 
                 2192 
                 2282552. 
                   
                 AAUUUAAA 
                 2192 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3118 
                 AAAUUAACAGUGCU 
                 2173- 
                 A- 
                 3567 
                 UAACAUUAGCACUGU 
                 2171- 
               
               
                 122308 
                 228255 
                   
                 AAUGUUA 
                 2193 
                 2282554. 
                   
                 UAAUUUAA 
                 2193 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3119 
                 AAUUAACAGUGCUA 
                 2174- 
                 A- 
                 3568 
                 UUAACAUUAGCACUG 
                 2172- 
               
               
                 122308 
                 228255 
                   
                 AUGUUAA 
                 2194 
                 2282556. 
                   
                 UUAAUUUA 
                 2194 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3120 
                 AUUAACAGUGCUAA 
                 2175- 
                 A- 
                 3569 
                 UAUAACAUUAGCACU 
                 2173- 
               
               
                 122308 
                 228255 
                   
                 UGUUAUA 
                 2195 
                 2282558. 
                   
                 GUUAAUUU 
                 2195 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3121 
                 UUAACAGUGCUAAU 
                 2176- 
                 A- 
                 3570 
                 UAAUAACAUUAGCAC 
                 2174- 
               
               
                 122309 
                 228255 
                   
                 GUUAUUA 
                 2196 
                 2282560. 
                   
                 UGUUAAUU 
                 2196 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3122 
                 UAACAGUGCUAAUG 
                 2177- 
                 A- 
                 3571 
                 UCAAUAACAUUAGCA 
                 2175- 
               
               
                 122309 
                 228256 
                   
                 UUAUUGA 
                 2197 
                 2282562. 
                   
                 CUGUUAAU 
                 2197 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3123 
                 AACAGUGCUAAUGU 
                 2178- 
                 A- 
                 3572 
                 UCCAAUAACAUUAGC 
                 2176- 
               
               
                 122309 
                 228256 
                   
                 UAUUGGA 
                 2198 
                 2282564. 
                   
                 ACUGUUAA 
                 2198 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3124 
                 ACAGUGCUAAUGUU 
                 2179- 
                 A- 
                 3573 
                 UACCAAUAACAUUAG 
                 2177- 
               
               
                 122309 
                 228256 
                   
                 AUUGGUA 
                 2199 
                 2282566. 
                   
                 CACUGUUA 
                 2199 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3125 
                 CAGUGCUAAUGUUA 
                 2180- 
                 A- 
                 3574 
                 UCACCAAUAACAUUA 
                 2178- 
               
               
                 122309 
                 228256 
                   
                 UUGGUGA 
                 2200 
                 2282568. 
                   
                 GCACUGUU 
                 2200 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3126 
                 GUGCUAAUGUUAUU 
                 2182- 
                 A- 
                 3575 
                 UGACACCAAUAACAU 
                 2180- 
               
               
                 122309 
                 228256 
                   
                 GGUGUCA 
                 2202 
                 2282570. 
                   
                 UAGCACUG 
                 2202 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3127 
                 UGCUAAUGUUAUUG 
                 2183- 
                 A- 
                 3576 
                 UAGACACCAAUAACA 
                 2181- 
               
               
                 122309 
                 228257 
                   
                 GUGUCUA 
                 2203 
                 2282572. 
                   
                 UUAGCACU 
                 2203 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3128 
                 GCUAAUGUUAUUGG 
                 2184- 
                 A- 
                 3577 
                 UAAGACACCAAUAAC 
                 2182- 
               
               
                 122309 
                 228257 
                   
                 UGUCUUA 
                 2204 
                 2282574. 
                   
                 AUUAGCAC 
                 2204 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3129 
                 CUAAUGUUAUUGGU 
                 2185- 
                 A- 
                 3578 
                 UGAAGACACCAAUAA 
                 2183- 
               
               
                 122309 
                 228257 
                   
                 GUCUUCA 
                 2205 
                 2282576. 
                   
                 CAUUAGCA 
                 2205 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3130 
                 UAAUGUUAUUGGUG 
                 2186- 
                 A- 
                 3579 
                 UUGAAGACACCAAUA 
                 2184- 
               
               
                 122309 
                 228257 
                   
                 UCUUCAA 
                 2206 
                 2282578. 
                   
                 ACAUUAGC 
                 2206 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3131 
                 AAUGUUAUUGGUGU 
                 2187- 
                 A- 
                 3580 
                 UGUGAAGACACCAAU 
                 2185- 
               
               
                 122310 
                 228257 
                   
                 CUUCACA 
                 2207 
                 2282580. 
                   
                 AACAUUAG 
                 2207 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3132 
                 AUGUUAUUGGUGUC 
                 2188- 
                 A- 
                 3581 
                 UAGUGAAGACACCAA 
                 2186- 
               
               
                 122310 
                 228258 
                   
                 UUCACUA 
                 2208 
                 2282582. 
                   
                 UAACAUUA 
                 2208 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3133 
                 UGUUAUUGGUGUCU 
                 2189- 
                 A- 
                 3582 
                 UCAGUGAAGACACCA 
                 2187- 
               
               
                 122310 
                 228258 
                   
                 UCACUGA 
                 2209 
                 2282584. 
                   
                 AUAACAUU 
                 2209 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3134 
                 GUUAUUGGUGUCUU 
                 2190- 
                 A- 
                 3583 
                 UCCAGUGAAGACACC 
                 2188- 
               
               
                 122310 
                 228258 
                   
                 CACUGGA 
                 2210 
                 2282586. 
                   
                 AAUAACAU 
                 2210 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3135 
                 UUAUUGGUGUCUUC 
                 2191- 
                 A- 
                 3584 
                 UUCCAGUGAAGACAC 
                 2189- 
               
               
                 122310 
                 228258 
                   
                 ACUGGAA 
                 2211 
                 2282588. 
                   
                 CAAUAACA 
                 2211 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3136 
                 UGGUGUCUUCACUGG 
                 2195- 
                 A- 
                 3585 
                 UUACAUCCAGUGAAG 
                 2193- 
               
               
                 122310 
                 228258 
                   
                 AUGUAA 
                 2215 
                 2282590. 
                   
                 ACACCAAU 
                 2215 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3137 
                 UGUCUUCACUGGAUG 
                 2198- 
                 A- 
                 3586 
                 UAAAUACAUCCAGUG 
                 2196- 
               
               
                 122310 
                 228259 
                   
                 UAUUUA 
                 2218 
                 2282592. 
                   
                 AAGACACC 
                 2218 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3138 
                 CACUGGAUGUAUUU 
                 2204- 
                 A- 
                 3587 
                 UGCAGUCAAAUACAU 
                 2202- 
               
               
                 122310 
                 228259 
                   
                 GACUGCA 
                 2224 
                 2282594. 
                   
                 CCAGUGAA 
                 2224 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3139 
                 ACUGGAUGUAUUUG 
                 2205- 
                 A- 
                 3588 
                 UAGCAGUCAAAUACA 
                 2203- 
               
               
                 122310 
                 228259 
                   
                 ACUGCUA 
                 2225 
                 2282596. 
                   
                 UCCAGUGA 
                 2225 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3140 
                 UGGAUGUAUUUGAC 
                 2207- 
                 A- 
                 3589 
                 UACAGCAGUCAAAUA 
                 2205- 
               
               
                 122310 
                 228259 
                   
                 UGCUGUA 
                 2227 
                 2282598. 
                   
                 CAUCCAGU 
                 2227 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3141 
                 UAUUUGACUGCUGU 
                 2213- 
                 A- 
                 3590 
                 UAAGUCCACAGCAGU 
                 2211- 
               
               
                 122311 
                 228259 
                   
                 GGACUUA 
                 2233 
                 2282600. 
                   
                 CAAAUACA 
                 2233 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3142 
                 UUUGACUGCUGUGG 
                 2215- 
                 A- 
                 3591 
                 UUCAAGUCCACAGCA 
                 2213- 
               
               
                 122311 
                 228260 
                   
                 ACUUGAA 
                 2235 
                 2282602. 
                   
                 GUCAAAUA 
                 2235 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3143 
                 GCUGUGGACUUGAG 
                 2222- 
                 A- 
                 3592 
                 UUCCCAACUCAAGUCC 
                 2220- 
               
               
                 122311 
                 228260 
                   
                 UUGGGAA 
                 2242 
                 2282604. 
                   
                 ACAGCAG 
                 2242 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3144 
                 UCCCACUCAGAUCCU 
                 2251- 
                 A- 
                 3593 
                 UCUGUCAGGAUCUGA 
                 2249- 
               
               
                 122311 
                 228260 
                   
                 GACAGA 
                 2271 
                 2282606. 
                   
                 GUGGGAAC 
                 2271 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3145 
                 CCCACUCAGAUCCUG 
                 2252- 
                 A- 
                 3594 
                 UCCUGUCAGGAUCUG 
                 2250- 
               
               
                 122311 
                 228260 
                   
                 ACAGGA 
                 2272 
                 2282608. 
                   
                 AGUGGGAA 
                 2272 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3146 
                 GGAGGAGAUGAGAG 
                 2277- 
                 A- 
                 3595 
                 UCAGAGUCUCUCAUC 
                 2275- 
               
               
                 122311 
                 228260 
                   
                 ACUCUGA 
                 2297 
                 2282610. 
                   
                 UCCUCCUC 
                 2297 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3147 
                 GAGGAGAUGAGAGA 
                 2278- 
                 A- 
                 3596 
                 UCCAGAGUCUCUCAU 
                 2276- 
               
               
                 122311 
                 228261 
                   
                 CUCUGGA 
                 2298 
                 2282612. 
                   
                 CUCCUCCU 
                 2298 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3148 
                 GGAGAUGAGAGACU 
                 2280- 
                 A- 
                 3597 
                 UUGCCAGAGUCUCUC 
                 2278- 
               
               
                 122311 
                 228261 
                   
                 CUGGCAA 
                 2300 
                 2282614. 
                   
                 AUCUCCUC 
                 2300 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3149 
                 GAGACUCUGGCAUGA 
                 2288- 
                 A- 
                 3598 
                 UAAAGAUCAUGCCAG 
                 2286- 
               
               
                 122311 
                 228261 
                   
                 UCUUUA 
                 2308 
                 2282616. 
                   
                 AGUCUCUC 
                 2308 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3150 
                 AGACUCUGGCAUGAU 
                 2289- 
                 A- 
                 3599 
                 UAAAAGAUCAUGCCA 
                 2287- 
               
               
                 122311 
                 228261 
                   
                 CUUUUA 
                 2309 
                 2282618. 
                   
                 GAGUCUCU 
                 2309 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3151 
                 UUUUGGGAACACCGA 
                 2392- 
                 A- 
                 3600 
                 UGUUUGUCGGUGUUC 
                 2390- 
               
               
                 122312 
                 228261 
                   
                 CAAACA 
                 2412 
                 2282620. 
                   
                 CCAAAACU 
                 2412 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3152 
                 GAGCUUCAGGACAUU 
                 2511- 
                 A- 
                 3601 
                 UACAGCAAUGUCCUG 
                 2509- 
               
               
                 122312 
                 228262 
                   
                 GCUGUA 
                 2531 
                 2282622. 
                   
                 AAGCUCCC 
                 2531 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3153 
                 GCUUCAGGACAUUGC 
                 2513- 
                 A- 
                 3602 
                 UGCACAGCAAUGUCC 
                 2511- 
               
               
                 122312 
                 228262 
                   
                 UGUGCA 
                 2533 
                 2282624. 
                   
                 UGAAGCUC 
                 2533 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3154 
                 CUUCAGGACAUUGCU 
                 2514- 
                 A- 
                 3603 
                 UAGCACAGCAAUGUC 
                 2512- 
               
               
                 122312 
                 228262 
                   
                 GUGCUA 
                 2534 
                 2282626. 
                   
                 CUGAAGCU 
                 2534 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3155 
                 UUCAGGACAUUGCUG 
                 2515- 
                 A- 
                 3604 
                 UAAGCACAGCAAUGU 
                 2513- 
               
               
                 122312 
                 228262 
                   
                 UGCUUA 
                 2535 
                 2282628. 
                   
                 CCUGAAGC 
                 2535 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3156 
                 UCAGGACAUUGCUGU 
                 2516- 
                 A- 
                 3605 
                 UAAAGCACAGCAAUG 
                 2514- 
               
               
                 122312 
                 228262 
                   
                 GCUUUA 
                 2536 
                 2282630. 
                   
                 UCCUGAAG 
                 2536 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3157 
                 CAGGACAUUGCUGUG 
                 2517- 
                 A- 
                 3606 
                 UCAAAGCACAGCAAU 
                 2515- 
               
               
                 122312 
                 228263 
                   
                 CUUUGA 
                 2537 
                 2282632. 
                   
                 GUCCUGAA 
                 2537 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3158 
                 CGCUUACUCUCACCU 
                 2615- 
                 A- 
                 3607 
                 UGAAGCAGGUGAGAG 
                 2613- 
               
               
                 122312 
                 228263 
                   
                 GCUUCA 
                 2635 
                 2282634. 
                   
                 UAAGCGAA 
                 2635 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3159 
                 GCUUACUCUCACCUG 
                 2616- 
                 A- 
                 3608 
                 UAGAAGCAGGUGAGA 
                 2614- 
               
               
                 122312 
                 228263 
                   
                 CUUCUA 
                 2636 
                 2282636. 
                   
                 GUAAGCGA 
                 2636 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3160 
                 UUACUCUCACCUGCU 
                 2618- 
                 A- 
                 3609 
                 UUCAGAAGCAGGUGA 
                 2616- 
               
               
                 122312 
                 228263 
                   
                 UCUGAA 
                 2638 
                 2282638. 
                   
                 GAGUAAGC 
                 2638 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3161 
                 CUCUCACCUGCUUCU 
                 2621- 
                 A- 
                 3610 
                 UAACUCAGAAGCAGG 
                 2619- 
               
               
                 122313 
                 228263 
                   
                 GAGUUA 
                 2641 
                 2282640. 
                   
                 UGAGAGUA 
                 2641 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3162 
                 UCUCACCUGCUUCUG 
                 2622- 
                 A- 
                 3611 
                 UCAACUCAGAAGCAG 
                 2620- 
               
               
                 122313 
                 228264 
                   
                 AGUUGA 
                 2642 
                 2282642. 
                   
                 GUGAGAGU 
                 2642 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3163 
                 CUCACCUGCUUCUGA 
                 2623- 
                 A- 
                 3612 
                 UGCAACUCAGAAGCA 
                 2621- 
               
               
                 122313 
                 228264 
                   
                 GUUGCA 
                 2643 
                 2282644. 
                   
                 GGUGAGAG 
                 2643 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3164 
                 UCACCUGCUUCUGAG 
                 2624- 
                 A- 
                 3613 
                 UGGCAACUCAGAAGC 
                 2622- 
               
               
                 122313 
                 228264 
                   
                 UUGCCA 
                 2644 
                 2282646. 
                   
                 AGGUGAGA 
                 2644 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3165 
                 CACCUGCUUCUGAGU 
                 2625- 
                 A- 
                 3614 
                 UGGGCAACUCAGAAG 
                 2623- 
               
               
                 122313 
                 228264 
                   
                 UGCCCA 
                 2645 
                 2282648. 
                   
                 CAGGUGAG 
                 2645 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3166 
                 ACCUGCUUCUGAGUU 
                 2626- 
                 A- 
                 3615 
                 UUGGGCAACUCAGAA 
                 2624- 
               
               
                 122313 
                 228264 
                   
                 GCCCAA 
                 2646 
                 2282650. 
                   
                 GCAGGUGA 
                 2646 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3167 
                 CCUGCUUCUGAGUUG 
                 2627- 
                 A- 
                 3616 
                 UCUGGGCAACUCAGA 
                 2625- 
               
               
                 122313 
                 228265 
                   
                 CCCAGA 
                 2647 
                 2282652. 
                   
                 AGCAGGUG 
                 2647 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3168 
                 CGGCGAAGAGAAGA 
                 2667- 
                 A- 
                 3617 
                 UUGUGUCUCUUCUCU 
                 2665- 
               
               
                 122313 
                 228265 
                   
                 GACACAA 
                 2687 
                 2282654. 
                   
                 UCGCCGGG 
                 2687 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3169 
                 GGCGAAGAGAAGAG 
                 2668- 
                 A- 
                 3618 
                 UAUGUGUCUCUUCUC 
                 2666- 
               
               
                 122313 
                 228265 
                   
                 ACACAUA 
                 2688 
                 2282656. 
                   
                 UUCGCCGG 
                 2688 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3170 
                 GCGAAGAGAAGAGA 
                 2669- 
                 A- 
                 3619 
                 UAAUGUGUCUCUUCU 
                 2667- 
               
               
                 122313 
                 228265 
                   
                 CACAUUA 
                 2689 
                 2282658. 
                   
                 CUUCGCCG 
                 2689 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3171 
                 CGAAGAGAAGAGAC 
                 2670- 
                 A- 
                 3620 
                 UCAAUGUGUCUCUUC 
                 2668- 
               
               
                 122314 
                 228265 
                   
                 ACAUUGA 
                 2690 
                 2282660. 
                   
                 UCUUCGCC 
                 2690 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3172 
                 GAAGAGAAGAGACA 
                 2671- 
                 A- 
                 3621 
                 UACAAUGUGUCUCUU 
                 2669- 
               
               
                 122314 
                 228266 
                   
                 CAUUGUA 
                 2691 
                 2282662. 
                   
                 CUCUUCGC 
                 2691 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3173 
                 AAGAGAAGAGACAC 
                 2672- 
                 A- 
                 3622 
                 UAACAAUGUGUCUCU 
                 2670- 
               
               
                 122314 
                 228266 
                   
                 AUUGUUA 
                 2692 
                 2282664. 
                   
                 UCUCUUCG 
                 2692 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3174 
                 AGAGAAGAGACACA 
                 2673- 
                 A- 
                 3623 
                 UCAACAAUGUGUCUC 
                 2671- 
               
               
                 122314 
                 228266 
                   
                 UUGUUGA 
                 2693 
                 2282666. 
                   
                 uucucuuc 
                 2693 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3175 
                 GAGAAGAGACACAU 
                 2674- 
                 A- 
                 3624 
                 UCCAACAAUGUGUCU 
                 2672- 
               
               
                 122314 
                 228266 
                   
                 UGUUGGA 
                 2694 
                 2282668. 
                   
                 cuucucuu 
                 2694 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3176 
                 AGAAGAGACACAUU 
                 2675- 
                 A- 
                 3625 
                 UUCCAACAAUGUGUC 
                 2673- 
               
               
                 122314 
                 228266 
                   
                 GUUGGAA 
                 2695 
                 2282670. 
                   
                 UCUUCUCU 
                 2695 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3177 
                 GAAGAGACACAUUG 
                 2676- 
                 A- 
                 3626 
                 UUUCCAACAAUGUGU 
                 2674- 
               
               
                 122314 
                 228267 
                   
                 UUGGAAA 
                 2696 
                 2282672. 
                   
                 CUCUUCUC 
                 2696 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3178 
                 AAGAGACACAUUGU 
                 2677- 
                 A- 
                 3627 
                 UCUUCCAACAAUGUG 
                 2675- 
               
               
                 122314 
                 228267 
                   
                 UGGAAGA 
                 2697 
                 2282674. 
                   
                 UCUCUUCU 
                 2697 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3179 
                 AGAGACACAUUGUU 
                 2678- 
                 A- 
                 3628 
                 UUCUUCCAACAAUGU 
                 2676- 
               
               
                 122314 
                 228267 
                   
                 GGAAGAA 
                 2698 
                 2282676. 
                   
                 GUCUCUUC 
                 2698 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3180 
                 GAGACACAUUGUUG 
                 2679- 
                 A- 
                 3629 
                 UUUCUUCCAACAAUG 
                 2677- 
               
               
                 122314 
                 228267 
                   
                 GAAGAAA 
                 2699 
                 2282678. 
                   
                 UGUCUCUU 
                 2699 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3181 
                 AGACACAUUGUUGG 
                 2680- 
                 A- 
                 3630 
                 UCUUCUUCCAACAAU 
                 2678- 
               
               
                 122315 
                 228267 
                   
                 AAGAAGA 
                 2700 
                 2282680. 
                   
                 GUGUCUCU 
                 2700 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3182 
                 GACACAUUGUUGGA 
                 2681- 
                 A- 
                 3631 
                 UGCUUCUUCCAACAA 
                 2679- 
               
               
                 122315 
                 228268 
                   
                 AGAAGCA 
                 2701 
                 2282682. 
                   
                 UGUGUCUC 
                 2701 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3183 
                 ACACAUUGUUGGAA 
                 2682- 
                 A- 
                 3632 
                 UUGCUUCUUCCAACA 
                 2680- 
               
               
                 122315 
                 228268 
                   
                 GAAGCAA 
                 2702 
                 2282684. 
                   
                 AUGUGUCU 
                 2702 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3184 
                 CACAUUGUUGGAAG 
                 2683- 
                 A- 
                 3633 
                 UCUGCUUCUUCCAAC 
                 2681- 
               
               
                 122315 
                 228268 
                   
                 AAGCAGA 
                 2703 
                 2282686. 
                   
                 AAUGUGUC 
                 2703 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3185 
                 UAUGUCCUCACACCA 
                 2781- 
                 A- 
                 3634 
                 UUUCAAUGGUGUGAG 
                 2779- 
               
               
                 122315 
                 228268 
                   
                 UUGAAA 
                 2801 
                 2282688. 
                   
                 GACAUAGG 
                 2801 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3186 
                 UCCUCACACCAUUGA 
                 2785- 
                 A- 
                 3635 
                 UUGGUUUCAAUGGUG 
                 2783- 
               
               
                 122315 
                 228268 
                   
                 AACCAA 
                 2805 
                 2282690. 
                   
                 UGAGGACA 
                 2805 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3187 
                 CCUCACACCAUUGAA 
                 2786- 
                 A- 
                 3636 
                 UGUGGUUUCAAUGGU 
                 2784- 
               
               
                 122315 
                 228269 
                   
                 ACCACA 
                 2806 
                 2282692. 
                   
                 GUGAGGAC 
                 2806 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3188 
                 CUCACACCAUUGAAA 
                 2787- 
                 A- 
                 3637 
                 UAGUGGUUUCAAUGG 
                 2785- 
               
               
                 122315 
                 228269 
                   
                 CCACUA 
                 2807 
                 2282694. 
                   
                 UGUGAGGA 
                 2807 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3189 
                 UCACACCAUUGAAAC 
                 2788- 
                 A- 
                 3638 
                 UUAGUGGUUUCAAUG 
                 2786- 
               
               
                 122315 
                 228269 
                   
                 CACUAA 
                 2808 
                 2282696. 
                   
                 GUGUGAGG 
                 2808 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3190 
                 CACACCAUUGAAACC 
                 2789- 
                 A- 
                 3639 
                 UCUAGUGGUUUCAAU 
                 2787- 
               
               
                 122315 
                 228269 
                   
                 ACUAGA 
                 2809 
                 2282698. 
                   
                 GGUGUGAG 
                 2809 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3191 
                 CCAUUGAAACCACUA 
                 2793- 
                 A- 
                 3640 
                 UAGAACUAGUGGUUU 
                 2791- 
               
               
                 122316 
                 228269 
                   
                 GUUCUA 
                 2813 
                 2282700. 
                   
                 CAAUGGUG 
                 2813 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3192 
                 CAUUGAAACCACUAG 
                 2794- 
                 A- 
                 3641 
                 UCAGAACUAGUGGUU 
                 2792- 
               
               
                 122316 
                 228270 
                   
                 UUCUGA 
                 2814 
                 2282702. 
                   
                 UCAAUGGU 
                 2814 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3193 
                 AUUGAAACCACUAGU 
                 2795- 
                 A- 
                 3642 
                 UACAGAACUAGUGGU 
                 2793- 
               
               
                 122316 
                 228270 
                   
                 UCUGUA 
                 2815 
                 2282704. 
                   
                 UUCAAUGG 
                 2815 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3194 
                 UUGAAACCACUAGUU 
                 2796- 
                 A- 
                 3643 
                 UGACAGAACUAGUGG 
                 2794- 
               
               
                 122316 
                 228270 
                   
                 CUGUCA 
                 2816 
                 2282706. 
                   
                 UUUCAAUG 
                 2816 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3195 
                 UGAAACCACUAGUUC 
                 2797- 
                 A- 
                 3644 
                 UGGACAGAACUAGUG 
                 2795- 
               
               
                 122316 
                 228270 
                   
                 UGUCCA 
                 2817 
                 2282708. 
                   
                 GUUUCAAU 
                 2817 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3196 
                 GACCUGGUUGUGUG 
                 2825- 
                 A- 
                 3645 
                 UCACACACACACAACC 
                 2823- 
               
               
                 122316 
                 228270 
                   
                 UGUGUGA 
                 2845 
                 2282710. 
                   
                 AGGUCUC 
                 2845 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3197 
                 ACCUGGUUGUGUGU 
                 2826- 
                 A- 
                 3646 
                 UUCACACACACACAAC 
                 2824- 
               
               
                 122316 
                 228271 
                   
                 GUGUGAA 
                 2846 
                 2282712. 
                   
                 CAGGUCU 
                 2846 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3198 
                 CCUGGUUGUGUGUG 
                 2827- 
                 A- 
                 3647 
                 UCUCACACACACACAA 
                 2825- 
               
               
                 122316 
                 228271 
                   
                 UGUGAGA 
                 2847 
                 2282714. 
                   
                 CCAGGUC 
                 2847 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3199 
                 CUGGUUGUGUGUGU 
                 2828- 
                 A- 
                 3648 
                 UACUCACACACACACA 
                 2826- 
               
               
                 122316 
                 228271 
                   
                 GUGAGUA 
                 2848 
                 2282716. 
                   
                 ACCAGGU 
                 2848 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3200 
                 UGGUUGUGUGUGUG 
                 2829- 
                 A- 
                 3649 
                 UCACUCACACACACAC 
                 2827- 
               
               
                 122316 
                 228271 
                   
                 UGAGUGA 
                 2849 
                 2282718. 
                   
                 AACCAGG 
                 2849 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3201 
                 GGUUGUGUGUGUGU 
                 2830- 
                 A- 
                 3650 
                 UCCACUCACACACACA 
                 2828- 
               
               
                 122317 
                 228271 
                   
                 GAGUGGA 
                 2850 
                 2282720. 
                   
                 CAACCAG 
                 2850 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3202 
                 GUGUGUGUGUGAGU 
                 2834- 
                 A- 
                 3651 
                 UUCAACCACUCACACA 
                 2832- 
               
               
                 122317 
                 228272 
                   
                 GGUUGAA 
                 2854 
                 2282722. 
                   
                 CACACAA 
                 2854 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3203 
                 UGUGUGUGUGAGUG 
                 2835- 
                 A- 
                 3652 
                 UGUCAACCACUCACAC 
                 2833- 
               
               
                 122317 
                 228272 
                   
                 GUUGACA 
                 2855 
                 2282724. 
                   
                 ACACACA 
                 2855 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3204 
                 UGUGUGUGAGUGGU 
                 2837- 
                 A- 
                 3653 
                 UAGGUCAACCACUCA 
                 2835- 
               
               
                 122317 
                 228272 
                   
                 UGACCUA 
                 2857 
                 2282726. 
                   
                 CACACACA 
                 2857 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3205 
                 UGUGUGAGUGGUUG 
                 2839- 
                 A- 
                 3654 
                 UGAAGGUCAACCACU 
                 2837- 
               
               
                 122317 
                 228272 
                   
                 ACCUUCA 
                 2859 
                 2282728. 
                   
                 CACACACA 
                 2859 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3206 
                 GUGUGAGUGGUUGA 
                 2840- 
                 A- 
                 3655 
                 UGGAAGGUCAACCAC 
                 2838- 
               
               
                 122317 
                 228272 
                   
                 CCUUCCA 
                 2860 
                 2282730. 
                   
                 UCACACAC 
                 2860 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3207 
                 UGUGAGUGGUUGAC 
                 2841- 
                 A- 
                 3656 
                 UAGGAAGGUCAACCA 
                 2839- 
               
               
                 122317 
                 228273 
                   
                 CUUCCUA 
                 2861 
                 2282732. 
                   
                 CUCACACA 
                 2861 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3208 
                 UGAGUGGUUGACCU 
                 2843- 
                 A- 
                 3657 
                 UGGAGGAAGGUCAAC 
                 2841- 
               
               
                 122317 
                 228273 
                   
                 UCCUCCA 
                 2863 
                 2282734. 
                   
                 CACUCACA 
                 2863 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3209 
                 GUGGUUGACCUUCCU 
                 2846- 
                 A- 
                 3658 
                 UGAUGGAGGAAGGUC 
                 2844- 
               
               
                 122317 
                 228273 
                   
                 CCAUCA 
                 2866 
                 2282736. 
                   
                 AACCACUC 
                 2866 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3210 
                 UUGUGGAGGCAGAG 
                 2926- 
                 A- 
                 3659 
                 UUCUUUUCUCUGCCU 
                 2924- 
               
               
                 122317 
                 228273 
                   
                 AAAAGAA 
                 2946 
                 2282738. 
                   
                 CCACAAUG 
                 2946 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3211 
                 UGUGGAGGCAGAGA 
                 2927- 
                 A- 
                 3660 
                 UCUCUUUUCUCUGCC 
                 2925- 
               
               
                 122318 
                 228273 
                   
                 AAAGAGA 
                 2947 
                 2282740. 
                   
                 UCCACAAU 
                 2947 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3212 
                 GUGGAGGCAGAGAA 
                 2928- 
                 A- 
                 3661 
                 UUCUCUUUUCUCUGC 
                 2926- 
               
               
                 122318 
                 228274 
                   
                 AAGAGAA 
                 2948 
                 2282742. 
                   
                 CUCCACAA 
                 2948 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3213 
                 UGGAGGCAGAGAAA 
                 2929- 
                 A- 
                 3662 
                 UUUCUCUUUUCUCUG 
                 2927- 
               
               
                 122318 
                 228274 
                   
                 AGAGAAA 
                 2949 
                 2282744. 
                   
                 CCUCCACA 
                 2949 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3214 
                 GGAGGCAGAGAAAA 
                 2930- 
                 A- 
                 3663 
                 UUUUCUCUUUUCUCU 
                 2928- 
               
               
                 122318 
                 228274 
                   
                 GAGAAAA 
                 2950 
                 2282746. 
                   
                 GCCUCCAC 
                 2950 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3215 
                 GAGGCAGAGAAAAG 
                 2931- 
                 A- 
                 3664 
                 UCUUUCUCUUUUCUC 
                 2929- 
               
               
                 122318 
                 228274 
                   
                 AGAAAGA 
                 2951 
                 2282748. 
                   
                 UGCCUCCA 
                 2951 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3216 
                 AGGCAGAGAAAAGA 
                 2932- 
                 A- 
                 3665 
                 UACUUUCUCUUUUCU 
                 2930- 
               
               
                 122318 
                 228274 
                   
                 GAAAGUA 
                 2952 
                 2282750. 
                   
                 CUGCCUCC 
                 2952 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3217 
                 GGCAGAGAAAAGAG 
                 2933- 
                 A- 
                 3666 
                 UCACUUUCUCUUUUC 
                 2931- 
               
               
                 122318 
                 228275 
                   
                 AAAGUGA 
                 2953 
                 2282752. 
                   
                 UCUGCCUC 
                 2953 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3218 
                 GCAGAGAAAAGAGA 
                 2934- 
                 A- 
                 3667 
                 UACACUUUCUCUUUU 
                 2932- 
               
               
                 122318 
                 228275 
                   
                 AAGUGUA 
                 2954 
                 2282754. 
                   
                 CUCUGCCU 
                 2954 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3219 
                 CAGAGAAAAGAGAA 
                 2935- 
                 A- 
                 3668 
                 UAACACUUUCUCUUU 
                 2933- 
               
               
                 122318 
                 228275 
                   
                 AGUGUUA 
                 2955 
                 2282756. 
                   
                 UCUCUGCC 
                 2955 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3220 
                 AGAGAAAAGAGAAA 
                 2936- 
                 A- 
                 3669 
                 UAAACACUUUCUCUU 
                 2934- 
               
               
                 122318 
                 228275 
                   
                 GUGUUUA 
                 2956 
                 2282758. 
                   
                 UUCUCUGC 
                 2956 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3221 
                 GAGAAAAGAGAAAG 
                 2937- 
                 A- 
                 3670 
                 UAAAACACUUUCUCU 
                 2935- 
               
               
                 122319 
                 228275 
                   
                 UGUUUUA 
                 2957 
                 2282760. 
                   
                 UUUCUCUG 
                 2957 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3222 
                 AGAAAAGAGAAAGU 
                 2938- 
                 A- 
                 3671 
                 UUAAAACACUUUCUC 
                 2936- 
               
               
                 122319 
                 228276 
                   
                 GUUUUAA 
                 2958 
                 2282762. 
                   
                 UUUUCUCU 
                 2958 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3223 
                 GAAAAGAGAAAGUG 
                 2939- 
                 A- 
                 3672 
                 UAUAAAACACUUUCU 
                 2937- 
               
               
                 122319 
                 228276 
                   
                 UUUUAUA 
                 2959 
                 2282764. 
                   
                 CUUUUCUC 
                 2959 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3224 
                 AAAAGAGAAAGUGU 
                 2940- 
                 A- 
                 3673 
                 UUAUAAAACACUUUC 
                 2938- 
               
               
                 122319 
                 228276 
                   
                 UUUAUAA 
                 2960 
                 2282766. 
                   
                 UCUUUUCU 
                 2960 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3225 
                 AAAGAGAAAGUGUU 
                 2941- 
                 A- 
                 3674 
                 UAUAUAAAACACUUU 
                 2939- 
               
               
                 122319 
                 228276 
                   
                 UUAUAUA 
                 2961 
                 2282768. 
                   
                 CUCUUUUC 
                 2961 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3226 
                 AAGAGAAAGUGUUU 
                 2942- 
                 A- 
                 3675 
                 UUAUAUAAAACACUU 
                 2940- 
               
               
                 122319 
                 228276 
                   
                 UAUAUAA 
                 2962 
                 2282770. 
                   
                 UCUCUUUU 
                 2962 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3227 
                 AGAGAAAGUGUUUU 
                 2943- 
                 A- 
                 3676 
                 UGUAUAUAAAACACU 
                 2941- 
               
               
                 122319 
                 228277 
                   
                 AUAUACA 
                 2963 
                 2282772. 
                   
                 UUCUCUUU 
                 2963 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3228 
                 GAGAAAGUGUUUUA 
                 2944- 
                 A- 
                 3677 
                 UCGUAUAUAAAACAC 
                 2942- 
               
               
                 122319 
                 228277 
                   
                 UAUACGA 
                 2964 
                 2282774. 
                   
                 UUUCUCUU 
                 2964 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3229 
                 AGAAAGUGUUUUAU 
                 2945- 
                 A- 
                 3678 
                 UCCGUAUAUAAAACA 
                 2943- 
               
               
                 122319 
                 228277 
                   
                 AUACGGA 
                 2965 
                 2282776. 
                   
                 CUUUCUCU 
                 2965 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3230 
                 AAAGUGUUUUAUAU 
                 2947- 
                 A- 
                 3679 
                 UUACCGUAUAUAAAA 
                 2945- 
               
               
                 122319 
                 228277 
                   
                 ACGGUAA 
                 2967 
                 2282778. 
                   
                 CACUUUCU 
                 2967 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3231 
                 AAGUGUUUUAUAUA 
                 2948- 
                 A- 
                 3680 
                 UGUACCGUAUAUAAA 
                 2946- 
               
               
                 122320 
                 228277 
                   
                 CGGUACA 
                 2968 
                 2282780. 
                   
                 ACACUUUC 
                 2968 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3232 
                 AGUGUUUUAUAUAC 
                 2949- 
                 A- 
                 3681 
                 UAGUACCGUAUAUAA 
                 2947- 
               
               
                 122320 
                 228278 
                   
                 GGUACUA 
                 2969 
                 2282782. 
                   
                 AACACUUU 
                 2969 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3233 
                 GUGUUUUAUAUACG 
                 2950- 
                 A- 
                 3682 
                 UAAGUACCGUAUAUA 
                 2948- 
               
               
                 122320 
                 228278 
                   
                 GUACUUA 
                 2970 
                 2282784. 
                   
                 AAACACUU 
                 2970 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3234 
                 UGUUUUAUAUACGG 
                 2951- 
                 A- 
                 3683 
                 UUAAGUACCGUAUAU 
                 2949- 
               
               
                 122320 
                 228278 
                   
                 UACUUAA 
                 2971 
                 2282786. 
                   
                 AAAACACU 
                 2971 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3235 
                 GUUUUAUAUACGGU 
                 2952- 
                 A- 
                 3684 
                 UAUAAGUACCGUAUA 
                 2950- 
               
               
                 122320 
                 228278 
                   
                 ACUUAUA 
                 2972 
                 2282788. 
                   
                 UAAAACAC 
                 2972 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3236 
                 UUUUAUAUACGGUA 
                 2953- 
                 A- 
                 3685 
                 UAAUAAGUACCGUAU 
                 2951- 
               
               
                 122320 
                 228278 
                   
                 CUUAUUA 
                 2973 
                 2282790. 
                   
                 AUAAAACA 
                 2973 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3237 
                 UUUAUAUACGGUAC 
                 2954- 
                 A- 
                 3686 
                 UAAAUAAGUACCGUA 
                 2952- 
               
               
                 122320 
                 228279 
                   
                 UUAUUUA 
                 2974 
                 2282792. 
                   
                 UAUAAAAC 
                 2974 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3238 
                 UUAUAUACGGUACU 
                 2955- 
                 A- 
                 3687 
                 UUAAAUAAGUACCGU 
                 2953- 
               
               
                 122320 
                 228279 
                   
                 UAUUUAA 
                 2975 
                 2282794. 
                   
                 AUAUAAAA 
                 2975 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3239 
                 UAUAUACGGUACUU 
                 2956- 
                 A- 
                 3688 
                 UUUAAAUAAGUACCG 
                 2954- 
               
               
                 122320 
                 228279 
                   
                 AUUUAAA 
                 2976 
                 2282796. 
                   
                 UAUAUAAA 
                 2976 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3240 
                 GUACUUAUUUAAUA 
                 2964- 
                 A- 
                 3689 
                 UAAGGGAUAUUAAAU 
                 2962- 
               
               
                 122320 
                 228279 
                   
                 UCCCUUA 
                 2984 
                 2282798. 
                   
                 AAGUACCG 
                 2984 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3241 
                 UACUUAUUUAAUAU 
                 2965- 
                 A- 
                 3690 
                 UAAAGGGAUAUUAAA 
                 2963- 
               
               
                 122321 
                 228279 
                   
                 CCCUUUA 
                 2985 
                 2282800. 
                   
                 UAAGUACC 
                 2985 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3242 
                 UUAUGAGAUGUAUC 
                 3068- 
                 A- 
                 3691 
                 UGCAAAAGAUACAUC 
                 3066- 
               
               
                 122321 
                 228280 
                   
                 UUUUGCA 
                 3088 
                 2282802. 
                   
                 UCAUAAAU 
                 3088 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3243 
                 UAUGAGAUGUAUCU 
                 3069- 
                 A- 
                 3692 
                 UAGCAAAAGAUACAU 
                 3067- 
               
               
                 122321 
                 228280 
                   
                 UUUGCUA 
                 3089 
                 2282804. 
                   
                 CUCAUAAA 
                 3089 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3244 
                 AUGAGAUGUAUCUU 
                 3070- 
                 A- 
                 3693 
                 UGAGCAAAAGAUACA 
                 3068- 
               
               
                 122321 
                 228280 
                   
                 UUGCUCA 
                 3090 
                 2282806. 
                   
                 UCUCAUAA 
                 3090 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3245 
                 UGAGAUGUAUCUUU 
                 3071- 
                 A- 
                 3694 
                 UAGAGCAAAAGAUAC 
                 3069- 
               
               
                 122321 
                 228280 
                   
                 UGCUCUA 
                 3091 
                 2282808. 
                   
                 AUCUCAUA 
                 3091 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3246 
                 GAGAUGUAUCUUUU 
                 3072- 
                 A- 
                 3695 
                 UGAGAGCAAAAGAUA 
                 3070- 
               
               
                 122321 
                 228280 
                   
                 GCUCUCA 
                 3092 
                 2282810. 
                   
                 CAUCUCAU 
                 3092 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3247 
                 AGAUGUAUCUUUUG 
                 3073- 
                 A- 
                 3696 
                 UAGAGAGCAAAAGAU 
                 3071- 
               
               
                 122321 
                 228281 
                   
                 CUCUCUA 
                 3093 
                 2282812. 
                   
                 ACAUCUCA 
                 3093 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3248 
                 GAUGUAUCUUUUGC 
                 3074- 
                 A- 
                 3697 
                 UGAGAGAGCAAAAGA 
                 3072- 
               
               
                 122321 
                 228281 
                   
                 UCUCUCA 
                 3094 
                 2282814. 
                   
                 UACAUCUC 
                 3094 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3249 
                 AUGUAUCUUUUGCUC 
                 3075- 
                 A- 
                 3698 
                 UAGAGAGAGCAAAAG 
                 3073- 
               
               
                 122321 
                 228281 
                   
                 UCUCUA 
                 3095 
                 2282816. 
                   
                 AUACAUCU 
                 3095 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3250 
                 GCUCUCUCUUGCUCU 
                 3086- 
                 A- 
                 3699 
                 UAUAAGAGAGCAAGA 
                 3084- 
               
               
                 122321 
                 228281 
                   
                 CUUAUA 
                 3106 
                 2282818. 
                   
                 GAGAGCAA 
                 3106 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3251 
                 CUCUCUCUUGCUCUC 
                 3087- 
                 A- 
                 3700 
                 UAAUAAGAGAGCAAG 
                 3085- 
               
               
                 122322 
                 228281 
                   
                 UUAUUA 
                 3107 
                 2282820. 
                   
                 AGAGAGCA 
                 3107 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3252 
                 UCUCUCUUGCUCUCU 
                 3088- 
                 A- 
                 3701 
                 UAAAUAAGAGAGCAA 
                 3086- 
               
               
                 122322 
                 228282 
                   
                 UAUUUA 
                 3108 
                 2282822. 
                   
                 GAGAGAGC 
                 3108 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3253 
                 CUCUCUUGCUCUCUU 
                 3089- 
                 A- 
                 3702 
                 UCAAAUAAGAGAGCA 
                 3087- 
               
               
                 122322 
                 228282 
                   
                 AUUUGA 
                 3109 
                 2282824. 
                   
                 AGAGAGAG 
                 3109 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3254 
                 UCUCUUGCUCUCUUA 
                 3090- 
                 A- 
                 3703 
                 UACAAAUAAGAGAGC 
                 3088- 
               
               
                 122322 
                 228282 
                   
                 UUUGUA 
                 3110 
                 2282826. 
                   
                 AAGAGAGA 
                 3110 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3255 
                 CUCUUGCUCUCUUAU 
                 3091- 
                 A- 
                 3704 
                 UUACAAAUAAGAGAG 
                 3089- 
               
               
                 122322 
                 228282 
                   
                 UUGUAA 
                 3111 
                 2282828. 
                   
                 CAAGAGAG 
                 3111 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3256 
                 UCUUGCUCUCUUAUU 
                 3092- 
                 A- 
                 3705 
                 UGUACAAAUAAGAGA 
                 3090- 
               
               
                 122322 
                 228282 
                   
                 UGUACA 
                 3112 
                 2282830. 
                   
                 GCAAGAGA 
                 3112 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3257 
                 CUUGCUCUCUUAUUU 
                 3093- 
                 A- 
                 3706 
                 UGGUACAAAUAAGAG 
                 3091- 
               
               
                 122322 
                 228283 
                   
                 GUACCA 
                 3113 
                 2282832. 
                   
                 AGCAAGAG 
                 3113 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3258 
                 UUGCUCUCUUAUUUG 
                 3094- 
                 A- 
                 3707 
                 UCGGUACAAAUAAGA 
                 3092- 
               
               
                 122322 
                 228283 
                   
                 UACCGA 
                 3114 
                 2282834. 
                   
                 GAGCAAGA 
                 3114 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3259 
                 UGCUCUCUUAUUUGU 
                 3095- 
                 A- 
                 3708 
                 UCCGGUACAAAUAAG 
                 3093- 
               
               
                 122322 
                 228283 
                   
                 ACCGGA 
                 3115 
                 2282836. 
                   
                 AGAGCAAG 
                 3115 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3260 
                 CUCUCUUAUUUGUAC 
                 3097- 
                 A- 
                 3709 
                 UAACCGGUACAAAUA 
                 3095- 
               
               
                 122322 
                 228283 
                   
                 CGGUUA 
                 3117 
                 2282838. 
                   
                 AGAGAGCA 
                 3117 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3261 
                 UCUCUUAUUUGUACC 
                 3098- 
                 A- 
                 3710 
                 UAAACCGGUACAAAU 
                 3096- 
               
               
                 122323 
                 228283 
                   
                 GGUUUA 
                 3118 
                 2282840. 
                   
                 AAGAGAGC 
                 3118 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3262 
                 CUCUUAUUUGUACCG 
                 3099- 
                 A- 
                 3711 
                 UAAAACCGGUACAAA 
                 3097- 
               
               
                 122323 
                 228284 
                   
                 GUUUUA 
                 3119 
                 2282842. 
                   
                 UAAGAGAG 
                 3119 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3263 
                 UCUUAUUUGUACCGG 
                 3100- 
                 A- 
                 3712 
                 UAAAAACCGGUACAA 
                 3098- 
               
               
                 122323 
                 228284 
                   
                 UUUUUA 
                 3120 
                 2282844. 
                   
                 AUAAGAGA 
                 3120 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3264 
                 CUUAUUUGUACCGGU 
                 3101- 
                 A- 
                 3713 
                 UCAAAAACCGGUACA 
                 3099- 
               
               
                 122323 
                 228284 
                   
                 UUUUGA 
                 3121 
                 2282846. 
                   
                 AAUAAGAG 
                 3121 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3265 
                 UUAUUUGUACCGGU 
                 3102- 
                 A- 
                 3714 
                 UACAAAAACCGGUAC 
                 3100- 
               
               
                 122323 
                 228284 
                   
                 UUUUGUA 
                 3122 
                 2282848. 
                   
                 AAAUAAGA 
                 3122 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3266 
                 UAUUUGUACCGGUU 
                 3103- 
                 A- 
                 3715 
                 UUACAAAAACCGGUA 
                 3101- 
               
               
                 122323 
                 228284 
                   
                 UUUGUAA 
                 3123 
                 2282850. 
                   
                 CAAAUAAG 
                 3123 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3267 
                 AUUUGUACCGGUUU 
                 3104- 
                 A- 
                 3716 
                 UAUACAAAAACCGGU 
                 3102- 
               
               
                 122323 
                 228285 
                   
                 UUGUAUA 
                 3124 
                 2282852. 
                   
                 ACAAAUAA 
                 3124 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3268 
                 UUUGUACCGGUUUU 
                 3105- 
                 A- 
                 3717 
                 UUAUACAAAAACCGG 
                 3103- 
               
               
                 122323 
                 228285 
                   
                 UGUAUAA 
                 3125 
                 2282854. 
                   
                 UACAAAUA 
                 3125 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3269 
                 UUGUACCGGUUUUU 
                 3106- 
                 A- 
                 3718 
                 UAUAUACAAAAACCG 
                 3104- 
               
               
                 122323 
                 228285 
                   
                 GUAUAUA 
                 3126 
                 2282856. 
                   
                 GUACAAAU 
                 3126 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3270 
                 UGUACCGGUUUUUG 
                 3107- 
                 A- 
                 3719 
                 UUAUAUACAAAAACC 
                 3105- 
               
               
                 122323 
                 228285 
                   
                 UAUAUAA 
                 3127 
                 2282858. 
                   
                 GGUACAAA 
                 3127 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3271 
                 GUACCGGUUUUUGU 
                 3108- 
                 A- 
                 3720 
                 UUUAUAUACAAAAAC 
                 3106- 
               
               
                 122324 
                 228285 
                   
                 AUAUAAA 
                 3128 
                 2282860. 
                   
                 CGGUACAA 
                 3128 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3272 
                 UACCGGUUUUUGUA 
                 3109- 
                 A- 
                 3721 
                 UUUUAUAUACAAAAA 
                 3107- 
               
               
                 122324 
                 228286 
                   
                 UAUAAAA 
                 3129 
                 2282862. 
                   
                 CCGGUACA 
                 3129 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3273 
                 ACCGGUUUUUGUAU 
                 3110- 
                 A- 
                 3722 
                 UUUUUAUAUACAAAA 
                 3108- 
               
               
                 122324 
                 228286 
                   
                 AUAAAAA 
                 3130 
                 2282864. 
                   
                 ACCGGUAC 
                 3130 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3274 
                 AUUCAUGUUUCCAAU 
                 3129- 
                 A- 
                 3723 
                 UGAGAGAUUGGAAAC 
                 3127- 
               
               
                 122324 
                 228286 
                   
                 CUCUCA 
                 3149 
                 2282866. 
                   
                 AUGAAUUU 
                 3149 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3275 
                 UUCAUGUUUCCAAUC 
                 3130- 
                 A- 
                 3724 
                 UAGAGAGAUUGGAAA 
                 3128- 
               
               
                 122324 
                 228286 
                   
                 UCUCUA 
                 3150 
                 2282868. 
                   
                 CAUGAAUU 
                 3150 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3276 
                 UCAUGUUUCCAAUCU 
                 3131- 
                 A- 
                 3725 
                 UGAGAGAGAUUGGAA 
                 3129- 
               
               
                 122324 
                 228286 
                   
                 CUCUCA 
                 3151 
                 2282870. 
                   
                 ACAUGAAU 
                 3151 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3277 
                 CAUGUUUCCAAUCUC 
                 3132- 
                 A- 
                 3726 
                 UAGAGAGAGAUUGGA 
                 3130- 
               
               
                 122324 
                 228287 
                   
                 UCUCUA 
                 3152 
                 2282872. 
                   
                 AACAUGAA 
                 3152 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3278 
                 AUGUUUCCAAUCUCU 
                 3133- 
                 A- 
                 3727 
                 UGAGAGAGAGAUUGG 
                 3131- 
               
               
                 122324 
                 228287 
                   
                 CUCUCA 
                 3153 
                 2282874. 
                   
                 AAACAUGA 
                 3153 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3279 
                 UGUUUCCAAUCUCUC 
                 3134- 
                 A- 
                 3728 
                 UGGAGAGAGAGAUUG 
                 3132- 
               
               
                 122324 
                 228287 
                   
                 UCUCCA 
                 3154 
                 2282876. 
                   
                 GAAACAUG 
                 3154 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3280 
                 UUUCCAAUCUCUCUC 
                 3136- 
                 A- 
                 3729 
                 UAGGGAGAGAGAGAU 
                 3134- 
               
               
                 122324 
                 228287 
                   
                 UCCCUA 
                 3156 
                 2282878. 
                   
                 UGGAAACA 
                 3156 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3281 
                 UCCAAUCUCUCUCUC 
                 3138- 
                 A- 
                 3730 
                 UUCAGGGAGAGAGAG 
                 3136- 
               
               
                 122325 
                 228287 
                   
                 CCUGAA 
                 3158 
                 2282880. 
                   
                 AUUGGAAA 
                 3158 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3282 
                 CGGUGACAGUCACUA 
                 3159- 
                 A- 
                 3731 
                 UUAAGCUAGUGACUG 
                 3157- 
               
               
                 122325 
                 228288 
                   
                 GCUUAA 
                 3179 
                 2282882. 
                   
                 UCACCGAU 
                 3179 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3283 
                 GGUGACAGUCACUAG 
                 3160- 
                 A- 
                 3732 
                 UAUAAGCUAGUGACU 
                 3158- 
               
               
                 122325 
                 228288 
                   
                 CUUAUA 
                 3180 
                 2282884. 
                   
                 GUCACCGA 
                 3180 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3284 
                 AGUCACUAGCUUAUC 
                 3166- 
                 A- 
                 3733 
                 UUUCAAGAUAAGCUA 
                 3164- 
               
               
                 122325 
                 228288 
                   
                 UUGAAA 
                 3186 
                 2282886. 
                   
                 GUGACUGU 
                 3186 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3285 
                 GUCACUAGCUUAUCU 
                 3167- 
                 A- 
                 3734 
                 UGUUCAAGAUAAGCU 
                 3165- 
               
               
                 122325 
                 228288 
                   
                 UGAACA 
                 3187 
                 2282888. 
                   
                 AGUGACUG 
                 3187 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3286 
                 UCACUAGCUUAUCUU 
                 3168- 
                 A- 
                 3735 
                 UUGUUCAAGAUAAGC 
                 3166- 
               
               
                 122325 
                 228288 
                   
                 GAACAA 
                 3188 
                 2282890. 
                   
                 UAGUGACU 
                 3188 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3287 
                 ACUAGCUUAUCUUGA 
                 3170- 
                 A- 
                 3736 
                 UUCUGUUCAAGAUAA 
                 3168- 
               
               
                 122325 
                 228289 
                   
                 ACAGAA 
                 3190 
                 2282892. 
                   
                 GCUAGUGA 
                 3190 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3288 
                 CUAGCUUAUCUUGAA 
                 3171- 
                 A- 
                 3737 
                 UAUCUGUUCAAGAUA 
                 3169- 
               
               
                 122325 
                 228289 
                   
                 CAGAUA 
                 3191 
                 2282894. 
                   
                 AGCUAGUG 
                 3191 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3289 
                 UAGCUUAUCUUGAAC 
                 3172- 
                 A- 
                 3738 
                 UUAUCUGUUCAAGAU 
                 3 no- 
               
               
                 122325 
                 228289 
                   
                 AGAUAA 
                 3192 
                 2282896. 
                   
                 AAGCUAGU 
                 3192 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3290 
                 AGCUUAUCUUGAACA 
                 3173- 
                 A- 
                 3739 
                 UAUAUCUGUUCAAGA 
                 3171- 
               
               
                 122325 
                 228289 
                   
                 GAUAUA 
                 3193 
                 2282898. 
                   
                 UAAGCUAG 
                 3193 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3291 
                 GCUUAUCUUGAACAG 
                 3174- 
                 A- 
                 3740 
                 UAAUAUCUGUUCAAG 
                 3172- 
               
               
                 122326 
                 228289 
                   
                 AUAUUA 
                 3194 
                 2282900. 
                   
                 AUAAGCUA 
                 3194 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3292 
                 CAGCACACAUUCCUU 
                 3241- 
                 A- 
                 3741 
                 UUUUCAAAGGAAUGU 
                 3239- 
               
               
                 122326 
                 228290 
                   
                 UGAAAA 
                 3261 
                 2282902. 
                   
                 GUGCUGGG 
                 3261 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3293 
                 AGCACACAUUCCUUU 
                 3242- 
                 A- 
                 3742 
                 UAUUUCAAAGGAAUG 
                 3240- 
               
               
                 122326 
                 228290 
                   
                 GAAAUA 
                 3262 
                 2282904. 
                   
                 UGUGCUGG 
                 3262 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3294 
                 GCACACAUUCCUUUG 
                 3243- 
                 A- 
                 3743 
                 UUAUUUCAAAGGAAU 
                 3241- 
               
               
                 122326 
                 228290 
                   
                 AAAUAA 
                 3263 
                 2282906. 
                   
                 GUGUGCUG 
                 3263 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3295 
                 CACACAUUCCUUUGA 
                 3244- 
                 A- 
                 3744 
                 UUUAUUUCAAAGGAA 
                 3242- 
               
               
                 122326 
                 228290 
                   
                 AAUAAA 
                 3264 
                 2282908. 
                   
                 UGUGUGCU 
                 3264 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3296 
                 CACAUUCCUUUGAAA 
                 3246- 
                 A- 
                 3745 
                 UCCUUAUUUCAAAGG 
                 3244- 
               
               
                 122326 
                 228290 
                   
                 UAAGGA 
                 3266 
                 2282910. 
                   
                 AAUGUGUG 
                 3266 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3297 
                 UCCUUUGAAAUAAG 
                 3251- 
                 A- 
                 3746 
                 UUGAAACCUUAUUUC 
                 3249- 
               
               
                 122326 
                 228291 
                   
                 GUUUCAA 
                 3271 
                 2282912. 
                   
                 AAAGGAAU 
                 3271 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3298 
                 CUUUGAAAUAAGGU 
                 3253- 
                 A- 
                 3747 
                 UAUUGAAACCUUAUU 
                 3251- 
               
               
                 122326 
                 228291 
                   
                 UUCAAUA 
                 3273 
                 2282914. 
                   
                 UCAAAGGA 
                 3273 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3299 
                 UUUGAAAUAAGGUU 
                 3254- 
                 A- 
                 3748 
                 UUAUUGAAACCUUAU 
                 3252- 
               
               
                 122326 
                 228291 
                   
                 UCAAUAA 
                 3274 
                 2282916. 
                   
                 UUCAAAGG 
                 3274 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3300 
                 AGGUUUCAAUAUAC 
                 3263- 
                 A- 
                 3749 
                 UGUAGAUGUAUAUUG 
                 3261- 
               
               
                 122326 
                 228291 
                   
                 AUCUACA 
                 3283 
                 2282918. 
                   
                 AAACCUUA 
                 3283 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3301 
                 GGUUUCAAUAUACA 
                 3264- 
                 A- 
                 3750 
                 UUGUAGAUGUAUAUU 
                 3262- 
               
               
                 122327 
                 228291 
                   
                 UCUACAA 
                 3284 
                 2282920. 
                   
                 GAAACCUU 
                 3284 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3302 
                 GUUUCAAUAUACAUC 
                 3265- 
                 A- 
                 3751 
                 UAUGUAGAUGUAUAU 
                 3263- 
               
               
                 122327 
                 228292 
                   
                 UACAUA 
                 3285 
                 2282922. 
                   
                 UGAAACCU 
                 3285 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3303 
                 UUUCAAUAUACAUCU 
                 3266- 
                 A- 
                 3752 
                 UUAUGUAGAUGUAUA 
                 3264- 
               
               
                 122327 
                 228292 
                   
                 ACAUAA 
                 3286 
                 2282924. 
                   
                 UUGAAACC 
                 3286 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3304 
                 UUCAAUAUACAUCUA 
                 3267- 
                 A- 
                 3753 
                 UGUAUGUAGAUGUAU 
                 3265- 
               
               
                 122327 
                 228292 
                   
                 CAUACA 
                 3287 
                 2282926. 
                   
                 AUUGAAAC 
                 3287 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3305 
                 UAUUUGGCAACUUG 
                 3295- 
                 A- 
                 3754 
                 UCAAAUACAAGUUGC 
                 3293- 
               
               
                 122327 
                 228292 
                   
                 UAUUUGA 
                 3315 
                 2282928. 
                   
                 CAAAUAUA 
                 3315 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3306 
                 UUUGGCAACUUGUA 
                 3297- 
                 A- 
                 3755 
                 UCACAAAUACAAGUU 
                 3295- 
               
               
                 122327 
                 228292 
                   
                 UUUGUGA 
                 3317 
                 2282930. 
                   
                 GCCAAAUA 
                 3317 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3307 
                 UGGCAACUUGUAUU 
                 3299- 
                 A- 
                 3756 
                 UCACACAAAUACAAG 
                 3297- 
               
               
                 122327 
                 228293 
                   
                 UGUGUGA 
                 3319 
                 2282932. 
                   
                 UUGCCAAA 
                 3319 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3308 
                 GGCAACUUGUAUUU 
                 3300- 
                 A- 
                 3757 
                 UACACACAAAUACAA 
                 3298- 
               
               
                 122327 
                 228293 
                   
                 GUGUGUA 
                 3320 
                 2282934. 
                   
                 GUUGCCAA 
                 3320 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3309 
                 GCAACUUGUAUUUG 
                 3301- 
                 A- 
                 3758 
                 UUACACACAAAUACA 
                 3299- 
               
               
                 122327 
                 228293 
                   
                 UGUGUAA 
                 3321 
                 2282936. 
                   
                 AGUUGCCA 
                 3321 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3310 
                 CAACUUGUAUUUGU 
                 3302- 
                 A- 
                 3759 
                 UAUACACACAAAUAC 
                 3300- 
               
               
                 122327 
                 228293 
                   
                 GUGUAUA 
                 3322 
                 2282938. 
                   
                 AAGUUGCC 
                 3322 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3311 
                 AACUUGUAUUUGUG 
                 3303- 
                 A- 
                 3760 
                 UUAUACACACAAAUA 
                 3301- 
               
               
                 122328 
                 228293 
                   
                 UGUAUAA 
                 3323 
                 2282940. 
                   
                 CAAGUUGC 
                 3323 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3312 
                 ACUUGUAUUUGUGU 
                 3304- 
                 A- 
                 3761 
                 UAUAUACACACAAAU 
                 3302- 
               
               
                 122328 
                 228294 
                   
                 GUAUAUA 
                 3324 
                 2282942. 
                   
                 ACAAGUUG 
                 3324 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3313 
                 UUCUGAUAAAAUAG 
                 3354- 
                 A- 
                 3762 
                 UCAAUGUCUAUUUUA 
                 3352- 
               
               
                 122328 
                 228294 
                   
                 ACAUUGA 
                 3374 
                 2282944. 
                   
                 UCAGAAUC 
                 3374 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3314 
                 UGAUAAAAUAGACA 
                 3357- 
                 A- 
                 3763 
                 UUAGCAAUGUCUAUU 
                 3355- 
               
               
                 122328 
                 228294 
                   
                 UUGCUAA 
                 3377 
                 2282946. 
                   
                 UUAUCAGA 
                 3377 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3315 
                 GAUAAAAUAGACAU 
                 3358- 
                 A- 
                 3764 
                 UAUAGCAAUGUCUAU 
                 3356- 
               
               
                 122328 
                 228294 
                   
                 UGCUAUA 
                 3378 
                 2282948. 
                   
                 UUUAUCAG 
                 3378 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3316 
                 UAAAAUAGACAUUG 
                 3360- 
                 A- 
                 3765 
                 UGAAUAGCAAUGUCU 
                 3358- 
               
               
                 122328 
                 228294 
                   
                 CUAUUCA 
                 3380 
                 2282950. 
                   
                 AUUUUAUC 
                 3380 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3317 
                 UAGACAUUGCUAUUC 
                 3365- 
                 A- 
                 3766 
                 UAAACAGAAUAGCAA 
                 3363- 
               
               
                 122328 
                 228295 
                   
                 UGUUUA 
                 3385 
                 2282952. 
                   
                 UGUCUAUU 
                 3385 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3318 
                 AGACAUUGCUAUUCU 
                 3366- 
                 A- 
                 3767 
                 UAAAACAGAAUAGCA 
                 3364- 
               
               
                 122328 
                 228295 
                   
                 GUUUUA 
                 3386 
                 2282954. 
                   
                 AUGUCUAU 
                 3386 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3319 
                 UCUACAUACUAAAUC 
                 3422- 
                 A- 
                 3768 
                 UAGAGAGAUUUAGUA 
                 3420- 
               
               
                 122328 
                 228295 
                   
                 UCUCUA 
                 3442 
                 2282956. 
                   
                 UGUAGAAU 
                 3442 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3320 
                 CUACAUACUAAAUCU 
                 3423- 
                 A- 
                 3769 
                 UGAGAGAGAUUUAGU 
                 3421- 
               
               
                 122328 
                 228295 
                   
                 CUCUCA 
                 3443 
                 2282958. 
                   
                 AUGUAGAA 
                 3443 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3321 
                 UACAUACUAAAUCUC 
                 3424- 
                 A- 
                 3770 
                 UGGAGAGAGAUUUAG 
                 3422- 
               
               
                 122329 
                 228295 
                   
                 UCUCCA 
                 3444 
                 2282960. 
                   
                 UAUGUAGA 
                 3444 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3322 
                 ACAUACUAAAUCUCU 
                 3425- 
                 A- 
                 3771 
                 UAGGAGAGAGAUUUA 
                 3423- 
               
               
                 122329 
                 228296 
                   
                 CUCCUA 
                 3445 
                 2282962. 
                   
                 GUAUGUAG 
                 3445 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3323 
                 CAUACUAAAUCUCUC 
                 3426- 
                 A- 
                 3772 
                 UAAGGAGAGAGAUUU 
                 3424- 
               
               
                 122329 
                 228296 
                   
                 UCCUUA 
                 3446 
                 2282964. 
                   
                 AGUAUGUA 
                 3446 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3324 
                 AUACUAAAUCUCUCU 
                 3427- 
                 A- 
                 3773 
                 UAAAGGAGAGAGAUU 
                 3425- 
               
               
                 122329 
                 228296 
                   
                 CCUUUA 
                 3447 
                 2282966. 
                   
                 UAGUAUGU 
                 3447 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3325 
                 UACUAAAUCUCUCUC 
                 3428- 
                 A- 
                 3774 
                 UAAAAGGAGAGAGAU 
                 3426- 
               
               
                 122329 
                 228296 
                   
                 CUUUUA 
                 3448 
                 2282968. 
                   
                 UUAGUAUG 
                 3448 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3326 
                 CAUUUAUUUAUUGG 
                 3468- 
                 A- 
                 3775 
                 UGUAGCACCAAUAAA 
                 3466- 
               
               
                 122329 
                 228296 
                   
                 UGCUACA 
                 3488 
                 2282970. 
                   
                 UAAAUGAU 
                 3488 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3327 
                 AUUUAUUUAUUGGU 
                 3469- 
                 A- 
                 3776 
                 UAGUAGCACCAAUAA 
                 3467- 
               
               
                 122329 
                 228297 
                   
                 GCUACUA 
                 3489 
                 2282972. 
                   
                 AUAAAUGA 
                 3489 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3328 
                 UUUAUUUAUUGGUG 
                 3470- 
                 A- 
                 3777 
                 UCAGUAGCACCAAUA 
                 3468- 
               
               
                 122329 
                 228297 
                   
                 CUACUGA 
                 3490 
                 2282974. 
                   
                 AAUAAAUG 
                 3490 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3329 
                 UUAUUUAUUGGUGC 
                 3471- 
                 A- 
                 3778 
                 UACAGUAGCACCAAU 
                 3469- 
               
               
                 122329 
                 228297 
                   
                 UACUGUA 
                 3491 
                 2282976. 
                   
                 AAAUAAAU 
                 3491 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3330 
                 UAUUUAUUGGUGCU 
                 3472- 
                 A- 
                 3779 
                 UAACAGUAGCACCAA 
                 3470- 
               
               
                 122329 
                 228297 
                   
                 ACUGUUA 
                 3492 
                 2282978. 
                   
                 UAAAUAAA 
                 3492 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3331 
                 AUUUAUUGGUGCUA 
                 3473- 
                 A- 
                 3780 
                 UAAACAGUAGCACCA 
                 3471- 
               
               
                 122330 
                 228297 
                   
                 CUGUUUA 
                 3493 
                 2282980. 
                   
                 AUAAAUAA 
                 3493 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3332 
                 UUAUUGGUGCUACU 
                 3475- 
                 A- 
                 3781 
                 UAUAAACAGUAGCAC 
                 3473- 
               
               
                 122330 
                 228298 
                   
                 GUUUAUA 
                 3495 
                 2282982. 
                   
                 CAAUAAAU 
                 3495 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3333 
                 AUUGGUGCUACUGU 
                 3477- 
                 A- 
                 3782 
                 UGGAUAAACAGUAGC 
                 3475- 
               
               
                 122330 
                 228298 
                   
                 UUAUCCA 
                 3497 
                 2282984. 
                   
                 ACCAAUAA 
                 3497 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3334 
                 GAAAAGAUAUUAAC 
                 3511- 
                 A- 
                 3783 
                 UCGUGAUGUUAAUAU 
                 3509- 
               
               
                 122330 
                 228298 
                   
                 AUCACGA 
                 3531 
                 2282986. 
                   
                 CUUUUCCC 
                 3531 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3335 
                 AACAUCACGUCUUUG 
                 3522- 
                 A- 
                 3784 
                 UAGAGACAAAGACGU 
                 3520- 
               
               
                 122330 
                 228298 
                   
                 UCUCUA 
                 3542 
                 2282988. 
                   
                 GAUGUUAA 
                 3542 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3336 
                 ACAUCACGUCUUUGU 
                 3523- 
                 A- 
                 3785 
                 UUAGAGACAAAGACG 
                 3521- 
               
               
                 122330 
                 228298 
                   
                 CUCUAA 
                 3543 
                 2282990. 
                   
                 UGAUGUUA 
                 3543 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3337 
                 GUCUUUGUCUCUAGU 
                 3530- 
                 A- 
                 3786 
                 UACUGCACUAGAGAC 
                 3528- 
               
               
                 122330 
                 228299 
                   
                 GCAGUA 
                 3550 
                 2282992. 
                   
                 AAAGACGU 
                 3550 
               
               
                 6.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3338 
                 UCUUUGUCUCUAGUG 
                 3531- 
                 A- 
                 3787 
                 UAACUGCACUAGAGA 
                 3529- 
               
               
                 122330 
                 228299 
                   
                 CAGUUA 
                 3551 
                 2282994. 
                   
                 CAAAGACG 
                 3551 
               
               
                 7.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3339 
                 CUUUGUCUCUAGUGC 
                 3532- 
                 A- 
                 3788 
                 UAAACUGCACUAGAG 
                 3530- 
               
               
                 122330 
                 228299 
                   
                 AGUUUA 
                 3552 
                 2282996. 
                   
                 ACAAAGAC 
                 3552 
               
               
                 8.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3340 
                 GAGAUAUUCCGUAG 
                 3555- 
                 A- 
                 3789 
                 UUAUGUACUACGGAA 
                 3553- 
               
               
                 122330 
                 228299 
                   
                 UACAUAA 
                 3575 
                 2282998. 
                   
                 UAUCUCGA 
                 3575 
               
               
                 9.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3341 
                 AGAUAUUCCGUAGU 
                 3556- 
                 A- 
                 3790 
                 UAUAUGUACUACGGA 
                 3554- 
               
               
                 122331 
                 228299 
                   
                 ACAUAUA 
                 3576 
                 2283000. 
                   
                 AUAUCUCG 
                 3576 
               
               
                 0.1 
                 9.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3342 
                 GAUAUUCCGUAGUAC 
                 3557- 
                 A- 
                 3791 
                 UAAUAUGUACUACGG 
                 3555- 
               
               
                 122331 
                 228300 
                   
                 AUAUUA 
                 3577 
                 2283002. 
                   
                 AAUAUCUC 
                 3577 
               
               
                 1.1 
                 1.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3343 
                 CGACAAAGAAAUACA 
                 3590- 
                 A- 
                 3792 
                 UAUAUCUGUAUUUCU 
                 3588- 
               
               
                 122331 
                 228300 
                   
                 GAUAUA 
                 3610 
                 2283004. 
                   
                 UUGUCGUU 
                 3610 
               
               
                 2.1 
                 3.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3344 
                 GACAAAGAAAUACA 
                 3591- 
                 A- 
                 3793 
                 UUAUAUCUGUAUUUC 
                 3589- 
               
               
                 122331 
                 228300 
                   
                 GAUAUAA 
                 3611 
                 2283006. 
                   
                 UUUGUCGU 
                 3611 
               
               
                 3.1 
                 5.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3345 
                 ACAAAGAAAUACAG 
                 3592- 
                 A- 
                 3794 
                 UAUAUAUCUGUAUUU 
                 3590- 
               
               
                 122331 
                 228300 
                   
                 AUAUAUA 
                 3612 
                 2283008. 
                   
                 CUUUGUCG 
                 3612 
               
               
                 4.1 
                 7.1 
                   
                   
                   
                 1 
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3346 
                 CAAAGAAAUACAGA 
                 3593- 
                 A- 
                 3795 
                 UGAUAUAUCUGUAUU 
                 3591- 
               
               
                 122331 
                 228300 
                   
                 UAUAUCA 
                 3613 
                 2283010. 
                   
                 UCUUUGUC 
                 3613 
               
               
                 5.1 
                 9.1 
                   
                   
                   
                 1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10A 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Modified Single Strands and Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                 Anti- 
                 SEQ ID 
                   
                 mRNA Target 
                 SEQ ID 
               
               
                   
                 Sense 
                 SEQ 
                   
                 sense 
                 NO: 
                   
                 Sequence 
                 NO: 
               
               
                 Duplex 
                 Oligo 
                 ID NO: 
                   
                 Oligo 
                 (Anti- 
                   
                   
                 (mRNA 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Name 
                 sense) 
                 Antisense Sequence 
                   
                 target) 
               
               
                   
               
               
                 AD- 
                 A- 
                 3796 
                 asasaag(Ahd)gadAadGugu 
                 A- 
                 3886 
                 VPusdTsaudAadAaca 
                 AGAAAAGAGAAA 
                 5149 
               
               
                 1353514.1 
                 2521322.1 
                   
                 uuuausasa 
                 2521323.1 
                   
                 cdTudTcdTcuuuuscsu 
                 GUGUUUUAUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3797 
                 asasaag(Ahd)gaAfAfGfug 
                 A- 
                 3887 
                 VPusdTsaudAadAaca 
                 AGAAAAGAGAAA 
                 5150 
               
               
                 1353484.1 
                 2521264.1 
                   
                 uuuuausasa 
                 2521265.1 
                   
                 cdTuUfcucuuuuscsu 
                 GUGUUUUAUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3798 
                 asasaag(Ahd)GfaAfAfGfu 
                 A- 
                 3888 
                 VPusUfsauaAfaacacu 
                 AGAAAAGAGAAA 
                 5151 
               
               
                 1353454.1 
                 2521212.1 
                   
                 guuuuausasa 
                 2282766.1 
                   
                 uUfcUfcuuuuscsu 
                 GUGUUUUAUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3799 
                 asasaga(Chd)ugAfUfAfca 
                 A- 
                 3889 
                 VPusdAsucdGudTcug 
                 GGAAAGACUGAU 
                 5152 
               
               
                 1353468.1 
                 2521232.1 
                   
                 gaacgasusa 
                 2521233.1 
                   
                 udAuCfagucuuuscsc 
                 ACAGAACGAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3800 
                 asasaga(Chd)ugdAudAcag 
                 A- 
                 3890 
                 VPusdAsucdGudTcug 
                 GGAAAGACUGAU 
                 5153 
               
               
                 1353498.1 
                 2521292.1 
                   
                 aacgasusa 
                 1800369.1 
                   
                 udAudCadGucuuuscsc 
                 ACAGAACGAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3801 
                 asasaga(Chd)UfgAfUfAfc 
                 A- 
                 3891 
                 VPusAfsucgUfucugua 
                 GGAAAGACUGAU 
                 5154 
               
               
                 1353438.1 
                 1700819.1 
                   
                 agaacgasusa 
                 2282346.1 
                   
                 uCfaGfucuuuscsc 
                 ACAGAACGAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3802 
                 asasagagaadAgdTguuu 
                 A- 
                 3892 
                 VPusdAsuadTadAaac 
                 GAAAAGAGAAAG 
                 5155 
               
               
                 1353515.1 
                 2521324.1 
                   
                 (Uhd)auasusa 
                 2521325.1 
                   
                 adCudTudCucuuususc 
                 UGUUUUAUAUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3803 
                 asasagagaaAfGfUfguuu 
                 A- 
                 3893 
                 VPusdAsuadTadAaac 
                 GAAAAGAGAAAG 
                 5156 
               
               
                 1353485.1 
                 2521266.1 
                   
                 (Uhd)auasusa 
                 2521267.1 
                   
                 adCuUfucucuuususc 
                 UGUUUUAUAUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3804 
                 asasagagAfaAfGfUfguuu 
                 A- 
                 3894 
                 VPusAfsuauAfaaacac 
                 GAAAAGAGAAAG 
                 5157 
               
               
                 1353455.1 
                 2521213.1 
                   
                 (Uhd)auasusa 
                 2282768.1 
                   
                 uUfuCfucuuususc 
                 UGUUUUAUAUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3805 
                 asascag(Uhd)gcdTadAugu 
                 A- 
                 3895 
                 VPusdCscadAudAaca 
                 UUAACAGUGCUA 
                 5158 
               
               
                 1353513.1 
                 2521320.1 
                   
                 uauugsgsa 
                 2521321.1 
                   
                 udTadGcdAcuguusgsg 
                 AUGUUAUUGGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3806 
                 asascag(Uhd)gcUfAfAfug 
                 A- 
                 3896 
                 VPusdCscadAudAaca 
                 UUAACAGUGCUA 
                 5159 
               
               
                 1353483.1 
                 2521262.1 
                   
                 uuauugsgsa 
                 2521263.1 
                   
                 udTaGfcacuguusgsg 
                 AUGUUAUUGGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3807 
                 asascag(Uhd)GfcUfAfAfu 
                 A- 
                 3897 
                 VPusCfscaaUfaacauua 
                 UUAACAGUGCUA 
                 5160 
               
               
                 1353453.1 
                 1700832.1 
                   
                 guuauugsgsa 
                 2521211.1 
                   
                 GfcAfcuguusgsg 
                 AUGUUAUUGGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3808 
                 asascga(Uhd)cgdAudAcag 
                 A- 
                 3898 
                 VPusdTsggdTu(U2p)c 
                 AGAACGAUCGAU 
                 5161 
               
               
                 1353502.1 
                 2521298.1 
                   
                 aaaccsasa 
                 2521299.1 
                   
                 ugudAudCgdAucguus 
                 ACAGAAACCAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3809 
                 asascga(Uhd)cgAfUfAfca 
                 A- 
                 3899 
                 VPusdTsggdTu(U2p)c 
                 AGAACGAUCGAU 
                 5162 
               
               
                 1353472.1 
                 2521240.1 
                   
                 gaaaccsasa 
                 2521241.1 
                   
                 ugudAuCfgaucguuscs 
                 ACAGAAACCAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3810 
                 asascga(Uhd)CfgAfUfAfc 
                 A- 
                 3900 
                 VPusUfsggdTu(U2p)c 
                 AGAACGAUCGAU 
                 5163 
               
               
                 1353442.1 
                 2521195.1 
                   
                 agaaaccsasa 
                 2521196.1 
                   
                 uguauCfgAfucguuscsu 
                 ACAGAAACCAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3811 
                 asasgac(Uhd)gadTadCaga 
                 A- 
                 3901 
                 VPusdGsaudCg(U2p) 
                 GAAAGACUGAUA 
                 5164 
               
               
                 1353499.1 
                 2483623.1 
                   
                 acgauscsa 
                 2521293.1 
                   
                 ucugdTadTedAgucuus 
                 CAGAACGAUCG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3812 
                 asasgac(Uhd)gaUfAfCfag 
                 A- 
                 3902 
                 VPusdGsaudCg(U2p) 
                 GAAAGACUGAUA 
                 5165 
               
               
                 1353469.1 
                 2521234.1 
                   
                 aacgauscsa 
                 2521235.1 
                   
                 ucugdTaUfcagucuusus 
                 CAGAACGAUCG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3813 
                 asasgac(Uhd)GfaUfAfCfa 
                 A- 
                 3903 
                 VPusGfsaudCg(U2p)u 
                 GAAAGACUGAUA 
                 5166 
               
               
                 1353439.1 
                 1700820.1 
                   
                 gaacgauscsa 
                 2521191.1 
                   
                 cuguaUfcAfgucuususc 
                 CAGAACGAUCG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3814 
                 asasgag(Ahd)aadGudGuu 
                 A- 
                 3904 
                 VPusdTsaudAudAaaa 
                 AAAAGAGAAAGU 
                 5167 
               
               
                 1353516.1 
                 2521326.1 
                   
                 uuauausasa 
                 2521327.1 
                   
                 cdAcdTudTcucuususu 
                 GUUUUAUAUAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3815 
                 asasgag(Ahd)aaGfUfGfuu 
                 A- 
                 3905 
                 VPusdTsaudAudAaaa 
                 AAAAGAGAAAGU 
                 5168 
               
               
                 1353486.1 
                 2521268.1 
                   
                 uuauausasa 
                 2521269.1 
                   
                 cdAcUfuucucuususu 
                 GUUUUAUAUAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3816 
                 asasgag(Ahd)AfaGfUfGfu 
                 A- 
                 3906 
                 VPusUfsauaUfaaaacac 
                 AAAAGAGAAAGU 
                 5169 
               
               
                 1353456.1 
                 2521214.1 
                   
                 uuuauausasa 
                 2282770.1 
                   
                 UfuUfcucuususu 
                 GUUUUAUAUAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3817 
                 asasuuggaudTcdGccau 
                 A- 
                 3907 
                 VPusdAsuadAadAugg 
                 GGAAUUGGAUUC 
                 5170 
               
               
                 1353509.1 
                 2521312.1 
                   
                 (Uhd)uuasusa 
                 2521313.1 
                   
                 cdGadAudCcaauuscsc 
                 GCCAUUUUAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3818 
                 asasuuggauUfCfGfccau 
                 A- 
                 3908 
                 VPusdAsuadAadAugg 
                 GGAAUUGGAUUC 
                 5171 
               
               
                 1353479.1 
                 2521254.1 
                   
                 (Uhd)uuasusa 
                 2521255.1 
                   
                 cdGaAfuccaauuscsc 
                 GCCAUUUUAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3819 
                 asasuuggAfuUfCfGfccau 
                 A- 
                 3909 
                 VPusAfsuaaAfauggcg 
                 GGAAUUGGAUUC 
                 5172 
               
               
                 1353449.1 
                 2521206.1 
                   
                 (Uhd)uuasusa 
                 2282454.1 
                   
                 aAfuCfcaauuscsc 
                 GCCAUUUUAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3820 
                 ascsaga(Ahd)cadGudCcuu 
                 A- 
                 3910 
                 VPusdTsggdAudTaag 
                 CGACAGAACAGUC 
                 5173 
               
               
                 1353503.1 
                 2521300.1 
                   
                 aauccsasa 
                 2521301.1 
                   
                 gdAcdTgdTucuguscsg 
                 CUUAAUCCAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3821 
                 ascsaga(Ahd)caGfUfCfcu 
                 A- 
                 3911 
                 VPusdTsggdAudTaag 
                 CGACAGAACAGUC 
                 5174 
               
               
                 1353473.1 
                 2521242.1 
                   
                 uaauccsasa 
                 2521243.1 
                   
                 gdAcUfguucuguscsg 
                 CUUAAUCCAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3822 
                 ascsaga(Ahd)CfaGfUfCfc 
                 A- 
                 3912 
                 VPusUfsggaUfuaagga 
                 CGACAGAACAGUC 
                 5175 
               
               
                 1353443.1 
                 2521197.1 
                   
                 uuaauccsasa 
                 2282402.1 
                   
                 cUfgUfucuguscsg 
                 CUUAAUCCAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3823 
                 ascsagu(Chd)cudTadAucc 
                 A- 
                 3913 
                 VPusdGsuudTc(U2p)g 
                 GAACAGUCCUUAA 
                 5176 
               
               
                 1353506.1 
                 2521306.1 
                   
                 agaaascsa 
                 2521307.1 
                   
                 gaudTadAgdGacugusu 
                 UCCAGAAACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3824 
                 ascsagu(Chd)cuUfAfAfuc 
                 A- 
                 3914 
                 VPusdGsuudTc(U2p)g 
                 GAACAGUCCUUAA 
                 5177 
               
               
                 1353476.1 
                 2521248.1 
                   
                 cagaaascsa 
                 2521249.1 
                   
                 gaudTaAfggacugususc 
                 UCCAGAAACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3825 
                 ascsagu(Chd)CfuUfAfAfu 
                 A- 
                 3915 
                 VPusGfsuudTc(U2p)g 
                 GAACAGUCCUUAA 
                 5178 
               
               
                 1353446.1 
                 2521201.1 
                   
                 ccagaaascsa 
                 2521202.1 
                   
                 gauuaAfgGfacugususc 
                 UCCAGAAACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3826 
                 ascscaggaadAgdAcuga 
                 A- 
                 3916 
                 VPusdCsugdTadTcag 
                 UCACCAGGAAAGA 
                 5179 
               
               
                 1353497.1 
                 2521290.1 
                   
                 (Uhd)acasgsa 
                 2521291.1 
                   
                 udCudTudCcuggusgsc 
                 CUGAUACAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3827 
                 ascscaggaaAfGfAfcuga 
                 A- 
                 3917 
                 VPusdCsugdTadTcag 
                 UCACCAGGAAAGA 
                 5180 
               
               
                 1353467.1 
                 2521230.1 
                   
                 (Uhd)acasgsa 
                 2521231.1 
                   
                 udCuUfuccuggusgsc 
                 CUGAUACAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3828 
                 ascscaggAfaAfGfAfcuga 
                 A- 
                 3918 
                 VPusCfsuguAfucaguc 
                 UCACCAGGAAAGA 
                 5181 
               
               
                 1353437.1 
                 2521189.1 
                   
                 (Uhd)acasgsa 
                 2521190.1 
                   
                 uUfuCfcuggusgsc 
                 CUGAUACAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3829 
                 ascscaugcadGadTuaug 
                 A- 
                 3919 
                 VPusdAsucdCg(C2p)a 
                 UCACCAUGCAGAU 
                 5182 
               
               
                 1353494.1 
                 2521284.1 
                   
                 (Chd)ggasusa 
                 2521285.1 
                   
                 uaadTcdTgdCauggusg 
                 UAUGCGGAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3830 
                 ascscaugcaGfAfUfuaug 
                 A- 
                 3920 
                 VPusdAsucdCg(C2p)a 
                 UCACCAUGCAGAU 
                 5183 
               
               
                 1353464.1 
                 2521224.1 
                   
                 (Chd)ggasusa 
                 2521225.1 
                   
                 uaadTcUfgcauggusgsc 
                 UAUGCGGAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3831 
                 ascscaugCfaGfAfUfuaug 
                 A- 
                 3921 
                 VPusAfsucdCg(C2p)a 
                 UCACCAUGCAGAU 
                 5184 
               
               
                 1353434.1 
                 2521183.1 
                   
                 (Chd)ggasusa 
                 2521184.1 
                   
                 uaaucUfgCfauggusgsc 
                 UAUGCGGAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3832 
                 asgsaac(Ahd)gudCcdTuaa 
                 A- 
                 3922 
                 VPusdTscudGg(A2p)u 
                 ACAGAACAGUCCU 
                 5185 
               
               
                 1353505.1 
                 2521304.1 
                   
                 uccagsasa 
                 2521305.1 
                   
                 uaadGgdAcdT guucusg 
                 UAAUCCAGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3833 
                 asgsaac(Ahd)guCfCfUfua 
                 A- 
                 3923 
                 VPusdTscudGg(A2p)u 
                 ACAGAACAGUCCU 
                 5186 
               
               
                 1353475.1 
                 2521246.1 
                   
                 auccagsasa 
                 2521247.1 
                   
                 uaadGgAfcuguucusgs 
                 UAAUCCAGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3834 
                 asgsaac(Ahd)GfuCfCfUfu 
                 A- 
                 3924 
                 VPusUfscudGg(A2p)u 
                 ACAGAACAGUCCU 
                 5187 
               
               
                 1353445.1 
                 2521199.1 
                   
                 aauccagsasa 
                 2521200.1 
                   
                 uaaggAfcUfguucusgsu 
                 UAAUCCAGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3835 
                 asgsaug(Uhd)audCudTuug 
                 A- 
                 3925 
                 VPusdAsgadGa(G2p)c 
                 UGAGAUGUAUCU 
                 5188 
               
               
                 1353518.1 
                 2521330.1 
                   
                 cucucsusa 
                 2521331.1 
                   
                 aaadAgdAudAcaucusc 
                 UUUGCUCUCUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3836 
                 asgsaug(Uhd)auCfUfUfuu 
                 A- 
                 3926 
                 VPusdAsgadGa(G2p)c 
                 UGAGAUGUAUCU 
                 5189 
               
               
                 1353490.1 
                 2521276.1 
                   
                 gcucucsusa 
                 2521277.1 
                   
                 aaadAgAfuacaucuscsg 
                 UUUGCUCUCUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3837 
                 asgsaug(Uhd)AfuCfUfUfu 
                 A- 
                 3927 
                 VPusAfsgadGa(G2p)c 
                 UGAGAUGUAUCU 
                 5190 
               
               
                 1353460.1 
                 2521217.1 
                   
                 ugcucucsusa 
                 2521218.1 
                   
                 aaaagAfuAfcaucuscsg 
                 UUUGCUCUCUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3838 
                 asgsauu(Ahd)gadGadGuu 
                 A- 
                 3928 
                 VPusdGsaadAudAaaa 
                 GAAGAUUAGAGA 
                 5191 
               
               
                 1353512.1 
                 2521318.1 
                   
                 uuauuuscsa 
                 2521319.1 
                   
                 cdTcdTcdTaaucususc 
                 GUUUUAUUUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3839 
                 asgsauu(Ahd)gaGfAfGfuu 
                 A- 
                 3929 
                 VPusdGsaadAudAaaa 
                 GAAGAUUAGAGA 
                 5192 
               
               
                 1353482.1 
                 2521260.1 
                   
                 uuauuuscsa 
                 2521261.1 
                   
                 cdTcUfcuaaucususc 
                 GUUUUAUUUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3840 
                 asgsauu(Ahd)GfaGfAfGfu 
                 A- 
                 3930 
                 VPusGfsaaaUfaaaacuc 
                 GAAGAUUAGAGA 
                 5193 
               
               
                 1353452.1 
                 2521210.1 
                   
                 uuuauuuscsa 
                 2282496.1 
                   
                 UfcUfaaucususc 
                 GUUUUAUUUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3841 
                 asusacagaadCgdAucga 
                 A- 
                 3931 
                 VPusdCsugdTa(U2p)c 
                 UGAUACAGAACG 
                 5194 
               
               
                 1353501.1 
                 2521296.1 
                   
                 (Uhd)acasgsa 
                 2521297.1 
                   
                 gaudCgdTudCuguausc 
                 AUCGAUACAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3842 
                 asusacagaaCfGfAfucga 
                 A- 
                 3932 
                 VPusdCsugdTa(U2p)c 
                 UGAUACAGAACG 
                 5195 
               
               
                 1353471.1 
                 2521238.1 
                   
                 (Uhd)acasgsa 
                 2521239.1 
                   
                 gaudCgUfucuguauscs 
                 AUCGAUACAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3843 
                 asusacagAfaCfGfAfucga 
                 A- 
                 3933 
                 VPusCfsugdTa(U2p)c 
                 UGAUACAGAACG 
                 5196 
               
               
                 1353441.1 
                 2521193.1 
                   
                 (Uhd)acasgsa 
                 2521194.1 
                   
                 gaucgUfuCfuguauscsg 
                 AUCGAUACAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3844 
                 asusgcagaudTadTgcgg 
                 A- 
                 3934 
                 VPusdTsugdAu(C2p)c 
                 CCAUGCAGAUUAU 
                 5197 
               
               
                 1353495.1 
                 2521286.1 
                   
                 (Ahd)ucasasa 
                 2521287.1 
                   
                 gcadTadAudCugcausg 
                 GCGGAUCAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3845 
                 asusgcagauUfAfUfgcgg 
                 A- 
                 3935 
                 VPusdTsugdAu(C2p)c 
                 CCAUGCAGAUUAU 
                 5198 
               
               
                 1353465.1 
                 2521226.1 
                   
                 (Ahd)ucasasa 
                 2521227.1 
                   
                 gcadTaAfucugcausgsg 
                 GCGGAUCAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3846 
                 asusgcagAfuUfAfUfgcgg 
                 A- 
                 3936 
                 VPusUfsugdAu(C2p)c 
                 CCAUGCAGAUUAU 
                 5199 
               
               
                 1353435.1 
                 2521185.1 
                   
                 (Ahd)ucasasa 
                 2521186.1 
                   
                 gcauaAfuCfugcausgsg 
                 GCGGAUCAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3847 
                 asusugg(Ahd)uudCgdCca 
                 A- 
                 3937 
                 VPusdAsaudAadAaug 
                 GAAUUGGAUUCG 
                 5200 
               
               
                 1353510.1 
                 2521314.1 
                   
                 uuuuaususa 
                 2521315.1 
                   
                 gdCgdAadTccaaususc 
                 CCAUUUUAUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3848 
                 asusugg(Ahd)uuCfGfCfca 
                 A- 
                 3938 
                 VPusdAsaudAadAaug 
                 GAAUUGGAUUCG 
                 5201 
               
               
                 1353480.1 
                 2521256.1 
                   
                 uuuuaususa 
                 2521257.1 
                   
                 gdCgAfauccaaususc 
                 CCAUUUUAUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3849 
                 asusugg(Ahd)UfuCfGfCfc 
                 A- 
                 3939 
                 VPusAfsauaAfaauggc 
                 GAAUUGGAUUCG 
                 5202 
               
               
                 1353450.1 
                 2521207.1 
                   
                 auuuuaususa 
                 2282456.1 
                   
                 gAfaUfccaaususc 
                 CCAUUUUAUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3850 
                 csasaca(Uhd)cadCcdAugc 
                 A- 
                 3940 
                 VPusdTsaadTc(U2p)g 
                 UCCAACAUCACCA 
                 5203 
               
               
                 1353492.1 
                 2521280.1 
                   
                 agauusasa 
                 2521281.1 
                   
                 caudGgdTgdAuguugs 
                 UGCAGAUUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3851 
                 csasaca(Uhd)caCfCfAfugc 
                 A- 
                 3941 
                 VPusdTsaadTc(U2p)g 
                 UCCAACAUCACCA 
                 5204 
               
               
                 1353462.1 
                 2521220.1 
                   
                 agauusasa 
                 2521221.1 
                   
                 caudGgUfgauguugsgs 
                 UGCAGAUUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3852 
                 csasaca(Uhd)CfaCfCfAfu 
                 A- 
                 3942 
                 VPusUfsaadTc(U2p)g 
                 UCCAACAUCACCA 
                 5205 
               
               
                 1353432.1 
                 2521180.1 
                   
                 gcagauusasa 
                 2521181.1 
                   
                 cauggUfgAfuguugsgsc 
                 UGCAGAUUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3853 
                 csasgaa(Chd)agdTcdCuua 
                 A- 
                 3943 
                 VPusdCsugdGa(U2p) 
                 GACAGAACAGUCC 
                 5206 
               
               
                 1353504.1 
                 2521302.1 
                   
                 auccasgsa 
                 2521303.1 
                   
                 uaagdGadCudGuucug 
                 UUAAUCCAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3854 
                 csasgaa(Chd)agUfCfCfuu 
                 A- 
                 3944 
                 VPusdCsugdGa(U2p) 
                 GACAGAACAGUCC 
                 5207 
               
               
                 1353474.1 
                 2521244.1 
                   
                 aauccasgsa 
                 2521245.1 
                   
                 uaagdGaCfuguucugsu 
                 UUAAUCCAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3855 
                 csasgaa(Chd)AfgUfCfCfu 
                 A- 
                 3945 
                 VPusCfsugdGa(U2p)u 
                 GACAGAACAGUCC 
                 5208 
               
               
                 1353444.1 
                 1700826.1 
                   
                 uaauccasgsa 
                 2521198.1 
                   
                 aaggaCfuGfuucugsusc 
                 UUAAUCCAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3856 
                 csasuca(Chd)cadTgdCaga 
                 A- 
                 3946 
                 VPusdGscadTadAucu 
                 AACAUCACCAUGC 
                 5209 
               
               
                 1353493.1 
                 2521282.1 
                   
                 uuaugscsa 
                 2521283.1 
                   
                 gdCadTgdGugaugsusu 
                 AGAUUAUGCG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3857 
                 csasuca(Chd)caUfGfCfaga 
                 A- 
                 3947 
                 VPusdGscadTadAucu 
                 AACAUCACCAUGC 
                 5210 
               
               
                 1353463.1 
                 2521222.1 
                   
                 uuaugscsa 
                 2521223.1 
                   
                 gdCaUfggugaugsusu 
                 AGAUUAUGCG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3858 
                 csasuca(Chd)CfaUfGfCfa 
                 A- 
                 3948 
                 VPusGfscauAfaucugc 
                 AACAUCACCAUGC 
                 5211 
               
               
                 1353433.1 
                 2521182.1 
                   
                 gauuaugscsa 
                 2282286.1 
                   
                 aUfgGfugaugsusu 
                 AGAUUAUGCG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3859 
                 cscsucu(Uhd)ggdAadTugg 
                 A- 
                 3949 
                 VPusdGscgdAadTcca 
                 UCCCUCUUGGAAU 
                 5212 
               
               
                 1353508.1 
                 2521310.1 
                   
                 auucgscsa 
                 2521311.1 
                   
                 adTudCcdAagaggsgsc 
                 UGGAUUCGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3860 
                 cscsucu(Uhd)ggAfAfUfug 
                 A- 
                 3950 
                 VPusdGscgdAadTcca 
                 UCCCUCUUGGAAU 
                 5213 
               
               
                 1353478.1 
                 2521252.1 
                   
                 gauucgscsa 
                 2521253.1 
                   
                 adTuCfcaagaggsgsc 
                 UGGAUUCGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3861 
                 cscsucu(Uhd)GfgAfAfUfu 
                 A- 
                 3951 
                 VPusGfscgaAfuccaau 
                 UCCCUCUUGGAAU 
                 5214 
               
               
                 1353448.1 
                 2521204.1 
                   
                 ggauucgscsa 
                 2521205.1 
                   
                 uCfcAfagaggsgsc 
                 UGGAUUCGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3862 
                 csusacagcadCadAcaaa 
                 A- 
                 3952 
                 VPusdTscadCadTuug 
                 UCCUACAGCACAA 
                 5215 
               
               
                 1353496.1 
                 2521288.1 
                   
                 (Uhd)gugsasa 
                 2521289.1 
                   
                 udTgdTgdCuguagsgsg 
                 CAAAUGUGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3863 
                 csusacagcaCfAfAfcaaa 
                 A- 
                 3953 
                 VPusdTscadCadTuug 
                 UCCUACAGCACAA 
                 5216 
               
               
                 1353466.1 
                 2521228.1 
                   
                 (Uhd)gugsasa 
                 2521229.1 
                   
                 udTgUfgcuguagsgsg 
                 CAAAUGUGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3864 
                 csusacagCfaCfAfAfcaaa 
                 A- 
                 3954 
                 VPusUfscacAfuuuguu 
                 UCCUACAGCACAA 
                 5217 
               
               
                 1353436.1 
                 2521187.1 
                   
                 (Uhd)gugsasa 
                 2521188.1 
                   
                 gUfgCfuguagsgsg 
                 CAAAUGUGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3865 
                 csusgau(Ahd)cadGadAcga 
                 A- 
                 3955 
                 VPusdTsaudCg(A2p)u 
                 GACUGAUACAGA 
                 5218 
               
               
                 1353500.1 
                 2521294.1 
                   
                 ucgausasa 
                 2521295.1 
                   
                 cgudTcdTgdTaucagsu 
                 ACGAUCGAUAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3866 
                 csusgau(Ahd)caGfAfAfcg 
                 A- 
                 3956 
                 VPusdTsaudCg(A2p)u 
                 GACUGAUACAGA 
                 5219 
               
               
                 1353470.1 
                 2521236.1 
                   
                 aucgausasa 
                 2521237.1 
                   
                 cgudTcUfguaucagsusc 
                 ACGAUCGAUAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3867 
                 csusgau(Ahd)CfaGfAfAfc 
                 A- 
                 3957 
                 VPusUfsaudCg(A2p)u 
                 GACUGAUACAGA 
                 5220 
               
               
                 1353440.1 
                 1700824.1 
                   
                 gaucgausasa 
                 2521192.1 
                   
                 cguucUfgUfaucagsusc 
                 ACGAUCGAUAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3868 
                 gsasaag(Uhd)gudTudTaua 
                 A- 
                 3958 
                 VPusdAsccdGudAuau 
                 GAGAAAGUGUUU 
                 5221 
               
               
                 1334067.3 
                 2483626.1 
                   
                 uacggsusa 
                 1800443.1 
                   
                 adAadAcdAcuuucsusc 
                 UAUAUACGGUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3869 
                 gsasaag(Uhd)guUfUfUfau 
                 A- 
                 3959 
                 VPusdAsccdGudAuau 
                 GAGAAAGUGUUU 
                 5222 
               
               
                 1353488.1 
                 2521272.1 
                   
                 auacggsusa 
                 2521273.1 
                   
                 adAaAfcacuuucsusc 
                 UAUAUACGGUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3870 
                 gsasaag(Uhd)GfuUfUfUfa 
                 A- 
                 3960 
                 VPusAfsccgUfauauaa 
                 GAGAAAGUGUUU 
                 5223 
               
               
                 1353458.1 
                 1700894.1 
                   
                 uauacggsusa 
                 2521215.1 
                   
                 aAfcAfcuuucsusc 
                 UAUAUACGGUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3871 
                 gsasgaa(Ahd)gudGudTuua 
                 A- 
                 3961 
                 VPusdCsgudAudAuaa 
                 AAGAGAAAGUGU 
                 5224 
               
               
                 1334065.3 
                 2483624.1 
                   
                 uauacsgsa 
                 1800396.1 
                   
                 adAcdAcdTuucucsusu 
                 UUUAUAUACGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3872 
                 gsasgaa(Ahd)guGfUfUfuu 
                 A- 
                 3962 
                 VPusdCsgudAudAuaa 
                 AAGAGAAAGUGU 
                 5225 
               
               
                 1353487.1 
                 2521270.1 
                   
                 auauacsgsa 
                 2521271.1 
                   
                 adAcAfcuuucucsusu 
                 UUUAUAUACGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3873 
                 gsasgaa(Ahd)GfuGfUfUfu 
                 A- 
                 3963 
                 VPusCfsguaUfauaaaac 
                 AAGAGAAAGUGU 
                 5226 
               
               
                 1353457.1 
                 1700845.1 
                   
                 uauauacsgsa 
                 2282774.1 
                   
                 AfcUfuucucsusu 
                 UUUAUAUACGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3874 
                 gsasuucgccdAudTuuau 
                 A- 
                 3964 
                 VPusdGsaadAadAuaa 
                 UGGAUUCGCCAUU 
                 5227 
               
               
                 1353511.1 
                 2521316.1 
                   
                 (Uhd)uuuscsa 
                 2521317.1 
                   
                 adAudGgdCgaaucscsg 
                 UUAUUUUUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3875 
                 gsasuucgccAfUfUfuuau 
                 A- 
                 3965 
                 VPusdGsaadAadAuaa 
                 UGGAUUCGCCAUU 
                 5228 
               
               
                 1353481.1 
                 2521258.1 
                   
                 (Uhd)uuuscsa 
                 2521259.1 
                   
                 adAuGfgcgaaucscsg 
                 UUAUUUUUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3876 
                 gsasuucgCfcAfUfUfuuau 
                 A- 
                 3966 
                 VPusGfsaaaAfauaaaau 
                 UGGAUUCGCCAUU 
                 5229 
               
               
                 1353451.1 
                 2521208.1 
                   
                 (Uhd)uuuscsa 
                 2521209.1 
                   
                 GfgCfgaaucscsg 
                 UUAUUUUUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3877 
                 gsusccu(Uhd)aadTcdCaga 
                 A- 
                 3967 
                 VPusdCsagdGudTucu 
                 CAGUCCUUAAUCC 
                 5230 
               
               
                 1353507.1 
                 2521308.1 
                   
                 aaccusgsa 
                 2521309.1 
                   
                 gdGadTudAaggacsusg 
                 AGAAACCUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3878 
                 gsusccu(Uhd)aaUfCfCfag 
                 A- 
                 3968 
                 VPusdCsagdGudTucu 
                 CAGUCCUUAAUCC 
                 5231 
               
               
                 1353477.1 
                 2521250.1 
                   
                 aaaccusgsa 
                 2521251.1 
                   
                 gdGaUfuaaggacsusg 
                 AGAAACCUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3879 
                 gsusccu(Uhd)AfaUfCfCfa 
                 A- 
                 3969 
                 VPusCfsaggUfuucugg 
                 CAGUCCUUAAUCC 
                 5232 
               
               
                 1353447.1 
                 2521203.1 
                   
                 gaaaccusgsa 
                 2282416.1 
                   
                 aUfuAfaggacsusg 
                 AGAAACCUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3880 
                 gsusguu(Uhd)uadTadTacg 
                 A- 
                 3970 
                 VPusdAsagdTadCcgu 
                 AAGUGUUUUAUA 
                 5233 
               
               
                 1353517.1 
                 2521328.1 
                   
                 guacususa 
                 2521329.1 
                   
                 adTadTadAaacacsusu 
                 UACGGUACUUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3881 
                 gsusguu(Uhd)uaUfAfUfac 
                 A- 
                 3971 
                 VPusdAsagdTadCcgu 
                 AAGUGUUUUAUA 
                 5234 
               
               
                 1353489.1 
                 2521274.1 
                   
                 gguacususa 
                 2521275.1 
                   
                 adTaUfaaaacacsusu 
                 UACGGUACUUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3882 
                 gsusguu(Uhd)UfaUfAfUfa 
                 A- 
                 3972 
                 VPusAfsaguAfccguau 
                 AAGUGUUUUAUA 
                 5235 
               
               
                 1353459.1 
                 2521216.1 
                   
                 cgguacususa 
                 2282784.1 
                   
                 aUfaAfaacacsusu 
                 UACGGUACUUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3883 
                 usasgac(Ahd)uudGcdTauu 
                 A- 
                 3973 
                 VPusdAsaadCadGaau 
                 AAUAGACAUUGC 
                 5236 
               
               
                 1353519.1 
                 2521332.1 
                   
                 cuguususa 
                 2521333.1 
                   
                 adGcdAadTgucuasusu 
                 UAUUCUGUUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3884 
                 usasgac(Ahd)uuGfCfUfau 
                 A- 
                 3974 
                 VPusdAsaadCadGaau 
                 AAUAGACAUUGC 
                 5237 
               
               
                 1353491.1 
                 2521278.1 
                   
                 ucuguususa 
                 2521279.1 
                   
                 adGcAfaugucuasusu 
                 UAUUCUGUUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 3885 
                 usasgac(Ahd)UfuGfCfUfa 
                 A- 
                 3975 
                 VPusAfsaacAfgaauag 
                 AAUAGACAUUGC 
                 5238 
               
               
                 1353461.1 
                 2521219.1 
                   
                 uucuguususa 
                 2282952.1 
                   
                 cAfaUfgucuasusu 
                 UAUUCUGUUUU 
                   
               
               
                   
                   
                   
                   
                 .1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10B 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Unmodified Single Strands and Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                 SEQ ID 
                   
                   
               
               
                   
                 Sense 
                 SEQ ID 
                   
                 mRNA 
                 Antisense 
                 NO: 
                   
                 mRNA 
               
               
                 Duplex 
                 Oligo 
                 NO: 
                   
                 Target 
                 Oligo 
                 (Anti- 
                   
                 Target 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Range 
                 Name 
                 sense) 
                 Antisense Sequence 
                 Range 
               
               
                   
               
               
                 AD- 
                 A- 
                 3976 
                 AAAAGAGAAAGUGU 
                 2940- 
                 A- 
                 4066 
                 UTAUAAAACACTUTCT 
                 2938- 
               
               
                 1353514.1 
                 2521322.1 
                   
                 UUUAUAA 
                 2960 
                 2521323.1 
                   
                 CUUUUCU 
                 2960 
               
               
                   
               
               
                 AD- 
                 A- 
                 3977 
                 AAAAGAGAAAGUGU 
                 2940- 
                 A- 
                 4067 
                 UTAUAAAACACTUUCU 
                 2938- 
               
               
                 1353484.1 
                 2521264.1 
                   
                 UUUAUAA 
                 2960 
                 2521265.1 
                   
                 CUUUUCU 
                 2960 
               
               
                   
               
               
                 AD- 
                 A- 
                 3978 
                 AAAAGAGAAAGUGU 
                 2940- 
                 A- 
                 4068 
                 UUAUAAAACACUUUC 
                 2938- 
               
               
                 1353454.1 
                 2521212.1 
                   
                 UUUAUAA 
                 2960 
                 2282766.1 
                   
                 UCUUUUCU 
                 2960 
               
               
                   
               
               
                 AD- 
                 A- 
                 3979 
                 AAAGACUGAUACAG 
                 1795- 
                 A- 
                 4069 
                 UAUCGUTCUGUAUCA 
                 1793- 
               
               
                 1353468.1 
                 2521232.1 
                   
                 AACGAUA 
                 1815 
                 2521233.1 
                   
                 GUCUUUCC 
                 1815 
               
               
                   
               
               
                 AD- 
                 A- 
                 3980 
                 AAAGACUGAUACAG 
                 1795- 
                 A- 
                 4070 
                 UAUCGUTCUGUAUCA 
                 1793- 
               
               
                 1353498.1 
                 2521292.1 
                   
                 AACGAUA 
                 1815 
                 1800369.1 
                   
                 GUCUUUCC 
                 1815 
               
               
                   
               
               
                 AD- 
                 A- 
                 3981 
                 AAAGACUGAUACAG 
                 1795- 
                 A- 
                 4071 
                 UAUCGUUCUGUAUCA 
                 1793- 
               
               
                 1353438.1 
                 1700819.1 
                   
                 AACGAUA 
                 1815 
                 2282346.1 
                   
                 GUCUUUCC 
                 1815 
               
               
                   
               
               
                 AD- 
                 A- 
                 3982 
                 AAAGAGAAAGTGUU 
                 2941- 
                 A- 
                 4072 
                 UAUATAAAACACUTUC 
                 2939- 
               
               
                 1353515.1 
                 2521324.1 
                   
                 UUAUAUA 
                 2961 
                 2521325.1 
                   
                 UCUUUUC 
                 2961 
               
               
                   
               
               
                 AD- 
                 A- 
                 3983 
                 AAAGAGAAAGUGUU 
                 2941- 
                 A- 
                 4073 
                 UAUATAAAACACUUU 
                 2939- 
               
               
                 1353485.1 
                 2521266.1 
                   
                 UUAUAUA 
                 2961 
                 2521267.1 
                   
                 CUCUUUUC 
                 2961 
               
               
                   
               
               
                 AD- 
                 A- 
                 3984 
                 AAAGAGAAAGUGUU 
                 2941- 
                 A- 
                 4074 
                 UAUAUAAAACACUUU 
                 2939- 
               
               
                 1353455.1 
                 2521213.1 
                   
                 UUAUAUA 
                 2961 
                 2282768.1 
                   
                 CUCUUUUC 
                 2961 
               
               
                   
               
               
                 AD- 
                 A- 
                 3985 
                 AACAGUGCTAAUGUU 
                 2178- 
                 A- 
                 4075 
                 UCCAAUAACAUTAGC 
                 2176- 
               
               
                 1353513.1 
                 2521320.1 
                   
                 AUUGGA 
                 2198 
                 2521321.1 
                   
                 ACUGUUGG 
                 2198 
               
               
                   
               
               
                 AD- 
                 A- 
                 3986 
                 AACAGUGCUAAUGU 
                 2178- 
                 A- 
                 4076 
                 UCCAAUAACAUTAGC 
                 2176- 
               
               
                 1353483.1 
                 2521262.1 
                   
                 UAUUGGA 
                 2198 
                 2521263.1 
                   
                 ACUGUUGG 
                 2198 
               
               
                   
               
               
                 AD- 
                 A- 
                 3987 
                 AACAGUGCUAAUGU 
                 2178- 
                 A- 
                 4077 
                 UCCAAUAACAUUAGC 
                 2176- 
               
               
                 1353453.1 
                 1700832.1 
                   
                 UAUUGGA 
                 2198 
                 2521211.1 
                   
                 ACUGUUGG 
                 2198 
               
               
                   
               
               
                 AD- 
                 A- 
                 3988 
                 AACGAUCGAUACAGA 
                 1809- 
                 A- 
                 4078 
                 UTGGTUUCUGUAUCG 
                 1807- 
               
               
                 1353502.1 
                 2521298.1 
                   
                 AACCAA 
                 1829 
                 2521299.1 
                   
                 AUCGUUCU 
                 1829 
               
               
                   
               
               
                 AD- 
                 A- 
                 3989 
                 AACGAUCGAUACAGA 
                 1809- 
                 A- 
                 4079 
                 UTGGTUUCUGUAUCG 
                 1807- 
               
               
                 1353472.1 
                 2521240.1 
                   
                 AACCAA 
                 1829 
                 2521241.1 
                   
                 AUCGUUCU 
                 1829 
               
               
                   
               
               
                 AD- 
                 A- 
                 3990 
                 AACGAUCGAUACAGA 
                 1809- 
                 A- 
                 4080 
                 UUGGTUUCUGUAUCG 
                 1807- 
               
               
                 1353442.1 
                 2521195.1 
                   
                 AACCAA 
                 1829 
                 2521196.1 
                   
                 AUCGUUCU 
                 1829 
               
               
                   
               
               
                 AD- 
                 A- 
                 3991 
                 AAGACUGATACAGAA 
                 1796- 
                 A- 
                 4081 
                 UGAUCGUUCUGTATCA 
                 1794- 
               
               
                 1353499.1 
                 2483623.1 
                   
                 CGAUCA 
                 1816 
                 2521293.1 
                   
                 GUCUUUC 
                 1816 
               
               
                   
               
               
                 AD- 
                 A- 
                 3992 
                 AAGACUGAUACAGA 
                 1796- 
                 A- 
                 4082 
                 UGAUCGUUCUGTAUC 
                 1794- 
               
               
                 1353469.1 
                 2521234.1 
                   
                 ACGAUCA 
                 1816 
                 2521235.1 
                   
                 AGUCUUUC 
                 1816 
               
               
                   
               
               
                 AD- 
                 A- 
                 3993 
                 AAGACUGAUACAGA 
                 1796- 
                 A- 
                 4083 
                 UGAUCGUUCUGUAUC 
                 1794- 
               
               
                 1353439.1 
                 1700820.1 
                   
                 ACGAUCA 
                 1816 
                 2521191.1 
                   
                 AGUCUUUC 
                 1816 
               
               
                   
               
               
                 AD- 
                 A- 
                 3994 
                 AAGAGAAAGUGUUU 
                 2942- 
                 A- 
                 4084 
                 UTAUAUAAAACACTUT 
                 2940- 
               
               
                 1353516.1 
                 2521326.1 
                   
                 UAUAUAA 
                 2962 
                 2521327.1 
                   
                 CUCUUUU 
                 2962 
               
               
                   
               
               
                 AD- 
                 A- 
                 3995 
                 AAGAGAAAGUGUUU 
                 2942- 
                 A- 
                 4085 
                 UTAUAUAAAACACUU 
                 2940- 
               
               
                 1353486.1 
                 2521268.1 
                   
                 UAUAUAA 
                 2962 
                 2521269.1 
                   
                 UCUCUUUU 
                 2962 
               
               
                   
               
               
                 AD- 
                 A- 
                 3996 
                 AAGAGAAAGUGUUU 
                 2942- 
                 A- 
                 4086 
                 UUAUAUAAAACACUU 
                 2940- 
               
               
                 1353456.1 
                 2521214.1 
                   
                 UAUAUAA 
                 2962 
                 2282770.1 
                   
                 UCUCUUUU 
                 2962 
               
               
                   
               
               
                 AD- 
                 A- 
                 3997 
                 AAUUGGAUTCGCCAU 
                 1987- 
                 A- 
                 4087 
                 UAUAAAAUGGCGAAU 
                 1985- 
               
               
                 1353509.1 
                 2521312.1 
                   
                 UUUAUA 
                 2007 
                 2521313.1 
                   
                 CCAAUUCC 
                 2007 
               
               
                   
               
               
                 AD- 
                 A- 
                 3998 
                 AAUUGGAUUCGCCAU 
                 1987- 
                 A- 
                 4088 
                 UAUAAAAUGGCGAAU 
                 1985- 
               
               
                 1353479.1 
                 2521254.1 
                   
                 UUUAUA 
                 2007 
                 2521255.1 
                   
                 CCAAUUCC 
                 2007 
               
               
                   
               
               
                 AD- 
                 A- 
                 3999 
                 AAUUGGAUUCGCCAU 
                 1987- 
                 A- 
                 4089 
                 UAUAAAAUGGCGAAU 
                 1985- 
               
               
                 1353449.1 
                 2521206.1 
                   
                 UUUAUA 
                 2007 
                 2282454.1 
                   
                 CCAAUUCC 
                 2007 
               
               
                   
               
               
                 AD- 
                 A- 
                 4000 
                 ACAGAACAGUCCUUA 
                 1857- 
                 A- 
                 4090 
                 UTGGAUTAAGGACTGT 
                 1855- 
               
               
                 1353503.1 
                 2521300.1 
                   
                 AUCCAA 
                 1877 
                 2521301.1 
                   
                 UCUGUCG 
                 1877 
               
               
                   
               
               
                 AD- 
                 A- 
                 4001 
                 ACAGAACAGUCCUUA 
                 1857- 
                 A- 
                 4091 
                 UTGGAUTAAGGACUG 
                 1855- 
               
               
                 1353473.1 
                 2521242.1 
                   
                 AUCCAA 
                 1877 
                 2521243.1 
                   
                 UUCUGUCG 
                 1877 
               
               
                   
               
               
                 AD- 
                 A- 
                 4002 
                 ACAGAACAGUCCUUA 
                 1857- 
                 A- 
                 4092 
                 UUGGAUUAAGGACUG 
                 1855- 
               
               
                 1353443.1 
                 2521197.1 
                   
                 AUCCAA 
                 1877 
                 2282402.1 
                   
                 UUCUGUCG 
                 1877 
               
               
                   
               
               
                 AD- 
                 A- 
                 4003 
                 ACAGUCCUTAAUCCA 
                 1862- 
                 A- 
                 4093 
                 UGUUTCUGGAUTAAG 
                 1860- 
               
               
                 1353506.1 
                 2521306.1 
                   
                 GAAACA 
                 1882 
                 2521307.1 
                   
                 GACUGUUC 
                 1882 
               
               
                   
               
               
                 AD- 
                 A- 
                 4004 
                 ACAGUCCUUAAUCCA 
                 1862- 
                 A- 
                 4094 
                 UGUUTCUGGAUTAAG 
                 1860- 
               
               
                 1353476.1 
                 2521248.1 
                   
                 GAAACA 
                 1882 
                 2521249.1 
                   
                 GACUGUUC 
                 1882 
               
               
                   
               
               
                 AD- 
                 A- 
                 4005 
                 ACAGUCCUUAAUCCA 
                 1862- 
                 A- 
                 4095 
                 UGUUTCUGGAUUAAG 
                 1860- 
               
               
                 1353446.1 
                 2521201.1 
                   
                 GAAACA 
                 1882 
                 2521202.1 
                   
                 GACUGUUC 
                 1882 
               
               
                   
               
               
                 AD- 
                 A- 
                 4006 
                 ACCAGGAAAGACUGA 
                 1789- 
                 A- 
                 4096 
                 UCUGTATCAGUCUTUC 
                 1787- 
               
               
                 1353497.1 
                 2521290.1 
                   
                 UACAGA 
                 1809 
                 2521291.1 
                   
                 CUGGUGC 
                 1809 
               
               
                   
               
               
                 AD- 
                 A- 
                 4007 
                 ACCAGGAAAGACUGA 
                 1789- 
                 A- 
                 4097 
                 UCUGTATCAGUCUUUC 
                 1787- 
               
               
                 1353467.1 
                 2521230.1 
                   
                 UACAGA 
                 1809 
                 2521231.1 
                   
                 CUGGUGC 
                 1809 
               
               
                   
               
               
                 AD- 
                 A- 
                 4008 
                 ACCAGGAAAGACUGA 
                 1789- 
                 A- 
                 4098 
                 UCUGUAUCAGUCUUU 
                 1787- 
               
               
                 1353437.1 
                 2521189.1 
                   
                 UACAGA 
                 1809 
                 2521190.1 
                   
                 CCUGGUGC 
                 1809 
               
               
                   
               
               
                 AD- 
                 A- 
                 4009 
                 ACCAUGCAGATUAUG 
                 1345- 
                 A- 
                 4099 
                 UAUCCGCAUAATCTGC 
                 1343- 
               
               
                 1353494.1 
                 2521284.1 
                   
                 CGGAUA 
                 1365 
                 2521285.1 
                   
                 AUGGUGC 
                 1365 
               
               
                   
               
               
                 AD- 
                 A- 
                 4010 
                 ACCAUGCAGAUUAUG 
                 1345- 
                 A- 
                 4100 
                 UAUCCGCAUAATCUGC 
                 1343- 
               
               
                 1353464.1 
                 2521224.1 
                   
                 CGGAUA 
                 1365 
                 2521225.1 
                   
                 AUGGUGC 
                 1365 
               
               
                   
               
               
                 AD- 
                 A- 
                 4011 
                 ACCAUGCAGAUUAUG 
                 1345- 
                 A- 
                 4101 
                 UAUCCGCAUAAUCUG 
                 1343- 
               
               
                 1353434.1 
                 2521183.1 
                   
                 CGGAUA 
                 1365 
                 2521184.1 
                   
                 CAUGGUGC 
                 1365 
               
               
                   
               
               
                 AD- 
                 A- 
                 4012 
                 AGAACAGUCCTUAAU 
                 1859- 
                 A- 
                 4102 
                 UTCUGGAUUAAGGAC 
                 1857- 
               
               
                 1353505.1 
                 2521304.1 
                   
                 CCAGAA 
                 1879 
                 2521305.1 
                   
                 TGUUCUGU 
                 1879 
               
               
                   
               
               
                 AD- 
                 A- 
                 4013 
                 AGAACAGUCCUUAAU 
                 1859- 
                 A- 
                 4103 
                 UTCUGGAUUAAGGAC 
                 1857- 
               
               
                 1353475.1 
                 2521246.1 
                   
                 CCAGAA 
                 1879 
                 2521247.1 
                   
                 UGUUCUGU 
                 1879 
               
               
                   
               
               
                 AD- 
                 A- 
                 4014 
                 AGAACAGUCCUUAAU 
                 1859- 
                 A- 
                 4104 
                 UUCUGGAUUAAGGAC 
                 1857- 
               
               
                 1353445.1 
                 2521199.1 
                   
                 CCAGAA 
                 1879 
                 2521200.1 
                   
                 UGUUCUGU 
                 1879 
               
               
                   
               
               
                 AD- 
                 A- 
                 4015 
                 AGAUGUAUCUTUUGC 
                 3073- 
                 A- 
                 4105 
                 UAGAGAGCAAAAGAU 
                 3071- 
               
               
                 1353518.1 
                 2521330.1 
                   
                 UCUCUA 
                 3093 
                 2521331.1 
                   
                 ACAUCUCG 
                 3093 
               
               
                   
               
               
                 AD- 
                 A- 
                 4016 
                 AGAUGUAUCUUUUG 
                 3073- 
                 A- 
                 4106 
                 UAGAGAGCAAAAGAU 
                 3071- 
               
               
                 1353490.1 
                 2521276.1 
                   
                 CUCUCUA 
                 3093 
                 2521277.1 
                   
                 ACAUCUCG 
                 3093 
               
               
                   
               
               
                 AD- 
                 A- 
                 4017 
                 AGAUGUAUCUUUUG 
                 3073- 
                 A- 
                 4107 
                 UAGAGAGCAAAAGAU 
                 3071- 
               
               
                 1353460.1 
                 2521217.1 
                   
                 CUCUCUA 
                 3093 
                 2521218.1 
                   
                 ACAUCUCG 
                 3093 
               
               
                   
               
               
                 AD- 
                 A- 
                 4018 
                 AGAUUAGAGAGUUU 
                 2037- 
                 A- 
                 4108 
                 UGAAAUAAAACTCTCT 
                 2035- 
               
               
                 1353512.1 
                 2521318.1 
                   
                 UAUUUCA 
                 2057 
                 2521319.1 
                   
                 AAUCUUC 
                 2057 
               
               
                   
               
               
                 AD- 
                 A- 
                 4019 
                 AGAUUAGAGAGUUU 
                 2037- 
                 A- 
                 4109 
                 UGAAAUAAAACTCUC 
                 2035- 
               
               
                 1353482.1 
                 2521260.1 
                   
                 UAUUUCA 
                 2057 
                 2521261.1 
                   
                 UAAUCUUC 
                 2057 
               
               
                   
               
               
                 AD- 
                 A- 
                 4020 
                 AGAUUAGAGAGUUU 
                 2037- 
                 A- 
                 4110 
                 UGAAAUAAAACUCUC 
                 2035- 
               
               
                 1353452.1 
                 2521210.1 
                   
                 UAUUUCA 
                 2057 
                 2282496.1 
                   
                 UAAUCUUC 
                 2057 
               
               
                   
               
               
                 AD- 
                 A- 
                 4021 
                 AUACAGAACGAUCGA 
                 1803- 
                 A- 
                 4111 
                 UCUGTAUCGAUCGTUC 
                 1801- 
               
               
                 1353501.1 
                 2521296.1 
                   
                 UACAGA 
                 1823 
                 2521297.1 
                   
                 UGUAUCG 
                 1823 
               
               
                   
               
               
                 AD- 
                 A- 
                 4022 
                 AUACAGAACGAUCGA 
                 1803- 
                 A- 
                 4112 
                 UCUGTAUCGAUCGUU 
                 1801- 
               
               
                 1353471.1 
                 2521238.1 
                   
                 UACAGA 
                 1823 
                 2521239.1 
                   
                 CUGUAUCG 
                 1823 
               
               
                   
               
               
                 AD- 
                 A- 
                 4023 
                 AUACAGAACGAUCGA 
                 1803- 
                 A- 
                 4113 
                 UCUGTAUCGAUCGUU 
                 1801- 
               
               
                 1353441.1 
                 2521193.1 
                   
                 UACAGA 
                 1823 
                 2521194.1 
                   
                 CUGUAUCG 
                 1823 
               
               
                   
               
               
                 AD- 
                 A- 
                 4024 
                 AUGCAGAUTATGCGG 
                 1348- 
                 A- 
                 4114 
                 UTUGAUCCGCATAAUC 
                 1346- 
               
               
                 1353495.1 
                 2521286.1 
                   
                 AUCAAA 
                 1368 
                 2521287.1 
                   
                 UGCAUGG 
                 1368 
               
               
                   
               
               
                 AD- 
                 A- 
                 4025 
                 AUGCAGAUUAUGCG 
                 1348- 
                 A- 
                 4115 
                 UTUGAUCCGCATAAUC 
                 1346- 
               
               
                 1353465.1 
                 2521226.1 
                   
                 GAUCAAA 
                 1368 
                 2521227.1 
                   
                 UGCAUGG 
                 1368 
               
               
                   
               
               
                 AD- 
                 A- 
                 4026 
                 AUGCAGAUUAUGCG 
                 1348- 
                 A- 
                 4116 
                 UUUGAUCCGCAUAAU 
                 1346- 
               
               
                 1353435.1 
                 2521185.1 
                   
                 GAUCAAA 
                 1368 
                 2521186.1 
                   
                 CUGCAUGG 
                 1368 
               
               
                   
               
               
                 AD- 
                 A- 
                 4027 
                 AUUGGAUUCGCCAUU 
                 1988- 
                 A- 
                 4117 
                 UAAUAAAAUGGCGAA 
                 1986- 
               
               
                 1353510.1 
                 2521314.1 
                   
                 UUAUUA 
                 2008 
                 2521315.1 
                   
                 TCCAAUUC 
                 2008 
               
               
                   
               
               
                 AD- 
                 A- 
                 4028 
                 AUUGGAUUCGCCAUU 
                 1988- 
                 A- 
                 4118 
                 UAAUAAAAUGGCGAA 
                 1986- 
               
               
                 1353480.1 
                 2521256.1 
                   
                 UUAUUA 
                 2008 
                 2521257.1 
                   
                 UCCAAUUC 
                 2008 
               
               
                   
               
               
                 AD- 
                 A- 
                 4029 
                 AUUGGAUUCGCCAUU 
                 1988- 
                 A- 
                 4119 
                 UAAUAAAAUGGCGAA 
                 1986- 
               
               
                 1353450.1 
                 2521207.1 
                   
                 UUAUUA 
                 2008 
                 2282456.1 
                   
                 UCCAAUUC 
                 2008 
               
               
                   
               
               
                 AD- 
                 A- 
                 4030 
                 CAACAUCACCAUGCA 
                 1338- 
                 A- 
                 4120 
                 UTAATCUGCAUGGTGA 
                 1336- 
               
               
                 1353492.1 
                 2521280.1 
                   
                 GAUUAA 
                 1358 
                 2521281.1 
                   
                 UGUUGGC 
                 1358 
               
               
                   
               
               
                 AD- 
                 A- 
                 4031 
                 CAACAUCACCAUGCA 
                 1338- 
                 A- 
                 4121 
                 UTAATCUGCAUGGUG 
                 1336- 
               
               
                 1353462.1 
                 2521220.1 
                   
                 GAUUAA 
                 1358 
                 2521221.1 
                   
                 AUGUUGGC 
                 1358 
               
               
                   
               
               
                 AD- 
                 A- 
                 4032 
                 CAACAUCACCAUGCA 
                 1338- 
                 A- 
                 4122 
                 UUAATCUGCAUGGUG 
                 1336- 
               
               
                 1353432.1 
                 2521180.1 
                   
                 GAUUAA 
                 1358 
                 2521181.1 
                   
                 AUGUUGGC 
                 1358 
               
               
                   
               
               
                 AD- 
                 A- 
                 4033 
                 CAGAACAGTCCUUAA 
                 1858- 
                 A- 
                 4123 
                 UCUGGAUUAAGGACU 
                 1856- 
               
               
                 1353504.1 
                 2521302.1 
                   
                 UCCAGA 
                 1878 
                 2521303.1 
                   
                 GUUCUGUC 
                 1878 
               
               
                   
               
               
                 AD- 
                 A- 
                 4034 
                 CAGAACAGUCCUUAA 
                 1858- 
                 A- 
                 4124 
                 UCUGGAUUAAGGACU 
                 1856- 
               
               
                 1353474.1 
                 2521244.1 
                   
                 UCCAGA 
                 1878 
                 2521245.1 
                   
                 GUUCUGUC 
                 1878 
               
               
                   
               
               
                 AD- 
                 A- 
                 4035 
                 CAGAACAGUCCUUAA 
                 1858- 
                 A- 
                 4125 
                 UCUGGAUUAAGGACU 
                 1856- 
               
               
                 1353444.1 
                 1700826.1 
                   
                 UCCAGA 
                 1878 
                 2521198.1 
                   
                 GUUCUGUC 
                 1878 
               
               
                   
               
               
                 AD- 
                 A- 
                 4036 
                 CAUCACCATGCAGAU 
                 1341- 
                 A- 
                 4126 
                 UGCATAAUCUGCATGG 
                 1339- 
               
               
                 1353493.1 
                 2521282.1 
                   
                 UAUGCA 
                 1361 
                 2521283.1 
                   
                 UGAUGUU 
                 1361 
               
               
                   
               
               
                 AD- 
                 A- 
                 4037 
                 CAUCACCAUGCAGAU 
                 1341- 
                 A- 
                 4127 
                 UGCATAAUCUGCAUG 
                 1339- 
               
               
                 1353463.1 
                 2521222.1 
                   
                 UAUGCA 
                 1361 
                 2521223.1 
                   
                 GUGAUGUU 
                 1361 
               
               
                   
               
               
                 AD- 
                 A- 
                 4038 
                 CAUCACCAUGCAGAU 
                 1341- 
                 A- 
                 4128 
                 UGCAUAAUCUGCAUG 
                 1339- 
               
               
                 1353433.1 
                 2521182.1 
                   
                 UAUGCA 
                 1361 
                 2282286.1 
                   
                 GUGAUGUU 
                 1361 
               
               
                   
               
               
                 AD- 
                 A- 
                 4039 
                 CCUCUUGGAATUGGA 
                 1979- 
                 A- 
                 4129 
                 UGCGAATCCAATUCCA 
                 1977- 
               
               
                 1353508.1 
                 2521310.1 
                   
                 UUCGCA 
                 1999 
                 2521311.1 
                   
                 AGAGGGC 
                 1999 
               
               
                   
               
               
                 AD- 
                 A- 
                 4040 
                 CCUCUUGGAAUUGGA 
                 1979- 
                 A- 
                 4130 
                 UGCGAATCCAATUCCA 
                 1977- 
               
               
                 1353478.1 
                 2521252.1 
                   
                 UUCGCA 
                 1999 
                 2521253.1 
                   
                 AGAGGGC 
                 1999 
               
               
                   
               
               
                 AD- 
                 A- 
                 4041 
                 CCUCUUGGAAUUGGA 
                 1979- 
                 A- 
                 4131 
                 UGCGAAUCCAAUUCC 
                 1977- 
               
               
                 1353448.1 
                 2521204.1 
                   
                 UUCGCA 
                 1999 
                 2521205.1 
                   
                 AAGAGGGC 
                 1999 
               
               
                   
               
               
                 AD- 
                 A- 
                 4042 
                 CUACAGCACAACAAA 
                 1405- 
                 A- 
                 4132 
                 UTCACATUUGUTGTGC 
                 1403- 
               
               
                 1353496.1 
                 2521288.1 
                   
                 UGUGAA 
                 1425 
                 2521289.1 
                   
                 UGUAGGG 
                 1425 
               
               
                   
               
               
                 AD- 
                 A- 
                 4043 
                 CUACAGCACAACAAA 
                 1405- 
                 A- 
                 4133 
                 UTCACATUUGUTGUGC 
                 1403- 
               
               
                 1353466.1 
                 2521228.1 
                   
                 UGUGAA 
                 1425 
                 2521229.1 
                   
                 UGUAGGG 
                 1425 
               
               
                   
               
               
                 AD- 
                 A- 
                 4044 
                 CUACAGCACAACAAA 
                 1405- 
                 A- 
                 4134 
                 UUCACAUUUGUUGUG 
                 1403- 
               
               
                 1353436.1 
                 2521187.1 
                   
                 UGUGAA 
                 1425 
                 2521188.1 
                   
                 CUGUAGGG 
                 1425 
               
               
                   
               
               
                 AD- 
                 A- 
                 4045 
                 CUGAUACAGAACGAU 
                 1800- 
                 A- 
                 4135 
                 UTAUCGAUCGUTCTGT 
                 1798- 
               
               
                 1353500.1 
                 2521294.1 
                   
                 CGAUAA 
                 1820 
                 2521295.1 
                   
                 AUCAGUC 
                 1820 
               
               
                   
               
               
                 AD- 
                 A- 
                 4046 
                 CUGAUACAGAACGAU 
                 1800- 
                 A- 
                 4136 
                 UTAUCGAUCGUTCUGU 
                 1798- 
               
               
                 1353470.1 
                 2521236.1 
                   
                 CGAUAA 
                 1820 
                 2521237.1 
                   
                 AUCAGUC 
                 1820 
               
               
                   
               
               
                 AD- 
                 A- 
                 4047 
                 CUGAUACAGAACGAU 
                 1800- 
                 A- 
                 4137 
                 UUAUCGAUCGUUCUG 
                 1798- 
               
               
                 1353440.1 
                 1700824.1 
                   
                 CGAUAA 
                 1820 
                 2521192.1 
                   
                 UAUCAGUC 
                 1820 
               
               
                   
               
               
                 AD- 
                 A- 
                 4048 
                 GAAAGUGUTUTAUAU 
                 2946- 
                 A- 
                 4138 
                 UACCGUAUAUAAAAC 
                 2944- 
               
               
                 1334067.3 
                 2483626.1 
                   
                 ACGGUA 
                 2966 
                 1800443.1 
                   
                 ACUUUCUC 
                 2966 
               
               
                   
               
               
                 AD- 
                 A- 
                 4049 
                 GAAAGUGUUUUAUA 
                 2946- 
                 A- 
                 4139 
                 UACCGUAUAUAAAAC 
                 2944- 
               
               
                 1353488.1 
                 2521272.1 
                   
                 UACGGUA 
                 2966 
                 2521273.1 
                   
                 ACUUUCUC 
                 2966 
               
               
                   
               
               
                 AD- 
                 A- 
                 4050 
                 GAAAGUGUUUUAUA 
                 2946- 
                 A- 
                 4140 
                 UACCGUAUAUAAAAC 
                 2944- 
               
               
                 1353458.1 
                 1700894.1 
                   
                 UACGGUA 
                 2966 
                 2521215.1 
                   
                 ACUUUCUC 
                 2966 
               
               
                   
               
               
                 AD- 
                 A- 
                 4051 
                 GAGAAAGUGUTUUA 
                 2944- 
                 A- 
                 4141 
                 UCGUAUAUAAAACAC 
                 2942- 
               
               
                 1334065.3 
                 2483624.1 
                   
                 UAUACGA 
                 2964 
                 1800396.1 
                   
                 TUUCUCUU 
                 2964 
               
               
                   
               
               
                 AD- 
                 A- 
                 4052 
                 GAGAAAGUGUUUUA 
                 2944- 
                 A- 
                 4142 
                 UCGUAUAUAAAACAC 
                 2942- 
               
               
                 1353487.1 
                 2521270.1 
                   
                 UAUACGA 
                 2964 
                 2521271.1 
                   
                 UUUCUCUU 
                 2964 
               
               
                   
               
               
                 AD- 
                 A- 
                 4053 
                 GAGAAAGUGUUUUA 
                 2944- 
                 A- 
                 4143 
                 UCGUAUAUAAAACAC 
                 2942- 
               
               
                 1353457.1 
                 1700845.1 
                   
                 UAUACGA 
                 2964 
                 2282774.1 
                   
                 UUUCUCUU 
                 2964 
               
               
                   
               
               
                 AD- 
                 A- 
                 4054 
                 GAUUCGCCAUTUUAU 
                 1992- 
                 A- 
                 4144 
                 UGAAAAAUAAAAUGG 
                 1990- 
               
               
                 1353511.1 
                 2521316.1 
                   
                 UUUUCA 
                 2012 
                 2521317.1 
                   
                 CGAAUCCG 
                 2012 
               
               
                   
               
               
                 AD- 
                 A- 
                 4055 
                 GAUUCGCCAUUUUAU 
                 1992- 
                 A- 
                 4145 
                 UGAAAAAUAAAAUGG 
                 1990- 
               
               
                 1353481.1 
                 2521258.1 
                   
                 UUUUCA 
                 2012 
                 2521259.1 
                   
                 CGAAUCCG 
                 2012 
               
               
                   
               
               
                 AD- 
                 A- 
                 4056 
                 GAUUCGCCAUUUUAU 
                 1992- 
                 A- 
                 4146 
                 UGAAAAAUAAAAUGG 
                 1990- 
               
               
                 1353451.1 
                 2521208.1 
                   
                 UUUUCA 
                 2012 
                 2521209.1 
                   
                 CGAAUCCG 
                 2012 
               
               
                   
               
               
                 AD- 
                 A- 
                 4057 
                 GUCCUUAATCCAGAA 
                 1865- 
                 A- 
                 4147 
                 UCAGGUTUCUGGATU 
                 1863- 
               
               
                 1353507.1 
                 2521308.1 
                   
                 ACCUGA 
                 1885 
                 2521309.1 
                   
                 AAGGACUG 
                 1885 
               
               
                   
               
               
                 AD- 
                 A- 
                 4058 
                 GUCCUUAAUCCAGAA 
                 1865- 
                 A- 
                 4148 
                 UCAGGUTUCUGGAUU 
                 1863- 
               
               
                 1353477.1 
                 2521250.1 
                   
                 ACCUGA 
                 1885 
                 2521251.1 
                   
                 AAGGACUG 
                 1885 
               
               
                   
               
               
                 AD- 
                 A- 
                 4059 
                 GUCCUUAAUCCAGAA 
                 1865- 
                 A- 
                 4149 
                 UCAGGUUUCUGGAUU 
                 1863- 
               
               
                 1353447.1 
                 2521203.1 
                   
                 ACCUGA 
                 1885 
                 2282416.1 
                   
                 AAGGACUG 
                 1885 
               
               
                   
               
               
                 AD- 
                 A- 
                 4060 
                 GUGUUUUATATACGG 
                 2950- 
                 A- 
                 4150 
                 UAAGTACCGUATATAA 
                 2948- 
               
               
                 1353517.1 
                 2521328.1 
                   
                 UACUUA 
                 2970 
                 2521329.1 
                   
                 AACACUU 
                 2970 
               
               
                   
               
               
                 AD- 
                 A- 
                 4061 
                 GUGUUUUAUAUACG 
                 2950- 
                 A- 
                 4151 
                 UAAGTACCGUATAUA 
                 2948- 
               
               
                 1353489.1 
                 2521274.1 
                   
                 GUACUUA 
                 2970 
                 2521275.1 
                   
                 AAACACUU 
                 2970 
               
               
                   
               
               
                 AD- 
                 A- 
                 4062 
                 GUGUUUUAUAUACG 
                 2950- 
                 A- 
                 4152 
                 UAAGUACCGUAUAUA 
                 2948- 
               
               
                 1353459.1 
                 2521216.1 
                   
                 GUACUUA 
                 2970 
                 2282784.1 
                   
                 AAACACUU 
                 2970 
               
               
                   
               
               
                 AD- 
                 A- 
                 4063 
                 UAGACAUUGCTAUUC 
                 3365- 
                 A- 
                 4153 
                 UAAACAGAAUAGCAA 
                 3363- 
               
               
                 1353519.1 
                 2521332.1 
                   
                 UGUUUA 
                 3385 
                 2521333.1 
                   
                 TGUCUAUU 
                 3385 
               
               
                   
               
               
                 AD- 
                 A- 
                 4064 
                 UAGACAUUGCUAUUC 
                 3365- 
                 A- 
                 4154 
                 UAAACAGAAUAGCAA 
                 3363- 
               
               
                 1353491.1 
                 2521278.1 
                   
                 UGUUUA 
                 3385 
                 2521279.1 
                   
                 UGUCUAUU 
                 3385 
               
               
                   
               
               
                 AD- 
                 A- 
                 4065 
                 UAGACAUUGCUAUUC 
                 3365- 
                 A- 
                 4155 
                 UAAACAGAAUAGCAA 
                 3363- 
               
               
                 1353461.1 
                 2521219.1 
                   
                 UGUUUA 
                 3385 
                 2282952.1 
                   
                 UGUCUAUU 
                 3385 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18A 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Modified Single Strands and Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 SEQ 
                   
                   
                   
               
               
                   
                   
                   
                   
                 Anti- 
                 ID 
                   
                   
                 SEQ ID 
               
               
                   
                 Sense 
                 SEQ ID 
                   
                 sense 
                 NO: 
                   
                   
                 NO: 
               
               
                 Duplex 
                 Oligo 
                 NO: 
                   
                 Oligo 
                 (Anti- 
                   
                 mRNA Target 
                 (mRNA 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Name 
                 sense) 
                 Antisense Sequence 
                 Sequence 
                 target) 
               
               
                   
               
               
                 AD- 
                 A- 
                 4164 
                 csgsaca(Ghd)AfaCfAfGf 
                 A- 
                 4176 
                 VPusGfsauua(Agn)ggac 
                 AUCGACAGAACA 
                 4188 
               
               
                 1020574 
                 1110770.1 
                   
                 uccuuaauscsa 
                 1701268.1 
                   
                 ugUfuCfugucgsasu 
                 GUCCUUAAUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4165 
                 csasgaa(Chd)AfgUfCfCf 
                 A- 
                 4177 
                 VPusCfsuggAfuUfAfag 
                 GACAGAACAGUC 
                 4189 
               
               
                 901094 
                 1700826.1 
                   
                 uuaauccasgsa 
                 1068918.1 
                   
                 gaCfuGfuucugsusc 
                 CUUAAUCCAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4166 
                 csasgaa(Chd)AfgUfCfCf 
                 A- 
                 4178 
                 VPusCfsugga(Tgn)uaag 
                 GACAGAACAGUC 
                 4190 
               
               
                 1020575 
                 1700826.1 
                   
                 uuaauccasgsa 
                 1701270.1 
                   
                 gaCfuGfuucugsusc 
                 CUUAAUCCAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4167 
                 asascag(Uhd)GfcUfAfAf 
                 A- 
                 4179 
                 VPusCfscaaUfaAfCfauu 
                 UUAACAGUGCUA 
                 4191 
               
               
                 901100 
                 1700832.1 
                   
                 uguuauugsgsa 
                 1069342.1 
                   
                 aGfcAfcuguusasa 
                 AUGUUAUUGGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4168 
                 asgsugc(Uhd)AfaUfGfUf 
                 A- 
                 4180 
                 VPusAfscacCfaAfUfaac 
                 ACAGUGCUAAUG 
                 4192 
               
               
                 901101 
                 1700833.1 
                   
                 uauuggugsusa 
                 1069348.1 
                   
                 aUfuAfgcacusgsu 
                 UUAUUGGUGUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4169 
                 gsasgaa(Ahd)GfuGfUfUf 
                 A- 
                 4181 
                 VPusCfsguaUfaUfAfaaa 
                 AAGAGAAAGUGU 
                 4193 
               
               
                 901113 
                 1700845.1 
                   
                 uuauauacsgsa 
                 1070290.1 
                   
                 cAfcUfuucucsusu 
                 UUUAUAUACGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4170 
                 asasaau(Ahd)GfaCfAfUf 
                 A- 
                 4182 
                 VPusAfsgaaUfaGfCfaau 
                 AUAAAAUAGACA 
                 4194 
               
               
                 901123 
                 1700855.1 
                   
                 ugcuauucsusa 
                 1070790.1 
                   
                 gUfcUfauuuusasu 
                 UUGCUAUUCUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4171 
                 asasaua(Ghd)AfcAfUfUf 
                 A- 
                 4183 
                 VPusCfsagaAfuAfGfcaa 
                 UAAAAUAGACAU 
                 4195 
               
               
                 901124 
                 1700856.1 
                   
                 gcuauucusgsa 
                 1070792.1 
                   
                 uGfuCfuauuususa 
                 UGCUAUUCUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4172 
                 gsasaag(Uhd)GfuUfUfUf 
                 A- 
                 4184 
                 VPusAfsccgUfaUfAfuaa 
                 GAGAAAGUGUUU 
                 4196 
               
               
                 901158 
                 1700894.1 
                   
                 auauacggsusa 
                 1070294.1 
                   
                 aAfcAfcuuucsusc 
                 UAUAUACGGUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4173 
                 gsusuuu(Ahd)UfaUfAfCf 
                 A- 
                 4185 
                 VPusAfsuaaGfuAfCfcgu 
                 GUGUUUUAUAUA 
                 4197 
               
               
                 901159 
                 1700895.1 
                   
                 gguacuuasusa 
                 1070306.1 
                   
                 aUfaUfaaaacsasc 
                 CGGUACUUAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4174 
                 asgsugc(Uhd)aadTgdTua 
                 A- 
                 4186 
                 VPusdAscadCcdAauaad 
                 ACAGUGCUAAUG 
                 4198 
               
               
                 1020573 
                 1890520.1 
                   
                 uuggugsusa 
                 1800384.1 
                   
                 CadTudAgcacusgsu 
                 UUAUUGGUGUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4175 
                 asasaau(Ahd)gadCadTug 
                 A- 
                 4187 
                 VPusdAsgadAudAgcaad 
                 AUAAAAUAGACA 
                 4199 
               
               
                 1023143 
                 1895607.1 
                   
                 cuauucsusa 
                 1800407.1 
                   
                 TgdTcdT auuuus asu 
                 UUGCUAUUCUG 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18B 
               
             
            
               
                   
               
               
                 Exemplary Human VEGF-A siRNA Unmodified Single Strands and Duplex Sequences 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                 SEQ ID 
                   
                 mRNA 
               
               
                   
                 Sense 
                 SEQ ID 
                   
                 mRNA 
                 Antisense 
                 NO: 
                   
                   
               
               
                 Duplex 
                 Oligo 
                 NO: 
                   
                 Target 
                 Oligo 
                 (Anti- 
                 Antisense 
                 Target 
               
               
                 Name 
                 Name 
                 (Sense) 
                 Sense Sequence 
                 Range 
                 Name 
                 sense) 
                 Sequence 
                 Range 
               
               
                   
               
               
                 AD- 
                 A- 
                 4200 
                 CGACAGAACAGUCCU 
                 1855- 
                 A- 
                 4212 
                 UGAUUAAGGACUGUU 
                 1853-1875 
               
               
                 1020574 
                 1110770.1 
                   
                 UAAUCA 
                 1875 
                 1701268.1 
                   
                 CUGUCGAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4201 
                 CAGAACAGUCCUUAA 
                 1858- 
                 A- 
                 4213 
                 UCUGGAUUAAGGACU 
                 1856-1878 
               
               
                 901094 
                 1700826.1 
                   
                 UCCAGA 
                 1878 
                 1068918.1 
                   
                 GUUCUGUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4202 
                 CAGAACAGUCCUUAA 
                 1858- 
                 A- 
                 4214 
                 UCUGGATUAAGGACU 
                 1856-1878 
               
               
                 1020575 
                 1700826.1 
                   
                 UCCAGA 
                 1878 
                 1701270.1 
                   
                 GUUCUGUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4203 
                 AACAGUGCUAAUGU 
                 2178- 
                 A- 
                 4215 
                 UCCAAUAACAUUAGC 
                 2176-2198 
               
               
                 901100 
                 1700832.1 
                   
                 UAUUGGA 
                 2198 
                 1069342.1 
                   
                 ACUGUUAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4204 
                 AGUGCUAAUGUUAU 
                 2181- 
                 A- 
                 4216 
                 UACACCAAUAACAUU 
                 2179-2201 
               
               
                 901101 
                 1700833.1 
                   
                 UGGUGUA 
                 2201 
                 1069348.1 
                   
                 AGCACUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4205 
                 GAGAAAGUGUUUUA 
                 2944- 
                 A- 
                 4217 
                 UCGUAUAUAAAACAC 
                 2942-2964 
               
               
                 901113 
                 1700845.1 
                   
                 UAUACGA 
                 2964 
                 1070290.1 
                   
                 UUUCUCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4206 
                 AAAAUAGACAUUGC 
                 3361- 
                 A- 
                 4218 
                 UAGAAUAGCAAUGUC 
                 3359-3381 
               
               
                 901123 
                 1700855.1 
                   
                 UAUUCUA 
                 3381 
                 1070790.1 
                   
                 UAUUUUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4207 
                 AAAUAGACAUUGCU 
                 3362- 
                 A- 
                 4219 
                 UCAGAAUAGCAAUGU 
                 3360-3382 
               
               
                 901124 
                 1700856.1 
                   
                 AUUCUGA 
                 3382 
                 1070792.1 
                   
                 CUAUUUUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4208 
                 GAAAGUGUUUUAUA 
                 2946- 
                 A- 
                 4220 
                 UACCGUAUAUAAAAC 
                 2944-2966 
               
               
                 901158 
                 1700894.1 
                   
                 UACGGUA 
                 2966 
                 1070294.1 
                   
                 ACUUUCUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4209 
                 GUUUUAUAUACGGU 
                 2952- 
                 A- 
                 4221 
                 UAUAAGUACCGUAUA 
                 2950-2972 
               
               
                 901159 
                 1700895.1 
                   
                 ACUUAUA 
                 2972 
                 1070306.1 
                   
                 UAAAACAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4210 
                 AGUGCUAATGTUAUU 
                 2181- 
                 A- 
                 4222 
                 UACACCAAUAACATU 
                 2179-2201 
               
               
                 1020573 
                 1890520.1 
                   
                 GGUGUA 
                 2201 
                 1800384.1 
                   
                 AGCACUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4211 
                 AAAAUAGACATUGCU 
                 3361- 
                 A- 
                 4223 
                 UAGAAUAGCAATGTCT 
                 3359-3381 
               
               
                 1023143 
                 1895607.1 
                   
                 AUUCUA 
                 3381 
                 1800407.1 
                   
                 AUUUUAU 
               
               
                   
               
            
           
         
       
     
     Example 2. In Vitro Screening of VEGF-A siRNA 
     Experimental Methods 
     Cell Culture and Transfections: 
     Cos 7 Cell Transfections 
     Cos-7 (ATCC) were transfected by adding 5 μl of 1 ng/μl psiCHECK2 vector (Blue Heron Biotechnology) containing either Cynomolgus monkey (XM_005552887) or mouse (NM_001025250), 4.9 μl of Opti-MEM, 0.1 μl of Lipofectamine 2000 (Invitrogen, Carlsbad Calif. cat #11668-019), and 5 μl of siRNA duplexes per well into a 384-well plate. Following a 15-minute incubation at room temperature, thirty-five μl of Dulbecco&#39;s Modified Eagle Medium (ThermoFisher) containing ˜5×10 3  cells were then added to the siRNA-transfection mixture. Cells were incubated for 48 hours followed by Firefly (transfection control) and  Renilla  (fused to target sequence) luciferase measurements. Experiments were performed at 10 nM, 1 nM, and 0.1 nM. 
     APRE-19 Cell, hTERT REP-1, and Primary Human Hepatocyte Cell Transfections 
     ARPE-19 cells, hTERT RPE-1, or primary human hepatocyte cells (ATCC) were transfected by adding 4.9 μl of Opti-MEM plus 0.1 μl of RNAiMAX per well (Invitrogen, Carlsbad Calif. cat #13778-150) to 5 μl of siRNA duplexes per well, with 4 replicates of each siRNA duplex, into a 384-well plate, and incubated at room temperature for 15 minutes. Forty μl of DMEM:F12 Medium (ThermoFisher) containing ˜5×10 3  cells were then added to the siRNA-transfection mixture. Cells were incubated for 24 hours prior to RNA purification. Experiments were performed at 50 nM, 10 nM, 1 nM, and 0.1 nM. 
     Free Uptake Transfection: 
     Cryopreserved primary human hepatocytes were thawed at 37° C. in a water bath immediately prior to usage and re-suspended at 0.26×10 6  cells/mL in InVitroGRO CP (plating) medium (Celsis In Vitro Technologies, catalog number Z99029). During transfections, cells were plated onto a BD BioCoat 96 well collagen plate (BD, 356407) at 25,000 cells per well and incubated at 37° C. in an atmosphere of 5% CO2. Free Uptake experiments were performed by adding 10 μL of siRNA duplexes in PBS per well into a 96 well plate. Ninety μL of complete growth media containing appropriate cell number for the cell was then added to the siRNA. Cells were incubated for 24 hours prior to RNA purification. Single dose experiments were performed at 500 nM, 100 nM, 10 nM, and 1 nM final duplex. 
     Total RNA Isolation Using DYNABEADS mRNA Isolation Kit: 
     RNA was isolated using an automated protocol on a BioTek-EL406 platform using DYNABEADs (Invitrogen, cat #61012). Briefly, 70 μl of Lysis/Binding Buffer and 10 μl of lysis buffer containing 3 μl of magnetic beads were added to the plate with cells. Plates were incubated on an electromagnetic shaker for 10 minutes at room temperature and then magnetic beads were captured and the supernatant was removed. Bead-bound RNA was then washed 2 times with 150 μl Wash Buffer A and once with Wash Buffer B. Beads were then washed with 150 μl Elution Buffer, re-captured and supernatant removed. 
     cDNA Synthesis Using ABI High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster City, Calif., Cat #4368813): 
     Ten μl of a master mix containing 1 μl 10× Buffer, 0.4 μl 25×dNTPs, 1 μl 10× Random primers, 0.5 μl Reverse Transcriptase, 0.5 μl RNase inhibitor and 6.6 μl of H2O per reaction was added to RNA isolated above. Plates were sealed, mixed, and incubated on an electromagnetic shaker for 10 minutes at room temperature, followed by 2 h 37° C. 
     Real Time PCR: 
     Two μl of cDNA and 50 Lightcycler 480 probe master mix (Roche Cat #04887301001) were added to either 0.5 μl of Human GAPDH TaqMan Probe (4326317E) and 0.5 μl VEGFA Human probe (Hs00900055_m1, Thermo) per well in a 384 well plates (Roche cat #04887301001). Real time PCR was done in a LightCycler480 Real Time PCR system (Roche). Each duplex was tested at least two times and data were normalized to cells transfected with a non-targeting control siRNA. To calculate relative fold change, real time data were analyzed using the ΔΔCt method and normalized to assays performed with cells transfected with a non-targeting control siRNA. 
     Results 
     The results of the multi-dose screen in human retinal pigment epithelial cells (ARPE-19) and human hTERT-immortalized retinal pigment epithelial cells (hTERT RPE-1) with three sets of exemplary human VEGF-A siRNAs are shown in Table 6A (correspond to siRNAs in Table 2A and Table 2B), Table 6B (correspond to siRNAs in Table 3A and Table 3B), and 6C (correspond to siRNAs in Table 4A and Table 4B). The multi-dose experiments were performed at 50 nM, 10 nM, 1 nM, and 0.1 nM final duplex concentrations and the data are expressed as percent message remaining relative to non-targeting control. Of the exemplary siRNA duplexes evaluated, 28 achieved a knockdown of VEGF-A of &gt;90%, 108 achieved a knockdown of 
     VEGF-A of ≥60%, and 229 achieved a knockdown of VEGF-A of ≥30% in in ARPE-19 cells when administered at the 10 nM concentration. 
     
       
         
           
               
             
               
                 TABLE 6A 
               
             
            
               
                   
               
               
                 VEGF-A endogenous in vitro multi-dose screen with one set of exemplary human VEGF-A siRNAs 
               
            
           
           
               
               
               
            
               
                   
                 ARPE-19 
                 hTERT RPE-1 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 50 
                   
                 10 
                   
                 1 
                   
                 0.1 
                   
                 50 
                   
                 10 
                   
                 1 
                   
                 0.1 
                   
               
               
                 Sample_Name 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 AD-901349.1 
                 29.9 
                 4.1 
                 24.7 
                 3.0 
                 34.0 
                 3.0 
                 54.3 
                 5.7 
                 26.5 
                 7.9 
                 26.0 
                 1.7 
                 64.1 
                 11.3 
                 94.0 
                 17.7 
               
               
                 AD-901376.1 
                 28.3 
                 4.6 
                 25.4 
                 7.6 
                 35.7 
                 8.8 
                 50.3 
                 14.1 
                 15.1 
                 2.7 
                 20.9 
                 4.1 
                 37.6 
                 8.3 
                 46.9 
                 4.6 
               
               
                 AD-901356.1 
                 30.6 
                 2.9 
                 27.9 
                 2.8 
                 36.5 
                 2.5 
                 60.3 
                 7.6 
                 21.0 
                 3.5 
                 25.3 
                 9.7 
                 39.3 
                 8.9 
                 91.6 
                 12.5 
               
               
                 AD-901355.1 
                 42.0 
                 2.2 
                 28.7 
                 3.7 
                 39.6 
                 0.2 
                 65.7 
                 11.5 
                 26.9 
                 2.3 
                 27.4 
                 9.6 
                 44.8 
                 4.0 
                 92.6 
                 22.9 
               
               
                 AD-901407.1 
                 27.8 
                 11.7 
                 30.9 
                 4.0 
                 55.4 
                 6.2 
                 106.1 
                 19.2 
                 39.0 
                 7.9 
                 41.1 
                 12.4 
                 69.5 
                 10.9 
                 87.5 
                 21.1 
               
               
                 AD-901367.1 
                 39.0 
                 4.8 
                 31.5 
                 3.7 
                 38.6 
                 7.1 
                 50.4 
                 2.2 
                 31.0 
                 6.3 
                 39.3 
                 5.5 
                 38.1 
                 5.2 
                 77.0 
                 13.4 
               
               
                 AD-901352.1 
                 42.7 
                 1.8 
                 34.6 
                 6.1 
                 48.5 
                 6.6 
                 57.4 
                 4.9 
                 27.1 
                 7.7 
                 28.9 
                 4.5 
                 51.6 
                 10.4 
                 76.8 
                 15.3 
               
               
                 AD-901348.1 
                 44.5 
                 7.3 
                 35.0 
                 7.2 
                 40.6 
                 4.7 
                 62.4 
                 9.1 
                 35.4 
                 6.8 
                 23.0 
                 4.2 
                 50.0 
                 18.5 
                 97.9 
                 21.6 
               
               
                 AD-901354.1 
                 45.0 
                 3.6 
                 35.9 
                 7.1 
                 40.9 
                 2.1 
                 61.2 
                 4.0 
                 34.1 
                 8.9 
                 27.0 
                 6.2 
                 34.7 
                 8.7 
                 81.9 
                 18.7 
               
               
                 AD-901353.1 
                 50.8 
                 5.9 
                 37.6 
                 8.6 
                 29.8 
                 4.7 
                 52.4 
                 2.4 
                 36.1 
                 6.5 
                 21.5 
                 4.3 
                 40.4 
                 8.7 
                 98.2 
                 11.7 
               
               
                 AD-901375.1 
                 44.5 
                 7.1 
                 40.2 
                 2.0 
                 43.0 
                 6.6 
                 60.0 
                 12.2 
                 30.5 
                 1.8 
                 30.4 
                 3.3 
                 46.9 
                 24.4 
                 61.3 
                 4.9 
               
               
                 AD-901345.1 
                 53.1 
                 6.0 
                 42.9 
                 9.0 
                 74.3 
                 13.7 
                 73.0 
                 16.3 
                 74.8 
                 12.7 
                 62.2 
                 18.1 
                 61.7 
                 9.5 
                 85.2 
                 14.5 
               
               
                 AD-901357.1 
                 39.8 
                 11.7 
                 42.9 
                 1.1 
                 54.2 
                 3.3 
                 78.1 
                 14.9 
                 37.2 
                 7.4 
                 42.3 
                 15.4 
                 43.2 
                 2.9 
                 97.9 
                 19.8 
               
               
                 AD-901334.1 
                 55.7 
                 4.7 
                 43.4 
                 7.2 
                 77.4 
                 9.8 
                 76.7 
                 6.0 
                 74.9 
                 18.4 
                 47.9 
                 12.8 
                 73.3 
                 17.2 
                 85.9 
                 8.5 
               
               
                 AD-901313.1 
                 32.9 
                 3.6 
                 44.2 
                 9.8 
                 77.8 
                 17.5 
                 64.1 
                 7.0 
                 39.7 
                 12.8 
                 47.9 
                 5.8 
                 101.3 
                 4.5 
                 69.6 
                 18.2 
               
               
                 AD-901344.1 
                 71.9 
                 5.4 
                 46.9 
                 6.7 
                 78.6 
                 16.2 
                 59.4 
                 9.0 
                 75.8 
                 6.0 
                 72.9 
                 21.0 
                 62.0 
                 13.2 
                 78.4 
                 7.8 
               
               
                 AD-901366.1 
                 56.1 
                 9.1 
                 47.2 
                 7.4 
                 61.9 
                 5.7 
                 69.1 
                 6.6 
                 42.5 
                 11.3 
                 49.6 
                 12.8 
                 58.3 
                 14.2 
                 97.4 
                 18.8 
               
               
                 AD-901337.1 
                 70.7 
                 7.9 
                 47.7 
                 9.4 
                 101.6 
                 21.1 
                 82.6 
                 9.4 
                 91.8 
                 17.2 
                 64.0 
                 25.7 
                 80.8 
                 21.3 
                 86.4 
                 7.4 
               
               
                 AD-901335.1 
                 58.7 
                 9.2 
                 48.0 
                 7.7 
                 109.6 
                 32.9 
                 84.5 
                 9.8 
                 75.6 
                 4.6 
                 62.1 
                 15.5 
                 72.2 
                 19.6 
                 92.4 
                 18.7 
               
               
                 AD-901398.1 
                 51.6 
                 2.2 
                 48.0 
                 8.3 
                 63.3 
                 5.6 
                 91.1 
                 11.3 
                 39.6 
                 8.2 
                 55.7 
                 9.8 
                 71.8 
                 10.1 
                 56.2 
                 8.4 
               
               
                 AD-901314.1 
                 43.1 
                 10.7 
                 48.7 
                 10.8 
                 94.3 
                 25.4 
                 99.6 
                 15.1 
                 49.9 
                 6.0 
                 50.9 
                 10.9 
                 67.9 
                 15.4 
                 100.9 
                 31.8 
               
               
                 AD-901386.1 
                 51.7 
                 6.0 
                 49.5 
                 2.7 
                 82.7 
                 59.5 
                 75.9 
                 21.6 
                 62.6 
                 20.0 
                 42.9 
                 8.8 
                 55.4 
                 20.7 
                 45.8 
                 8.9 
               
               
                 AD-901336.1 
                 67.6 
                 5.1 
                 51.4 
                 12.8 
                 88.0 
                 14.9 
                 74.3 
                 9.5 
                 88.1 
                 10.2 
                 51.7 
                 16.0 
                 77.8 
                 19.7 
                 85.0 
                 16.0 
               
               
                 AD-901310.1 
                 40.9 
                 8.2 
                 53.0 
                 5.6 
                 88.6 
                 18.3 
                 82.0 
                 5.8 
                 46.8 
                 7.6 
                 52.4 
                 10.7 
                 71.9 
                 11.7 
                 76.1 
                 7.3 
               
               
                 AD-901321.1 
                 41.4 
                 7.4 
                 53.1 
                 13.3 
                 87.7 
                 15.2 
                 67.0 
                 16.0 
                 36.4 
                 8.2 
                 40.2 
                 4.3 
                 87.2 
                 13.0 
                 89.2 
                 8.0 
               
               
                 AD-901382.1 
                 57.5 
                 4.2 
                 53.7 
                 3.0 
                 62.8 
                 4.5 
                 90.1 
                 19.4 
                 41.0 
                 12.4 
                 37.9 
                 9.3 
                 68.2 
                 10.5 
                 63.9 
                 9.5 
               
               
                 AD-901384.1 
                 49.7 
                 6.8 
                 53.8 
                 12.8 
                 54.0 
                 12.3 
                 87.8 
                 38.9 
                 43.5 
                 5.7 
                 52.6 
                 5.1 
                 60.1 
                 9.4 
                 56.1 
                 12.1 
               
               
                 AD-901339.1 
                 80.3 
                 16.6 
                 54.0 
                 7.4 
                 76.7 
                 11.8 
                 74.7 
                 3.5 
                 96.3 
                 18.7 
                 68.3 
                 12.5 
                 68.9 
                 13.3 
                 89.7 
                 11.8 
               
               
                 AD-901363.1 
                 68.5 
                 11.9 
                 55.2 
                 9.3 
                 54.3 
                 4.3 
                 71.2 
                 8.6 
                 52.2 
                 5.7 
                 54.8 
                 12.0 
                 45.5 
                 1.5 
                 86.0 
                 15.8 
               
               
                 AD-901325.1 
                 71.6 
                 2.4 
                 55.6 
                 7.1 
                 111.4 
                 11.4 
                 95.5 
                 4.4 
                 77.5 
                 15.7 
                 69.8 
                 10.8 
                 88.4 
                 10.0 
                 96.8 
                 6.0 
               
               
                 AD-901350.1 
                 60.4 
                 9.5 
                 56.5 
                 8.4 
                 66.9 
                 6.6 
                 73.3 
                 3.1 
                 50.7 
                 6.7 
                 45.6 
                 3.9 
                 85.0 
                 8.9 
                 92.4 
                 12.9 
               
               
                 AD-901365.1 
                 68.6 
                 5.1 
                 56.5 
                 6.6 
                 64.8 
                 7.6 
                 79.6 
                 12.3 
                 48.9 
                 18.5 
                 52.3 
                 13.3 
                 56.8 
                 16.7 
                 96.1 
                 8.8 
               
               
                 AD-901306.1 
                 55.1 
                 12.5 
                 57.7 
                 5.8 
                 96.6 
                 17.2 
                 97.3 
                 24.5 
                 66.5 
                 10.5 
                 74.7 
                 16.8 
                 75.6 
                 9.7 
                 108.6 
                 25.5 
               
               
                 AD-901361.1 
                 50.8 
                 6.9 
                 58.5 
                 18.8 
                 45.6 
                 3.1 
                 68.6 
                 10.3 
                 44.9 
                 4.3 
                 36.2 
                 9.9 
                 57.7 
                 6.5 
                 95.4 
                 14.9 
               
               
                 AD-901320.1 
                 52.3 
                 11.4 
                 60.0 
                 5.7 
                 94.3 
                 23.4 
                 69.8 
                 3.8 
                 48.1 
                 19.3 
                 48.3 
                 3.8 
                 68.9 
                 13.2 
                 84.4 
                 18.8 
               
               
                 AD-901405.1 
                 64.5 
                 3.4 
                 60.5 
                 9.8 
                 80.4 
                 7.5 
                 83.6 
                 15.4 
                 63.1 
                 9.2 
                 72.3 
                 21.9 
                 74.6 
                 9.3 
                 55.6 
                 6.4 
               
               
                 AD-901338.1 
                 52.7 
                 5.1 
                 61.7 
                 4.1 
                 82.0 
                 12.2 
                 86.9 
                 13.2 
                 73.4 
                 8.4 
                 60.8 
                 20.1 
                 58.8 
                 9.8 
                 103.1 
                 16.6 
               
               
                 AD-901383.1 
                 62.0 
                 8.9 
                 62.2 
                 7.7 
                 78.2 
                 11.8 
                 92.7 
                 14.8 
                 57.0 
                 9.8 
                 62.6 
                 11.9 
                 75.1 
                 16.6 
                 75.2 
                 7.0 
               
               
                 AD-901333.1 
                 82.0 
                 7.2 
                 62.5 
                 12.2 
                 94.1 
                 17.3 
                 85.2 
                 6.9 
                 92.2 
                 5.4 
                 66.8 
                 12.1 
                 79.2 
                 15.9 
                 70.5 
                 37.8 
               
               
                 AD-901330.1 
                 75.7 
                 8.7 
                 63.0 
                 9.7 
                 96.4 
                 6.3 
                 104.5 
                 23.5 
                 90.8 
                 8.4 
                 63.2 
                 16.4 
                 82.5 
                 16.6 
                 109.3 
                 30.1 
               
               
                 AD-901360.1 
                 61.4 
                 8.8 
                 64.0 
                 10.3 
                 59.9 
                 6.5 
                 90.6 
                 32.4 
                 77.5 
                 3.7 
                 63.7 
                 6.4 
                 64.1 
                 14.7 
                 95.1 
                 14.9 
               
               
                 AD-901358.1 
                 67.4 
                 11.4 
                 65.3 
                 5.4 
                 71.0 
                 3.6 
                 82.3 
                 6.7 
                 58.5 
                 5.3 
                 49.5 
                 6.5 
                 62.8 
                 4.6 
                 94.4 
                 11.9 
               
               
                 AD-901406.1 
                 67.6 
                 7.4 
                 65.6 
                 7.7 
                 77.2 
                 6.7 
                 93.5 
                 2.0 
                 63.3 
                 13.4 
                 65.2 
                 5.7 
                 69.4 
                 9.5 
                 86.9 
                 30.3 
               
               
                 AD-901326.1 
                 78.8 
                 14.8 
                 65.8 
                 16.8 
                 120.8 
                 26.0 
                 88.1 
                 8.0 
                 85.9 
                 5.7 
                 69.6 
                 11.8 
                 88.6 
                 15.2 
                 98.3 
                 14.6 
               
               
                 AD-901377.1 
                 47.2 
                 7.3 
                 65.8 
                 11.4 
                 57.5 
                 12.7 
                 68.0 
                 22.8 
                 42.8 
                 6.2 
                 47.4 
                 6.3 
                 54.8 
                 10.2 
                 63.4 
                 15.1 
               
               
                 AD-901351.1 
                 69.4 
                 9.6 
                 66.9 
                 10.1 
                 82.5 
                 6.8 
                 85.7 
                 5.3 
                 73.9 
                 8.0 
                 56.8 
                 13.1 
                 81.2 
                 30.7 
                 97.6 
                 36.5 
               
               
                 AD-901415.1 
                 77.8 
                 13.7 
                 68.1 
                 18.4 
                 78.6 
                 14.7 
                 119.6 
                 45.3 
                 85.6 
                 6.4 
                 57.2 
                 10.5 
                 83.8 
                 7.7 
                 78.5 
                 19.4 
               
               
                 AD-901342.1 
                 87.4 
                 20.2 
                 70.1 
                 10.3 
                 113.4 
                 21.8 
                 79.3 
                 12.1 
                 90.5 
                 27.6 
                 56.2 
                 11.2 
                 80.2 
                 21.4 
                 91.5 
                 14.4 
               
               
                 AD-901420.1 
                 61.1 
                 7.0 
                 71.0 
                 5.7 
                 75.3 
                 4.0 
                 107.9 
                 37.3 
                 52.4 
                 2.8 
                 43.5 
                 7.9 
                 67.8 
                 13.7 
                 80.8 
                 8.9 
               
               
                 AD-901312.1 
                 62.1 
                 10.7 
                 71.2 
                 8.0 
                 102.4 
                 22.9 
                 76.5 
                 2.4 
                 75.1 
                 7.7 
                 60.1 
                 15.4 
                 100.2 
                 30.7 
                 73.8 
                 17.5 
               
               
                 AD-901340.1 
                 88.8 
                 12.8 
                 71.6 
                 10.3 
                 100.4 
                 19.9 
                 93.3 
                 12.4 
                 94.1 
                 31.9 
                 69.3 
                 11.0 
                 87.6 
                 24.7 
                 100.6 
                 10.9 
               
               
                 AD-901392.1 
                 49.7 
                 9.0 
                 71.6 
                 13.2 
                 69.0 
                 4.0 
                 81.0 
                 47.1 
                 41.3 
                 2.9 
                 61.4 
                 10.0 
                 77.7 
                 12.1 
                 74.3 
                 5.4 
               
               
                 AD-901327.1 
                 72.4 
                 15.6 
                 71.8 
                 8.7 
                 114.4 
                 13.3 
                 80.6 
                 2.7 
                 89.8 
                 13.6 
                 75.7 
                 12.3 
                 82.7 
                 23.2 
                 92.0 
                 8.8 
               
               
                 AD-901328.1 
                 77.7 
                 13.0 
                 72.6 
                 6.3 
                 104.1 
                 10.6 
                 76.9 
                 7.7 
                 87.2 
                 16.3 
                 70.5 
                 4.1 
                 89.5 
                 8.4 
                 86.4 
                 10.7 
               
               
                 AD-901370.1 
                 65.9 
                 6.5 
                 72.9 
                 7.8 
                 79.9 
                 6.7 
                 70.6 
                 4.4 
                 67.8 
                 9.5 
                 81.6 
                 5.6 
                 70.3 
                 16.6 
                 52.8 
                 35.3 
               
               
                 AD-901399.1 
                 63.2 
                 10.4 
                 72.9 
                 7.8 
                 79.3 
                 5.9 
                 98.0 
                 11.8 
                 52.6 
                 4.9 
                 78.5 
                 18.2 
                 62.3 
                 12.7 
                 68.9 
                 7.0 
               
               
                 AD-901359.1 
                 83.7 
                 13.3 
                 73.4 
                 12.1 
                 66.6 
                 8.8 
                 69.4 
                 7.1 
                 80.2 
                 20.5 
                 63.3 
                 20.6 
                 70.5 
                 6.9 
                 90.7 
                 19.1 
               
               
                 AD-901373.1 
                 81.5 
                 10.9 
                 73.4 
                 4.6 
                 73.5 
                 2.4 
                 69.8 
                 8.7 
                 52.1 
                 11.0 
                 61.9 
                 17.9 
                 60.7 
                 10.9 
                 56.7 
                 12.5 
               
               
                 AD-901332.1 
                 79.6 
                 17.9 
                 73.7 
                 4.9 
                 123.3 
                 17.1 
                 93.6 
                 6.1 
                 95.2 
                 13.6 
                 56.4 
                 15.2 
                 96.5 
                 7.9 
                 89.0 
                 14.4 
               
               
                 AD-901311.1 
                 53.7 
                 10.4 
                 74.5 
                 9.5 
                 98.0 
                 27.9 
                 72.0 
                 4.0 
                 67.5 
                 16.0 
                 69.0 
                 9.2 
                 64.6 
                 10.3 
                 73.9 
                 3.3 
               
               
                 AD-901423.1 
                 61.8 
                 10.6 
                 74.5 
                 9.5 
                 72.3 
                 8.7 
                 104.0 
                 24.4 
                 48.8 
                 3.6 
                 56.4 
                 10.5 
                 68.3 
                 12.8 
                 73.5 
                 8.2 
               
               
                 AD-901374.1 
                 92.4 
                 18.4 
                 74.5 
                 9.6 
                 86.9 
                 12.5 
                 71.0 
                 14.7 
                 90.5 
                 13.9 
                 52.7 
                 13.4 
                 81.5 
                 12.0 
                 61.3 
                 12.7 
               
               
                 AD-901319.1 
                 73.3 
                 19.5 
                 75.1 
                 6.3 
                 126.0 
                 19.4 
                 77.4 
                 7.6 
                 88.5 
                 16.0 
                 81.3 
                 7.2 
                 64.0 
                 20.9 
                 93.5 
                 33.9 
               
               
                 AD-901341.1 
                 88.8 
                 12.2 
                 75.5 
                 8.1 
                 107.3 
                 10.6 
                 79.2 
                 5.8 
                 77.2 
                 20.8 
                 86.1 
                 24.0 
                 96.8 
                 15.9 
                 93.0 
                 10.6 
               
               
                 AD-901422.1 
                 51.3 
                 3.2 
                 75.8 
                 5.2 
                 55.6 
                 5.8 
                 95.6 
                 25.5 
                 40.2 
                 4.1 
                 39.9 
                 9.4 
                 61.8 
                 15.0 
                 76.2 
                 19.9 
               
               
                 AD-901385.1 
                 67.7 
                 13.9 
                 75.8 
                 16.1 
                 86.8 
                 10.9 
                 93.1 
                 21.7 
                 72.9 
                 11.6 
                 72.2 
                 14.5 
                 76.4 
                 13.2 
                 65.1 
                 10.3 
               
               
                 AD-901391.1 
                 72.0 
                 11.9 
                 76.2 
                 8.8 
                 82.3 
                 12.0 
                 76.8 
                 22.5 
                 71.6 
                 14.7 
                 63.4 
                 16.7 
                 81.2 
                 6.6 
                 85.9 
                 13.3 
               
               
                 AD-901329.1 
                 72.5 
                 10.6 
                 76.3 
                 11.1 
                 107.1 
                 12.2 
                 79.8 
                 9.2 
                 98.2 
                 17.4 
                 75.5 
                 10.9 
                 100.5 
                 15.9 
                 93.9 
                 6.9 
               
               
                 AD-901331.1 
                 101.1 
                 11.5 
                 77.9 
                 13.7 
                 120.0 
                 24.9 
                 84.0 
                 10.0 
                 126.3 
                 25.1 
                 76.3 
                 19.3 
                 82.2 
                 6.1 
                 79.0 
                 22.0 
               
               
                 AD-901368.1 
                 73.7 
                 9.1 
                 79.5 
                 11.1 
                 82.4 
                 5.5 
                 90.1 
                 31.1 
                 98.3 
                 21.8 
                 97.4 
                 7.8 
                 64.4 
                 19.9 
                 85.4 
                 4.9 
               
               
                 AD-901364.1 
                 82.5 
                 10.9 
                 79.5 
                 16.7 
                 75.7 
                 8.9 
                 81.4 
                 2.6 
                 65.8 
                 7.1 
                 65.3 
                 18.7 
                 48.4 
                 7.4 
                 90.9 
                 5.5 
               
               
                 AD-901389.1 
                 69.1 
                 10.2 
                 80.3 
                 6.1 
                 80.4 
                 9.2 
                 87.2 
                 22.8 
                 50.7 
                 2.4 
                 55.9 
                 6.4 
                 82.8 
                 21.5 
                 59.0 
                 16.1 
               
               
                 AD-901421.1 
                 54.9 
                 7.1 
                 80.9 
                 6.9 
                 63.4 
                 9.2 
                 96.5 
                 25.7 
                 50.4 
                 9.2 
                 37.8 
                 3.8 
                 70.9 
                 15.3 
                 61.1 
                 11.7 
               
               
                 AD-901380.1 
                 85.6 
                 16.8 
                 81.0 
                 6.5 
                 60.9 
                 9.0 
                 83.7 
                 9.2 
                 74.9 
                 12.3 
                 77.7 
                 6.6 
                 54.5 
                 11.3 
                 75.8 
                 19.3 
               
               
                 AD-901343.1 
                 102.8 
                 17.6 
                 81.8 
                 13.7 
                 127.7 
                 32.4 
                 99.8 
                 11.8 
                 133.1 
                 18.9 
                 81.7 
                 20.5 
                 93.1 
                 6.4 
                 81.8 
                 13.4 
               
               
                 AD-901317.1 
                 89.8 
                 12.2 
                 81.8 
                 4.8 
                 131.2 
                 51.1 
                 90.6 
                 5.2 
                 120.7 
                 22.3 
                 86.4 
                 4.5 
                 69.7 
                 11.0 
                 76.7 
                 7.1 
               
               
                 AD-901424.1 
                 62.9 
                 4.8 
                 82.2 
                 14.8 
                 64.9 
                 10.2 
                 86.0 
                 8.1 
                 68.7 
                 13.3 
                 63.1 
                 22.6 
                 76.5 
                 15.9 
                 71.8 
                 24.4 
               
               
                 AD-901431.1 
                 84.8 
                 11.4 
                 82.9 
                 20.5 
                 75.7 
                 10.5 
                 96.4 
                 29.5 
                 79.4 
                 15.9 
                 88.8 
                 25.2 
                 85.1 
                 8.9 
                 80.8 
                 21.7 
               
               
                 AD-901378.1 
                 71.4 
                 5.4 
                 82.9 
                 5.5 
                 77.3 
                 8.5 
                 80.6 
                 9.3 
                 56.8 
                 14.3 
                 40.8 
                 13.4 
                 82.0 
                 24.4 
                 78.9 
                 14.1 
               
               
                 AD-901434.1 
                 70.3 
                 11.3 
                 83.8 
                 8.4 
                 59.4 
                 1.3 
                 92.1 
                 11.3 
                 62.6 
                 8.3 
                 72.7 
                 17.5 
                 69.9 
                 12.0 
                 82.0 
                 11.3 
               
               
                 AD-901412.1 
                 83.4 
                 15.9 
                 84.5 
                 32.2 
                 94.4 
                 4.4 
                 81.6 
                 19.4 
                 82.3 
                 3.9 
                 50.8 
                 5.2 
                 85.6 
                 21.9 
                 74.5 
                 8.0 
               
               
                 AD-901426.1 
                 96.7 
                 7.7 
                 85.1 
                 13.5 
                 68.2 
                 7.2 
                 104.4 
                 9.3 
                 92.5 
                 15.3 
                 61.5 
                 4.0 
                 56.0 
                 7.0 
                 80.4 
                 15.0 
               
               
                 AD-901322.1 
                 74.9 
                 14.5 
                 85.5 
                 12.4 
                 118.1 
                 15.9 
                 117.4 
                 22.0 
                 107.2 
                 20.0 
                 92.5 
                 15.9 
                 98.9 
                 16.0 
                 107.3 
                 8.5 
               
               
                 AD-901381.1 
                 92.6 
                 10.5 
                 85.7 
                 4.9 
                 93.9 
                 10.2 
                 90.8 
                 17.0 
                 72.5 
                 15.0 
                 74.0 
                 16.8 
                 85.0 
                 21.6 
                 71.5 
                 16.1 
               
               
                 AD-901324.1 
                 93.0 
                 10.1 
                 87.3 
                 14.3 
                 142.1 
                 25.2 
                 92.9 
                 5.5 
                 133.9 
                 8.1 
                 94.9 
                 11.1 
                 94.3 
                 9.2 
                 91.4 
                 4.7 
               
               
                 AD-901347.1 
                 84.2 
                 11.6 
                 87.7 
                 9.5 
                 101.8 
                 19.4 
                 83.9 
                 4.4 
                 96.1 
                 10.3 
                 84.6 
                 25.5 
                 105.8 
                 6.4 
                 96.3 
                 13.4 
               
               
                 AD-901379.1 
                 81.1 
                 5.9 
                 87.8 
                 6.2 
                 72.1 
                 6.9 
                 80.4 
                 6.7 
                 79.3 
                 7.6 
                 59.9 
                 15.5 
                 82.5 
                 18.4 
                 59.1 
                 18.7 
               
               
                 AD-901428.1 
                 71.8 
                 4.4 
                 88.2 
                 18.3 
                 74.5 
                 8.0 
                 93.0 
                 16.6 
                 89.7 
                 13.0 
                 52.5 
                 12.6 
                 65.9 
                 17.7 
                 76.7 
                 13.3 
               
               
                 AD-901371.1 
                 75.5 
                 7.5 
                 88.2 
                 15.6 
                 77.3 
                 5.7 
                 82.5 
                 5.9 
                 71.7 
                 8.5 
                 56.8 
                 12.0 
                 68.6 
                 10.7 
                 71.2 
                 20.0 
               
               
                 AD-901408.1 
                 74.4 
                 14.1 
                 88.8 
                 30.8 
                 91.5 
                 5.1 
                 85.5 
                 11.2 
                 75.4 
                 14.5 
                 57.2 
                 15.1 
                 97.4 
                 21.5 
                 76.5 
                 13.3 
               
               
                 AD-901417.1 
                 94.8 
                 14.8 
                 89.2 
                 14.0 
                 101.7 
                 5.9 
                 117.2 
                 33.3 
                 85.4 
                 23.1 
                 76.9 
                 12.4 
                 92.6 
                 6.8 
                 76.2 
                 21.6 
               
               
                 AD-901400.1 
                 82.9 
                 10.1 
                 89.7 
                 8.6 
                 97.9 
                 11.3 
                 97.7 
                 22.9 
                 97.5 
                 12.8 
                 101.9 
                 12.3 
                 98.8 
                 13.0 
                 65.3 
                 17.5 
               
               
                 AD-901323.1 
                 74.6 
                 14.8 
                 90.4 
                 12.0 
                 130.1 
                 25.7 
                 86.8 
                 3.3 
                 101.8 
                 5.7 
                 93.7 
                 18.2 
                 80.4 
                 12.4 
                 96.3 
                 20.5 
               
               
                 AD-901316.1 
                 91.0 
                 18.0 
                 90.8 
                 8.3 
                 139.5 
                 42.5 
                 96.3 
                 3.1 
                 99.6 
                 17.7 
                 93.6 
                 8.8 
                 80.1 
                 28.4 
                 96.5 
                 18.2 
               
               
                 AD-901315.1 
                 86.7 
                 14.1 
                 90.8 
                 6.4 
                 130.0 
                 40.3 
                 92.6 
                 4.0 
                 125.3 
                 13.0 
                 107.4 
                 11.9 
                 72.7 
                 22.2 
                 97.5 
                 7.6 
               
               
                 AD-901395.1 
                 77.9 
                 11.7 
                 90.9 
                 5.9 
                 80.0 
                 4.0 
                 86.9 
                 20.7 
                 65.9 
                 13.2 
                 63.8 
                 10.5 
                 87.3 
                 8.0 
                 74.9 
                 19.2 
               
               
                 AD-901318.1 
                 78.6 
                 6.2 
                 92.1 
                 11.8 
                 131.0 
                 50.7 
                 90.2 
                 11.5 
                 112.5 
                 21.6 
                 91.5 
                 12.2 
                 73.0 
                 12.4 
                 83.6 
                 15.4 
               
               
                 AD-901390.1 
                 75.3 
                 12.2 
                 93.3 
                 5.9 
                 95.8 
                 9.4 
                 96.1 
                 23.2 
                 47.0 
                 6.9 
                 66.4 
                 7.4 
                 71.5 
                 4.7 
                 64.3 
                 14.3 
               
               
                 AD-901387.1 
                 91.5 
                 9.4 
                 94.9 
                 6.0 
                 100.0 
                 18.9 
                 93.5 
                 10.9 
                 131.7 
                 17.8 
                 89.3 
                 10.7 
                 89.1 
                 17.7 
                 69.4 
                 13.4 
               
               
                 AD-901307.1 
                 66.0 
                 13.3 
                 95.4 
                 11.1 
                 105.1 
                 21.0 
                 90.1 
                 4.9 
                 119.0 
                 15.4 
                 100.5 
                 12.7 
                 74.3 
                 28.2 
                 105.8 
                 10.9 
               
               
                 AD-901410.1 
                 91.1 
                 15.6 
                 96.5 
                 28.2 
                 104.3 
                 15.4 
                 91.4 
                 7.4 
                 93.9 
                 9.4 
                 55.3 
                 10.6 
                 98.9 
                 32.4 
                 79.6 
                 13.4 
               
               
                 AD-901433.1 
                 86.9 
                 4.6 
                 96.9 
                 18.9 
                 74.6 
                 2.3 
                 98.2 
                 8.3 
                 81.1 
                 19.2 
                 58.0 
                 15.9 
                 81.0 
                 12.6 
                 73.6 
                 12.0 
               
               
                 AD-901308.1 
                 67.0 
                 5.1 
                 97.7 
                 18.4 
                 136.0 
                 31.1 
                 89.2 
                 5.3 
                 116.8 
                 18.1 
                 109.3 
                 4.6 
                 99.4 
                 12.4 
                 80.8 
                 8.5 
               
               
                 AD-901414.1 
                 88.8 
                 12.1 
                 98.1 
                 31.3 
                 94.5 
                 2.6 
                 94.0 
                 16.9 
                 88.5 
                 4.8 
                 64.8 
                 17.5 
                 70.2 
                 8.3 
                 82.3 
                 11.3 
               
               
                 AD-901309.1 
                 67.5 
                 6.9 
                 98.7 
                 12.4 
                 124.9 
                 29.1 
                 91.8 
                 3.9 
                 111.9 
                 21.4 
                 84.7 
                 12.8 
                 97.9 
                 16.1 
                 88.3 
                 18.1 
               
               
                 AD-901362.1 
                 75.1 
                 11.6 
                 99.1 
                 22.7 
                 91.0 
                 7.1 
                 91.6 
                 12.6 
                 93.3 
                 9.1 
                 99.8 
                 38.1 
                 69.3 
                 19.5 
                 92.9 
                 13.0 
               
               
                 AD-901397.1 
                 86.1 
                 9.0 
                 99.3 
                 8.7 
                 94.9 
                 5.6 
                 88.4 
                 19.5 
                 99.2 
                 14.2 
                 119.6 
                 15.6 
                 83.0 
                 11.1 
                 67.2 
                 17.1 
               
               
                 AD-901419.1 
                 74.3 
                 12.2 
                 100.1 
                 11.9 
                 80.7 
                 8.0 
                 116.8 
                 34.6 
                 74.5 
                 14.5 
                 49.9 
                 4.4 
                 89.7 
                 14.6 
                 72.7 
                 12.1 
               
               
                 AD-901413.1 
                 92.5 
                 12.3 
                 101.4 
                 37.9 
                 97.6 
                 3.4 
                 96.1 
                 18.3 
                 77.1 
                 5.9 
                 59.3 
                 11.9 
                 75.0 
                 18.1 
                 67.4 
                 2.0 
               
               
                 AD-901401.1 
                 95.3 
                 6.8 
                 101.8 
                 10.4 
                 116.3 
                 16.9 
                 98.8 
                 24.7 
                 138.0 
                 19.8 
                 97.0 
                 15.7 
                 102.4 
                 24.1 
                 81.1 
                 10.2 
               
               
                 AD-901411.1 
                 83.9 
                 8.7 
                 102.6 
                 36.0 
                 93.3 
                 8.6 
                 105.0 
                 4.3 
                 79.2 
                 14.1 
                 55.2 
                 8.4 
                 80.4 
                 7.4 
                 75.1 
                 28.5 
               
               
                 AD-901372.1 
                 85.7 
                 9.4 
                 103.1 
                 18.7 
                 89.3 
                 4.3 
                 89.9 
                 12.5 
                 100.5 
                 7.7 
                 97.0 
                 20.4 
                 73.8 
                 9.6 
                 47.5 
                 4.4 
               
               
                 AD-901425.1 
                 86.6 
                 13.9 
                 104.1 
                 15.8 
                 100.2 
                 12.0 
                 110.9 
                 21.8 
                 88.0 
                 11.6 
                 66.1 
                 22.7 
                 87.1 
                 20.1 
                 74.9 
                 17.6 
               
               
                 AD-901409.1 
                 110.5 
                 16.6 
                 106.3 
                 26.4 
                 112.3 
                 10.1 
                 98.9 
                 9.1 
                 102.0 
                 12.9 
                 53.7 
                 18.0 
                 90.5 
                 8.8 
                 87.0 
                 24.0 
               
               
                 AD-901418.1 
                 91.4 
                 17.7 
                 106.6 
                 12.5 
                 104.2 
                 5.8 
                 115.4 
                 41.5 
                 84.9 
                 16.8 
                 58.5 
                 14.0 
                 94.1 
                 2.4 
                 79.4 
                 3.5 
               
               
                 AD-901393.1 
                 95.9 
                 14.4 
                 107.2 
                 19.2 
                 104.5 
                 7.5 
                 79.9 
                 14.8 
                 95.8 
                 15.0 
                 101.9 
                 28.1 
                 94.8 
                 18.2 
                 65.6 
                 22.0 
               
               
                 AD-901388.1 
                 83.2 
                 14.1 
                 108.9 
                 4.0 
                 102.2 
                 9.0 
                 96.5 
                 10.3 
                 69.7 
                 4.2 
                 93.0 
                 12.0 
                 90.5 
                 5.4 
                 63.6 
                 22.4 
               
               
                 AD-901404.1 
                 99.7 
                 7.5 
                 110.2 
                 6.7 
                 119.3 
                 24.1 
                 94.8 
                 6.8 
                 130.3 
                 22.2 
                 108.2 
                 6.2 
                 83.6 
                 13.6 
                 84.4 
                 9.4 
               
               
                 AD-901346.1 
                 78.3 
                 11.7 
                 110.7 
                 28.7 
                 97.5 
                 15.9 
                 70.1 
                 4.8 
                 89.4 
                 8.0 
                 75.4 
                 20.2 
                 76.7 
                 24.4 
                 105.1 
                 10.9 
               
               
                 AD-901403.1 
                 92.7 
                 11.1 
                 111.4 
                 9.2 
                 101.5 
                 5.3 
                 96.1 
                 9.3 
                 94.2 
                 13.5 
                 111.6 
                 19.8 
                 79.3 
                 7.0 
                 62.3 
                 6.4 
               
               
                 AD-901396.1 
                 95.6 
                 12.6 
                 112.1 
                 20.6 
                 101.1 
                 10.1 
                 97.7 
                 11.4 
                 88.7 
                 6.9 
                 116.5 
                 36.0 
                 89.3 
                 3.2 
                 79.8 
                 22.4 
               
               
                 AD-901432.1 
                 86.4 
                 16.0 
                 113.4 
                 16.6 
                 68.0 
                 6.3 
                 97.4 
                 15.6 
                 98.3 
                 13.9 
                 67.9 
                 6.9 
                 81.5 
                 17.3 
                 77.7 
                 17.1 
               
               
                 AD-901435.1 
                 93.4 
                 6.6 
                 115.4 
                 12.9 
                 82.5 
                 12.0 
                 97.1 
                 10.8 
                 100.4 
                 9.0 
                 68.1 
                 31.6 
                 82.2 
                 25.7 
                 78.0 
                 11.7 
               
               
                 AD-901416.1 
                 103.4 
                 18.0 
                 116.6 
                 18.3 
                 110.7 
                 16.3 
                 98.3 
                 27.8 
                 102.4 
                 25.4 
                 77.5 
                 16.6 
                 100.2 
                 4.4 
                 82.1 
                 22.3 
               
               
                 AD-901394.1 
                 106.8 
                 12.4 
                 118.1 
                 11.0 
                 111.8 
                 9.5 
                 92.1 
                 16.4 
                 137.8 
                 38.9 
                 117.2 
                 37.8 
                 100.6 
                 17.2 
                 71.2 
                 11.1 
               
               
                 AD-901429.1 
                 94.4 
                 7.7 
                 118.8 
                 28.5 
                 93.2 
                 6.7 
                 101.2 
                 12.0 
                 92.5 
                 7.3 
                 64.3 
                 18.4 
                 85.1 
                 6.6 
                 75.3 
                 16.0 
               
               
                 AD-901402.1 
                 99.4 
                 13.8 
                 118.9 
                 25.5 
                 107.3 
                 6.3 
                 100.5 
                 9.5 
                 99.8 
                 15.7 
                 108.9 
                 8.5 
                 94.6 
                 9.5 
                 75.2 
                 18.7 
               
               
                 AD-901430.1 
                 95.7 
                 16.4 
                 119.8 
                 30.7 
                 82.8 
                 5.5 
                 98.2 
                 12.4 
                 95.2 
                 10.9 
                 90.0 
                 30.2 
                 72.8 
                 6.4 
                 74.4 
                 9.7 
               
               
                 AD-901369.1 
                 79.4 
                 12.7 
                 135.3 
                 57.4 
                 89.5 
                 2.4 
                 75.0 
                 10.6 
                 112.5 
                 21.8 
                 82.9 
                 15.8 
                 88.4 
                 2.8 
                 66.5 
                 21.4 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6B 
               
             
            
               
                   
               
               
                 VEGF-A endogenous in vitro multi-dose screen with one set of exemplary human VEGF-A siRNAs 
               
            
           
           
               
               
               
            
               
                   
                 ARPE-19 
                 hTERT RPE-1 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 50 
                   
                 10 
                   
                 1 
                   
                 0.1 
                   
                 50 
                   
                 10 
                   
                 1 
                   
                 0.1 
                   
               
               
                 Sample Name 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 AD-953340.1 
                 18.6 
                 2.1 
                 2.7 
                 0.7 
                 28.5 
                 3.4 
                 106.5 
                 28.3 
                 40.1 
                 3.9 
                 25.2 
                 10.0 
                 38.7 
                 7.5 
                 52.2 
                 15.2 
               
               
                 AD-953336.1 
                 25.7 
                 1.4 
                 3.7 
                 0.9 
                 26.5 
                 0.5 
                 159.2 
                 61.6 
                 45.5 
                 5.2 
                 26.3 
                 8.1 
                 41.0 
                 8.9 
                 68.2 
                 8.3 
               
               
                 AD-953363.1 
                 17.3 
                 2.9 
                 3.9 
                 0.9 
                 33.5 
                 6.0 
                 57.0 
                 7.1 
                 37.2 
                 6.8 
                 24.6 
                 5.6 
                 38.1 
                 5.9 
                 39.4 
                 8.0 
               
               
                 AD-953338.1 
                 23.1 
                 2.7 
                 4.8 
                 1.8 
                 41.2 
                 8.4 
                 92.1 
                 21.1 
                 54.6 
                 7.9 
                 35.3 
                 7.5 
                 51.1 
                 1.4 
                 76.1 
                 10.8 
               
               
                 AD-953367.1 
                 25.6 
                 1.6 
                 5.1 
                 0.6 
                 39.3 
                 6.9 
                 55.8 
                 5.1 
                 62.2 
                 8.0 
                 33.2 
                 10.3 
                 61.2 
                 8.6 
                 49.4 
                 7.6 
               
               
                 AD-953337.1 
                 29.5 
                 4.0 
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                 3.4 
                 28.2 
                 2.0 
                 129.8 
                 30.5 
                 45.4 
                 8.6 
                 23.8 
                 4.5 
                 44.8 
                 3.6 
                 60.6 
                 8.0 
               
               
                 AD-953342.1 
                 18.9 
                 2.3 
                 5.6 
                 3.6 
                 31.6 
                 4.9 
                 149.8 
                 56.1 
                 35.2 
                 4.0 
                 28.4 
                 6.6 
                 39.0 
                 2.7 
                 73.7 
                 11.9 
               
               
                 AD-953350.1 
                 30.0 
                 3.6 
                 5.8 
                 4.1 
                 46.6 
                 8.3 
                 78.3 
                 22.9 
                 70.5 
                 10.7 
                 42.6 
                 14.8 
                 49.3 
                 14.2 
                 85.8 
                 3.8 
               
               
                 AD-953352.1 
                 28.5 
                 2.8 
                 6.1 
                 0.5 
                 41.5 
                 5.7 
                 113.4 
                 13.2 
                 52.8 
                 5.8 
                 40.1 
                 9.3 
                 53.0 
                 7.6 
                 72.9 
                 7.3 
               
               
                 AD-953368.1 
                 33.3 
                 1.6 
                 6.2 
                 1.0 
                 35.2 
                 2.3 
                 48.2 
                 3.6 
                 58.8 
                 5.7 
                 39.5 
                 11.2 
                 50.1 
                 7.2 
                 50.5 
                 2.2 
               
               
                 AD-953344.1 
                 17.8 
                 1.6 
                 6.5 
                 1.9 
                 38.5 
                 5.7 
                 66.5 
                 11.3 
                 29.5 
                 4.0 
                 28.9 
                 7.1 
                 49.6 
                 7.0 
                 75.8 
                 12.9 
               
               
                 AD-953339.1 
                 26.5 
                 4.9 
                 6.7 
                 5.5 
                 34.4 
                 6.2 
                 120.0 
                 30.4 
                 41.7 
                 3.6 
                 26.2 
                 3.7 
                 36.0 
                 9.0 
                 59.1 
                 7.0 
               
               
                 AD-953387.1 
                 20.6 
                 1.0 
                 6.9 
                 0.3 
                 40.9 
                 5.4 
                 64.9 
                 6.1 
                 21.0 
                 2.8 
                 31.3 
                 5.4 
                 69.7 
                 15.0 
                 57.4 
                 7.3 
               
               
                 AD-953375.1 
                 37.1 
                 2.8 
                 7.4 
                 1.1 
                 48.8 
                 6.5 
                 73.4 
                 3.9 
                 90.7 
                 19.7 
                 62.5 
                 8.1 
                 72.2 
                 11.9 
                 64.3 
                 16.3 
               
               
                 AD-953355.1 
                 42.7 
                 5.3 
                 7.5 
                 0.7 
                 62.2 
                 2.4 
                 137.9 
                 24.5 
                 43.9 
                 5.5 
                 40.6 
                 8.0 
                 52.6 
                 10.0 
                 67.1 
                 5.5 
               
               
                 AD-953341.1 
                 20.2 
                 2.9 
                 7.7 
                 4.5 
                 22.3 
                 3.3 
                 106.6 
                 21.7 
                 55.5 
                 5.5 
                 34.7 
                 7.7 
                 32.2 
                 8.3 
                 68.4 
                 5.8 
               
               
                 AD-953370.1 
                 36.8 
                 3.0 
                 7.8 
                 1.9 
                 55.5 
                 7.5 
                 72.3 
                 6.0 
                 38.0 
                 7.8 
                 26.9 
                 4.7 
                 63.9 
                 12.6 
                 51.9 
                 6.9 
               
               
                 AD-953362.1 
                 57.6 
                 4.3 
                 8.2 
                 1.1 
                 54.3 
                 8.3 
                 76.8 
                 3.6 
                 108.9 
                 11.3 
                 48.1 
                 10.1 
                 63.0 
                 11.0 
                 52.1 
                 10.4 
               
               
                 AD-953322.1 
                 59.6 
                 3.6 
                 8.2 
                 1.3 
                 61.4 
                 4.5 
                 105.4 
                 14.2 
                 103.5 
                 9.6 
                 55.4 
                 15.9 
                 66.5 
                 7.4 
                 78.4 
                 11.5 
               
               
                 AD-953332.1 
                 59.2 
                 3.3 
                 8.3 
                 1.3 
                 58.3 
                 3.8 
                 106.7 
                 20.6 
                 95.1 
                 15.8 
                 55.0 
                 9.1 
                 74.5 
                 1.5 
                 66.2 
                 8.9 
               
               
                 AD-953371.1 
                 41.1 
                 3.2 
                 8.5 
                 2.6 
                 49.1 
                 7.2 
                 64.1 
                 10.0 
                 75.1 
                 16.0 
                 51.2 
                 18.1 
                 60.0 
                 8.7 
                 53.0 
                 11.6 
               
               
                 AD-953331.1 
                 68.0 
                 1.2 
                 8.8 
                 1.7 
                 60.3 
                 5.5 
                 92.6 
                 24.7 
                 151.3 
                 18.2 
                 88.8 
                 33.3 
                 85.2 
                 21.0 
                 87.4 
                 5.6 
               
               
                 AD-953323.1 
                 66.8 
                 5.0 
                 9.1 
                 1.7 
                 64.2 
                 2.1 
                 109.8 
                 19.9 
                 93.6 
                 2.2 
                 53.0 
                 7.3 
                 74.7 
                 4.9 
                 77.0 
                 11.6 
               
               
                 AD-953351.1 
                 21.2 
                 2.3 
                 9.2 
                 9.5 
                 39.8 
                 6.9 
                 74.4 
                 8.0 
                 49.7 
                 3.2 
                 26.0 
                 2.5 
                 41.2 
                 11.0 
                 63.6 
                 8.2 
               
               
                 AD-953386.1 
                 31.8 
                 1.6 
                 9.3 
                 1.0 
                 65.3 
                 6.3 
                 87.4 
                 5.1 
                 38.7 
                 0.4 
                 50.4 
                 11.0 
                 82.9 
                 17.7 
                 67.9 
                 13.0 
               
               
                 AD-953394.1 
                 35.4 
                 2.0 
                 9.5 
                 5.1 
                 50.8 
                 5.3 
                 72.7 
                 3.3 
                 66.5 
                 16.5 
                 49.7 
                 10.5 
                 77.2 
                 14.7 
                 57.8 
                 21.7 
               
               
                 AD-953359.1 
                 36.4 
                 3.8 
                 9.7 
                 2.9 
                 46.9 
                 6.3 
                 72.9 
                 7.4 
                 74.8 
                 9.6 
                 46.2 
                 6.0 
                 63.9 
                 10.8 
                 50.7 
                 7.9 
               
               
                 AD-953329.1 
                 68.0 
                 10.2 
                 9.7 
                 1.7 
                 59.7 
                 1.6 
                 100.3 
                 22.8 
                 94.3 
                 7.1 
                 56.9 
                 16.4 
                 76.7 
                 10.0 
                 79.8 
                 9.0 
               
               
                 AD-953361.1 
                 45.2 
                 2.9 
                 10.4 
                 8.6 
                 53.6 
                 4.8 
                 68.4 
                 5.4 
                 78.6 
                 10.9 
                 50.2 
                 11.3 
                 68.6 
                 9.3 
                 47.8 
                 9.6 
               
               
                 AD-953319.1 
                 100.2 
                 2.8 
                 10.6 
                 1.4 
                 71.5 
                 10.3 
                 161.5 
                 76.4 
                 189.6 
                 19.4 
                 69.0 
                 22.5 
                 84.3 
                 4.7 
                 93.2 
                 18.2 
               
               
                 AD-953360.1 
                 96.2 
                 10.8 
                 10.7 
                 1.5 
                 49.6 
                 5.2 
                 76.7 
                 6.2 
                 140.9 
                 16.5 
                 69.1 
                 20.5 
                 82.4 
                 9.0 
                 54.9 
                 2.8 
               
               
                 AD-953324.1 
                 63.0 
                 2.8 
                 11.2 
                 4.8 
                 53.8 
                 4.5 
                 96.6 
                 27.2 
                 131.1 
                 18.6 
                 67.5 
                 16.9 
                 86.3 
                 18.2 
                 75.5 
                 18.1 
               
               
                 AD-953378.1 
                 57.9 
                 8.3 
                 11.5 
                 2.3 
                 72.2 
                 7.6 
                 92.4 
                 6.2 
                 47.1 
                 10.1 
                 55.3 
                 8.2 
                 85.7 
                 17.9 
                 60.5 
                 14.4 
               
               
                 AD-953369.1 
                 43.6 
                 4.7 
                 11.8 
                 6.0 
                 64.4 
                 10.3 
                 79.8 
                 5.1 
                 68.6 
                 9.7 
                 56.3 
                 9.1 
                 70.2 
                 5.4 
                 58.7 
                 14.7 
               
               
                 AD-953347.1 
                 77.6 
                 5.1 
                 11.9 
                 3.7 
                 63.3 
                 7.7 
                 66.5 
                 16.2 
                 112.3 
                 25.0 
                 62.1 
                 13.1 
                 62.8 
                 13.8 
                 76.4 
                 6.3 
               
               
                 AD-953365.1 
                 28.7 
                 4.1 
                 12.3 
                 3.5 
                 35.7 
                 4.9 
                 61.7 
                 7.9 
                 36.6 
                 7.3 
                 23.6 
                 5.0 
                 56.5 
                 3.9 
                 50.9 
                 4.6 
               
               
                 AD-953374.1 
                 10.7 
                 0.3 
                 12.3 
                 18.3 
                 35.8 
                 27.4 
                 33.8 
                 7.4 
                 30.0 
                 3.5 
                 33.2 
                 4.8 
                 39.2 
                 4.0 
                 46.2 
                 7.9 
               
               
                 AD-953384.1 
                 57.1 
                 2.9 
                 12.9 
                 4.8 
                 76.3 
                 9.0 
                 82.4 
                 5.1 
                 86.2 
                 5.2 
                 67.4 
                 3.8 
                 105.9 
                 23.9 
                 66.1 
                 13.2 
               
               
                 AD-953376.1 
                 57.8 
                 2.7 
                 12.9 
                 2.0 
                 81.7 
                 9.3 
                 94.3 
                 1.0 
                 69.2 
                 14.7 
                 73.1 
                 23.1 
                 96.7 
                 8.4 
                 70.3 
                 10.8 
               
               
                 AD-953354.1 
                 49.1 
                 5.5 
                 13.5 
                 5.6 
                 67.9 
                 5.6 
                 141.1 
                 30.9 
                 40.5 
                 6.7 
                 42.2 
                 10.8 
                 57.0 
                 6.1 
                 78.8 
                 9.6 
               
               
                 AD-953385.1 
                 65.0 
                 3.9 
                 13.5 
                 2.0 
                 79.8 
                 8.9 
                 97.1 
                 13.1 
                 115.8 
                 16.5 
                 107.5 
                 18.6 
                 124.6 
                 8.8 
                 71.9 
                 7.1 
               
               
                 AD-953346.1 
                 38.0 
                 3.2 
                 14.1 
                 11.9 
                 56.3 
                 4.7 
                 68.3 
                 13.8 
                 58.6 
                 8.1 
                 42.7 
                 7.4 
                 53.9 
                 11.6 
                 75.2 
                 5.3 
               
               
                 AD-953366.1 
                 28.1 
                 3.0 
                 14.3 
                 18.9 
                 47.6 
                 4.2 
                 72.4 
                 7.9 
                 47.0 
                 5.3 
                 32.5 
                 6.0 
                 40.4 
                 8.8 
                 61.7 
                 14.1 
               
               
                 AD-953382.1 
                 67.1 
                 5.3 
                 14.6 
                 3.6 
                 80.8 
                 7.7 
                 99.5 
                 6.7 
                 143.5 
                 30.8 
                 67.6 
                 18.2 
                 91.3 
                 11.9 
                 67.0 
                 12.6 
               
               
                 AD-953320.1 
                 65.2 
                 3.4 
                 14.7 
                 6.0 
                 69.8 
                 9.1 
                 139.3 
                 11.6 
                 121.6 
                 7.8 
                 55.2 
                 11.1 
                 97.9 
                 7.0 
                 92.3 
                 10.4 
               
               
                 AD-953379.1 
                 64.5 
                 8.5 
                 17.0 
                 5.4 
                 76.3 
                 3.5 
                 85.5 
                 6.7 
                 60.1 
                 12.9 
                 68.0 
                 26.1 
                 85.4 
                 3.5 
                 49.6 
                 12.0 
               
               
                 AD-953321.1 
                 66.2 
                 5.0 
                 17.1 
                 13.7 
                 58.7 
                 5.7 
                 125.7 
                 34.8 
                 111.0 
                 19.6 
                 59.2 
                 14.5 
                 72.7 
                 12.4 
                 80.3 
                 11.7 
               
               
                 AD-953377.1 
                 55.4 
                 3.9 
                 17.2 
                 8.0 
                 75.0 
                 6.1 
                 83.8 
                 4.1 
                 54.9 
                 8.5 
                 57.6 
                 9.1 
                 82.9 
                 6.1 
                 70.7 
                 12.3 
               
               
                 AD-953392.1 
                 88.8 
                 1.4 
                 17.5 
                 2.0 
                 90.9 
                 10.8 
                 96.0 
                 3.6 
                 125.6 
                 16.1 
                 102.0 
                 20.4 
                 117.0 
                 26.2 
                 88.2 
                 14.3 
               
               
                 AD-953373.1 
                 35.7 
                 3.9 
                 17.7 
                 12.7 
                 41.4 
                 3.3 
                 61.2 
                 9.4 
                 56.7 
                 9.0 
                 50.8 
                 5.4 
                 66.6 
                 5.1 
                 70.4 
                 14.3 
               
               
                 AD-953364.1 
                 22.5 
                 1.9 
                 18.1 
                 6.4 
                 35.7 
                 2.4 
                 53.4 
                 3.8 
                 21.2 
                 2.6 
                 20.1 
                 5.9 
                 30.5 
                 4.3 
                 45.0 
                 7.9 
               
               
                 AD-953330.1 
                 56.3 
                 6.5 
                 18.2 
                 8.1 
                 54.0 
                 2.8 
                 97.5 
                 23.3 
                 109.0 
                 14.5 
                 69.9 
                 11.8 
                 68.7 
                 8.6 
                 74.6 
                 9.6 
               
               
                 AD-953353.1 
                 30.9 
                 2.4 
                 19.3 
                 14.9 
                 51.1 
                 3.9 
                 145.6 
                 33.7 
                 59.1 
                 11.7 
                 45.4 
                 10.7 
                 57.3 
                 8.9 
                 80.5 
                 6.8 
               
               
                 AD-953343.1 
                 28.4 
                 1.6 
                 19.4 
                 24.7 
                 31.5 
                 2.1 
                 50.2 
                 12.1 
                 51.1 
                 7.7 
                 41.1 
                 4.8 
                 50.6 
                 3.0 
                 76.9 
                 6.2 
               
               
                 AD-953390.1 
                 82.4 
                 4.8 
                 19.8 
                 2.3 
                 92.7 
                 10.4 
                 103.4 
                 7.6 
                 132.1 
                 19.0 
                 96.0 
                 20.4 
                 114.6 
                 24.4 
                 80.3 
                 14.4 
               
               
                 AD-953345.1 
                 26.9 
                 4.4 
                 20.4 
                 16.6 
                 51.9 
                 6.3 
                 91.9 
                 13.0 
                 35.7 
                 10.4 
                 33.1 
                 6.6 
                 37.6 
                 9.9 
                 65.9 
                 6.8 
               
               
                 AD-953358.1 
                 30.5 
                 1.7 
                 20.6 
                 17.0 
                 40.7 
                 6.0 
                 66.2 
                 3.7 
                 67.1 
                 7.3 
                 46.2 
                 13.7 
                 62.8 
                 16.0 
                 52.4 
                 10.8 
               
               
                 AD-953383.1 
                 58.5 
                 4.0 
                 21.4 
                 9.2 
                 65.7 
                 5.7 
                 83.3 
                 3.1 
                 70.5 
                 9.4 
                 65.2 
                 10.6 
                 82.7 
                 14.0 
                 80.7 
                 8.9 
               
               
                 AD-953372.1 
                 34.3 
                 4.8 
                 24.0 
                 7.7 
                 45.9 
                 5.8 
                 65.7 
                 4.7 
                 52.6 
                 5.2 
                 42.1 
                 13.1 
                 65.9 
                 9.1 
                 54.7 
                 6.6 
               
               
                 AD-953328.1 
                 54.5 
                 3.9 
                 24.1 
                 19.0 
                 60.6 
                 5.7 
                 112.1 
                 3.8 
                 137.7 
                 50.8 
                 66.1 
                 5.8 
                 82.7 
                 13.1 
                 79.1 
                 7.2 
               
               
                 AD-953393.1 
                 42.8 
                 3.6 
                 25.9 
                 33.0 
                 63.6 
                 6.1 
                 87.9 
                 3.4 
                 49.7 
                 9.2 
                 56.8 
                 6.9 
                 81.0 
                 6.8 
                 74.0 
                 14.3 
               
               
                 AD-953307.1 
                 39.3 
                 2.0 
                 26.1 
                 2.3 
                 50.3 
                 3.0 
                 144.4 
                 30.6 
                 49.9 
                 4.0 
                 34.1 
                 7.3 
                 65.1 
                 4.0 
                 56.8 
                 9.9 
               
               
                 AD-953308.1 
                 36.9 
                 6.6 
                 26.3 
                 1.3 
                 50.9 
                 3.7 
                 136.2 
                 32.8 
                 30.3 
                 7.1 
                 24.2 
                 4.4 
                 53.4 
                 4.8 
                 42.3 
                 8.9 
               
               
                 AD-953327.1 
                 63.7 
                 9.2 
                 27.4 
                 29.5 
                 52.5 
                 1.5 
                 108.8 
                 24.5 
                 85.5 
                 42.1 
                 48.8 
                 10.7 
                 72.2 
                 10.9 
                 82.3 
                 7.2 
               
               
                 AD-953335.1 
                 77.1 
                 5.8 
                 28.3 
                 19.0 
                 53.0 
                 4.4 
                 115.1 
                 32.1 
                 144.1 
                 17.3 
                 72.8 
                 17.2 
                 84.8 
                 11.6 
                 95.4 
                 8.0 
               
               
                 AD-953414.1 
                 21.5 
                 1.7 
                 28.3 
                 1.6 
                 41.8 
                 4.6 
                 61.5 
                 8.3 
                 40.1 
                 2.5 
                 31.3 
                 7.9 
                 49.3 
                 12.3 
                 66.0 
                 17.8 
               
               
                 AD-953412.1 
                 16.3 
                 0.7 
                 28.4 
                 3.6 
                 33.1 
                 5.3 
                 65.1 
                 4.0 
                 37.5 
                 11.0 
                 35.3 
                 3.6 
                 35.8 
                 9.0 
                 70.7 
                 14.2 
               
               
                 AD-953411.1 
                 15.4 
                 2.0 
                 29.5 
                 3.7 
                 42.7 
                 5.0 
                 65.5 
                 6.0 
                 30.9 
                 9.0 
                 26.2 
                 4.3 
                 48.9 
                 7.9 
                 57.2 
                 13.3 
               
               
                 AD-953410.1 
                 16.4 
                 1.2 
                 29.6 
                 2.0 
                 44.7 
                 3.6 
                 68.0 
                 2.7 
                 26.2 
                 3.8 
                 26.4 
                 7.0 
                 49.8 
                 9.2 
                 55.9 
                 17.7 
               
               
                 AD-953408.1 
                 21.0 
                 1.4 
                 29.7 
                 2.3 
                 38.4 
                 4.8 
                 72.1 
                 6.4 
                 33.1 
                 4.7 
                 35.5 
                 2.9 
                 60.9 
                 14.6 
                 80.9 
                 23.6 
               
               
                 AD-953326.1 
                 53.8 
                 7.2 
                 30.2 
                 17.6 
                 50.4 
                 3.4 
                 115.3 
                 25.4 
                 115.2 
                 12.1 
                 59.7 
                 19.5 
                 77.5 
                 18.1 
                 83.0 
                 11.6 
               
               
                 AD-953300.1 
                 49.4 
                 5.2 
                 30.6 
                 1.7 
                 52.2 
                 5.5 
                 176.7 
                 31.5 
                 51.7 
                 16.4 
                 44.1 
                 6.6 
                 65.9 
                 17.3 
                 39.7 
                 7.3 
               
               
                 AD-953389.1 
                 90.9 
                 7.3 
                 31.6 
                 16.2 
                 93.6 
                 8.0 
                 99.4 
                 7.4 
                 144.1 
                 18.2 
                 126.7 
                 8.2 
                 114.4 
                 15.0 
                 93.8 
                 22.2 
               
               
                 AD-953415.1 
                 23.3 
                 1.8 
                 32.0 
                 1.8 
                 41.3 
                 3.0 
                 62.8 
                 8.8 
                 65.9 
                 6.6 
                 52.5 
                 5.9 
                 53.3 
                 18.2 
                 70.5 
                 19.8 
               
               
                 AD-953309.1 
                 42.1 
                 1.6 
                 32.3 
                 3.0 
                 69.9 
                 2.0 
                 148.4 
                 9.6 
                 40.6 
                 7.2 
                 42.0 
                 7.1 
                 91.4 
                 19.0 
                 48.5 
                 11.7 
               
               
                 AD-953391.1 
                 78.3 
                 7.4 
                 32.9 
                 32.3 
                 86.1 
                 7.2 
                 95.6 
                 4.9 
                 108.7 
                 4.5 
                 93.3 
                 10.9 
                 119.0 
                 24.5 
                 87.2 
                 15.4 
               
               
                 AD-953395.1 
                 53.9 
                 5.2 
                 33.3 
                 21.8 
                 70.2 
                 7.5 
                 87.9 
                 3.9 
                 42.9 
                 5.1 
                 49.4 
                 8.8 
                 83.2 
                 6.3 
                 62.2 
                 11.3 
               
               
                 AD-953303.1 
                 48.8 
                 2.8 
                 34.0 
                 9.2 
                 44.4 
                 3.8 
                 133.6 
                 33.0 
                 69.9 
                 7.6 
                 42.4 
                 3.8 
                 62.7 
                 7.0 
                 54.4 
                 12.6 
               
               
                 AD-953405.1 
                 37.6 
                 9.8 
                 34.2 
                 5.3 
                 42.1 
                 8.8 
                 60.5 
                 3.6 
                 58.3 
                 17.4 
                 37.6 
                 7.0 
                 59.1 
                 16.6 
                 78.3 
                 6.9 
               
               
                 AD-953305.1 
                 52.0 
                 6.9 
                 34.8 
                 1.6 
                 56.5 
                 5.1 
                 108.4 
                 23.2 
                 73.0 
                 10.3 
                 41.9 
                 6.0 
                 68.4 
                 9.8 
                 69.3 
                 6.9 
               
               
                 AD-953380.1 
                 63.5 
                 8.0 
                 35.1 
                 28.6 
                 72.8 
                 5.2 
                 84.6 
                 3.4 
                 54.0 
                 2.4 
                 49.6 
                 9.1 
                 82.2 
                 16.6 
                 54.1 
                 9.0 
               
               
                 AD-953349.1 
                 62.9 
                 2.8 
                 35.3 
                 4.1 
                 61.4 
                 6.2 
                 71.3 
                 23.0 
                 106.7 
                 20.9 
                 64.7 
                 14.2 
                 67.5 
                 26.3 
                 92.3 
                 7.5 
               
               
                 AD-953381.1 
                 66.3 
                 2.9 
                 35.5 
                 22.1 
                 83.5 
                 7.5 
                 99.8 
                 6.3 
                 80.8 
                 10.0 
                 67.8 
                 8.9 
                 99.2 
                 18.4 
                 76.9 
                 21.1 
               
               
                 AD-953318.1 
                 73.1 
                 4.0 
                 37.6 
                 32.2 
                 63.4 
                 2.6 
                 198.1 
                 91.7 
                 132.1 
                 16.9 
                 66.1 
                 30.7 
                 81.7 
                 17.2 
                 88.7 
                 3.1 
               
               
                 AD-953348.1 
                 46.6 
                 2.7 
                 38.4 
                 9.6 
                 52.5 
                 5.4 
                 136.3 
                 31.4 
                 46.5 
                 14.1 
                 38.9 
                 9.4 
                 48.8 
                 9.2 
                 74.5 
                 10.8 
               
               
                 AD-953409.1 
                 24.1 
                 1.4 
                 39.4 
                 2.8 
                 46.7 
                 7.0 
                 76.5 
                 7.7 
                 32.7 
                 3.5 
                 28.5 
                 4.8 
                 59.1 
                 9.8 
                 65.9 
                 21.4 
               
               
                 AD-953306.1 
                 69.9 
                 8.3 
                 39.7 
                 4.7 
                 62.4 
                 5.2 
                 134.9 
                 32.7 
                 127.5 
                 9.5 
                 69.9 
                 20.8 
                 84.4 
                 4.7 
                 44.9 
                 5.0 
               
               
                 AD-953316.1 
                 59.6 
                 4.5 
                 40.3 
                 3.9 
                 54.4 
                 3.5 
                 94.5 
                 8.4 
                 129.3 
                 20.3 
                 58.5 
                 9.4 
                 72.2 
                 12.8 
                 58.6 
                 15.8 
               
               
                 AD-953325.1 
                 69.2 
                 6.7 
                 41.8 
                 24.8 
                 68.9 
                 7.7 
                 153.7 
                 53.1 
                 112.9 
                 25.0 
                 66.6 
                 11.7 
                 76.9 
                 13.0 
                 70.1 
                 9.9 
               
               
                 AD-953299.1 
                 64.9 
                 6.3 
                 42.3 
                 2.6 
                 70.3 
                 5.0 
                 164.5 
                 59.7 
                 67.8 
                 20.4 
                 65.1 
                 16.9 
                 83.0 
                 9.2 
                 50.0 
                 7.5 
               
               
                 AD-953416.1 
                 29.1 
                 3.7 
                 42.4 
                 3.1 
                 41.8 
                 3.8 
                 53.8 
                 4.6 
                 79.4 
                 10.1 
                 51.0 
                 9.1 
                 57.1 
                 5.1 
                 63.4 
                 7.3 
               
               
                 AD-953315.1 
                 62.1 
                 5.3 
                 42.6 
                 1.1 
                 55.8 
                 2.8 
                 95.3 
                 27.0 
                 134.9 
                 23.0 
                 84.8 
                 6.7 
                 73.0 
                 6.5 
                 58.6 
                 17.0 
               
               
                 AD-953314.1 
                 55.4 
                 5.5 
                 42.6 
                 2.8 
                 55.8 
                 3.3 
                 115.4 
                 15.1 
                 106.7 
                 3.2 
                 62.9 
                 8.0 
                 81.7 
                 8.5 
                 53.3 
                 21.1 
               
               
                 AD-953298.1 
                 65.3 
                 4.3 
                 44.0 
                 2.2 
                 67.5 
                 6.6 
                 165.9 
                 13.3 
                 60.5 
                 6.8 
                 46.5 
                 9.6 
                 89.0 
                 8.6 
                 57.6 
                 7.6 
               
               
                 AD-953406.1 
                 27.2 
                 1.4 
                 44.5 
                 5.0 
                 58.8 
                 5.8 
                 84.3 
                 2.0 
                 50.0 
                 4.6 
                 37.8 
                 4.4 
                 74.7 
                 8.6 
                 75.2 
                 29.3 
               
               
                 AD-953399.1 
                 32.1 
                 2.3 
                 45.5 
                 1.4 
                 44.3 
                 3.6 
                 64.6 
                 2.8 
                 84.3 
                 9.4 
                 43.2 
                 8.2 
                 80.6 
                 5.7 
                 79.7 
                 20.7 
               
               
                 AD-953333.1 
                 54.7 
                 4.9 
                 45.7 
                 17.9 
                 63.1 
                 3.7 
                 139.5 
                 14.5 
                 104.8 
                 10.4 
                 50.6 
                 15.6 
                 65.9 
                 13.4 
                 66.1 
                 14.1 
               
               
                 AD-953313.1 
                 57.3 
                 3.7 
                 45.9 
                 2.5 
                 64.6 
                 2.4 
                 107.6 
                 22.5 
                 81.2 
                 19.1 
                 61.7 
                 8.4 
                 89.7 
                 4.0 
                 83.2 
                 4.5 
               
               
                 AD-953302.1 
                 49.5 
                 2.8 
                 47.0 
                 5.0 
                 61.7 
                 3.9 
                 108.3 
                 31.0 
                 41.6 
                 11.9 
                 48.7 
                 7.2 
                 57.5 
                 8.9 
                 68.8 
                 4.8 
               
               
                 AD-953317.1 
                 76.9 
                 5.3 
                 50.0 
                 3.1 
                 72.6 
                 9.3 
                 145.3 
                 34.8 
                 77.9 
                 18.1 
                 60.9 
                 12.4 
                 71.3 
                 9.7 
                 50.4 
                 14.7 
               
               
                 AD-953357.1 
                 61.0 
                 5.5 
                 50.3 
                 33.1 
                 70.6 
                 8.6 
                 94.4 
                 5.1 
                 70.4 
                 16.9 
                 59.5 
                 19.7 
                 99.6 
                 27.9 
                 52.4 
                 8.5 
               
               
                 AD-953301.1 
                 62.2 
                 7.8 
                 50.5 
                 5.6 
                 82.8 
                 5.7 
                 193.0 
                 33.0 
                 47.3 
                 16.7 
                 38.2 
                 3.8 
                 63.5 
                 8.8 
                 53.8 
                 10.8 
               
               
                 AD-953304.1 
                 60.9 
                 6.6 
                 51.4 
                 2.2 
                 75.4 
                 1.9 
                 133.7 
                 36.1 
                 133.7 
                 5.8 
                 89.6 
                 12.1 
                 95.5 
                 8.0 
                 65.9 
                 8.4 
               
               
                 AD-953297.1 
                 77.5 
                 3.2 
                 52.2 
                 4.2 
                 74.9 
                 4.8 
                 142.3 
                 32.5 
                 118.2 
                 19.7 
                 85.8 
                 5.2 
                 99.1 
                 11.6 
                 59.7 
                 8.0 
               
               
                 AD-953388.1 
                 80.1 
                 5.6 
                 53.7 
                 40.5 
                 91.0 
                 9.7 
                 95.9 
                 10.1 
                 139.5 
                 8.4 
                 89.7 
                 6.8 
                 107.9 
                 17.8 
                 98.0 
                 21.3 
               
               
                 AD-953407.1 
                 37.2 
                 4.3 
                 53.9 
                 9.4 
                 47.8 
                 6.2 
                 72.1 
                 4.3 
                 61.2 
                 7.6 
                 43.4 
                 16.4 
                 66.1 
                 17.3 
                 74.5 
                 6.9 
               
               
                 AD-953397.1 
                 56.1 
                 5.0 
                 57.1 
                 3.8 
                 58.1 
                 9.9 
                 77.8 
                 5.1 
                 96.4 
                 13.5 
                 52.9 
                 9.6 
                 94.9 
                 13.8 
                 76.0 
                 9.4 
               
               
                 AD-953398.1 
                 47.8 
                 2.1 
                 57.4 
                 6.6 
                 51.1 
                 5.3 
                 71.6 
                 2.3 
                 62.1 
                 7.0 
                 51.9 
                 7.5 
                 99.5 
                 13.7 
                 93.8 
                 13.7 
               
               
                 AD-953396.1 
                 52.3 
                 7.4 
                 59.5 
                 5.6 
                 63.4 
                 6.2 
                 86.9 
                 5.8 
                 85.3 
                 10.0 
                 52.7 
                 5.7 
                 98.7 
                 8.2 
                 101.8 
                 11.6 
               
               
                 AD-953356.1 
                 80.6 
                 1.8 
                 63.1 
                 11.3 
                 82.1 
                 13.5 
                 119.0 
                 27.2 
                 93.5 
                 11.4 
                 65.8 
                 9.2 
                 76.8 
                 20.8 
                 61.8 
                 12.3 
               
               
                 AD-953422.1 
                 47.6 
                 4.2 
                 63.3 
                 7.6 
                 189.1 
                 56.5 
                 87.2 
                 3.9 
                 56.5 
                 5.7 
                 58.9 
                 8.6 
                 36.4 
                 2.3 
                 74.3 
                 18.0 
               
               
                 AD-953413.1 
                 56.5 
                 4.9 
                 64.0 
                 8.2 
                 68.9 
                 4.5 
                 95.5 
                 9.7 
                 78.1 
                 8.7 
                 72.4 
                 12.0 
                 81.1 
                 9.4 
                 90.4 
                 15.6 
               
               
                 AD-953294.1 
                 97.1 
                 15.2 
                 64.2 
                 4.2 
                 77.3 
                 15.5 
                 96.7 
                 15.6 
                 96.8 
                 35.0 
                 71.6 
                 5.9 
                 76.3 
                 3.3 
                 69.9 
                 12.0 
               
               
                 AD-953421.1 
                 53.2 
                 6.7 
                 65.0 
                 2.9 
                 197.8 
                 29.8 
                 101.0 
                 7.9 
                 102.0 
                 13.5 
                 65.6 
                 7.9 
                 49.4 
                 12.2 
                 94.1 
                 8.4 
               
               
                 AD-953310.1 
                 117.3 
                 11.7 
                 66.7 
                 16.2 
                 93.9 
                 3.2 
                 148.4 
                 45.0 
                 149.3 
                 31.4 
                 91.4 
                 14.3 
                 97.9 
                 3.5 
                 72.3 
                 17.0 
               
               
                 AD-953296.1 
                 103.9 
                 2.9 
                 67.6 
                 5.3 
                 85.2 
                 8.1 
                 137.2 
                 17.9 
                 187.5 
                 42.8 
                 110.2 
                 4.6 
                 116.2 
                 10.5 
                 56.8 
                 9.4 
               
               
                 AD-953402.1 
                 55.1 
                 2.2 
                 67.6 
                 4.0 
                 63.8 
                 6.1 
                 84.1 
                 7.6 
                 83.2 
                 19.9 
                 75.6 
                 8.7 
                 89.0 
                 23.0 
                 77.5 
                 11.6 
               
               
                 AD-953312.1 
                 86.0 
                 14.3 
                 71.1 
                 4.1 
                 74.3 
                 3.3 
                 145.1 
                 57.4 
                 171.9 
                 22.0 
                 84.6 
                 5.5 
                 100.5 
                 13.7 
                 94.5 
                 9.6 
               
               
                 AD-953295.1 
                 94.5 
                 4.7 
                 71.6 
                 3.7 
                 83.7 
                 11.4 
                 136.9 
                 20.4 
                 122.9 
                 21.2 
                 90.4 
                 14.2 
                 85.2 
                 26.5 
                 64.3 
                 18.0 
               
               
                 AD-953420.1 
                 58.3 
                 2.3 
                 72.8 
                 7.3 
                 177.1 
                 37.4 
                 91.6 
                 3.5 
                 74.6 
                 3.6 
                 60.0 
                 6.7 
                 52.2 
                 7.9 
                 96.5 
                 11.0 
               
               
                 AD-953423.1 
                 47.1 
                 3.4 
                 73.0 
                 14.3 
                 215.7 
                 13.2 
                 93.0 
                 6.7 
                 90.7 
                 6.7 
                 64.9 
                 9.2 
                 43.6 
                 7.2 
                 89.1 
                 15.2 
               
               
                 AD-953403.1 
                 62.9 
                 12.6 
                 73.9 
                 5.6 
                 58.5 
                 5.9 
                 77.8 
                 6.5 
                 102.6 
                 12.5 
                 62.1 
                 6.0 
                 96.2 
                 14.6 
                 75.4 
                 7.3 
               
               
                 AD-953400.1 
                 52.1 
                 2.7 
                 74.8 
                 10.9 
                 58.9 
                 4.4 
                 78.3 
                 6.7 
                 83.2 
                 11.5 
                 48.5 
                 14.9 
                 86.8 
                 26.5 
                 84.6 
                 8.4 
               
               
                 AD-953404.1 
                 73.3 
                 4.0 
                 76.2 
                 8.8 
                 72.0 
                 3.4 
                 92.1 
                 3.5 
                 133.1 
                 19.8 
                 70.7 
                 8.1 
                 103.8 
                 14.5 
                 97.1 
                 12.4 
               
               
                 AD-953334.1 
                 59.9 
                 3.8 
                 76.5 
                 27.3 
                 57.6 
                 1.4 
                 115.3 
                 6.2 
                 178.1 
                 16.6 
                 89.4 
                 25.1 
                 78.2 
                 17.1 
                 98.1 
                 8.5 
               
               
                 AD-953418.1 
                 57.2 
                 3.7 
                 79.6 
                 12.5 
                 81.6 
                 6.1 
                 92.3 
                 4.1 
                 100.0 
                 20.4 
                 57.2 
                 11.1 
                 70.4 
                 11.1 
                 79.1 
                 4.1 
               
               
                 AD-953401.1 
                 61.5 
                 3.7 
                 81.6 
                 4.1 
                 78.6 
                 9.2 
                 96.9 
                 10.8 
                 93.0 
                 8.4 
                 67.9 
                 27.9 
                 105.6 
                 5.0 
                 84.0 
                 6.1 
               
               
                 AD-953417.1 
                 57.8 
                 1.8 
                 82.5 
                 1.5 
                 84.7 
                 11.1 
                 89.1 
                 6.1 
                 86.4 
                 8.4 
                 65.7 
                 14.4 
                 69.9 
                 7.2 
                 82.8 
                 8.5 
               
               
                 AD-953311.1 
                 113.2 
                 5.8 
                 91.3 
                 6.1 
                 93.9 
                 8.2 
                 108.7 
                 25.4 
                 156.0 
                 13.3 
                 86.4 
                 10.1 
                 92.6 
                 5.7 
                 77.0 
                 15.2 
               
               
                 AD-953419.1 
                 74.7 
                 3.6 
                 94.8 
                 6.4 
                 93.2 
                 5.5 
                 92.2 
                 5.3 
                 85.9 
                 13.4 
                 57.3 
                 8.4 
                 84.5 
                 16.8 
                 76.8 
                 7.9 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6C 
               
             
            
               
                   
               
               
                 VEGF-A endogenous in vitro multi-dose screen with one set of exemplary human VEGF-A siRNAs 
               
            
           
           
               
               
               
            
               
                   
                 ARPE-19 
                 hTERT RPE-1 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 50 
                   
                 10 
                   
                 1 
                   
                 0.1 
                   
                 50 
                   
                 10 
                   
                 1 
                   
                 0.1 
                   
               
               
                 Sample Name 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
                 nM 
                 StDev 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 AD-953504.1 
                 17.3 
                 0.6 
                 19.8 
                 5.4 
                 48.7 
                 32.4 
                 56.5 
                 9.3 
                 19.9 
                 3.2 
                 22.2 
                 2.8 
                 61.7 
                 21.8 
                 65.7 
                 15.9 
               
               
                 AD-953481.1 
                 33.7 
                 2.2 
                 28.1 
                 2.4 
                 60.4 
                 3.8 
                 72.8 
                 1.5 
                 42.5 
                 9.2 
                 25.3 
                 3.5 
                 68.8 
                 28.1 
                 78.2 
                 28.1 
               
               
                 AD-953472.1 
                 31.3 
                 1.6 
                 30.1 
                 1.2 
                 54.1 
                 4.4 
                 80.0 
                 6.6 
                 45.9 
                 7.1 
                 30.6 
                 2.9 
                 64.9 
                 14.9 
                 91.0 
                 18.4 
               
               
                 AD-953517.1 
                 29.5 
                 3.2 
                 30.3 
                 1.4 
                 45.6 
                 5.1 
                 74.4 
                 4.9 
                 37.6 
                 4.9 
                 36.3 
                 7.9 
                 69.4 
                 18.5 
                 74.5 
                 10.3 
               
               
                 AD-953471.1 
                 33.4 
                 0.9 
                 30.5 
                 2.2 
                 47.1 
                 5.1 
                 87.8 
                 15.3 
                 39.7 
                 11.2 
                 28.0 
                 5.0 
                 68.2 
                 12.1 
                 77.6 
                 14.1 
               
               
                 AD-953493.1 
                 46.0 
                 10.0 
                 33.3 
                 4.0 
                 64.9 
                 9.0 
                 81.1 
                 4.1 
                 24.9 
                 5.5 
                 22.5 
                 2.5 
                 50.8 
                 23.2 
                 54.0 
                 12.0 
               
               
                 AD-953498.1 
                 46.8 
                 3.8 
                 34.5 
                 1.5 
                 55.9 
                 5.9 
                 76.7 
                 8.9 
                 43.1 
                 2.2 
                 31.2 
                 4.9 
                 64.8 
                 16.8 
                 78.0 
                 19.6 
               
               
                 AD-953467.1 
                 42.3 
                 6.8 
                 34.6 
                 3.5 
                 59.8 
                 14.0 
                 78.3 
                 11.6 
                 42.8 
                 3.2 
                 31.1 
                 8.9 
                 56.9 
                 9.0 
                 94.4 
                 12.2 
               
               
                 AD-953545.1 
                 31.2 
                 0.8 
                 35.4 
                 8.1 
                 48.5 
                 6.1 
                 73.7 
                 7.0 
                 55.3 
                 8.9 
                 42.0 
                 8.6 
                 85.9 
                 16.6 
                 79.4 
                 7.1 
               
               
                 AD-953466.1 
                 53.7 
                 2.9 
                 36.9 
                 3.0 
                 61.5 
                 20.5 
                 74.1 
                 8.9 
                 62.8 
                 5.4 
                 39.6 
                 3.4 
                 65.3 
                 7.7 
                 103.3 
                 34.2 
               
               
                 AD-953494.1 
                 49.2 
                 2.9 
                 38.4 
                 1.6 
                 66.3 
                 7.1 
                 85.6 
                 4.5 
                 32.7 
                 3.4 
                 26.5 
                 8.0 
                 46.1 
                 7.1 
                 45.7 
                 6.8 
               
               
                 AD-953470.1 
                 66.5 
                 2.0 
                 40.5 
                 3.4 
                 63.8 
                 13.5 
                 74.9 
                 5.0 
                 56.4 
                 9.5 
                 34.8 
                 7.3 
                 64.6 
                 9.9 
                 105.6 
                 20.0 
               
               
                 AD-953473.1 
                 59.2 
                 2.9 
                 42.3 
                 5.7 
                 61.7 
                 4.1 
                 80.9 
                 4.5 
                 72.8 
                 11.9 
                 44.2 
                 3.0 
                 77.6 
                 25.2 
                 110.0 
                 27.1 
               
               
                 AD-953474.1 
                 61.5 
                 7.9 
                 42.4 
                 1.6 
                 72.9 
                 7.5 
                 86.4 
                 5.6 
                 63.8 
                 4.5 
                 48.8 
                 2.4 
                 85.5 
                 29.3 
                 107.1 
                 18.8 
               
               
                 AD-953480.1 
                 41.7 
                 3.9 
                 43.3 
                 1.9 
                 72.9 
                 5.0 
                 91.6 
                 11.4 
                 47.1 
                 9.2 
                 47.2 
                 16.2 
                 77.8 
                 38.4 
                 93.8 
                 27.0 
               
               
                 AD-953503.1 
                 56.4 
                 2.3 
                 43.9 
                 4.9 
                 59.9 
                 7.6 
                 88.7 
                 10.2 
                 44.2 
                 13.0 
                 57.5 
                 9.7 
                 90.0 
                 9.8 
                 83.2 
                 11.7 
               
               
                 AD-953478.1 
                 55.1 
                 8.7 
                 44.3 
                 4.1 
                 64.1 
                 4.5 
                 83.3 
                 8.7 
                 38.9 
                 3.2 
                 52.3 
                 22.9 
                 70.3 
                 23.4 
                 78.1 
                 9.5 
               
               
                 AD-953540.1 
                 29.4 
                 2.2 
                 44.6 
                 10.3 
                 60.9 
                 5.7 
                 94.9 
                 10.3 
                 23.4 
                 6.6 
                 22.7 
                 7.9 
                 59.7 
                 12.0 
                 81.5 
                 3.3 
               
               
                 AD-953500.1 
                 46.3 
                 10.0 
                 45.8 
                 4.0 
                 70.6 
                 10.0 
                 91.2 
                 4.6 
                 30.4 
                 4.6 
                 31.2 
                 1.2 
                 79.7 
                 16.0 
                 80.1 
                 10.5 
               
               
                 AD-953476.1 
                 45.9 
                 6.5 
                 46.7 
                 2.3 
                 78.7 
                 3.7 
                 91.8 
                 4.7 
                 40.4 
                 4.4 
                 44.7 
                 10.0 
                 84.2 
                 14.5 
                 118.2 
                 21.3 
               
               
                 AD-953492.1 
                 61.2 
                 1.9 
                 47.1 
                 3.8 
                 71.8 
                 6.2 
                 85.2 
                 8.4 
                 58.2 
                 7.0 
                 44.7 
                 4.1 
                 79.6 
                 20.6 
                 73.1 
                 13.5 
               
               
                 AD-953495.1 
                 60.7 
                 3.5 
                 47.4 
                 3.9 
                 64.3 
                 15.3 
                 84.0 
                 5.7 
                 54.3 
                 7.7 
                 39.5 
                 8.5 
                 69.7 
                 9.1 
                 68.8 
                 26.1 
               
               
                 AD-953497.1 
                 55.5 
                 1.6 
                 47.9 
                 5.1 
                 65.9 
                 9.6 
                 89.9 
                 8.5 
                 61.5 
                 11.8 
                 45.8 
                 11.0 
                 81.4 
                 21.9 
                 86.5 
                 11.4 
               
               
                 AD-953535.1 
                 52.1 
                 10.8 
                 48.3 
                 10.8 
                 56.0 
                 5.5 
                 76.1 
                 4.9 
                 52.6 
                 8.9 
                 42.6 
                 8.1 
                 94.1 
                 22.4 
                 100.5 
                 4.2 
               
               
                 AD-953505.1 
                 60.3 
                 6.1 
                 48.4 
                 2.0 
                 64.4 
                 2.4 
                 94.7 
                 10.5 
                 54.9 
                 8.8 
                 59.1 
                 7.3 
                 104.2 
                 19.2 
                 88.3 
                 14.3 
               
               
                 AD-953524.1 
                 57.5 
                 1.2 
                 48.9 
                 2.1 
                 50.9 
                 20.8 
                 93.7 
                 6.7 
                 44.2 
                 4.8 
                 51.2 
                 8.8 
                 68.3 
                 25.3 
                 64.5 
                 14.1 
               
               
                 AD-953475.1 
                 55.7 
                 2.1 
                 49.6 
                 3.8 
                 69.2 
                 7.9 
                 83.9 
                 5.0 
                 54.2 
                 11.0 
                 41.8 
                 8.6 
                 87.2 
                 24.9 
                 105.6 
                 23.8 
               
               
                 AD-953491.1 
                 68.9 
                 9.7 
                 49.9 
                 4.6 
                 69.4 
                 2.7 
                 92.7 
                 10.9 
                 54.5 
                 8.4 
                 54.9 
                 20.8 
                 72.8 
                 15.0 
                 73.5 
                 16.3 
               
               
                 AD-953436.1 
                 96.6 
                 1.6 
                 50.6 
                 2.1 
                 63.1 
                 13.9 
                 80.4 
                 4.8 
                 72.6 
                 8.9 
                 72.9 
                 2.2 
                 108.8 
                 9.8 
                 67.6 
                 24.6 
               
               
                 AD-953502.1 
                 62.8 
                 9.4 
                 50.8 
                 3.8 
                 74.9 
                 6.4 
                 87.0 
                 13.4 
                 52.2 
                 4.0 
                 42.0 
                 8.7 
                 75.8 
                 17.7 
                 49.4 
                 4.5 
               
               
                 AD-953461.1 
                 61.7 
                 5.8 
                 51.1 
                 5.0 
                 74.3 
                 17.8 
                 74.6 
                 2.7 
                 66.9 
                 10.6 
                 62.6 
                 8.7 
                 78.9 
                 3.2 
                 94.0 
                 19.6 
               
               
                 AD-953544.1 
                 42.2 
                 3.8 
                 51.3 
                 8.4 
                 61.5 
                 6.6 
                 89.4 
                 2.2 
                 47.4 
                 9.0 
                 45.8 
                 10.0 
                 83.1 
                 19.6 
                 92.4 
                 16.0 
               
               
                 AD-953462.1 
                 64.6 
                 3.0 
                 51.5 
                 5.9 
                 84.5 
                 16.8 
                 80.3 
                 6.5 
                 53.0 
                 14.9 
                 48.2 
                 11.8 
                 84.0 
                 18.2 
                 114.8 
                 20.3 
               
               
                 AD-953496.1 
                 52.0 
                 5.9 
                 51.6 
                 5.0 
                 79.2 
                 5.6 
                 89.8 
                 6.5 
                 55.1 
                 5.5 
                 58.3 
                 4.8 
                 97.3 
                 22.7 
                 83.9 
                 25.2 
               
               
                 AD-953516.1 
                 59.7 
                 7.4 
                 51.9 
                 2.3 
                 71.2 
                 11.2 
                 93.4 
                 13.2 
                 49.8 
                 14.2 
                 43.5 
                 13.2 
                 86.5 
                 9.4 
                 78.4 
                 11.1 
               
               
                 AD-953483.1 
                 61.6 
                 4.6 
                 52.0 
                 2.3 
                 69.5 
                 17.6 
                 92.7 
                 9.0 
                 52.2 
                 7.3 
                 47.3 
                 13.2 
                 99.1 
                 21.9 
                 94.1 
                 22.9 
               
               
                 AD-953499.1 
                 64.5 
                 8.2 
                 52.7 
                 3.2 
                 71.1 
                 11.7 
                 105.8 
                 6.7 
                 70.7 
                 10.1 
                 46.6 
                 5.0 
                 90.6 
                 15.3 
                 85.6 
                 14.6 
               
               
                 AD-953541.1 
                 48.8 
                 10.7 
                 53.1 
                 12.9 
                 55.9 
                 6.0 
                 90.1 
                 9.3 
                 32.7 
                 6.8 
                 31.2 
                 3.2 
                 68.9 
                 24.2 
                 79.9 
                 10.0 
               
               
                 AD-953538.1 
                 38.4 
                 5.2 
                 54.1 
                 10.1 
                 68.1 
                 9.3 
                 99.0 
                 6.5 
                 32.1 
                 8.8 
                 29.3 
                 3.2 
                 89.4 
                 17.2 
                 88.1 
                 7.9 
               
               
                 AD-953430.1 
                 85.4 
                 7.5 
                 54.7 
                 2.9 
                 90.8 
                 20.1 
                 82.8 
                 2.9 
                 57.6 
                 4.4 
                 55.1 
                 11.1 
                 80.2 
                 14.7 
                 65.6 
                 13.5 
               
               
                 AD-953485.1 
                 66.8 
                 2.1 
                 54.9 
                 3.8 
                 84.8 
                 6.5 
                 90.0 
                 2.2 
                 39.0 
                 8.2 
                 42.3 
                 5.6 
                 66.0 
                 8.7 
                 95.6 
                 22.6 
               
               
                 AD-953468.1 
                 65.7 
                 3.5 
                 55.1 
                 2.6 
                 86.4 
                 11.6 
                 97.3 
                 11.9 
                 50.2 
                 8.8 
                 41.0 
                 3.6 
                 88.9 
                 21.6 
                 108.5 
                 25.1 
               
               
                 AD-953444.1 
                 63.2 
                 2.2 
                 55.3 
                 3.8 
                 81.6 
                 15.3 
                 87.3 
                 9.0 
                 55.0 
                 5.1 
                 76.5 
                 12.6 
                 108.8 
                 22.7 
                 70.4 
                 18.1 
               
               
                 AD-953460.1 
                 65.6 
                 10.0 
                 55.6 
                 3.2 
                 85.2 
                 10.4 
                 83.1 
                 6.6 
                 56.8 
                 15.0 
                 46.3 
                 6.9 
                 87.1 
                 6.8 
                 121.0 
                 12.9 
               
               
                 AD-953539.1 
                 67.0 
                 8.5 
                 56.1 
                 11.5 
                 62.2 
                 2.9 
                 97.3 
                 4.3 
                 47.1 
                 5.3 
                 30.5 
                 6.1 
                 65.5 
                 15.9 
                 89.6 
                 10.6 
               
               
                 AD-953484.1 
                 60.1 
                 16.2 
                 56.6 
                 5.9 
                 86.0 
                 4.8 
                 94.4 
                 6.4 
                 41.3 
                 9.9 
                 46.9 
                 10.8 
                 81.1 
                 26.2 
                 97.8 
                 20.4 
               
               
                 AD-953457.1 
                 69.0 
                 26.0 
                 57.8 
                 5.5 
                 79.7 
                 22.5 
                 78.0 
                 8.4 
                 96.5 
                 61.4 
                 42.8 
                 3.1 
                 85.0 
                 11.8 
                 84.4 
                 28.0 
               
               
                 AD-953459.1 
                 67.3 
                 9.8 
                 57.9 
                 4.0 
                 82.0 
                 15.1 
                 85.5 
                 2.9 
                 66.1 
                 9.8 
                 52.4 
                 5.4 
                 90.4 
                 4.6 
                 111.4 
                 7.6 
               
               
                 AD-953437.1 
                 74.6 
                 5.0 
                 58.6 
                 4.4 
                 87.7 
                 20.7 
                 84.6 
                 6.4 
                 53.5 
                 5.2 
                 70.2 
                 20.0 
                 89.8 
                 7.7 
                 77.7 
                 21.8 
               
               
                 AD-953458.1 
                 70.7 
                 8.8 
                 59.3 
                 2.4 
                 81.8 
                 21.2 
                 79.2 
                 5.7 
                 75.8 
                 13.1 
                 47.7 
                 2.1 
                 97.0 
                 12.3 
                 107.7 
                 31.1 
               
               
                 AD-953453.1 
                 69.9 
                 3.5 
                 59.5 
                 4.3 
                 74.0 
                 17.2 
                 84.4 
                 11.6 
                 61.1 
                 9.9 
                 59.0 
                 5.7 
                 89.6 
                 5.5 
                 88.0 
                 27.3 
               
               
                 AD-953428.1 
                 67.5 
                 3.0 
                 60.6 
                 2.3 
                 92.1 
                 20.1 
                 86.2 
                 0.7 
                 36.2 
                 5.6 
                 59.5 
                 10.0 
                 108.5 
                 13.2 
                 70.4 
                 11.3 
               
               
                 AD-953501.1 
                 77.3 
                 7.8 
                 60.9 
                 5.8 
                 91.7 
                 5.6 
                 100.8 
                 7.2 
                 67.9 
                 9.6 
                 61.3 
                 14.9 
                 80.5 
                 24.9 
                 73.2 
                 5.7 
               
               
                 AD-953482.1 
                 76.7 
                 1.5 
                 61.5 
                 3.4 
                 94.6 
                 8.4 
                 100.1 
                 5.4 
                 71.8 
                 9.0 
                 53.7 
                 8.6 
                 115.9 
                 9.7 
                 101.9 
                 20.8 
               
               
                 AD-953446.1 
                 94.0 
                 4.3 
                 61.6 
                 5.8 
                 76.4 
                 15.8 
                 75.6 
                 5.7 
                 64.1 
                 4.6 
                 74.9 
                 8.7 
                 96.8 
                 19.8 
                 64.5 
                 10.4 
               
               
                 AD-953488.1 
                 65.7 
                 3.3 
                 61.8 
                 3.9 
                 81.2 
                 15.8 
                 95.9 
                 9.8 
                 81.3 
                 5.3 
                 60.2 
                 18.5 
                 123.3 
                 46.3 
                 76.4 
                 23.7 
               
               
                 AD-953434.1 
                 58.9 
                 3.9 
                 61.9 
                 3.1 
                 91.4 
                 17.9 
                 94.1 
                 10.6 
                 49.7 
                 5.3 
                 92.6 
                 15.2 
                 123.1 
                 12.0 
                 71.5 
                 10.1 
               
               
                 AD-953546.1 
                 49.9 
                 1.9 
                 63.3 
                 14.5 
                 59.7 
                 4.4 
                 80.8 
                 2.1 
                 48.2 
                 2.7 
                 41.6 
                 12.9 
                 72.9 
                 5.4 
                 72.9 
                 8.7 
               
               
                 AD-953529.1 
                 59.0 
                 3.6 
                 64.8 
                 9.9 
                 63.9 
                 2.4 
                 78.3 
                 1.9 
                 61.5 
                 5.7 
                 48.5 
                 7.4 
                 117.3 
                 20.3 
                 91.1 
                 15.1 
               
               
                 AD-953433.1 
                 95.2 
                 10.7 
                 64.8 
                 6.3 
                 78.5 
                 16.2 
                 82.5 
                 2.6 
                 69.0 
                 5.2 
                 109.4 
                 7.2 
                 107.4 
                 13.2 
                 98.9 
                 35.0 
               
               
                 AD-953456.1 
                 68.1 
                 8.4 
                 64.9 
                 4.7 
                 95.7 
                 22.5 
                 94.1 
                 2.7 
                 86.8 
                 14.7 
                 56.3 
                 7.0 
                 89.1 
                 10.7 
                 89.1 
                 12.9 
               
               
                 AD-953435.1 
                 69.8 
                 3.4 
                 65.1 
                 4.1 
                 88.1 
                 18.6 
                 92.9 
                 4.8 
                 57.5 
                 9.2 
                 75.3 
                 5.7 
                 104.3 
                 2.4 
                 71.9 
                 13.2 
               
               
                 AD-953438.1 
                 70.2 
                 4.8 
                 66.4 
                 5.8 
                 105.5 
                 19.6 
                 88.2 
                 3.9 
                 46.0 
                 7.7 
                 61.7 
                 19.7 
                 90.1 
                 14.9 
                 71.7 
                 16.9 
               
               
                 AD-953452.1 
                 80.0 
                 5.5 
                 66.9 
                 6.7 
                 96.6 
                 21.5 
                 89.5 
                 10.8 
                 53.2 
                 3.6 
                 46.9 
                 7.7 
                 94.3 
                 14.7 
                 104.6 
                 25.8 
               
               
                 AD-953489.1 
                 86.9 
                 6.5 
                 69.3 
                 5.5 
                 89.1 
                 10.0 
                 97.0 
                 8.7 
                 82.0 
                 16.1 
                 80.6 
                 15.6 
                 125.9 
                 15.7 
                 77.4 
                 19.4 
               
               
                 AD-953445.1 
                 104.1 
                 7.0 
                 71.5 
                 3.4 
                 88.6 
                 21.2 
                 85.2 
                 10.1 
                 68.1 
                 3.0 
                 91.0 
                 8.8 
                 103.1 
                 9.2 
                 80.5 
                 32.1 
               
               
                 AD-953432.1 
                 62.6 
                 4.1 
                 71.6 
                 4.0 
                 106.7 
                 23.0 
                 109.1 
                 13.6 
                 38.2 
                 5.3 
                 69.3 
                 6.0 
                 104.2 
                 19.0 
                 88.8 
                 34.4 
               
               
                 AD-953509.1 
                 96.2 
                 8.8 
                 71.8 
                 2.2 
                 68.5 
                 36.5 
                 93.1 
                 7.2 
                 71.0 
                 33.3 
                 70.4 
                 7.3 
                 77.7 
                 11.3 
                 65.4 
                 12.1 
               
               
                 AD-953490.1 
                 89.4 
                 6.4 
                 72.2 
                 2.5 
                 85.2 
                 6.8 
                 95.5 
                 8.7 
                 109.5 
                 9.8 
                 68.7 
                 8.2 
                 106.9 
                 14.9 
                 74.4 
                 6.7 
               
               
                 AD-953448.1 
                 67.8 
                 3.6 
                 72.7 
                 5.1 
                 101.5 
                 20.3 
                 94.8 
                 9.3 
                 76.1 
                 25.3 
                 61.8 
                 6.4 
                 110.6 
                 35.5 
                 79.5 
                 29.6 
               
               
                 AD-953450.1 
                 78.6 
                 2.3 
                 72.8 
                 5.4 
                 96.9 
                 14.3 
                 91.0 
                 7.6 
                 72.1 
                 7.7 
                 53.3 
                 4.3 
                 120.8 
                 11.3 
                 117.2 
                 41.1 
               
               
                 AD-953443.1 
                 96.4 
                 8.9 
                 73.3 
                 2.2 
                 96.4 
                 22.9 
                 90.7 
                 4.5 
                 60.8 
                 3.2 
                 100.7 
                 16.4 
                 95.8 
                 18.2 
                 83.7 
                 14.5 
               
               
                 AD-953525.1 
                 81.5 
                 6.2 
                 73.4 
                 4.5 
                 79.8 
                 16.8 
                 90.4 
                 2.8 
                 53.0 
                 4.5 
                 69.3 
                 8.5 
                 86.0 
                 16.0 
                 90.0 
                 8.6 
               
               
                 AD-953523.1 
                 74.3 
                 4.9 
                 73.4 
                 8.8 
                 88.1 
                 6.8 
                 100.9 
                 5.1 
                 58.3 
                 15.3 
                 91.1 
                 6.6 
                 116.2 
                 14.1 
                 78.2 
                 3.5 
               
               
                 AD-953507.1 
                 78.1 
                 8.2 
                 73.7 
                 5.3 
                 86.3 
                 6.8 
                 98.8 
                 5.4 
                 51.1 
                 14.2 
                 64.7 
                 6.5 
                 104.2 
                 32.5 
                 75.3 
                 23.7 
               
               
                 AD-953451.1 
                 87.6 
                 7.6 
                 74.0 
                 8.2 
                 92.4 
                 16.6 
                 90.3 
                 3.1 
                 95.8 
                 23.0 
                 56.1 
                 5.2 
                 112.4 
                 8.5 
                 110.3 
                 6.9 
               
               
                 AD-953429.1 
                 91.2 
                 8.9 
                 74.2 
                 4.9 
                 99.8 
                 24.4 
                 93.0 
                 7.0 
                 57.0 
                 9.1 
                 66.7 
                 10.2 
                 99.6 
                 11.7 
                 79.4 
                 16.7 
               
               
                 AD-953469.1 
                 84.5 
                 11.2 
                 74.6 
                 5.1 
                 109.2 
                 18.8 
                 95.6 
                 5.9 
                 75.1 
                 4.5 
                 62.7 
                 8.0 
                 88.1 
                 7.8 
                 117.5 
                 17.4 
               
               
                 AD-953463.1 
                 88.7 
                 17.1 
                 74.8 
                 4.8 
                 101.9 
                 20.8 
                 99.2 
                 5.1 
                 70.1 
                 8.6 
                 75.6 
                 20.8 
                 80.2 
                 25.5 
                 88.4 
                 11.1 
               
               
                 AD-953454.1 
                 106.1 
                 7.0 
                 74.9 
                 6.7 
                 95.6 
                 26.8 
                 86.4 
                 9.1 
                 76.3 
                 20.1 
                 67.7 
                 21.9 
                 95.9 
                 14.3 
                 84.0 
                 35.8 
               
               
                 AD-953455.1 
                 99.0 
                 14.1 
                 75.0 
                 5.4 
                 101.7 
                 25.0 
                 98.1 
                 5.5 
                 81.5 
                 17.4 
                 72.9 
                 19.3 
                 76.3 
                 14.6 
                 69.1 
                 15.5 
               
               
                 AD-953511.1 
                 83.7 
                 3.8 
                 75.3 
                 6.2 
                 86.7 
                 5.4 
                 100.7 
                 8.8 
                 76.0 
                 31.8 
                 71.6 
                 10.7 
                 131.4 
                 22.1 
                 94.7 
                 13.1 
               
               
                 AD-953447.1 
                 95.2 
                 8.5 
                 75.6 
                 4.2 
                 101.4 
                 18.3 
                 89.6 
                 4.2 
                 67.5 
                 9.6 
                 73.0 
                 10.4 
                 75.9 
                 14.6 
                 76.1 
                 16.4 
               
               
                 AD-953424.1 
                 78.8 
                 3.7 
                 75.8 
                 8.2 
                 96.4 
                 26.2 
                 99.3 
                 5.8 
                 56.2 
                 9.0 
                 98.3 
                 31.6 
                 112.0 
                 18.9 
                 68.1 
                 16.5 
               
               
                 AD-953506.1 
                 82.9 
                 3.4 
                 76.4 
                 3.9 
                 94.6 
                 10.2 
                 98.2 
                 7.0 
                 54.4 
                 7.9 
                 80.4 
                 12.3 
                 104.5 
                 27.0 
                 85.1 
                 2.6 
               
               
                 AD-953537.1 
                 71.6 
                 3.2 
                 76.4 
                 16.4 
                 81.7 
                 10.1 
                 93.7 
                 6.6 
                 61.5 
                 11.6 
                 52.7 
                 14.9 
                 104.7 
                 9.9 
                 102.3 
                 8.2 
               
               
                 AD-953477.1 
                 104.2 
                 11.7 
                 76.5 
                 4.8 
                 93.7 
                 6.9 
                 90.6 
                 5.6 
                 77.5 
                 20.8 
                 62.6 
                 12.8 
                 75.1 
                 22.1 
                 105.4 
                 29.2 
               
               
                 AD-953479.1 
                 90.5 
                 8.9 
                 77.0 
                 10.7 
                 99.9 
                 16.6 
                 109.0 
                 9.6 
                 99.6 
                 9.7 
                 74.8 
                 9.6 
                 116.9 
                 25.5 
                 104.0 
                 21.8 
               
               
                 AD-953439.1 
                 102.3 
                 7.6 
                 77.2 
                 4.5 
                 100.8 
                 26.6 
                 97.8 
                 5.7 
                 68.0 
                 8.2 
                 80.5 
                 24.1 
                 72.4 
                 18.5 
                 66.2 
                 17.0 
               
               
                 AD-953431.1 
                 86.4 
                 7.7 
                 77.5 
                 7.5 
                 116.2 
                 20.7 
                 93.5 
                 15.3 
                 52.4 
                 2.4 
                 45.7 
                 9.6 
                 71.9 
                 3.0 
                 62.8 
                 10.1 
               
               
                 AD-953442.1 
                 89.4 
                 4.5 
                 78.2 
                 5.5 
                 99.8 
                 20.9 
                 90.2 
                 7.4 
                 69.0 
                 13.2 
                 95.2 
                 19.1 
                 119.3 
                 10.1 
                 77.5 
                 19.9 
               
               
                 AD-953449.1 
                 81.5 
                 5.9 
                 78.3 
                 5.3 
                 95.1 
                 23.3 
                 90.1 
                 7.6 
                 82.6 
                 15.4 
                 72.5 
                 14.2 
                 113.9 
                 14.0 
                 93.2 
                 12.8 
               
               
                 AD-953510.1 
                 94.1 
                 6.6 
                 78.6 
                 6.2 
                 85.2 
                 8.5 
                 88.6 
                 4.2 
                 62.7 
                 11.1 
                 74.3 
                 3.6 
                 73.1 
                 12.6 
                 30.5 
                 6.0 
               
               
                 AD-953514.1 
                 98.5 
                 10.4 
                 78.8 
                 9.3 
                 95.6 
                 4.4 
                 89.4 
                 4.6 
                 80.1 
                 19.3 
                 89.0 
                 3.5 
                 118.7 
                 18.7 
                 94.8 
                 19.4 
               
               
                 AD-953508.1 
                 96.9 
                 7.3 
                 78.9 
                 7.1 
                 96.5 
                 24.7 
                 98.7 
                 8.7 
                 68.5 
                 15.8 
                 76.9 
                 13.9 
                 94.3 
                 15.5 
                 75.2 
                 11.5 
               
               
                 AD-953531.1 
                 70.3 
                 2.0 
                 80.7 
                 17.0 
                 82.8 
                 4.0 
                 90.6 
                 4.3 
                 80.9 
                 15.6 
                 62.5 
                 12.3 
                 98.0 
                 12.4 
                 73.4 
                 7.0 
               
               
                 AD-953427.1 
                 105.8 
                 12.1 
                 81.1 
                 4.6 
                 91.0 
                 25.6 
                 90.0 
                 3.7 
                 65.3 
                 3.7 
                 100.2 
                 12.6 
                 109.0 
                 17.8 
                 66.6 
                 15.2 
               
               
                 AD-953512.1 
                 94.6 
                 2.1 
                 83.9 
                 4.5 
                 91.3 
                 10.6 
                 96.7 
                 7.7 
                 84.8 
                 13.3 
                 84.0 
                 11.0 
                 129.5 
                 10.3 
                 88.3 
                 15.8 
               
               
                 AD-953533.1 
                 102.2 
                 9.2 
                 85.2 
                 21.1 
                 82.6 
                 15.3 
                 108.6 
                 13.4 
                 85.5 
                 12.3 
                 66.0 
                 13.3 
                 89.2 
                 14.1 
                 73.0 
                 12.3 
               
               
                 AD-953464.1 
                 76.9 
                 3.8 
                 86.1 
                 6.5 
                 104.6 
                 21.8 
                 99.9 
                 10.3 
                 110.5 
                 10.6 
                 74.5 
                 5.0 
                 87.7 
                 18.7 
                 111.9 
                 6.1 
               
               
                 AD-953542.1 
                 51.8 
                 2.5 
                 86.3 
                 24.8 
                 66.0 
                 11.3 
                 98.1 
                 17.1 
                 54.8 
                 9.9 
                 69.8 
                 2.3 
                 95.8 
                 13.9 
                 104.4 
                 4.4 
               
               
                 AD-953426.1 
                 102.2 
                 10.9 
                 87.8 
                 5.7 
                 103.4 
                 24.0 
                 97.1 
                 2.0 
                 67.3 
                 5.4 
                 120.7 
                 18.0 
                 117.5 
                 16.3 
                 74.5 
                 27.0 
               
               
                 AD-953515.1 
                 92.6 
                 5.7 
                 88.4 
                 6.2 
                 84.6 
                 21.4 
                 98.2 
                 9.4 
                 95.5 
                 21.8 
                 84.9 
                 10.3 
                 124.9 
                 28.4 
                 86.9 
                 4.2 
               
               
                 AD-953487.1 
                 99.3 
                 9.8 
                 88.7 
                 12.4 
                 90.1 
                 13.7 
                 95.1 
                 3.2 
                 106.9 
                 17.5 
                 88.1 
                 5.6 
                 118.9 
                 35.4 
                 57.1 
                 14.7 
               
               
                 AD-953521.1 
                 104.2 
                 20.4 
                 89.0 
                 1.5 
                 109.1 
                 13.9 
                 96.2 
                 9.4 
                 76.6 
                 12.8 
                 89.5 
                 10.4 
                 131.6 
                 23.9 
                 81.8 
                 10.5 
               
               
                 AD-953425.1 
                 81.5 
                 13.2 
                 90.2 
                 4.0 
                 99.5 
                 24.2 
                 94.8 
                 6.2 
                 63.6 
                 4.3 
                 114.5 
                 27.3 
                 142.3 
                 60.9 
                 75.3 
                 25.7 
               
               
                 AD-953536.1 
                 75.4 
                 13.1 
                 90.2 
                 23.7 
                 86.6 
                 4.9 
                 98.4 
                 8.1 
                 75.0 
                 8.5 
                 58.1 
                 20.2 
                 120.5 
                 32.6 
                 96.6 
                 11.8 
               
               
                 AD-953465.1 
                 97.2 
                 10.0 
                 91.4 
                 6.6 
                 114.1 
                 30.7 
                 91.7 
                 5.7 
                 92.3 
                 7.4 
                 78.6 
                 6.8 
                 99.2 
                 29.1 
                 131.0 
                 23.9 
               
               
                 AD-953552.1 
                 82.6 
                 7.9 
                 92.5 
                 22.4 
                 88.2 
                 4.8 
                 102.3 
                 6.4 
                 86.4 
                 15.8 
                 85.2 
                 16.6 
                 55.7 
                 16.7 
                 89.0 
                 12.2 
               
               
                 AD-953528.1 
                 87.5 
                 15.0 
                 93.5 
                 11.1 
                 83.9 
                 8.8 
                 85.7 
                 4.5 
                 111.2 
                 40.7 
                 69.5 
                 16.7 
                 142.9 
                 10.9 
                 103.3 
                 8.0 
               
               
                 AD-953519.1 
                 107.5 
                 2.3 
                 93.5 
                 4.8 
                 96.1 
                 5.2 
                 91.0 
                 3.3 
                 92.7 
                 9.0 
                 113.7 
                 6.9 
                 146.7 
                 24.6 
                 121.8 
                 38.4 
               
               
                 AD-953486.1 
                 105.6 
                 3.7 
                 94.2 
                 5.6 
                 103.9 
                 8.6 
                 96.7 
                 6.1 
                 75.6 
                 1.5 
                 106.1 
                 34.1 
                 83.7 
                 17.1 
                 78.1 
                 21.7 
               
               
                 AD-953522.1 
                 97.7 
                 9.0 
                 94.3 
                 4.2 
                 100.0 
                 16.6 
                 99.0 
                 8.4 
                 98.8 
                 21.3 
                 87.2 
                 16.4 
                 106.8 
                 15.9 
                 84.1 
                 7.4 
               
               
                 AD-953530.1 
                 76.4 
                 4.7 
                 94.3 
                 19.0 
                 90.2 
                 8.9 
                 93.8 
                 9.9 
                 72.4 
                 16.7 
                 67.0 
                 12.1 
                 93.5 
                 11.7 
                 93.3 
                 11.8 
               
               
                 AD-953513.1 
                 104.1 
                 3.5 
                 95.5 
                 7.9 
                 92.8 
                 9.4 
                 103.5 
                 10.8 
                 90.2 
                 28.8 
                 76.6 
                 6.8 
                 144.6 
                 24.5 
                 101.7 
                 12.6 
               
               
                 AD-953441.1 
                 97.5 
                 8.0 
                 95.5 
                 5.0 
                 114.8 
                 18.2 
                 106.5 
                 8.7 
                 63.8 
                 4.1 
                 105.6 
                 4.8 
                 125.4 
                 24.0 
                 80.4 
                 27.5 
               
               
                 AD-953440.1 
                 87.8 
                 6.4 
                 95.5 
                 12.2 
                 112.8 
                 26.2 
                 97.9 
                 1.2 
                 83.3 
                 7.9 
                 106.5 
                 13.4 
                 118.0 
                 10.0 
                 75.4 
                 27.2 
               
               
                 AD-953518.1 
                 91.0 
                 4.9 
                 96.1 
                 3.4 
                 99.6 
                 2.8 
                 93.9 
                 12.4 
                 96.6 
                 24.0 
                 91.4 
                 16.4 
                 126.5 
                 19.7 
                 108.8 
                 16.1 
               
               
                 AD-953520.1 
                 92.8 
                 7.3 
                 96.1 
                 3.8 
                 99.9 
                 18.5 
                 99.9 
                 7.3 
                 91.8 
                 18.0 
                 89.3 
                 13.6 
                 140.3 
                 21.3 
                 96.0 
                 17.7 
               
               
                 AD-953532.1 
                 92.3 
                 7.2 
                 99.5 
                 16.4 
                 96.9 
                 11.9 
                 93.0 
                 4.9 
                 87.9 
                 12.7 
                 67.9 
                 9.0 
                 89.9 
                 24.8 
                 70.6 
                 13.2 
               
               
                 AD-953548.1 
                 85.7 
                 8.0 
                 100.5 
                 20.0 
                 89.8 
                 7.6 
                 99.4 
                 7.1 
                 58.8 
                 8.9 
                 67.7 
                 24.6 
                 80.1 
                 6.0 
                 78.0 
                 9.0 
               
               
                 AD-953527.1 
                 91.5 
                 2.8 
                 101.9 
                 15.1 
                 92.3 
                 14.5 
                 102.6 
                 4.5 
                 113.8 
                 41.2 
                 69.2 
                 18.2 
                 132.4 
                 36.0 
                 108.0 
                 10.6 
               
               
                 AD-953551.1 
                 91.4 
                 4.5 
                 103.0 
                 24.3 
                 94.8 
                 1.1 
                 101.1 
                 5.4 
                 130.4 
                 41.4 
                 78.2 
                 20.9 
                 65.8 
                 13.8 
                 102.2 
                 11.8 
               
               
                 AD-953553.1 
                 93.9 
                 1.2 
                 103.2 
                 25.6 
                 93.3 
                 6.6 
                 100.2 
                 4.2 
                 88.5 
                 10.1 
                 93.5 
                 20.0 
                 65.1 
                 15.8 
                 93.0 
                 13.6 
               
               
                 AD-953547.1 
                 89.1 
                 3.6 
                 104.0 
                 18.7 
                 94.3 
                 7.6 
                 97.6 
                 3.0 
                 65.0 
                 6.4 
                 60.7 
                 16.1 
                 85.8 
                 9.7 
                 86.6 
                 8.6 
               
               
                 AD-953526.1 
                 88.7 
                 5.7 
                 110.0 
                 23.2 
                 95.7 
                 3.2 
                 100.8 
                 12.4 
                 117.9 
                 52.9 
                 75.4 
                 16.8 
                 115.9 
                 12.6 
                 102.1 
                 10.6 
               
               
                 AD-953549.1 
                 94.4 
                 8.8 
                 113.8 
                 25.9 
                 70.6 
                 23.4 
                 106.6 
                 12.7 
                 54.1 
                 8.2 
                 55.2 
                 18.7 
                 85.6 
                 31.6 
                 81.4 
                 15.2 
               
               
                 AD-953534.1 
                 102.5 
                 8.5 
                 117.9 
                 27.3 
                 95.0 
                 14.1 
                 79.9 
                 5.5 
                 137.0 
                 23.5 
                 81.4 
                 20.8 
                 141.1 
                 19.1 
                 103.4 
                 12.1 
               
               
                 AD-953543.1 
                 99.3 
                 3.5 
                 118.0 
                 17.9 
                 89.7 
                 4.0 
                 96.9 
                 4.6 
                 111.5 
                 41.1 
                 99.7 
                 30.4 
                 123.8 
                 17.6 
                 104.4 
                 15.0 
               
               
                 AD-953550.1 
                 96.0 
                 5.8 
                 121.6 
                 19.6 
                 98.9 
                 12.3 
                 99.0 
                 9.0 
                 119.6 
                 20.5 
                 101.5 
                 20.0 
                 52.7 
                 10.9 
                 93.6 
                 13.1 
               
               
                   
               
            
           
         
       
     
     The results of the multi-dose screen in African green monkey kidney cells (Cos-7) transfected with Cynomolgus monkey VEGF-A with a set of exemplary rat VEGF-A siRNAs are shown in Table 7A (correspond to siRNAs in Table 5A and Table 5B). The results of the multi-dose screen in Cos-7 cells transfected with mouse VEGF-A with a set of exemplary rat VEGF-A siRNAs are shown in Table 7B (correspond to siRNAs in Table 5A and Table 5B). The multi-dose experiments were performed at 10 nM, 1 nM, and 0.1 nM final duplex concentrations and the data are expressed as percent message remaining relative to non-targeting control. 
     
       
         
           
               
             
               
                 TABLE 7A 
               
             
            
               
                   
               
               
                 Cynomolgus monkey VEGF-A in vitro multi-dose  
               
               
                 screen with one set of exemplary rat VEGF-A siRNAs 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 Dose 
               
               
                   
                 Duplex Name 
                 Average 
                 StDev 
                 Dose 
                 Unit 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 AD-579911.1 
                 21.79 
                 0.50 
                 10 
                 nM 
               
               
                   
                 AD-579912.1 
                 20.38 
                 3.81 
                 10 
                 nM 
               
               
                   
                 AD-579913.1 
                 16.71 
                 8.39 
                 10 
                 nM 
               
               
                   
                 AD-579914.1 
                 45.98 
                 4.11 
                 10 
                 nM 
               
               
                   
                 AD-579915.1 
                 35.03 
                 7.59 
                 10 
                 nM 
               
               
                   
                 AD-579916.1 
                 12.14 
                 1.83 
                 10 
                 nM 
               
               
                   
                 AD-579917.1 
                 25.40 
                 3.24 
                 10 
                 nM 
               
               
                   
                 AD-579918.1 
                 26.56 
                 2.53 
                 10 
                 nM 
               
               
                   
                 AD-579919.1 
                 10.58 
                 2.15 
                 10 
                 nM 
               
               
                   
                 AD-579921.1 
                 12.64 
                 2.73 
                 10 
                 nM 
               
               
                   
                 AD-579922.1 
                 13.78 
                 0.77 
                 10 
                 nM 
               
               
                   
                 AD-579923.1 
                 17.37 
                 1.62 
                 10 
                 nM 
               
               
                   
                 AD-579924.1 
                 49.49 
                 4.24 
                 10 
                 nM 
               
               
                   
                 AD-579925.1 
                 10.62 
                 1.31 
                 10 
                 nM 
               
               
                   
                 AD-579926.1 
                 13.23 
                 2.83 
                 10 
                 nM 
               
               
                   
                 AD-579927.1 
                 25.34 
                 3.60 
                 10 
                 nM 
               
               
                   
                 AD-579929.1 
                 26.33 
                 1.74 
                 10 
                 nM 
               
               
                   
                 AD-579930.1 
                 81.28 
                 12.54 
                 10 
                 nM 
               
               
                   
                 AD-579931.1 
                 41.52 
                 7.38 
                 10 
                 nM 
               
               
                   
                 AD-579932.1 
                 12.14 
                 3.92 
                 10 
                 nM 
               
               
                   
                 AD-579933.1 
                 30.75 
                 3.29 
                 10 
                 nM 
               
               
                   
                 AD-579934.1 
                 186.16 
                 29.32 
                 10 
                 nM 
               
               
                   
                 AD-579935.1 
                 67.60 
                 6.57 
                 10 
                 nM 
               
               
                   
                 AD-579936.1 
                 81.10 
                 20.59 
                 10 
                 nM 
               
               
                   
                 AD-579937.1 
                 25.95 
                 3.27 
                 10 
                 nM 
               
               
                   
                 AD-579938.1 
                 60.65 
                 8.90 
                 10 
                 nM 
               
               
                   
                 AD-579939.1 
                 72.01 
                 14.89 
                 10 
                 nM 
               
               
                   
                 AD-579940.1 
                 96.52 
                 8.39 
                 10 
                 nM 
               
               
                   
                 AD-579941.1 
                 106.40 
                 13.04 
                 10 
                 nM 
               
               
                   
                 AD-579942.1 
                 61.87 
                 12.12 
                 10 
                 nM 
               
               
                   
                 AD-579943.1 
                 12.46 
                 4.75 
                 10 
                 nM 
               
               
                   
                 AD-579944.1 
                 28.49 
                 4.13 
                 10 
                 nM 
               
               
                   
                 AD-579945.1 
                 70.53 
                 8.74 
                 10 
                 nM 
               
               
                   
                 AD-579946.1 
                 24.47 
                 6.19 
                 10 
                 nM 
               
               
                   
                 AD-579947.1 
                 68.58 
                 4.38 
                 10 
                 nM 
               
               
                   
                 AD-579948.1 
                 77.63 
                 5.92 
                 10 
                 nM 
               
               
                   
                 AD-579949.1 
                 96.51 
                 8.80 
                 10 
                 nM 
               
               
                   
                 AD-579950.1 
                 230.10 
                 21.51 
                 10 
                 nM 
               
               
                   
                 AD-579951.1 
                 66.36 
                 16.79 
                 10 
                 nM 
               
               
                   
                 AD-579953.1 
                 18.42 
                 5.42 
                 10 
                 nM 
               
               
                   
                 AD-579954.1 
                 21.24 
                 4.31 
                 10 
                 nM 
               
               
                   
                 AD-579955.1 
                 69.32 
                 6.99 
                 10 
                 nM 
               
               
                   
                 AD-579956.1 
                 99.49 
                 25.18 
                 10 
                 nM 
               
               
                   
                 AD-579957.1 
                 49.05 
                 14.80 
                 10 
                 nM 
               
               
                   
                 AD-579958.1 
                 88.74 
                 8.73 
                 10 
                 nM 
               
               
                   
                 AD-579959.1 
                 100.41 
                 9.53 
                 10 
                 nM 
               
               
                   
                 AD-579960.1 
                 39.31 
                 3.68 
                 10 
                 nM 
               
               
                   
                 AD-579961.1 
                 96.81 
                 13.20 
                 10 
                 nM 
               
               
                   
                 AD-579962.1 
                 53.43 
                 6.50 
                 10 
                 nM 
               
               
                   
                 AD-579963.1 
                 21.24 
                 3.25 
                 10 
                 nM 
               
               
                   
                 AD-579964.1 
                 17.83 
                 7.13 
                 10 
                 nM 
               
               
                   
                 AD-579965.1 
                 92.27 
                 14.22 
                 10 
                 nM 
               
               
                   
                 AD-579966.1 
                 88.97 
                 9.79 
                 10 
                 nM 
               
               
                   
                 AD-579967.1 
                 47.49 
                 7.04 
                 10 
                 nM 
               
               
                   
                 AD-579968.1 
                 76.96 
                 8.70 
                 10 
                 nM 
               
               
                   
                 AD-579969.1 
                 90.81 
                 8.30 
                 10 
                 nM 
               
               
                   
                 AD-579970.1 
                 104.42 
                 26.45 
                 10 
                 nM 
               
               
                   
                 AD-579971.1 
                 14.37 
                 6.47 
                 10 
                 nM 
               
               
                   
                 AD-579972.1 
                 57.43 
                 2.61 
                 10 
                 nM 
               
               
                   
                 AD-579973.1 
                 103.95 
                 3.97 
                 10 
                 nM 
               
               
                   
                 AD-579974.1 
                 81.04 
                 3.86 
                 10 
                 nM 
               
               
                   
                 AD-579975.1 
                 33.28 
                 7.01 
                 10 
                 nM 
               
               
                   
                 AD-579976.1 
                 79.49 
                 2.88 
                 10 
                 nM 
               
               
                   
                 AD-579977.1 
                 80.67 
                 6.29 
                 10 
                 nM 
               
               
                   
                 AD-579978.1 
                 66.72 
                 3.59 
                 10 
                 nM 
               
               
                   
                 AD-579979.1 
                 92.24 
                 3.77 
                 10 
                 nM 
               
               
                   
                 AD-579980.1 
                 25.30 
                 3.08 
                 10 
                 nM 
               
               
                   
                 AD-579981.1 
                 48.69 
                 11.03 
                 10 
                 nM 
               
               
                   
                 AD-579982.1 
                 49.50 
                 15.70 
                 10 
                 nM 
               
               
                   
                 AD-579983.1 
                 10.78 
                 4.14 
                 10 
                 nM 
               
               
                   
                 AD-579984.1 
                 16.79 
                 1.90 
                 10 
                 nM 
               
               
                   
                 AD-579985.1 
                 11.35 
                 0.96 
                 10 
                 nM 
               
               
                   
                 AD-579986.1 
                 33.51 
                 4.42 
                 10 
                 nM 
               
               
                   
                 AD-579987.1 
                 26.04 
                 3.89 
                 10 
                 nM 
               
               
                   
                 AD-579988.1 
                 30.67 
                 3.01 
                 10 
                 nM 
               
               
                   
                 AD-579989.1 
                 33.51 
                 6.72 
                 10 
                 nM 
               
               
                   
                 AD-579990.1 
                 72.51 
                 4.50 
                 10 
                 nM 
               
               
                   
                 AD-579992.1 
                 61.70 
                 6.74 
                 10 
                 nM 
               
               
                   
                 AD-579993.1 
                 92.69 
                 10.40 
                 10 
                 nM 
               
               
                   
                 AD-579995.1 
                 30.40 
                 4.51 
                 10 
                 nM 
               
               
                   
                 AD-579996.1 
                 94.02 
                 11.86 
                 10 
                 nM 
               
               
                   
                 AD-579997.1 
                 34.79 
                 5.90 
                 10 
                 nM 
               
               
                   
                 AD-579998.1 
                 31.10 
                 6.52 
                 10 
                 nM 
               
               
                   
                 AD-579999.1 
                 137.05 
                 8.03 
                 10 
                 nM 
               
               
                   
                 AD-580000.1 
                 162.84 
                 26.73 
                 10 
                 nM 
               
               
                   
                 AD-580001.1 
                 125.00 
                 7.31 
                 10 
                 nM 
               
               
                   
                 AD-580002.1 
                 186.90 
                 14.34 
                 10 
                 nM 
               
               
                   
                 AD-579911.1 
                 34.63 
                 4.90 
                 1 
                 nM 
               
               
                   
                 AD-579912.1 
                 31.99 
                 3.89 
                 1 
                 nM 
               
               
                   
                 AD-579913.1 
                 36.38 
                 2.19 
                 1 
                 nM 
               
               
                   
                 AD-579914.1 
                 47.66 
                 5.91 
                 1 
                 nM 
               
               
                   
                 AD-579915.1 
                 33.92 
                 0.98 
                 1 
                 nM 
               
               
                   
                 AD-579916.1 
                 25.64 
                 5.85 
                 1 
                 nM 
               
               
                   
                 AD-579917.1 
                 38.41 
                 8.43 
                 1 
                 nM 
               
               
                   
                 AD-579918.1 
                 37.12 
                 9.78 
                 1 
                 nM 
               
               
                   
                 AD-579919.1 
                 13.33 
                 2.62 
                 1 
                 nM 
               
               
                   
                 AD-579921.1 
                 24.01 
                 3.06 
                 1 
                 nM 
               
               
                   
                 AD-579922.1 
                 21.65 
                 1.29 
                 1 
                 nM 
               
               
                   
                 AD-579923.1 
                 32.00 
                 1.21 
                 1 
                 nM 
               
               
                   
                 AD-579924.1 
                 74.46 
                 5.43 
                 1 
                 nM 
               
               
                   
                 AD-579925.1 
                 27.19 
                 4.59 
                 1 
                 nM 
               
               
                   
                 AD-579926.1 
                 23.17 
                 2.37 
                 1 
                 nM 
               
               
                   
                 AD-579927.1 
                 44.62 
                 10.37 
                 1 
                 nM 
               
               
                   
                 AD-579929.1 
                 32.40 
                 3.90 
                 1 
                 nM 
               
               
                   
                 AD-579930.1 
                 82.85 
                 10.31 
                 1 
                 nM 
               
               
                   
                 AD-579931.1 
                 53.35 
                 11.21 
                 1 
                 nM 
               
               
                   
                 AD-579932.1 
                 25.97 
                 4.61 
                 1 
                 nM 
               
               
                   
                 AD-579933.1 
                 64.26 
                 11.63 
                 1 
                 nM 
               
               
                   
                 AD-579934.1 
                 110.08 
                 21.79 
                 1 
                 nM 
               
               
                   
                 AD-579935.1 
                 75.45 
                 3.94 
                 1 
                 nM 
               
               
                   
                 AD-579936.1 
                 88.42 
                 7.56 
                 1 
                 nM 
               
               
                   
                 AD-579937.1 
                 25.63 
                 2.94 
                 1 
                 nM 
               
               
                   
                 AD-579938.1 
                 67.82 
                 2.00 
                 1 
                 nM 
               
               
                   
                 AD-579939.1 
                 69.81 
                 7.16 
                 1 
                 nM 
               
               
                   
                 AD-579940.1 
                 99.17 
                 5.18 
                 1 
                 nM 
               
               
                   
                 AD-579941.1 
                 108.34 
                 7.84 
                 1 
                 nM 
               
               
                   
                 AD-579942.1 
                 70.36 
                 12.47 
                 1 
                 nM 
               
               
                   
                 AD-579943.1 
                 26.50 
                 3.47 
                 1 
                 nM 
               
               
                   
                 AD-579944.1 
                 35.87 
                 5.32 
                 1 
                 nM 
               
               
                   
                 AD-579945.1 
                 82.17 
                 15.84 
                 1 
                 nM 
               
               
                   
                 AD-579946.1 
                 28.27 
                 2.22 
                 1 
                 nM 
               
               
                   
                 AD-579947.1 
                 77.96 
                 16.94 
                 1 
                 nM 
               
               
                   
                 AD-579948.1 
                 79.99 
                 3.99 
                 1 
                 nM 
               
               
                   
                 AD-579949.1 
                 108.10 
                 12.09 
                 1 
                 nM 
               
               
                   
                 AD-579950.1 
                 134.00 
                 16.20 
                 1 
                 nM 
               
               
                   
                 AD-579951.1 
                 66.05 
                 9.65 
                 1 
                 nM 
               
               
                   
                 AD-579953.1 
                 27.50 
                 5.68 
                 1 
                 nM 
               
               
                   
                 AD-579954.1 
                 20.74 
                 3.51 
                 1 
                 nM 
               
               
                   
                 AD-579955.1 
                 74.44 
                 17.09 
                 1 
                 nM 
               
               
                   
                 AD-579956.1 
                 113.45 
                 9.64 
                 1 
                 nM 
               
               
                   
                 AD-579957.1 
                 73.78 
                 1.80 
                 1 
                 nM 
               
               
                   
                 AD-579958.1 
                 94.21 
                 11.02 
                 1 
                 nM 
               
               
                   
                 AD-579959.1 
                 95.73 
                 17.31 
                 1 
                 nM 
               
               
                   
                 AD-579960.1 
                 37.92 
                 6.36 
                 1 
                 nM 
               
               
                   
                 AD-579961.1 
                 95.86 
                 5.08 
                 1 
                 nM 
               
               
                   
                 AD-579962.1 
                 79.16 
                 6.58 
                 1 
                 nM 
               
               
                   
                 AD-579963.1 
                 22.85 
                 4.33 
                 1 
                 nM 
               
               
                   
                 AD-579964.1 
                 23.33 
                 2.88 
                 1 
                 nM 
               
               
                   
                 AD-579965.1 
                 96.34 
                 24.13 
                 1 
                 nM 
               
               
                   
                 AD-579966.1 
                 85.86 
                 12.83 
                 1 
                 nM 
               
               
                   
                 AD-579967.1 
                 59.03 
                 6.42 
                 1 
                 nM 
               
               
                   
                 AD-579968.1 
                 72.33 
                 7.43 
                 1 
                 nM 
               
               
                   
                 AD-579969.1 
                 86.79 
                 3.22 
                 1 
                 nM 
               
               
                   
                 AD-579970.1 
                 100.80 
                 8.64 
                 1 
                 nM 
               
               
                   
                 AD-579971.1 
                 12.62 
                 2.38 
                 1 
                 nM 
               
               
                   
                 AD-579972.1 
                 52.06 
                 7.34 
                 1 
                 nM 
               
               
                   
                 AD-579973.1 
                 96.38 
                 18.09 
                 1 
                 nM 
               
               
                   
                 AD-579974.1 
                 90.54 
                 6.77 
                 1 
                 nM 
               
               
                   
                 AD-579975.1 
                 54.49 
                 4.18 
                 1 
                 nM 
               
               
                   
                 AD-579976.1 
                 83.49 
                 18.12 
                 1 
                 nM 
               
               
                   
                 AD-579977.1 
                 86.21 
                 10.51 
                 1 
                 nM 
               
               
                   
                 AD-579978.1 
                 73.79 
                 28.62 
                 1 
                 nM 
               
               
                   
                 AD-579979.1 
                 102.91 
                 17.40 
                 1 
                 nM 
               
               
                   
                 AD-579980.1 
                 22.61 
                 1.11 
                 1 
                 nM 
               
               
                   
                 AD-579981.1 
                 62.79 
                 8.71 
                 1 
                 nM 
               
               
                   
                 AD-579982.1 
                 57.63 
                 7.73 
                 1 
                 nM 
               
               
                   
                 AD-579983.1 
                 17.63 
                 2.73 
                 1 
                 nM 
               
               
                   
                 AD-579984.1 
                 25.44 
                 1.54 
                 1 
                 nM 
               
               
                   
                 AD-579985.1 
                 20.01 
                 6.16 
                 1 
                 nM 
               
               
                   
                 AD-579986.1 
                 45.92 
                 2.90 
                 1 
                 nM 
               
               
                   
                 AD-579987.1 
                 35.60 
                 5.94 
                 1 
                 nM 
               
               
                   
                 AD-579988.1 
                 41.30 
                 3.29 
                 1 
                 nM 
               
               
                   
                 AD-579989.1 
                 35.25 
                 1.19 
                 1 
                 nM 
               
               
                   
                 AD-579990.1 
                 75.79 
                 12.51 
                 1 
                 nM 
               
               
                   
                 AD-579992.1 
                 70.19 
                 10.59 
                 1 
                 nM 
               
               
                   
                 AD-579993.1 
                 81.86 
                 8.27 
                 1 
                 nM 
               
               
                   
                 AD-579995.1 
                 32.90 
                 4.47 
                 1 
                 nM 
               
               
                   
                 AD-579996.1 
                 91.93 
                 9.06 
                 1 
                 nM 
               
               
                   
                 AD-579997.1 
                 54.91 
                 2.41 
                 1 
                 nM 
               
               
                   
                 AD-579998.1 
                 35.62 
                 5.31 
                 1 
                 nM 
               
               
                   
                 AD-579999.1 
                 105.80 
                 11.56 
                 1 
                 nM 
               
               
                   
                 AD-580000.1 
                 151.28 
                 8.84 
                 1 
                 nM 
               
               
                   
                 AD-580001.1 
                 117.48 
                 17.60 
                 1 
                 nM 
               
               
                   
                 AD-580002.1 
                 148.64 
                 32.44 
                 1 
                 nM 
               
               
                   
                 AD-579911.1 
                 60.59 
                 5.99 
                 0.1 
                 nM 
               
               
                   
                 AD-579912.1 
                 58.68 
                 4.12 
                 0.1 
                 nM 
               
               
                   
                 AD-579913.1 
                 64.23 
                 5.02 
                 0.1 
                 nM 
               
               
                   
                 AD-579914.1 
                 74.48 
                 8.13 
                 0.1 
                 nM 
               
               
                   
                 AD-579915.1 
                 56.70 
                 3.72 
                 0.1 
                 nM 
               
               
                   
                 AD-579916.1 
                 41.93 
                 5.43 
                 0.1 
                 nM 
               
               
                   
                 AD-579917.1 
                 78.90 
                 9.40 
                 0.1 
                 nM 
               
               
                   
                 AD-579918.1 
                 66.57 
                 10.31 
                 0.1 
                 nM 
               
               
                   
                 AD-579919.1 
                 29.08 
                 2.79 
                 0.1 
                 nM 
               
               
                   
                 AD-579921.1 
                 59.28 
                 4.60 
                 0.1 
                 nM 
               
               
                   
                 AD-579922.1 
                 56.67 
                 8.89 
                 0.1 
                 nM 
               
               
                   
                 AD-579923.1 
                 75.33 
                 12.81 
                 0.1 
                 nM 
               
               
                   
                 AD-579924.1 
                 100.79 
                 20.47 
                 0.1 
                 nM 
               
               
                   
                 AD-579925.1 
                 72.05 
                 13.30 
                 0.1 
                 nM 
               
               
                   
                 AD-579926.1 
                 63.98 
                 8.75 
                 0.1 
                 nM 
               
               
                   
                 AD-579927.1 
                 78.12 
                 11.58 
                 0.1 
                 nM 
               
               
                   
                 AD-579929.1 
                 67.27 
                 19.11 
                 0.1 
                 nM 
               
               
                   
                 AD-579930.1 
                 96.27 
                 17.88 
                 0.1 
                 nM 
               
               
                   
                 AD-579931.1 
                 75.81 
                 15.09 
                 0.1 
                 nM 
               
               
                   
                 AD-579932.1 
                 61.06 
                 2.54 
                 0.1 
                 nM 
               
               
                   
                 AD-579933.1 
                 85.95 
                 8.05 
                 0.1 
                 nM 
               
               
                   
                 AD-579934.1 
                 100.61 
                 4.77 
                 0.1 
                 nM 
               
               
                   
                 AD-579935.1 
                 88.00 
                 10.57 
                 0.1 
                 nM 
               
               
                   
                 AD-579936.1 
                 88.13 
                 9.64 
                 0.1 
                 nM 
               
               
                   
                 AD-579937.1 
                 55.87 
                 4.99 
                 0.1 
                 nM 
               
               
                   
                 AD-579938.1 
                 90.35 
                 12.54 
                 0.1 
                 nM 
               
               
                   
                 AD-579939.1 
                 100.22 
                 5.50 
                 0.1 
                 nM 
               
               
                   
                 AD-579940.1 
                 117.60 
                 9.00 
                 0.1 
                 nM 
               
               
                   
                 AD-579941.1 
                 100.53 
                 13.72 
                 0.1 
                 nM 
               
               
                   
                 AD-579942.1 
                 100.72 
                 12.00 
                 0.1 
                 nM 
               
               
                   
                 AD-579943.1 
                 41.23 
                 3.38 
                 0.1 
                 nM 
               
               
                   
                 AD-579944.1 
                 73.67 
                 9.65 
                 0.1 
                 nM 
               
               
                   
                 AD-579945.1 
                 101.57 
                 13.70 
                 0.1 
                 nM 
               
               
                   
                 AD-579946.1 
                 42.00 
                 1.99 
                 0.1 
                 nM 
               
               
                   
                 AD-579947.1 
                 88.52 
                 29.57 
                 0.1 
                 nM 
               
               
                   
                 AD-579948.1 
                 94.78 
                 13.34 
                 0.1 
                 nM 
               
               
                   
                 AD-579949.1 
                 106.50 
                 4.63 
                 0.1 
                 nM 
               
               
                   
                 AD-579950.1 
                 112.38 
                 10.41 
                 0.1 
                 nM 
               
               
                   
                 AD-579951.1 
                 81.88 
                 7.61 
                 0.1 
                 nM 
               
               
                   
                 AD-579953.1 
                 65.43 
                 5.35 
                 0.1 
                 nM 
               
               
                   
                 AD-579954.1 
                 29.05 
                 3.98 
                 0.1 
                 nM 
               
               
                   
                 AD-579955.1 
                 101.64 
                 8.13 
                 0.1 
                 nM 
               
               
                   
                 AD-579956.1 
                 109.12 
                 12.60 
                 0.1 
                 nM 
               
               
                   
                 AD-579957.1 
                 95.19 
                 6.14 
                 0.1 
                 nM 
               
               
                   
                 AD-579958.1 
                 99.02 
                 14.55 
                 0.1 
                 nM 
               
               
                   
                 AD-579959.1 
                 96.08 
                 7.16 
                 0.1 
                 nM 
               
               
                   
                 AD-579960.1 
                 65.43 
                 20.16 
                 0.1 
                 nM 
               
               
                   
                 AD-579961.1 
                 89.02 
                 11.37 
                 0.1 
                 nM 
               
               
                   
                 AD-579962.1 
                 107.63 
                 11.06 
                 0.1 
                 nM 
               
               
                   
                 AD-579963.1 
                 54.55 
                 6.58 
                 0.1 
                 nM 
               
               
                   
                 AD-579964.1 
                 37.19 
                 5.60 
                 0.1 
                 nM 
               
               
                   
                 AD-579965.1 
                 93.32 
                 9.87 
                 0.1 
                 nM 
               
               
                   
                 AD-579966.1 
                 93.21 
                 13.54 
                 0.1 
                 nM 
               
               
                   
                 AD-579967.1 
                 78.97 
                 5.07 
                 0.1 
                 nM 
               
               
                   
                 AD-579968.1 
                 83.13 
                 8.48 
                 0.1 
                 nM 
               
               
                   
                 AD-579969.1 
                 97.62 
                 21.40 
                 0.1 
                 nM 
               
               
                   
                 AD-579970.1 
                 102.49 
                 8.36 
                 0.1 
                 nM 
               
               
                   
                 AD-579971.1 
                 22.84 
                 3.85 
                 0.1 
                 nM 
               
               
                   
                 AD-579972.1 
                 83.71 
                 13.31 
                 0.1 
                 nM 
               
               
                   
                 AD-579973.1 
                 97.02 
                 12.16 
                 0.1 
                 nM 
               
               
                   
                 AD-579974.1 
                 87.05 
                 8.86 
                 0.1 
                 nM 
               
               
                   
                 AD-579975.1 
                 85.49 
                 9.25 
                 0.1 
                 nM 
               
               
                   
                 AD-579976.1 
                 89.61 
                 16.73 
                 0.1 
                 nM 
               
               
                   
                 AD-579977.1 
                 93.52 
                 7.83 
                 0.1 
                 nM 
               
               
                   
                 AD-579978.1 
                 87.68 
                 5.19 
                 0.1 
                 nM 
               
               
                   
                 AD-579979.1 
                 93.22 
                 6.02 
                 0.1 
                 nM 
               
               
                   
                 AD-579980.1 
                 39.04 
                 7.41 
                 0.1 
                 nM 
               
               
                   
                 AD-579981.1 
                 75.66 
                 11.68 
                 0.1 
                 nM 
               
               
                   
                 AD-579982.1 
                 90.44 
                 10.96 
                 0.1 
                 nM 
               
               
                   
                 AD-579983.1 
                 50.03 
                 2.51 
                 0.1 
                 nM 
               
               
                   
                 AD-579984.1 
                 58.06 
                 3.26 
                 0.1 
                 nM 
               
               
                   
                 AD-579985.1 
                 33.30 
                 3.60 
                 0.1 
                 nM 
               
               
                   
                 AD-579986.1 
                 74.91 
                 4.29 
                 0.1 
                 nM 
               
               
                   
                 AD-579987.1 
                 71.15 
                 8.39 
                 0.1 
                 nM 
               
               
                   
                 AD-579988.1 
                 81.86 
                 6.80 
                 0.1 
                 nM 
               
               
                   
                 AD-579989.1 
                 59.63 
                 7.75 
                 0.1 
                 nM 
               
               
                   
                 AD-579990.1 
                 95.13 
                 9.94 
                 0.1 
                 nM 
               
               
                   
                 AD-579992.1 
                 94.26 
                 5.07 
                 0.1 
                 nM 
               
               
                   
                 AD-579993.1 
                 99.78 
                 15.90 
                 0.1 
                 nM 
               
               
                   
                 AD-579995.1 
                 73.91 
                 9.98 
                 0.1 
                 nM 
               
               
                   
                 AD-579996.1 
                 101.07 
                 13.27 
                 0.1 
                 nM 
               
               
                   
                 AD-579997.1 
                 89.33 
                 7.03 
                 0.1 
                 nM 
               
               
                   
                 AD-579998.1 
                 60.03 
                 5.93 
                 0.1 
                 nM 
               
               
                   
                 AD-579999.1 
                 109.04 
                 17.76 
                 0.1 
                 nM 
               
               
                   
                 AD-580000.1 
                 108.28 
                 13.14 
                 0.1 
                 nM 
               
               
                   
                 AD-580001.1 
                 88.49 
                 11.96 
                 0.1 
                 nM 
               
               
                   
                 AD-580002.1 
                 122.07 
                 18.09 
                 0.1 
                 nM 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7B 
               
             
            
               
                   
               
               
                 Mouse VEGF-A in vitro multi-dose screen  
               
               
                 with one set of exemplary rat VEGF-A siRNAs 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                   
                 Dose 
               
               
                 Duplex Name 
                 Average 
                 StDev 
                 Dose 
                 Unit 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AD-579911.1 
                 21.27 
                 3.91 
                 10 
                 nM 
               
               
                 AD-579912.1 
                 16.53 
                 5.79 
                 10 
                 nM 
               
               
                 AD-579913.1 
                 16.73 
                 4.22 
                 10 
                 nM 
               
               
                 AD-579914.1 
                 16.51 
                 1.15 
                 10 
                 nM 
               
               
                 AD-579915.1 
                 18.33 
                 6.95 
                 10 
                 nM 
               
               
                 AD-579916.1 
                 25.18 
                 1.82 
                 10 
                 nM 
               
               
                 AD-579917.1 
                 12.22 
                 1.48 
                 10 
                 nM 
               
               
                 AD-579918.1 
                 11.07 
                 2.65 
                 10 
                 nM 
               
               
                 AD-579919.1 
                 12.63 
                 1.67 
                 10 
                 nM 
               
               
                 AD-579921.1 
                 11.45 
                 2.37 
                 10 
                 nM 
               
               
                 AD-579922.1 
                 14.90 
                 3.21 
                 10 
                 nM 
               
               
                 AD-579923.1 
                 13.67 
                 3.59 
                 10 
                 nM 
               
               
                 AD-579924.1 
                 26.37 
                 2.49 
                 10 
                 nM 
               
               
                 AD-579925.1 
                 10.16 
                 1.07 
                 10 
                 nM 
               
               
                 AD-579926.1 
                 14.22 
                 0.82 
                 10 
                 nM 
               
               
                 AD-579927.1 
                 32.32 
                 5.45 
                 10 
                 nM 
               
               
                 AD-579929.1 
                 22.15 
                 6.29 
                 10 
                 nM 
               
               
                 AD-579930.1 
                 74.90 
                 13.83 
                 10 
                 nM 
               
               
                 AD-579931.1 
                 53.69 
                 19.88 
                 10 
                 nM 
               
               
                 AD-579932.1 
                 24.54 
                 2.62 
                 10 
                 nM 
               
               
                 AD-579933.1 
                 20.31 
                 4.52 
                 10 
                 nM 
               
               
                 AD-579934.1 
                 36.61 
                 3.37 
                 10 
                 nM 
               
               
                 AD-579935.1 
                 24.55 
                 4.10 
                 10 
                 nM 
               
               
                 AD-579936.1 
                 22.50 
                 4.65 
                 10 
                 nM 
               
               
                 AD-579937.1 
                 32.75 
                 3.55 
                 10 
                 nM 
               
               
                 AD-579938.1 
                 13.39 
                 2.36 
                 10 
                 nM 
               
               
                 AD-579939.1 
                 4.62 
                 0.19 
                 10 
                 nM 
               
               
                 AD-579940.1 
                 3.68 
                 1.38 
                 10 
                 nM 
               
               
                 AD-579941.1 
                 8.87 
                 1.96 
                 10 
                 nM 
               
               
                 AD-579942.1 
                 3.71 
                 1.54 
                 10 
                 nM 
               
               
                 AD-579943.1 
                 11.89 
                 1.92 
                 10 
                 nM 
               
               
                 AD-579944.1 
                 12.26 
                 1.40 
                 10 
                 nM 
               
               
                 AD-579945.1 
                 16.73 
                 1.86 
                 10 
                 nM 
               
               
                 AD-579946.1 
                 18.67 
                 5.27 
                 10 
                 nM 
               
               
                 AD-579947.1 
                 6.39 
                 1.71 
                 10 
                 nM 
               
               
                 AD-579948.1 
                 27.00 
                 3.21 
                 10 
                 nM 
               
               
                 AD-579949.1 
                 35.57 
                 2.31 
                 10 
                 nM 
               
               
                 AD-579950.1 
                 53.80 
                 4.29 
                 10 
                 nM 
               
               
                 AD-579951.1 
                 17.89 
                 3.43 
                 10 
                 nM 
               
               
                 AD-579953.1 
                 24.48 
                 3.96 
                 10 
                 nM 
               
               
                 AD-579954.1 
                 21.78 
                 1.63 
                 10 
                 nM 
               
               
                 AD-579955.1 
                 30.54 
                 3.58 
                 10 
                 nM 
               
               
                 AD-579956.1 
                 27.17 
                 1.58 
                 10 
                 nM 
               
               
                 AD-579957.1 
                 16.61 
                 1.30 
                 10 
                 nM 
               
               
                 AD-579958.1 
                 53.03 
                 4.43 
                 10 
                 nM 
               
               
                 AD-579959.1 
                 40.73 
                 3.55 
                 10 
                 nM 
               
               
                 AD-579960.1 
                 41.68 
                 1.59 
                 10 
                 nM 
               
               
                 AD-579961.1 
                 29.58 
                 7.59 
                 10 
                 nM 
               
               
                 AD-579962.1 
                 19.90 
                 1.25 
                 10 
                 nM 
               
               
                 AD-579963.1 
                 14.55 
                 3.30 
                 10 
                 nM 
               
               
                 AD-579964.1 
                 23.53 
                 4.62 
                 10 
                 nM 
               
               
                 AD-579965.1 
                 5.85 
                 1.35 
                 10 
                 nM 
               
               
                 AD-579966.1 
                 3.37 
                 0.46 
                 10 
                 nM 
               
               
                 AD-579967.1 
                 8.12 
                 3.03 
                 10 
                 nM 
               
               
                 AD-579968.1 
                 15.39 
                 2.69 
                 10 
                 nM 
               
               
                 AD-579969.1 
                 41.77 
                 5.27 
                 10 
                 nM 
               
               
                 AD-579970.1 
                 35.40 
                 4.42 
                 10 
                 nM 
               
               
                 AD-579971.1 
                 9.46 
                 1.20 
                 10 
                 nM 
               
               
                 AD-579972.1 
                 13.66 
                 4.21 
                 10 
                 nM 
               
               
                 AD-579973.1 
                 15.20 
                 4.13 
                 10 
                 nM 
               
               
                 AD-579974.1 
                 3.60 
                 1.49 
                 10 
                 nM 
               
               
                 AD-579975.1 
                 3.08 
                 0.33 
                 10 
                 nM 
               
               
                 AD-579976.1 
                 7.90 
                 0.37 
                 10 
                 nM 
               
               
                 AD-579977.1 
                 22.23 
                 1.40 
                 10 
                 nM 
               
               
                 AD-579978.1 
                 15.03 
                 2.22 
                 10 
                 nM 
               
               
                 AD-579979.1 
                 29.83 
                 5.08 
                 10 
                 nM 
               
               
                 AD-579980.1 
                 25.34 
                 2.41 
                 10 
                 nM 
               
               
                 AD-579981.1 
                 20.80 
                 1.40 
                 10 
                 nM 
               
               
                 AD-579982.1 
                 20.12 
                 8.04 
                 10 
                 nM 
               
               
                 AD-579983.1 
                 22.13 
                 4.26 
                 10 
                 nM 
               
               
                 AD-579984.1 
                 11.34 
                 1.30 
                 10 
                 nM 
               
               
                 AD-579985.1 
                 10.84 
                 0.91 
                 10 
                 nM 
               
               
                 AD-579986.1 
                 22.36 
                 1.53 
                 10 
                 nM 
               
               
                 AD-579987.1 
                 26.77 
                 5.29 
                 10 
                 nM 
               
               
                 AD-579988.1 
                 25.91 
                 6.97 
                 10 
                 nM 
               
               
                 AD-579989.1 
                 17.89 
                 1.51 
                 10 
                 nM 
               
               
                 AD-579990.1 
                 29.33 
                 3.43 
                 10 
                 nM 
               
               
                 AD-579992.1 
                 19.38 
                 7.67 
                 10 
                 nM 
               
               
                 AD-579993.1 
                 23.19 
                 0.70 
                 10 
                 nM 
               
               
                 AD-579995.1 
                 4.97 
                 1.31 
                 10 
                 nM 
               
               
                 AD-579996.1 
                 63.08 
                 6.91 
                 10 
                 nM 
               
               
                 AD-579997.1 
                 26.46 
                 4.46 
                 10 
                 nM 
               
               
                 AD-579998.1 
                 17.58 
                 4.81 
                 10 
                 nM 
               
               
                 AD-579999.1 
                 33.79 
                 5.04 
                 10 
                 nM 
               
               
                 AD-580000.1 
                 28.19 
                 4.07 
                 10 
                 nM 
               
               
                 AD-580001.1 
                 23.17 
                 4.55 
                 10 
                 nM 
               
               
                 AD-580002.1 
                 51.58 
                 4.73 
                 10 
                 nM 
               
               
                 AD-579911.1 
                 29.66 
                 4.64 
                 1 
                 nM 
               
               
                 AD-579912.1 
                 26.43 
                 3.94 
                 1 
                 nM 
               
               
                 AD-579913.1 
                 40.12 
                 5.03 
                 1 
                 nM 
               
               
                 AD-579914.1 
                 24.93 
                 2.78 
                 1 
                 nM 
               
               
                 AD-579915.1 
                 34.06 
                 4.64 
                 1 
                 nM 
               
               
                 AD-579916.1 
                 45.46 
                 4.47 
                 1 
                 nM 
               
               
                 AD-579917.1 
                 19.16 
                 2.98 
                 1 
                 nM 
               
               
                 AD-579918.1 
                 16.77 
                 1.65 
                 1 
                 nM 
               
               
                 AD-579919.1 
                 17.09 
                 1.57 
                 1 
                 nM 
               
               
                 AD-579921.1 
                 21.90 
                 0.76 
                 1 
                 nM 
               
               
                 AD-579922.1 
                 24.16 
                 3.67 
                 1 
                 nM 
               
               
                 AD-579923.1 
                 28.64 
                 5.98 
                 1 
                 nM 
               
               
                 AD-579924.1 
                 54.14 
                 8.12 
                 1 
                 nM 
               
               
                 AD-579925.1 
                 27.88 
                 2.54 
                 1 
                 nM 
               
               
                 AD-579926.1 
                 29.26 
                 2.01 
                 1 
                 nM 
               
               
                 AD-579927.1 
                 44.60 
                 5.25 
                 1 
                 nM 
               
               
                 AD-579929.1 
                 31.53 
                 4.15 
                 1 
                 nM 
               
               
                 AD-579930.1 
                 93.72 
                 13.68 
                 1 
                 nM 
               
               
                 AD-579931.1 
                 54.78 
                 5.31 
                 1 
                 nM 
               
               
                 AD-579932.1 
                 46.12 
                 4.65 
                 1 
                 nM 
               
               
                 AD-579933.1 
                 27.01 
                 5.56 
                 1 
                 nM 
               
               
                 AD-579934.1 
                 40.35 
                 6.96 
                 1 
                 nM 
               
               
                 AD-579935.1 
                 31.13 
                 5.41 
                 1 
                 nM 
               
               
                 AD-579936.1 
                 29.73 
                 3.71 
                 1 
                 nM 
               
               
                 AD-579937.1 
                 44.09 
                 4.36 
                 1 
                 nM 
               
               
                 AD-579938.1 
                 21.66 
                 3.66 
                 1 
                 nM 
               
               
                 AD-579939.1 
                 4.58 
                 0.75 
                 1 
                 nM 
               
               
                 AD-579940.1 
                 3.56 
                 0.91 
                 1 
                 nM 
               
               
                 AD-579941.1 
                 7.55 
                 2.31 
                 1 
                 nM 
               
               
                 AD-579942.1 
                 5.56 
                 2.57 
                 1 
                 nM 
               
               
                 AD-579943.1 
                 19.30 
                 3.06 
                 1 
                 nM 
               
               
                 AD-579944.1 
                 18.70 
                 1.80 
                 1 
                 nM 
               
               
                 AD-579945.1 
                 26.86 
                 1.35 
                 1 
                 nM 
               
               
                 AD-579946.1 
                 21.86 
                 3.32 
                 1 
                 nM 
               
               
                 AD-579947.1 
                 9.84 
                 0.95 
                 1 
                 nM 
               
               
                 AD-579948.1 
                 26.84 
                 1.26 
                 1 
                 nM 
               
               
                 AD-579949.1 
                 57.75 
                 9.08 
                 1 
                 nM 
               
               
                 AD-579950.1 
                 54.60 
                 4.99 
                 1 
                 nM 
               
               
                 AD-579951.1 
                 23.18 
                 1.60 
                 1 
                 nM 
               
               
                 AD-579953.1 
                 35.85 
                 4.89 
                 1 
                 nM 
               
               
                 AD-579954.1 
                 33.37 
                 3.57 
                 1 
                 nM 
               
               
                 AD-579955.1 
                 43.72 
                 4.02 
                 1 
                 nM 
               
               
                 AD-579956.1 
                 40.52 
                 0.43 
                 1 
                 nM 
               
               
                 AD-579957.1 
                 22.05 
                 1.37 
                 1 
                 nM 
               
               
                 AD-579958.1 
                 63.71 
                 6.37 
                 1 
                 nM 
               
               
                 AD-579959.1 
                 54.17 
                 7.09 
                 1 
                 nM 
               
               
                 AD-579960.1 
                 45.58 
                 4.07 
                 1 
                 nM 
               
               
                 AD-579961.1 
                 40.91 
                 2.43 
                 1 
                 nM 
               
               
                 AD-579962.1 
                 28.65 
                 3.39 
                 1 
                 nM 
               
               
                 AD-579963.1 
                 22.65 
                 6.61 
                 1 
                 nM 
               
               
                 AD-579964.1 
                 28.01 
                 5.38 
                 1 
                 nM 
               
               
                 AD-579965.1 
                 3.88 
                 1.04 
                 1 
                 nM 
               
               
                 AD-579966.1 
                 4.08 
                 1.00 
                 1 
                 nM 
               
               
                 AD-579967.1 
                 14.72 
                 0.97 
                 1 
                 nM 
               
               
                 AD-579968.1 
                 19.71 
                 4.24 
                 1 
                 nM 
               
               
                 AD-579969.1 
                 54.35 
                 7.63 
                 1 
                 nM 
               
               
                 AD-579970.1 
                 52.04 
                 1.90 
                 1 
                 nM 
               
               
                 AD-579971.1 
                 13.28 
                 3.80 
                 1 
                 nM 
               
               
                 AD-579972.1 
                 22.49 
                 5.22 
                 1 
                 nM 
               
               
                 AD-579973.1 
                 23.49 
                 2.63 
                 1 
                 nM 
               
               
                 AD-579974.1 
                 6.50 
                 0.84 
                 1 
                 nM 
               
               
                 AD-579975.1 
                 3.65 
                 1.14 
                 1 
                 nM 
               
               
                 AD-579976.1 
                 10.00 
                 2.25 
                 1 
                 nM 
               
               
                 AD-579977.1 
                 30.06 
                 5.34 
                 1 
                 nM 
               
               
                 AD-579978.1 
                 21.05 
                 2.77 
                 1 
                 nM 
               
               
                 AD-579979.1 
                 54.05 
                 6.94 
                 1 
                 nM 
               
               
                 AD-579980.1 
                 26.38 
                 3.38 
                 1 
                 nM 
               
               
                 AD-579981.1 
                 22.68 
                 2.02 
                 1 
                 nM 
               
               
                 AD-579982.1 
                 39.84 
                 3.32 
                 1 
                 nM 
               
               
                 AD-579983.1 
                 34.64 
                 6.02 
                 1 
                 nM 
               
               
                 AD-579984.1 
                 16.95 
                 2.53 
                 1 
                 nM 
               
               
                 AD-579985.1 
                 31.39 
                 1.48 
                 1 
                 nM 
               
               
                 AD-579986.1 
                 27.74 
                 3.81 
                 1 
                 nM 
               
               
                 AD-579987.1 
                 51.76 
                 4.91 
                 1 
                 nM 
               
               
                 AD-579988.1 
                 29.45 
                 2.77 
                 1 
                 nM 
               
               
                 AD-579989.1 
                 21.33 
                 2.08 
                 1 
                 nM 
               
               
                 AD-579990.1 
                 47.89 
                 1.76 
                 1 
                 nM 
               
               
                 AD-579992.1 
                 30.71 
                 4.73 
                 1 
                 nM 
               
               
                 AD-579993.1 
                 35.91 
                 7.25 
                 1 
                 nM 
               
               
                 AD-579995.1 
                 6.70 
                 0.49 
                 1 
                 nM 
               
               
                 AD-579996.1 
                 74.23 
                 4.02 
                 1 
                 nM 
               
               
                 AD-579997.1 
                 51.99 
                 10.00 
                 1 
                 nM 
               
               
                 AD-579998.1 
                 20.92 
                 4.64 
                 1 
                 nM 
               
               
                 AD-579999.1 
                 40.31 
                 1.99 
                 1 
                 nM 
               
               
                 AD-580000.1 
                 38.17 
                 1.63 
                 1 
                 nM 
               
               
                 AD-580001.1 
                 28.86 
                 5.37 
                 1 
                 nM 
               
               
                 AD-580002.1 
                 51.52 
                 7.91 
                 1 
                 nM 
               
               
                 AD-579911.1 
                 59.37 
                 8.87 
                 0.1 
                 nM 
               
               
                 AD-579912.1 
                 59.39 
                 5.09 
                 0.1 
                 nM 
               
               
                 AD-579913.1 
                 64.08 
                 23.73 
                 0.1 
                 nM 
               
               
                 AD-579914.1 
                 49.48 
                 3.64 
                 0.1 
                 nM 
               
               
                 AD-579915.1 
                 56.56 
                 6.31 
                 0.1 
                 nM 
               
               
                 AD-579916.1 
                 96.79 
                 16.03 
                 0.1 
                 nM 
               
               
                 AD-579917.1 
                 45.36 
                 7.75 
                 0.1 
                 nM 
               
               
                 AD-579918.1 
                 57.38 
                 4.03 
                 0.1 
                 nM 
               
               
                 AD-579919.1 
                 55.62 
                 5.60 
                 0.1 
                 nM 
               
               
                 AD-579921.1 
                 53.70 
                 9.76 
                 0.1 
                 nM 
               
               
                 AD-579922.1 
                 62.44 
                 4.87 
                 0.1 
                 nM 
               
               
                 AD-579923.1 
                 63.54 
                 9.06 
                 0.1 
                 nM 
               
               
                 AD-579924.1 
                 92.45 
                 9.57 
                 0.1 
                 nM 
               
               
                 AD-579925.1 
                 61.94 
                 18.45 
                 0.1 
                 nM 
               
               
                 AD-579926.1 
                 70.86 
                 8.69 
                 0.1 
                 nM 
               
               
                 AD-579927.1 
                 78.15 
                 23.69 
                 0.1 
                 nM 
               
               
                 AD-579929.1 
                 71.46 
                 14.26 
                 0.1 
                 nM 
               
               
                 AD-579930.1 
                 90.78 
                 6.27 
                 0.1 
                 nM 
               
               
                 AD-579931.1 
                 68.75 
                 9.57 
                 0.1 
                 nM 
               
               
                 AD-579932.1 
                 77.69 
                 9.74 
                 0.1 
                 nM 
               
               
                 AD-579933.1 
                 51.36 
                 9.29 
                 0.1 
                 nM 
               
               
                 AD-579934.1 
                 77.13 
                 7.91 
                 0.1 
                 nM 
               
               
                 AD-579935.1 
                 49.67 
                 7.46 
                 0.1 
                 nM 
               
               
                 AD-579936.1 
                 44.13 
                 6.15 
                 0.1 
                 nM 
               
               
                 AD-579937.1 
                 77.96 
                 4.22 
                 0.1 
                 nM 
               
               
                 AD-579938.1 
                 29.19 
                 7.09 
                 0.1 
                 nM 
               
               
                 AD-579939.1 
                 10.14 
                 1.04 
                 0.1 
                 nM 
               
               
                 AD-579940.1 
                 6.98 
                 3.06 
                 0.1 
                 nM 
               
               
                 AD-579941.1 
                 7.68 
                 1.31 
                 0.1 
                 nM 
               
               
                 AD-579942.1 
                 8.97 
                 1.33 
                 0.1 
                 nM 
               
               
                 AD-579943.1 
                 37.14 
                 5.93 
                 0.1 
                 nM 
               
               
                 AD-579944.1 
                 39.47 
                 3.54 
                 0.1 
                 nM 
               
               
                 AD-579945.1 
                 54.76 
                 10.45 
                 0.1 
                 nM 
               
               
                 AD-579946.1 
                 54.38 
                 7.47 
                 0.1 
                 nM 
               
               
                 AD-579947.1 
                 22.79 
                 5.03 
                 0.1 
                 nM 
               
               
                 AD-579948.1 
                 38.00 
                 6.15 
                 0.1 
                 nM 
               
               
                 AD-579949.1 
                 80.25 
                 7.57 
                 0.1 
                 nM 
               
               
                 AD-579950.1 
                 73.79 
                 5.42 
                 0.1 
                 nM 
               
               
                 AD-579951.1 
                 47.34 
                 5.57 
                 0.1 
                 nM 
               
               
                 AD-579953.1 
                 75.21 
                 13.06 
                 0.1 
                 nM 
               
               
                 AD-579954.1 
                 49.75 
                 4.87 
                 0.1 
                 nM 
               
               
                 AD-579955.1 
                 84.04 
                 10.95 
                 0.1 
                 nM 
               
               
                 AD-579956.1 
                 73.48 
                 18.05 
                 0.1 
                 nM 
               
               
                 AD-579957.1 
                 37.29 
                 3.15 
                 0.1 
                 nM 
               
               
                 AD-579958.1 
                 96.73 
                 8.67 
                 0.1 
                 nM 
               
               
                 AD-579959.1 
                 86.90 
                 10.17 
                 0.1 
                 nM 
               
               
                 AD-579960.1 
                 71.64 
                 12.07 
                 0.1 
                 nM 
               
               
                 AD-579961.1 
                 86.22 
                 11.71 
                 0.1 
                 nM 
               
               
                 AD-579962.1 
                 59.52 
                 4.17 
                 0.1 
                 nM 
               
               
                 AD-579963.1 
                 53.65 
                 1.36 
                 0.1 
                 nM 
               
               
                 AD-579964.1 
                 60.89 
                 5.53 
                 0.1 
                 nM 
               
               
                 AD-579965.1 
                 10.37 
                 1.33 
                 0.1 
                 nM 
               
               
                 AD-579966.1 
                 9.37 
                 1.18 
                 0.1 
                 nM 
               
               
                 AD-579967.1 
                 33.20 
                 1.60 
                 0.1 
                 nM 
               
               
                 AD-579968.1 
                 36.38 
                 8.49 
                 0.1 
                 nM 
               
               
                 AD-579969.1 
                 83.90 
                 5.81 
                 0.1 
                 nM 
               
               
                 AD-579970.1 
                 104.17 
                 11.38 
                 0.1 
                 nM 
               
               
                 AD-579971.1 
                 29.04 
                 4.62 
                 0.1 
                 nM 
               
               
                 AD-579972.1 
                 47.77 
                 5.87 
                 0.1 
                 nM 
               
               
                 AD-579973.1 
                 67.38 
                 5.17 
                 0.1 
                 nM 
               
               
                 AD-579974.1 
                 21.80 
                 3.23 
                 0.1 
                 nM 
               
               
                 AD-579975.1 
                 10.78 
                 2.10 
                 0.1 
                 nM 
               
               
                 AD-579976.1 
                 20.60 
                 3.17 
                 0.1 
                 nM 
               
               
                 AD-579977.1 
                 86.60 
                 5.20 
                 0.1 
                 nM 
               
               
                 AD-579978.1 
                 53.36 
                 3.32 
                 0.1 
                 nM 
               
               
                 AD-579979.1 
                 92.09 
                 11.37 
                 0.1 
                 nM 
               
               
                 AD-579980.1 
                 52.60 
                 2.36 
                 0.1 
                 nM 
               
               
                 AD-579981.1 
                 46.23 
                 7.60 
                 0.1 
                 nM 
               
               
                 AD-579982.1 
                 94.15 
                 11.36 
                 0.1 
                 nM 
               
               
                 AD-579983.1 
                 76.94 
                 11.93 
                 0.1 
                 nM 
               
               
                 AD-579984.1 
                 34.98 
                 2.84 
                 0.1 
                 nM 
               
               
                 AD-579985.1 
                 69.50 
                 9.11 
                 0.1 
                 nM 
               
               
                 AD-579986.1 
                 62.04 
                 6.78 
                 0.1 
                 nM 
               
               
                 AD-579987.1 
                 89.22 
                 9.48 
                 0.1 
                 nM 
               
               
                 AD-579988.1 
                 72.80 
                 14.40 
                 0.1 
                 nM 
               
               
                 AD-579989.1 
                 52.85 
                 3.85 
                 0.1 
                 nM 
               
               
                 AD-579990.1 
                 94.01 
                 8.85 
                 0.1 
                 nM 
               
               
                 AD-579992.1 
                 67.82 
                 6.38 
                 0.1 
                 nM 
               
               
                 AD-579993.1 
                 81.30 
                 15.42 
                 0.1 
                 nM 
               
               
                 AD-579995.1 
                 19.72 
                 5.72 
                 0.1 
                 nM 
               
               
                 AD-579996.1 
                 97.03 
                 10.38 
                 0.1 
                 nM 
               
               
                 AD-579997.1 
                 87.06 
                 12.93 
                 0.1 
                 nM 
               
               
                 AD-579998.1 
                 52.54 
                 4.98 
                 0.1 
                 nM 
               
               
                 AD-579999.1 
                 71.80 
                 3.62 
                 0.1 
                 nM 
               
               
                 AD-580000.1 
                 75.04 
                 9.15 
                 0.1 
                 nM 
               
               
                 AD-580001.1 
                 59.52 
                 8.32 
                 0.1 
                 nM 
               
               
                 AD-580002.1 
                 90.07 
                 10.26 
                 0.1 
                 nM 
               
               
                   
               
            
           
         
       
     
     The results of the multi-dose screen in primary human hepatocytes transfected with one set of exemplary human VEGF-A siRNAs is shown in Table 9A (correspond to siRNAs in Table 8A and 8B) The multi-dose experiments were performed at 50 nM, 10 nM, 1 nM, and 0.1 nM final duplex concentrations and the data are expressed as percent message remaining relative to non-targeting control. 
     Of the exemplary siRNA duplexes evaluated in Table 9A, 1 achieved a knockdown of VEGF-A of ≥80%, 119 achieved a knockdown of VEGF-A of ≥60%, and 363 achieved a knockdown of VEGF-A of ≥30% when administered at the 50 nM concentration. 
     Of the exemplary siRNA duplexes evaluated in Table 9A, 2 achieved a knockdown of VEGF-A of ≥80%, 103 achieved a knockdown of VEGF-A of ≥60%, and 364 achieved a knockdown of VEGF-A of ≥30% when administered at the 10 nM concentration. 
     Of the exemplary siRNA duplexes evaluated in Table 9A, 13 achieved a knockdown of VEGF-A of ≥70%, 52 achieved a knockdown of VEGF-A of ≥60%, and 312 achieved a knockdown of VEGF-A of ≥30% when administered at the 1 nM concentration. 
     Of the exemplary siRNA duplexes evaluated in Table 9A, 8 achieved a knockdown of VEGF-A of ≥50%, 75 achieved a knockdown of VEGF-A of ≥40%, and 170 achieved a knockdown of VEGF-A of ≥30% when administered at the 0.1 nM concentration. 
     
       
         
           
               
             
               
                 TABLE 9A 
               
             
            
               
                   
               
               
                 VEGF-A endogenous in vitro multi-dose screen following cellular 
               
               
                 transfection with one set of exemplary human VEGF-A siRNAs 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 DuplexID 
                 50 nM 
                 StDev 
                 10 nM 
                 StDev 
                 1 nM 
                 StDev 
                 0.1 nM 
                 StDev 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 AD-1222866.1 
                 70 
                 22 
                 58 
                 9 
                 69 
                 9 
                 60 
                 6 
               
               
                 AD-1222867.1 
                 64 
                 14 
                 38 
                 6 
                 55 
                 3 
                 54 
                 2 
               
               
                 AD-1222868.1 
                 60 
                 7 
                 42 
                 6 
                 56 
                 8 
                 55 
                 3 
               
               
                 AD-1222869.1 
                 61 
                 3 
                 51 
                 1 
                 56 
                 3 
                 56 
                 0 
               
               
                 AD-1222870.1 
                 43 
                 7 
                 39 
                 6 
                 47 
                 7 
                 52 
                 4 
               
               
                 AD-1222871.1 
                 41 
                 3 
                 38 
                 7 
                 42 
                 2 
                 56 
                 3 
               
               
                 AD-1222872.1 
                 54 
                 4 
                 46 
                 9 
                 50 
                 1 
                 56 
                 2 
               
               
                 AD-1222873.1 
                 44 
                 1 
                 44 
                 4 
                 46 
                 2 
                 58 
                 1 
               
               
                 AD-1222874.1 
                 78 
                 22 
                 66 
                 18 
                 69 
                 4 
                 70 
                 2 
               
               
                 AD-1222875.1 
                 56 
                 7 
                 51 
                 5 
                 64 
                 3 
                 59 
                 4 
               
               
                 AD-1222876.1 
                 56 
                 9 
                 64 
                 6 
                 71 
                 8 
                 67 
                 4 
               
               
                 AD-1222877.1 
                 60 
                 19 
                 50 
                 5 
                 59 
                 7 
                 67 
                 3 
               
               
                 AD-1222878.1 
                 64 
                 7 
                 60 
                 2 
                 63 
                 3 
                 72 
                 4 
               
               
                 AD-1222879.1 
                 64 
                 3 
                 57 
                 9 
                 52 
                 4 
                 64 
                 9 
               
               
                 AD-1222880.1 
                 54 
                 4 
                 53 
                 9 
                 49 
                 4 
                 57 
                 4 
               
               
                 AD-1222881.1 
                 58 
                 10 
                 51 
                 2 
                 46 
                 1 
                 63 
                 9 
               
               
                 AD-1222882.1 
                 93 
                 12 
                 74 
                 14 
                 93 
                 12 
                 91 
                 12 
               
               
                 AD-1222883.1 
                 72 
                 12 
                 59 
                 10 
                 64 
                 7 
                 78 
                 9 
               
               
                 AD-1222884.1 
                 63 
                 5 
                 58 
                 8 
                 61 
                 0 
                 79 
                 10 
               
               
                 AD-1222885.1 
                 70 
                 12 
                 66 
                 9 
                 69 
                 11 
                 81 
                 4 
               
               
                 AD-1222886.1 
                 77 
                 7 
                 76 
                 7 
                 69 
                 3 
                 80 
                 6 
               
               
                 AD-1222887.1 
                 62 
                 5 
                 58 
                 11 
                 57 
                 4 
                 70 
                 9 
               
               
                 AD-1222888.1 
                 69 
                 6 
                 68 
                 8 
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                 59 
                 0 
                 63 
                 12 
                 72 
                 1 
                 79 
                 5 
               
               
                 AD-1223246.1 
                 52 
                 4 
                 51 
                 9 
                 44 
                 4 
                 71 
                 9 
               
               
                 AD-1223247.1 
                 68 
                 9 
                 58 
                 4 
                 49 
                 3 
                 61 
                 9 
               
               
                 AD-1223248.1 
                 80 
                 9 
                 58 
                 8 
                 50 
                 5 
                 54 
                 7 
               
               
                 AD-1223249.1 
                 81 
                 16 
                 69 
                 4 
                 96 
                 25 
                 63 
                 13 
               
               
                 AD-1223250.1 
                 77 
                 16 
                 72 
                 11 
                 123 
                 20 
                 65 
                 14 
               
               
                 AD-1223251.1 
                 58 
                 15 
                 65 
                 7 
                 88 
                 7 
                 60 
                 9 
               
               
                 AD-1223252.1 
                 69 
                 12 
                 60 
                 8 
                 80 
                 12 
                 80 
                 21 
               
               
                 AD-1223253.1 
                 68 
                 31 
                 48 
                 5 
                 67 
                 13 
                 53 
                 1 
               
               
                 AD-1223254.1 
                 49 
                 7 
                 56 
                 12 
                 84 
                 0 
                 54 
                 7 
               
               
                 AD-1223255.1 
                 46 
                 5 
                 50 
                 8 
                 59 
                 6 
                 46 
                 8 
               
               
                 AD-1223256.1 
                 63 
                 21 
                 53 
                 5 
                 75 
                 16 
                 73 
                 2 
               
               
                 AD-1223257.1 
                 74 
                 34 
                 70 
                 3 
                 88 
                 14 
                 71 
                 11 
               
               
                 AD-1223258.1 
                 68 
                 19 
                 73 
                 14 
                 91 
                 17 
                 104 
                 7 
               
               
                 AD-1223259.1 
                 92 
                 37 
                 106 
                 2 
                 114 
                 20 
                 101 
                 3 
               
               
                 AD-1223260.1 
                 59 
                 12 
                 79 
                 8 
                 79 
                 16 
                 99 
                 13 
               
               
                 AD-1223261.1 
                 47 
                 13 
                 66 
                 15 
                 86 
                 8 
                 77 
                 15 
               
               
                 AD-1223262.1 
                 39 
                 6 
                 45 
                 4 
                 68 
                 12 
                 58 
                 4 
               
               
                 AD-1223263.1 
                 39 
                 3 
                 44 
                 2 
                 64 
                 1 
                 44 
                 9 
               
               
                 AD-1223264.1 
                 42 
                 10 
                 43 
                 3 
                 79 
                 20 
                 59 
                 8 
               
               
                 AD-1223265.1 
                 58 
                 11 
                 56 
                 10 
                 101 
                 7 
                 88 
                 8 
               
               
                 AD-1223266.1 
                 49 
                 5 
                 48 
                 7 
                 68 
                 5 
                 72 
                 6 
               
               
                 AD-1223267.1 
                 79 
                 30 
                 70 
                 14 
                 95 
                 11 
                 102 
                 19 
               
               
                 AD-1223268.1 
                 54 
                 7 
                 64 
                 7 
                 83 
                 9 
                 96 
                 6 
               
               
                 AD-1223269.1 
                 45 
                 13 
                 49 
                 8 
                 78 
                 16 
                 80 
                 9 
               
               
                 AD-1223270.1 
                 53 
                 14 
                 70 
                 16 
                 76 
                 4 
                 70 
                 6 
               
               
                 AD-1223271.1 
                 55 
                 17 
                 61 
                 5 
                 88 
                 14 
                 83 
                 13 
               
               
                 AD-1223272.1 
                 57 
                 28 
                 60 
                 6 
                 75 
                 9 
                 77 
                 6 
               
               
                 AD-1223273.1 
                 33 
                 3 
                 56 
                 7 
                 77 
                 17 
                 94 
                 6 
               
               
                 AD-1223274.1 
                 49 
                 5 
                 67 
                 14 
                 81 
                 9 
                 110 
                 17 
               
               
                 AD-1223275.1 
                 53 
                 4 
                 63 
                 11 
                 67 
                 6 
                 115 
                 15 
               
               
                 AD-1223276.1 
                 53 
                 3 
                 80 
                 15 
                 89 
                 6 
                 98 
                 9 
               
               
                 AD-1223277.1 
                 41 
                 7 
                 67 
                 14 
                 75 
                 6 
                 82 
                 19 
               
               
                 AD-1223278.1 
                 47 
                 2 
                 60 
                 7 
                 69 
                 6 
                 58 
                 7 
               
               
                 AD-1223279.1 
                 57 
                 9 
                 64 
                 8 
                 93 
                 12 
                 102 
                 24 
               
               
                 AD-1223280.1 
                 59 
                 8 
                 72 
                 2 
                 86 
                 11 
                 100 
                 9 
               
               
                 AD-1223281.1 
                 52 
                 5 
                 66 
                 8 
                 86 
                 17 
                 95 
                 13 
               
               
                 AD-1223282.1 
                 35 
                 4 
                 56 
                 9 
                 67 
                 4 
                 103 
                 18 
               
               
                 AD-1223283.1 
                 36 
                 5 
                 43 
                 3 
                 46 
                 2 
                 97 
                 3 
               
               
                 AD-1223284.1 
                 32 
                 1 
                 51 
                 9 
                 60 
                 15 
                 65 
                 7 
               
               
                 AD-1223285.1 
                 37 
                 4 
                 64 
                 19 
                 57 
                 7 
                 76 
                 6 
               
               
                 AD-1223286.1 
                 37 
                 7 
                 38 
                 6 
                 51 
                 7 
                 56 
                 8 
               
               
                 AD-1223287.1 
                 36 
                 8 
                 40 
                 5 
                 60 
                 8 
                 73 
                 23 
               
               
                 AD-1223288.1 
                 46 
                 6 
                 64 
                 10 
                 87 
                 5 
                 77 
                 6 
               
               
                 AD-1223289.1 
                 41 
                 7 
                 61 
                 7 
                 78 
                 1 
                 119 
                 2 
               
               
                 AD-1223290.1 
                 46 
                 6 
                 56 
                 5 
                 76 
                 12 
                 98 
                 9 
               
               
                 AD-1223291.1 
                 41 
                 4 
                 68 
                 9 
                 81 
                 9 
                 94 
                 15 
               
               
                 AD-1223292.1 
                 39 
                 10 
                 84 
                 36 
                 71 
                 4 
                 73 
                 9 
               
               
                 AD-1223293.1 
                 47 
                 7 
                 53 
                 1 
                 65 
                 11 
                 59 
                 7 
               
               
                 AD-1223294.1 
                 38 
                 1 
                 53 
                 4 
                 59 
                 1 
                 61 
                 20 
               
               
                 AD-1223295.1 
                 58 
                 3 
                 67 
                 7 
                 81 
                 8 
                 106 
                 8 
               
               
                 AD-1223296.1 
                 72 
                 1 
                 87 
                 10 
                 87 
                 14 
                 113 
                 19 
               
               
                 AD-1223297.1 
                 54 
                 9 
                 73 
                 11 
                 78 
                 9 
                 99 
                 2 
               
               
                 AD-1223298.1 
                 55 
                 17 
                 65 
                 10 
                 75 
                 9 
                 94 
                 11 
               
               
                 AD-1223299.1 
                 58 
                 9 
                 78 
                 8 
                 85 
                 12 
                 73 
                 12 
               
               
                 AD-1223300.1 
                 54 
                 6 
                 67 
                 7 
                 79 
                 20 
                 70 
                 9 
               
               
                 AD-1223301.1 
                 44 
                 6 
                 61 
                 4 
                 66 
                 4 
                 58 
                 8 
               
               
                 AD-1223302.1 
                 44 
                 6 
                 67 
                 10 
                 77 
                 3 
                 75 
                 9 
               
               
                 AD-1223303.1 
                 37 
                 2 
                 70 
                 9 
                 79 
                 8 
                 74 
                 14 
               
               
                 AD-1223304.1 
                 49 
                 3 
                 71 
                 8 
                 75 
                 9 
                 111 
                 13 
               
               
                 AD-1223305.1 
                 42 
                 4 
                 53 
                 6 
                 71 
                 11 
                 79 
                 9 
               
               
                 AD-1223306.1 
                 39 
                 1 
                 60 
                 12 
                 64 
                 4 
                 71 
                 9 
               
               
                 AD-1223307.1 
                 37 
                 2 
                 62 
                 5 
                 70 
                 17 
                 76 
                 4 
               
               
                 AD-1223308.1 
                 33 
                 1 
                 51 
                 12 
                 57 
                 15 
                 58 
                 6 
               
               
                 AD-1223309.1 
                 45 
                 10 
                 62 
                 14 
                 61 
                 3 
                 63 
                 14 
               
               
                 AD-1223310.1 
                 41 
                 6 
                 54 
                 14 
                 62 
                 2 
                 62 
                 20 
               
               
                 AD-1223311.1 
                 54 
                 5 
                 66 
                 11 
                 72 
                 16 
                 66 
                 12 
               
               
                 AD-1223312.1 
                 38 
                 7 
                 39 
                 2 
                 54 
                 8 
                 67 
                 19 
               
               
                 AD-1223313.1 
                 29 
                 2 
                 40 
                 2 
                 57 
                 6 
                 51 
                 3 
               
               
                 AD-1223314.1 
                 33 
                 9 
                 43 
                 1 
                 47 
                 7 
                 58 
                 8 
               
               
                 AD-1223315.1 
                 28 
                 1 
                 40 
                 4 
                 48 
                 11 
                 61 
                 15 
               
               
                   
               
            
           
         
       
     
     The results of the multi-dose screen in primary human hepatocytes allowed to freely uptake one set of exemplary human VEGF-A siRNAs is shown in Table 9B (correspond to siRNAs in Table 8A and 8B) The multi-dose experiments were performed at 500 nM, 100 nM, 10 nM, and 1 nM final duplex concentrations and the data are expressed as percent message remaining relative to non-targeting control. 
     Of the exemplary siRNA duplexes evaluated in Table 9B, 2 achieved a knockdown of VEGF-A of ≥80%, 53 achieved a knockdown of VEGF-A of ≥60%, and 239 achieved a knockdown of VEGF-A of ≥30% when administered at the 500 nM concentration. 
     Of the exemplary siRNA duplexes evaluated in Table 9B, 4 achieved a knockdown of VEGF-A of ≥70%, 33 achieved a knockdown of VEGF-A of ≥60%, and 235 achieved a knockdown of VEGF-A of ≥30% when administered at the 100 nM concentration. 
     Of the exemplary siRNA duplexes evaluated in Table 9B, 3 achieved a knockdown of VEGF-A of ≥60%, 52 achieved a knockdown of VEGF-A of ≥40%, and 113 achieved a knockdown of VEGF-A of ≥30% when administered at the 10 nM concentration. 
     Of the exemplary siRNA duplexes evaluated in Table 9B, 13 achieved a knockdown of VEGF-A of ≥50%, 88 achieved a knockdown of VEGF-A of ≥30%, and 146 achieved a knockdown of VEGF-A of ≥20% when administered at the 1 nM concentration. 
     
       
         
           
               
             
               
                 TABLE 9B 
               
             
            
               
                   
               
               
                 VEGF-A endogenous in vitro multi-dose screen following 
               
               
                 free uptake of one set of exemplary human VEGF-A siRNAs 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 DuplexID 
                 500 nM 
                 StDev 
                 100 nM 
                 StDev 
                 10 nM 
                 StDev 
                 1 nM 
                 StDev 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 AD-1222866.1 
                 114 
                 23 
                 103 
                 40 
                 117 
                 14 
                 117 
                 9 
               
               
                 AD-1222867.1 
                 114 
                 11 
                 176 
                 58 
                 104 
                 9 
                 134 
                 24 
               
               
                 AD-1222868.1 
                 140 
                 19 
                 168 
                 85 
                 123 
                 18 
                 134 
                 6 
               
               
                 AD-1222869.1 
                 110 
                 12 
                 149 
                 62 
                 149 
                 23 
                 131 
                 25 
               
               
                 AD-1222870.1 
                 107 
                 20 
                 191 
                 9 
                 138 
                 24 
                 124 
                 15 
               
               
                 AD-1222871.1 
                 102 
                 11 
                 140 
                 48 
                 130 
                 13 
                 138 
                 18 
               
               
                 AD-1222872.1 
                 95 
                 20 
                 112 
                 27 
                 112 
                 15 
                 120 
                 9 
               
               
                 AD-1222873.1 
                 73 
                 17 
                 94 
                 10 
                 107 
                 1 
                 110 
                 6 
               
               
                 AD-1222874.1 
                 148 
                 27 
                 109 
                 6 
                 137 
                 5 
                 113 
                 9 
               
               
                 AD-1222875.1 
                 132 
                 7 
                 93 
                 4 
                 161 
                 25 
                 139 
                 11 
               
               
                 AD-1222876.1 
                 142 
                 12 
                 141 
                 1 
                 131 
                 11 
                 145 
                 8 
               
               
                 AD-1222877.1 
                 119 
                 2 
                 111 
                 3 
                 176 
                 15 
                 132 
                 4 
               
               
                 AD-1222878.1 
                 160 
                 43 
                 128 
                 10 
                 139 
                 8 
                 128 
                 16 
               
               
                 AD-1222879.1 
                 150 
                 21 
                 119 
                 13 
                 139 
                 22 
                 116 
                 16 
               
               
                 AD-1222880.1 
                 107 
                 22 
                 113 
                 9 
                 145 
                 21 
                 120 
                 7 
               
               
                 AD-1222881.1 
                 90 
                 28 
                 91 
                 4 
                 106 
                 2 
                 113 
                 7 
               
               
                 AD-1222882.1 
                 151 
                 4 
                 118 
                 7 
                 136 
                 4 
                 114 
                 4 
               
               
                 AD-1222883.1 
                 143 
                 13 
                 120 
                 11 
                 147 
                 12 
                 129 
                 8 
               
               
                 AD-1222884.1 
                 137 
                 22 
                 135 
                 23 
                 174 
                 18 
                 120 
                 12 
               
               
                 AD-1222885.1 
                 162 
                 16 
                 130 
                 13 
                 169 
                 15 
                 120 
                 4 
               
               
                 AD-1222886.1 
                 128 
                 26 
                 114 
                 1 
                 155 
                 16 
                 107 
                 14 
               
               
                 AD-1222887.1 
                 143 
                 32 
                 128 
                 24 
                 124 
                 10 
                 116 
                 13 
               
               
                 AD-1222888.1 
                 77 
                 7 
                 113 
                 2 
                 123 
                 1 
                 116 
                 10 
               
               
                 AD-1222889.1 
                 142 
                 11 
                 92 
                 18 
                 143 
                 31 
                 113 
                 13 
               
               
                 AD-1222890.1 
                 160 
                 11 
                 129 
                 12 
                 166 
                 27 
                 133 
                 2 
               
               
                 AD-1222891.1 
                 138 
                 12 
                 126 
                 6 
                 173 
                 27 
                 136 
                 17 
               
               
                 AD-1222892.1 
                 136 
                 7 
                 127 
                 9 
                 153 
                 27 
                 106 
                 7 
               
               
                 AD-1222893.1 
                 111 
                 11 
                 118 
                 6 
                 141 
                 10 
                 130 
                 16 
               
               
                 AD-1222894.1 
                 111 
                 12 
                 118 
                 10 
                 119 
                 24 
                 123 
                 2 
               
               
                 AD-1222895.1 
                 96 
                 8 
                 103 
                 0 
                 121 
                 27 
                 122 
                 18 
               
               
                 AD-1222896.1 
                 142 
                 23 
                 97 
                 18 
                 134 
                 6 
                 113 
                 3 
               
               
                 AD-1222897.1 
                 155 
                 13 
                 126 
                 6 
                 157 
                 21 
                 129 
                 12 
               
               
                 AD-1222898.1 
                 152 
                 53 
                 124 
                 18 
                 141 
                 19 
                 111 
                 10 
               
               
                 AD-1222899.1 
                 138 
                 21 
                 110 
                 9 
                 147 
                 28 
                 120 
                 1 
               
               
                 AD-1222900.1 
                 123 
                 15 
                 115 
                 20 
                 166 
                 13 
                 108 
                 8 
               
               
                 AD-1222901.1 
                 106 
                 6 
                 116 
                 6 
                 161 
                 17 
                 105 
                 15 
               
               
                 AD-1222902.1 
                 86 
                 7 
                 106 
                 12 
                 126 
                 28 
                 91 
                 3 
               
               
                 AD-1222903.1 
                 84 
                 5 
                 95 
                 2 
                 138 
                 6 
                 112 
                 23 
               
               
                 AD-1222904.1 
                 115 
                 19 
                 92 
                 3 
                 127 
                 2 
                 103 
                 7 
               
               
                 AD-1222905.1 
                 137 
                 10 
                 129 
                 11 
                 132 
                 22 
                 107 
                 3 
               
               
                 AD-1222906.1 
                 122 
                 23 
                 142 
                 8 
                 131 
                 19 
                 119 
                 15 
               
               
                 AD-1222907.1 
                 126 
                 35 
                 120 
                 11 
                 143 
                 22 
                 103 
                 3 
               
               
                 AD-1222908.1 
                 113 
                 12 
                 108 
                 7 
                 155 
                 32 
                 91 
                 10 
               
               
                 AD-1222909.1 
                 104 
                 2 
                 106 
                 13 
                 134 
                 23 
                 106 
                 2 
               
               
                 AD-1222910.1 
                 79 
                 1 
                 102 
                 4 
                 104 
                 14 
                 82 
                 9 
               
               
                 AD-1222911.1 
                 114 
                 8 
                 106 
                 22 
                 98 
                 11 
                 102 
                 6 
               
               
                 AD-1222912.1 
                 107 
                 4 
                 120 
                 14 
                 119 
                 4 
                 114 
                 13 
               
               
                 AD-1222913.1 
                 126 
                 31 
                 115 
                 5 
                 109 
                 13 
                 103 
                 11 
               
               
                 AD-1222914.1 
                 109 
                 17 
                 118 
                 20 
                 116 
                 5 
                 108 
                 18 
               
               
                 AD-1222915.1 
                 88 
                 3 
                 95 
                 11 
                 120 
                 21 
                 88 
                 14 
               
               
                 AD-1222916.1 
                 91 
                 12 
                 98 
                 13 
                 114 
                 27 
                 99 
                 18 
               
               
                 AD-1222917.1 
                 70 
                 1 
                 93 
                 6 
                 88 
                 16 
                 86 
                 2 
               
               
                 AD-1222918.1 
                 93 
                 6 
                 104 
                 6 
                 85 
                 3 
                 101 
                 5 
               
               
                 AD-1222920.1 
                 88 
                 12 
                 90 
                 10 
                 95 
                 6 
                 100 
                 8 
               
               
                 AD-1222921.1 
                 109 
                 19 
                 108 
                 5 
                 111 
                 27 
                 105 
                 18 
               
               
                 AD-1222922.1 
                 91 
                 20 
                 87 
                 5 
                 124 
                 12 
                 104 
                 10 
               
               
                 AD-1222923.1 
                 70 
                 19 
                 91 
                 6 
                 109 
                 11 
                 82 
                 2 
               
               
                 AD-1222924.1 
                 85 
                 14 
                 103 
                 13 
                 107 
                 14 
                 83 
                 17 
               
               
                 AD-1222925.1 
                 82 
                 22 
                 97 
                 14 
                 88 
                 12 
                 78 
                 4 
               
               
                 AD-1222926.1 
                 103 
                 9 
                 86 
                 14 
                 92 
                 18 
                 93 
                 13 
               
               
                 AD-1222927.1 
                 73 
                 8 
                 59 
                 11 
                 78 
                 16 
                 80 
                 2 
               
               
                 AD-1222928.1 
                 80 
                 1 
                 71 
                 11 
                 85 
                 9 
                 94 
                 7 
               
               
                 AD-1222929.1 
                 80 
                 8 
                 85 
                 3 
                 80 
                 5 
                 94 
                 17 
               
               
                 AD-1222930.1 
                 76 
                 6 
                 85 
                 6 
                 97 
                 11 
                 74 
                 3 
               
               
                 AD-1222931.1 
                 79 
                 18 
                 89 
                 9 
                 90 
                 15 
                 74 
                 10 
               
               
                 AD-1222932.1 
                 85 
                 1 
                 81 
                 16 
                 76 
                 3 
                 57 
                 7 
               
               
                 AD-1222933.1 
                 62 
                 2 
                 64 
                 4 
                 77 
                 5 
                 67 
                 10 
               
               
                 AD-1222934.1 
                 43 
                 3 
                 45 
                 9 
                 63 
                 6 
                 62 
                 1 
               
               
                 AD-1222935.1 
                 43 
                 3 
                 53 
                 12 
                 73 
                 2 
                 78 
                 2 
               
               
                 AD-1222936.1 
                 66 
                 11 
                 56 
                 11 
                 65 
                 10 
                 75 
                 6 
               
               
                 AD-1222937.1 
                 72 
                 13 
                 75 
                 5 
                 90 
                 16 
                 72 
                 5 
               
               
                 AD-1222938.1 
                 65 
                 6 
                 71 
                 14 
                 78 
                 11 
                 81 
                 8 
               
               
                 AD-1222939.1 
                 55 
                 6 
                 70 
                 4 
                 77 
                 10 
                 85 
                 7 
               
               
                 AD-1222940.1 
                 61 
                 16 
                 44 
                 1 
                 71 
                 6 
                 74 
                 2 
               
               
                 AD-1222941.1 
                 44 
                 7 
                 42 
                 10 
                 51 
                 5 
                 43 
                 4 
               
               
                 AD-1222942.1 
                 31 
                 0 
                 37 
                 3 
                 64 
                 8 
                 59 
                 6 
               
               
                 AD-1222943.1 
                 58 
                 7 
                 54 
                 11 
                 65 
                 2 
                 58 
                 11 
               
               
                 AD-1222944.1 
                 46 
                 6 
                 49 
                 6 
                 69 
                 7 
                 63 
                 12 
               
               
                 AD-1222945.1 
                 57 
                 6 
                 62 
                 14 
                 69 
                 11 
                 55 
                 11 
               
               
                 AD-1222946.1 
                 50 
                 5 
                 60 
                 16 
                 55 
                 2 
                 57 
                 3 
               
               
                 AD-1222947.1 
                 37 
                 4 
                 43 
                 9 
                 59 
                 5 
                 62 
                 9 
               
               
                 AD-1222948.1 
                 60 
                 1 
                 63 
                 16 
                 61 
                 13 
                 57 
                 1 
               
               
                 AD-1222949.1 
                 40 
                 7 
                 41 
                 12 
                 61 
                 7 
                 46 
                 1 
               
               
                 AD-1222950.1 
                 36 
                 4 
                 36 
                 7 
                 55 
                 1 
                 44 
                 4 
               
               
                 AD-1222951.1 
                 34 
                 5 
                 32 
                 6 
                 52 
                 4 
                 41 
                 5 
               
               
                 AD-1222952.1 
                 61 
                 6 
                 48 
                 14 
                 65 
                 7 
                 44 
                 8 
               
               
                 AD-1222953.1 
                 34 
                 6 
                 30 
                 5 
                 51 
                 6 
                 43 
                 1 
               
               
                 AD-1222954.1 
                 15 
                 2 
                 25 
                 5 
                 47 
                 4 
                 36 
                 1 
               
               
                 AD-1222955.1 
                 19 
                 3 
                 26 
                 5 
                 52 
                 8 
                 40 
                 1 
               
               
                 AD-1222956.1 
                 64 
                 8 
                 72 
                 5 
                 110 
                 6 
                 123 
                 6 
               
               
                 AD-1222957.1 
                 132 
                 19 
                 98 
                 5 
                 109 
                 14 
                 122 
                 3 
               
               
                 AD-1222958.1 
                 72 
                 10 
                 96 
                 7 
                 120 
                 26 
                 133 
                 3 
               
               
                 AD-1222959.1 
                 76 
                 13 
                 88 
                 2 
                 119 
                 29 
                 125 
                 4 
               
               
                 AD-1222960.1 
                 71 
                 3 
                 123 
                 14 
                 136 
                 39 
                 141 
                 8 
               
               
                 AD-1222961.1 
                 112 
                 10 
                 119 
                 10 
                 128 
                 41 
                 115 
                 1 
               
               
                 AD-1222962.1 
                 88 
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                 50 
                 6 
               
               
                   
               
            
           
         
       
     
     The results of the multi-dose screen in primary human hepatocytes transfected with an additional set of exemplary human VEGF-A siRNAs is shown in Table 11 (correspond to modified siRNAs in Table 10A). The multi-dose experiments were performed at 50 nM, 10 nM, 1 nM, and 0.1 nM final duplex concentrations and the data are expressed as percent message remaining relative to non-targeting control. 
     Of the exemplary siRNA duplexes evaluated in Table 11, 6 achieved a knockdown of VEGF-A of ≥70%, 34 achieved a knockdown of VEGF-A of ≥60%, 49 achieved a knockdown of VEGF-A of ≥50%, 62 achieved a knockdown of VEGF-A of ≥30%, and 75 achieved a knockdown of VEGF-A of ≥20% when administered at the 50 nM concentration. 
     Of the exemplary siRNA duplexes evaluated in Table 11, 2 achieved a knockdown of VEGF-A of ≥70%, 18 achieved a knockdown of VEGF-A of ≥60%, 35 achieved a knockdown of VEGF-A of ≥50%, 66 achieved a knockdown of VEGF-A of ≥30%, and 77 achieved a knockdown of VEGF-A of ≥20% when administered at the 10 nM concentration. 
     Of the exemplary siRNA duplexes evaluated in Table 11, 13 achieved a knockdown of VEGF-A of ≥50%, 33 achieved a knockdown of VEGF-A of ≥40%, 49 achieved a knockdown of VEGF-A of ≥30%, 62 achieved a knockdown of VEGF-A of ≥20%, and 74 achieved a knockdown of VEGF-A of ≥10% when administered at the 1 nM concentration. 
     Of the exemplary siRNA duplexes evaluated in Table 11, 2 achieved a knockdown of VEGF-A of ≥40%, 7 achieved a knockdown of VEGF-A of ≥30%, 25 achieved a knockdown of VEGF-A of ≥20%, 46 achieved a knockdown of VEGF-A of ≥10%, and 55 achieved a knockdown of VEGF-A of ≥5% when administered at the 0.1 nM concentration. 
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 VEGF-A endogenous in vitro multi-dose screen following cellular 
               
               
                 transfection with additional set of exemplary human VEGF-A siRNAs 
               
            
           
           
               
               
               
               
               
            
               
                   
                 50 nM dose 
                 10 nM dose 
                 1 nM dose 
                 0.1 nM dose 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Duplex 
                 Avg 
                 SD 
                 Avg 
                 SD 
                 Avg 
                 SD 
                 Avg 
                 SD 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 AD-1353514.1 
                 73.2 
                 14.7 
                 47.83 
                 6.33 
                 89.52 
                 8.82 
                 108.56 
                 17.50 
               
               
                 AD-1353484.1 
                 60.9 
                 2.1 
                 30.99 
                 3.11 
                 46.98 
                 8.32 
                 74.34 
                 10.43 
               
               
                 AD-1353454.1 
                 32.1 
                 2.1 
                 31.33 
                 5.04 
                 48.05 
                 7.92 
                 52.74 
                 3.79 
               
               
                 AD-1353468.1 
                 36.5 
                 10.1 
                 37.70 
                 11.20 
                 54.44 
                 8.95 
                 76.93 
                 5.45 
               
               
                 AD-1353498.1 
                 71.4 
                 8.9 
                 70.68 
                 17.79 
                 91.31 
                 15.16 
                 119.43 
                 2.90 
               
               
                 AD-1353438.1 
                 30.4 
                 5.0 
                 36.17 
                 11.97 
                 49.92 
                 9.56 
                 68.61 
                 10.47 
               
               
                 AD-1353515.1 
                 85.4 
                 4.7 
                 59.45 
                 15.56 
                 86.89 
                 15.76 
                 119.70 
                 10.55 
               
               
                 AD-1353485.1 
                 61.2 
                 3.6 
                 67.37 
                 28.56 
                 73.00 
                 19.46 
                 101.36 
                 12.30 
               
               
                 AD-1353455.1 
                 37.7 
                 5.8 
                 39.73 
                 4.39 
                 57.46 
                 11.43 
                 75.26 
                 9.60 
               
               
                 AD-1353513.1 
                 72.4 
                 19.2 
                 70.36 
                 7.66 
                 65.81 
                 2.00 
                 99.31 
                 4.26 
               
               
                 AD-1353483.1 
                 45.4 
                 7.9 
                 59.48 
                 13.52 
                 63.00 
                 1.14 
                 88.59 
                 7.06 
               
               
                 AD-1353453.1 
                 49.4 
                 3.1 
                 52.47 
                 11.81 
                 73.02 
                 14.48 
                 87.42 
                 1.86 
               
               
                 AD-1353502.1 
                 111.8 
                 3.9 
                 122.89 
                 9.45 
                 108.63 
                 2.65 
                 101.24 
                 12.32 
               
               
                 AD-1353472.1 
                 77.7 
                 1.1 
                 77.95 
                 21.21 
                 82.89 
                 10.59 
                 110.13 
                 1.33 
               
               
                 AD-1353442.1 
                 43.1 
                 5.9 
                 58.75 
                 26.58 
                 53.92 
                 6.62 
                 86.50 
                 13.94 
               
               
                 AD-1353499.1 
                 52.6 
                 8.5 
                 50.86 
                 1.41 
                 60.86 
                 4.25 
                 68.29 
                 32.87 
               
               
                 AD-1353469.1 
                 34.2 
                 4.9 
                 26.91 
                 8.25 
                 52.31 
                 12.97 
                 68.94 
                 3.00 
               
               
                 AD-1353439.1 
                 40.5 
                 7.0 
                 33.92 
                 5.01 
                 47.72 
                 5.18 
                 59.98 
                 0.64 
               
               
                 AD-1353516.1 
                 73.4 
                 2.3 
                 91.54 
                 6.70 
                 96.22 
                 13.84 
                 109.69 
                 16.01 
               
               
                 AD-1353486.1 
                 55.2 
                 10.8 
                 69.54 
                 22.45 
                 66.89 
                 15.26 
                 85.60 
                 12.44 
               
               
                 AD-1353456.1 
                 36.7 
                 2.3 
                 40.99 
                 2.33 
                 47.06 
                 0.75 
                 77.80 
                 12.27 
               
               
                 AD-1353509.1 
                 78.2 
                 15.5 
                 65.05 
                 19.24 
                 79.91 
                 15.99 
                 92.15 
                 6.76 
               
               
                 AD-1353479.1 
                 34.1 
                 1.7 
                 59.07 
                 11.65 
                 61.37 
                 12.56 
                 81.86 
                 11.12 
               
               
                 AD-1353449.1 
                 37.2 
                 3.1 
                 43.76 
                 2.00 
                 64.46 
                 14.54 
                 94.21 
                 15.51 
               
               
                 AD-1353503.1 
                 107.2 
                 12.2 
                 124.19 
                 25.48 
                 129.99 
                 12.55 
                 103.32 
                 5.51 
               
               
                 AD-1353473.1 
                 69.5 
                 12.8 
                 81.70 
                 4.74 
                 73.09 
                 4.34 
                 96.57 
                 7.16 
               
               
                 AD-1353443.1 
                 56.0 
                 5.3 
                 47.76 
                 1.37 
                 60.14 
                 2.14 
                 78.45 
                 2.90 
               
               
                 AD-1353506.1 
                 125.4 
                 15.1 
                 72.10 
                 10.55 
                 98.53 
                 31.92 
                 139.95 
                 25.71 
               
               
                 AD-1353476.1 
                 31.1 
                 0.9 
                 52.33 
                 18.02 
                 53.46 
                 8.06 
                 81.81 
                 20.46 
               
               
                 AD-1353446.1 
                 33.5 
                 3.9 
                 49.43 
                 19.14 
                 48.57 
                 12.81 
                 89.09 
                 18.37 
               
               
                 AD-1353497.1 
                 73.7 
                 15.2 
                 76.17 
                 18.94 
                 110.55 
                 19.54 
                 108.38 
                 14.24 
               
               
                 AD-1353467.1 
                 24.1 
                 1.6 
                 68.83 
                 36.91 
                 60.52 
                 9.05 
                 88.11 
                 6.79 
               
               
                 AD-1353437.1 
                 26.6 
                 1.3 
                 36.54 
                 18.99 
                 58.73 
                 11.11 
                 78.39 
                 13.30 
               
               
                 AD-1353494.1 
                 78.9 
                 18.5 
                 64.78 
                 5.56 
                 80.76 
                 28.61 
                 105.16 
                 8.40 
               
               
                 AD-1353464.1 
                 39.2 
                 11.1 
                 43.51 
                 10.28 
                 46.64 
                 1.22 
                 86.15 
                 13.43 
               
               
                 AD-1353434.1 
                 25.8 
                 2.3 
                 35.87 
                 7.53 
                 46.49 
                 2.58 
                 88.48 
                 12.93 
               
               
                 AD-1353505.1 
                 79.3 
                 14.0 
                 90.37 
                 26.82 
                 88.87 
                 9.99 
                 118.05 
                 27.89 
               
               
                 AD-1353475.1 
                 45.8 
                 4.4 
                 81.74 
                 24.42 
                 61.65 
                 9.73 
                 113.65 
                 24.35 
               
               
                 AD-1353445.1 
                 33.1 
                 4.6 
                 34.12 
                 2.32 
                 58.71 
                 12.42 
                 76.70 
                 5.84 
               
               
                 AD-1353518.1 
                 106.7 
                 9.5 
                 66.77 
                 10.60 
                 101.34 
                 19.91 
                 116.14 
                 13.23 
               
               
                 AD-1353490.1 
                 57.6 
                 2.9 
                 65.55 
                 2.51 
                 59.72 
                 1.89 
                 82.32 
                 10.94 
               
               
                 AD-1353460.1 
                 43.3 
                 2.2 
                 57.20 
                 17.51 
                 57.83 
                 6.41 
                 81.60 
                 3.42 
               
               
                 AD-1353512.1 
                 49.3 
                 2.8 
                 56.05 
                 16.30 
                 73.12 
                 5.01 
                 80.00 
                 12.61 
               
               
                 AD-1353482.1 
                 31.8 
                 7.0 
                 41.02 
                 4.08 
                 49.87 
                 13.58 
                 75.30 
                 11.76 
               
               
                 AD-1353452.1 
                 22.0 
                 0.8 
                 27.69 
                 6.99 
                 49.18 
                 8.36 
                 64.25 
                 8.77 
               
               
                 AD-1353501.1 
                 93.4 
                 14.4 
                 73.05 
                 23.54 
                 91.52 
                 22.64 
                 118.07 
                 3.73 
               
               
                 AD-1353471.1 
                 35.3 
                 16.6 
                 55.66 
                 10.36 
                 62.03 
                 8.43 
                 74.30 
                 10.30 
               
               
                 AD-1353441.1 
                 42.8 
                 12.1 
                 37.07 
                 2.05 
                 55.05 
                 11.83 
                 87.87 
                 11.35 
               
               
                 AD-1353495.1 
                 64.9 
                 6.6 
                 57.36 
                 3.08 
                 76.11 
                 7.59 
                 91.83 
                 2.54 
               
               
                 AD-1353465.1 
                 46.1 
                 9.0 
                 52.06 
                 2.82 
                 71.33 
                 9.34 
                 96.77 
                 3.94 
               
               
                 AD-1353435.1 
                 26.6 
                 0.6 
                 34.92 
                 2.32 
                 52.83 
                 10.26 
                 75.24 
                 2.38 
               
               
                 AD-1353510.1 
                 119.8 
                 18.1 
                 101.24 
                 29.18 
                 93.46 
                 10.24 
                 113.16 
                 12.92 
               
               
                 AD-1353480.1 
                 31.4 
                 6.3 
                 39.32 
                 0.42 
                 41.34 
                 14.17 
                 67.02 
                 5.59 
               
               
                 AD-1353450.1 
                 34.6 
                 7.4 
                 66.32 
                 23.95 
                 50.20 
                 0.35 
                 73.85 
                 1.29 
               
               
                 AD-1353492.1 
                 77.7 
                 10.8 
                 71.56 
                 11.36 
                 77.86 
                 8.02 
                 121.84 
                 4.81 
               
               
                 AD-1353462.1 
                 77.9 
                 8.7 
                 61.05 
                 3.21 
                 84.55 
                 11.04 
                 95.78 
                 4.27 
               
               
                 AD-1353432.1 
                 53.3 
                 2.4 
                 54.18 
                 15.15 
                 77.02 
                 10.61 
                 91.59 
                 3.58 
               
               
                 AD-1353504.1 
                 112.3 
                 16.9 
                 103.54 
                 22.58 
                 96.95 
                 21.25 
                 104.68 
                 1.67 
               
               
                 AD-1353474.1 
                 37.3 
                 0.8 
                 45.61 
                 7.93 
                 64.86 
                 13.55 
                 90.57 
                 9.24 
               
               
                 AD-1353444.1 
                 34.6 
                 2.7 
                 46.49 
                 12.28 
                 64.50 
                 3.69 
                 90.43 
                 15.39 
               
               
                 AD-1353493.1 
                 115.2 
                 3.5 
                 109.69 
                 24.35 
                 115.11 
                 15.22 
                 148.20 
                 6.03 
               
               
                 AD-1353463.1 
                 37.4 
                 10.6 
                 39.98 
                 1.58 
                 67.51 
                 13.18 
                 101.55 
                 10.32 
               
               
                 AD-1353433.1 
                 41.6 
                 2.6 
                 49.27 
                 11.07 
                 57.69 
                 7.11 
                 85.23 
                 1.77 
               
               
                 AD-1353508.1 
                 99.1 
                 18.5 
                 108.35 
                 7.54 
                 119.28 
                 22.06 
                 127.04 
                 26.81 
               
               
                 AD-1353478.1 
                 61.3 
                 7.9 
                 80.29 
                 6.74 
                 84.40 
                 5.07 
                 106.24 
                 18.11 
               
               
                 AD-1353448.1 
                 46.8 
                 10.5 
                 45.28 
                 0.83 
                 70.79 
                 13.97 
                 93.49 
                 2.61 
               
               
                 AD-1353496.1 
                 71.4 
                 11.4 
                 72.67 
                 26.10 
                 75.08 
                 10.38 
                 78.24 
                 0.83 
               
               
                 AD-1353466.1 
                 27.1 
                 2.2 
                 41.23 
                 4.27 
                 46.93 
                 8.96 
                 74.57 
                 10.13 
               
               
                 AD-1353436.1 
                 34.3 
                 12.7 
                 44.21 
                 16.99 
                 76.15 
                 17.23 
                 100.46 
                 13.86 
               
               
                 AD-1353500.1 
                 93.3 
                 10.4 
                 71.79 
                 21.42 
                 90.97 
                 13.97 
                 121.98 
                 8.36 
               
               
                 AD-1353470.1 
                 56.5 
                 18.5 
                 68.60 
                 21.85 
                 66.08 
                 16.35 
                 98.20 
                 16.07 
               
               
                 AD-1353440.1 
                 42.7 
                 13.9 
                 32.74 
                 2.42 
                 47.72 
                 4.01 
                 87.22 
                 13.60 
               
               
                 AD-1334067.3 
                 62.0 
                 5.0 
                 66.03 
                 15.65 
                 104.31 
                 6.24 
                 118.77 
                 15.26 
               
               
                 AD-1353488.1 
                 45.4 
                 9.5 
                 54.95 
                 18.87 
                 66.30 
                 5.64 
                 93.92 
                 6.82 
               
               
                 AD-1353458.1 
                 49.9 
                 2.7 
                 42.68 
                 4.29 
                 52.79 
                 7.82 
                 86.26 
                 5.91 
               
               
                 AD-1334065.3 
                 71.1 
                 12.6 
                 78.09 
                 22.23 
                 84.66 
                 18.18 
                 114.25 
                 13.96 
               
               
                 AD-1353487.1 
                 34.9 
                 4.5 
                 66.90 
                 18.73 
                 56.96 
                 8.69 
                 78.72 
                 9.61 
               
               
                 AD-1353457.1 
                 38.2 
                 9.3 
                 58.10 
                 28.97 
                 54.23 
                 13.92 
                 72.52 
                 6.80 
               
               
                 AD-1353511.1 
                 83.9 
                 11.7 
                 62.66 
                 20.11 
                 82.39 
                 4.29 
                 108.94 
                 17.57 
               
               
                 AD-1353481.1 
                 37.4 
                 5.3 
                 33.15 
                 14.70 
                 53.45 
                 6.54 
                 89.49 
                 20.18 
               
               
                 AD-1353451.1 
                 36.5 
                 3.0 
                 50.19 
                 3.34 
                 70.69 
                 2.05 
                 89.11 
                 5.24 
               
               
                 AD-1353507.1 
                 88.8 
                 24.1 
                 103.80 
                 3.43 
                 118.16 
                 22.78 
                 109.81 
                 8.53 
               
               
                 AD-1353477.1 
                 58.1 
                 13.7 
                 71.67 
                 24.75 
                 89.22 
                 12.01 
                 97.98 
                 5.38 
               
               
                 AD-1353447.1 
                 35.9 
                 5.8 
                 35.44 
                 0.37 
                 69.83 
                 7.21 
                 93.70 
                 5.60 
               
               
                 AD-1353517.1 
                 81.4 
                 27.8 
                 65.25 
                 15.18 
                 87.98 
                 15.64 
                 87.33 
                 5.55 
               
               
                 AD-1353489.1 
                 39.1 
                 8.5 
                 48.80 
                 14.60 
                 53.72 
                 2.50 
                 78.25 
                 4.63 
               
               
                 AD-1353459.1 
                 36.3 
                 3.0 
                 42.48 
                 5.66 
                 55.07 
                 0.79 
                 88.61 
                 15.57 
               
               
                 AD-1353519.1 
                 99.4 
                 27.7 
                 81.48 
                 9.81 
                 93.30 
                 21.44 
                 129.30 
                 24.38 
               
               
                 AD-1353491.1 
                 49.6 
                 22.3 
                 68.94 
                 16.28 
                 84.63 
                 0.34 
                 82.41 
                 4.90 
               
               
                 AD-1353461.1 
                 36.0 
                 7.6 
                 42.22 
                 11.83 
                 52.71 
                 11.40 
                 75.56 
                 6.49 
               
               
                   
               
            
           
         
       
     
     Example 3. In Vivo Screening of VEGF-A siRNA 
     This Example investigates the effects of the exemplary VEGF-A targeting siRNAs for in vivo efficacy for human VEGF-A knockdown in AAV mice. The first exemplary set of VEGF-A targeting siRNAs investigated includes AD-64228, AD-953374, AD-953504, AD-953336, AD-953337, AD-901376, AD-953364, AD-953340, AD-953351, AD-953342, AD-953308, AD-953344, AD-953339, and AD-953363 (summarized in Table 12 and  FIGS.  1 A- 1 B ). The second set of exemplary VEGF-A targeting siRNAs investigated included AD-901349, AD-953481, AD-901356, AD-901355, AD-953365, AD-953410, AD-953411, AD-953338, AD-953350, AD-953375, AD-953341, AD-953370, AD-953386, AD-64958 (summarized in Table 13 and  FIGS.  3 A- 3 B ) The final set of exemplary VEGF-A targeting siRNAs investigated included AD-1397050, AD-1397051, AD-1397052, AD-1397053, AD-1397054, AD-1397055, AD-1397056, AD-1397058, AD-1397059, AD-1397060, AD-1397061, AD-1397062, AD-1397064, AD-1397065, AD-1397066, AD-1397067, AD-1397068, AD-1397069, and AD-64958 (summarized in Table 14 and  FIGS.  5 A- 5 C ). 
     
       
         
           
               
             
               
                 TABLE 12 
               
             
            
               
                   
               
               
                 VEGF-A in vivo single-dose screen with one set of exemplary VEGF-A siRNA 
               
               
                 duplexes. In this table the column “Duplex Name” provides the numerical part 
               
               
                 of the duplex name. The duplex name can comprise a suffix (number following 
               
               
                 the decimal point in a duplex name) that merely refers to a batch  production 
               
               
                 number. The suffix can be omitted from the duplex name without changing the 
               
               
                 chemical structure. For example, duplex AD-953504.1 in Table 4A refers to the 
               
               
                 same duplex as AD-953504 in Table 12. 
               
            
           
           
               
               
               
               
               
            
               
                 Duplex 
                   
                   
                   
                 SEQ ID 
               
               
                 Name 
                 Strand 
                 Target 
                 Modified Sequence (5′-3′) 
                 NO 
               
               
                   
               
               
                 AD-64228 
                 sense 
                 None 
                 asascaguGfuUfCfUfugcucuauaaL96 
                 4162 
               
               
                   
                 anti- 
                 mTTR 
                 usUfsauaGfaGfCfaagaAfcAfcuguususu 
                 4163 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953504 
                 sense 
                 VEGF-A 
                 asasaau(Ahd)gadCadTugcuauucuaL96 
                 1037 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusdAsgadAudAgcaadTgdTcdTauuuusasu 
                 1167 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953308 
                 sense 
                 VEGF-A 
                 csascca(Uhd)GfcAfGfAfuuaugcggaaL96 
                  579 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusUfsccgCfaUfAfaucuGfcAfuggugsasu 
                  709 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953336 
                 sense 
                 VEGF-A 
                 asasaga(Chd)UfgAfUfAfcagaacgauaL96 
                  518 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusAfsucgUfuCfUfguauCfaGfucuuuscsc 
                  648 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953337 
                 sense 
                 VEGF-A 
                 asasgac(Uhd)GfaUfAfCfagaacgaucaL96 
                  522 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusGfsaucGfuUfCfuguaUfcAfgucuususc 
                  652 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953339 
                 sense 
                 VEGF-A 
                 gsascug(Ahd)UfaCfAfGfaacgaucgaaL96 
                  528 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusUfscgaUfcGfUfucugUfaUfcagucsusu 
                  658 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953340 
                 sense 
                 VEGF-A 
                 ascsuga(Uhd)AfcAfGfAfacgaucgauaL96 
                  517 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusAfsucgAfuCfGfuucuGfuAfucaguscsu 
                  647 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953342 
                 sense 
                 VEGF-A 
                 asusaca(Ghd)AfaCfGfAfucgauacagaL96 
                  523 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusCfsuguAfuCfGfaucgUfuCfuguauscsa 
                  653 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953344 
                 sense 
                 VEGF-A 
                 csasgaa(Chd)AfgUfCfCfuuaauccagaL96 
                  527 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusCfsuggAfuUfAfaggaCfuGfuucugsusc 
                  657 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953351 
                 sense 
                 VEGF-A 
                 asgsugc(Uhd)AfaUfGfUfuauugguguaL96 
                  540 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusAfscacCfaAfUfaacaUfuAfgcacusgsu 
                  670 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953363 
                 sense 
                 VEGF-A 
                 gsasgaa(Ahd)GfuGfUfUfuuauauacgaL96 
                  519 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusCfsguaUfaUfAfaaacAfcUfuucucsusu 
                  649 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953364 
                 sense 
                 VEGF-A 
                 ascsggu(Ahd)CfuUfAfUfuuaauauccaL96 
                  567 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusGfsgauAfuUfAfaauaAfgUfaccgusasu 
                  697 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-901376 
                 sense 
                 VEGF-A 
                 ascsggu(Ahd)CfuUfAfUfuuaauauccaL96 
                 4157 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusGfsgaua(Tgn)uaaauaAfgUfaccgusasu 
                  131 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953374 
                 sense 
                 VEGF-A 
                 asasaau(Ahd)GfaCfAfUfugcuauucuaL96 
                  553 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusAfsgaaUfaGfCfaaugUfcUfauuuusasu 
                  683 
               
               
                   
                 sense 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13 
               
             
            
               
                   
               
               
                 VEGF-A in vivo single-dose screen with one set of exemplary VEGF-A siRNA 
               
               
                 duplexes. In this table the column “Duplex Name” provides the numerical part of the 
               
               
                 duplex name. The duplex name can comprise a suffix (number following the decimal point 
               
               
                 in a duplex name) that merely refers to a batch production number. The suffix can be 
               
               
                 omitted from the duplex name without changing the chemical structure. For example, 
               
               
                 duplex AD-953481.1 in Table 4A refers to the same duplex as AD-953481 in Table 13. 
               
            
           
           
               
               
               
               
               
            
               
                 Duplex 
                   
                   
                   
                   
               
               
                 Name 
                 Strand 
                 Target 
                 Modified Sequence (5′-3′) 
                 SEQ ID NO 
               
               
                   
               
               
                 AD-64958 
                 sense 
                 None 
                 asascaguGfuUfCfUfugcucuauaaL96 
                 5003 
               
               
                   
                 anti- 
                 None 
                 usUfsauaGfagcaagaAfcAfcuguususu 
                 5004 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953481 
                 sense 
                 VEGF-A 
                 asgsugc(Uhd)aadTgdTuauugguguaL96 
                 1038 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusdAscadCcdAauaadCadTudAgcacusgsu 
                 1168 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-901349 
                 sense 
                 VEGF-A 
                 asasgac(Uhd)GfaUfAfCfagaacgaucaL96 
                 4156 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusGfsaucg(Tgn)ucuguaUfcAfgucuususc 
                  130 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953338 
                 sense 
                 VEGF-A 
                 asgsacu(Ghd)AfuAfCfAfgaacgaucgaL96 
                  520 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusCfsgauCfgUfUfcuguAfuCfagucususu 
                  650 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953341 
                 sense 
                 VEGF-A 
                 csusgau(Ahd)CfaGfAfAfcgaucgauaaL96 
                  532 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusUfsaucGfaUfCfguucUfgUfaucagsusc 
                  662 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-901355 
                 sense 
                 VEGF-A 
                 csgsaca(Ghd)AfaCfAfGfuccuuaaucaL96 
                    4 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusGfsauua(Agn)ggacugUfuCfugucgsasu 
                  133 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-901356 
                 sense 
                 VEGF-A 
                 csasgaa(Chd)AfgUfCfCfuuaauccagaL96 
                    3 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusCfsugga(Tgn)uaaggaCfuGfuucugsusc 
                  132 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953350 
                 sense 
                 VEGF-A 
                 asascag(Uhd)GfcUfAfAfuguuauuggaL96 
                  524 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusCfscaaUfaAfCfauuaGfcAfcuguusasa 
                  654 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953365 
                 sense 
                 VEGF-A 
                 csgsgua(Chd)UfuAfUfUfuaauaucccaL96 
                  552 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusGfsggaUfaUfUfaaauAfaGfuaccgsusa 
                  682 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953370 
                 sense 
                 VEGF-A 
                 gscsucu(Chd)UfuAfUfUfuguaccgguaL96 
                  533 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusAfsccgGfuAfCfaaauAfaGfagagcsasa 
                  663 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953375 
                 sense 
                 VEGF-A 
                 asasaua(Ghd)AfcAfUfUfgcuauucugaL96 
                  530 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusCfsagaAfuAfGfcaauGfuCfuauuususa 
                  660 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953386 
                 sense 
                 VEGF-A 
                 csgsaag(Uhd)GfgUfGfAfaguucauggaL96 
                  541 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusCfscauGfaAfCfuucaCfcAfcuucgsusg 
                  671 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953410 
                 sense 
                 VEGF-A 
                 gsasaag(Uhd)GfuUfUfUfauauacgguaL96 
                  585 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusAfsccgUfaUfAfuaaaAfcAfcuuucsusc 
                  715 
               
               
                   
                 sense 
                   
                   
                   
               
               
                   
               
               
                 AD-953411 
                 sense 
                 VEGF-A 
                 gsusuuu(Ahd)UfaUfAfCfgguacuuauaL96 
                  584 
               
               
                   
                 anti- 
                 VEGF-A 
                 VPusAfsuaaGfuAfCfcguaUfaUfaaaacsasc 
                  714 
               
               
                   
                 sense 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14 
               
             
            
               
                   
               
               
                 VEGF-A in vivo single-dose screen with one set of exemplary VEGF-A siRNA 
               
               
                 duplexes. In this table, the columns “Duplex Name” and “Strand Name” provide the numerical 
               
               
                 part of the duplex or strand name. The duplex or strand name can comprise a suffix (number 
               
               
                 following the decimal point in a duplex name) that merely refers to a batch production number. 
               
               
                 The suffix can be omitted from the duplex name without changing the chemical structure. For 
               
               
                 example, the antisense strand name A-2521293.1 in Table 10A refers to the same antisense 
               
               
                 strand as A-2521293 in Table 14. 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                 SEQ 
                   
                 Unmodified 
                 SEQID NO 
               
               
                 Duplex 
                 Strand 
                   
                   
                 ID NO 
                 Modified Sequence 
                 Sequence 
                 (un- 
               
               
                 Name 
                 Name 
                 Strand 
                 Target 
                 (modified) 
                 (5′-3′) 
                 (5′-3′) 
                 modified) 
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 None 
                 5003 
                 asascaguGfuUfCfUfu 
                 AACAGUGUUC 
                 5021 
               
               
                 64958 
                 128009 
                   
                   
                   
                 gcucuauaaL96 
                 UUGCUCUAUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 None 
                 5004 
                 usUfsauaGfagcaaga 
                 UUAUAGAGCA 
                 5022 
               
               
                   
                 126312 
                 sense 
                   
                   
                 AfcAfcuguususu 
                 AGAACACUGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 UUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 1044 
                 asasgac(Uhd)gadTad 
                 AAGACUGATAC 
                 1304 
               
               
                 1397068 
                 1700995 
                   
                 A 
                   
                 CagaacgaucaL96 
                 AGAACGAUCA 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3901 
                 VPusdGsaudCg(U2p) 
                 UGAUCGUUCU 
                 4081 
               
               
                   
                 2521293 
                 sense 
                 A 
                   
                 ucugdTadTcdAgucu 
                 GTATCAGUCU 
                   
               
               
                   
                   
                   
                   
                   
                 USUSC 
                 UUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 10 
                 csusgau(Ahd)CfaGfA 
                 CUGAUACAGA 
                 268 
               
               
                 1397052 
                 1701263 
                   
                 A 
                   
                 fAfcgaucgauaaL96 
                 ACGAUCGAUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3957 
                 VPusUfsaudCg(A2p) 
                 UUAUCGAUCG 
                 4137 
               
               
                   
                 2521192 
                 sense 
                 A 
                   
                 ucguucUfgUfaucags 
                 UUCUGUAUCA 
                   
               
               
                   
                   
                   
                   
                   
                 use 
                 GUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5005 
                 asusgcagAfuUfAfUfg 
                 AUGCAGAUUA 
                 5023 
               
               
                 1397050 
                 2600337 
                   
                 A 
                   
                 cgg(Ahd)ucaaaL96 
                 UGCGGAUCAA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3936 
                 VPusUfsugdAu(C2p) 
                 UUUGAUCCGC 
                 4116 
               
               
                   
                 2521186 
                 sense 
                 A 
                   
                 cgcauaAfuCfugcausg 
                 AUAAUCUGCA 
                   
               
               
                   
                   
                   
                   
                   
                 sg 
                 UGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5006 
                 ascscaggAfaAfGfAfc 
                 ACCAGGAAAG 
                 5024 
               
               
                 1397051 
                 2600338 
                   
                 A 
                   
                 uga(Uhd)acagaL96 
                 ACUGAUACAG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3918 
                 VPusCfsuguAfucagu 
                 UCUGUAUCAG 
                 4098 
               
               
                   
                 2521190 
                 sense 
                 A 
                   
                 cuUfuCfcuggusgsc 
                 UCUUUCCUGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 UGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5007 
                 asgsaac(Ahd)GfuCfC 
                 AGAACAGUCC 
                 5025 
               
               
                 1397053 
                 2600339 
                   
                 A 
                   
                 fUfuaauccagaaL96 
                 UUAAUCCAGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3924 
                 VPusUfscudGg(A2p) 
                 UUCUGGAUUA 
                 4104 
               
               
                   
                 2521200 
                 sense 
                 A 
                   
                 uuaaggAfcUfguucus 
                 AGGACUGUUC 
                   
               
               
                   
                   
                   
                   
                   
                 gsu 
                 UGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5008 
                 asgsauu(Ahd)GfaGfA 
                 AGAUUAGAGA 
                 5026 
               
               
                 1397054 
                 2600340 
                   
                 A 
                   
                 fGfuuuuauuucaL96 
                 GUUUUAUUUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 2640 
                 VPusGfsaaaUfaaaac 
                 UGAAAUAAAA 
                 4110 
               
               
                   
                 2282496 
                 sense 
                 A 
                   
                 ucUfcUfaaucususc 
                 CUCUCUAAUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 UUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5009 
                 asasaag(Ahd)GfaAfA 
                 AAAAGAGAAA 
                 5027 
               
               
                 1397055 
                 2600341 
                   
                 A 
                   
                 fGfuguuuuauaaL96 
                 GUGUUUUAUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 2775 
                 VPusUfsauaAfaacac 
                 UUAUAAAACA 
                 3673 
               
               
                   
                 2282766 
                 sense 
                 A 
                   
                 uuUfcUfcuuuuscsu 
                 CUUUCUCUUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 UCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5010 
                 asasagagAfaAfGfUfg 
                 AAAGAGAAAG 
                 5028 
               
               
                 1397056 
                 2600342 
                   
                 A 
                   
                 uuu(Uhd)auauaL96 
                 UGUUUUAUAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 2776 
                 VPusAfsuauAfaaaca 
                 UAUAUAAAAC 
                 3674 
               
               
                   
                 2282768 
                 sense 
                 A 
                   
                 cuUfuCfucuuususc 
                 ACUUUCUCUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 UUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5011 
                 csusacagcaCfAfAfca 
                 CUACAGCACAA 
                 5029 
               
               
                 1397058 
                 2600344 
                   
                 A 
                   
                 aa(Uhd)gugaaL96 
                 CAAAUGUGAA 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3953 
                 VPusdTscadCadTuug 
                 UTCACATUUG 
                 4133 
               
               
                   
                 2521229 
                 sense 
                 A 
                   
                 udTgUfgcuguagsgsg 
                 UTGUGCUGUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 GGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5012 
                 asasaga(Chd)ugAfUf 
                 AAAGACUGAU 
                 5030 
               
               
                 1397059 
                 2600345 
                   
                 A 
                   
                 AfcagaacgauaL96 
                 ACAGAACGAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3889 
                 VPusdAsucdGudTcu 
                 UAUCGUTCUG 
                 4069 
               
               
                   
                 2521233 
                 sense 
                 A 
                   
                 gudAuCfagucuuuscs 
                 UAUCAGUCUU 
                   
               
               
                   
                   
                   
                   
                   
                 c 
                 UCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5013 
                 asasgac(Uhd)gaUfAf 
                 AAGACUGAUA 
                 5031 
               
               
                 1397060 
                 2600346 
                   
                 A 
                   
                 CfagaacgaucaL96 
                 CAGAACGAUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3902 
                 VPusdGsaudCg(U2p) 
                 UGAUCGUUCU 
                 5039 
               
               
                   
                 2521235 
                 sense 
                 A 
                   
                 ucugdTaUfcagucuus 
                 GTAUCAGUCU 
                   
               
               
                   
                   
                   
                   
                   
                 use 
                 UUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5014 
                 asusacagaaCfGfAfuc 
                 AUACAGAACG 
                 5032 
               
               
                 1397061 
                 2600347 
                   
                 A 
                   
                 ga(Uhd)acagaL96 
                 AUCGAUACAG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3932 
                 VPusdCsugdTa(U2p) 
                 UCUGTAUCGA 
                 4112 
               
               
                   
                 2521239 
                 sense 
                 A 
                   
                 cgaudCgUfucuguaus 
                 UCGUUCUGUA 
                   
               
               
                   
                   
                   
                   
                   
                 esg 
                 UCG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5015 
                 csasgaa(Chd)agUfCf 
                 CAGAACAGUCC 
                 5033 
               
               
                 1397062 
                 2600348 
                   
                 A 
                   
                 CfuuaauccagaL96 
                 UUAAUCCAGA 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3944 
                 VPusdCsugdGa(U2p) 
                 UCUGGAUUAA 
                 4124 
               
               
                   
                 2521245 
                 sense 
                 A 
                   
                 uaagdGaCfuguucugs 
                 GGACUGUUCU 
                   
               
               
                   
                   
                   
                   
                   
                 use 
                 GUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5016 
                 asusugg(Ahd)uuCfGf 
                 AUUGGAUUCG 
                 5034 
               
               
                 1397064 
                 2600350 
                   
                 A 
                   
                 CfcauuuuauuaL96 
                 CCAUUUUAUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3938 
                 VPusdAsaudAadAau 
                 UAAUAAAAUG 
                 4118 
               
               
                   
                 2521257 
                 sense 
                 A 
                   
                 ggdCgAfauccaaususc 
                 GCGAAUCCAA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 UUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5017 
                 gsasuucgccAfUfUfuu 
                 GAUUCGCCAU 
                 5035 
               
               
                 1397065 
                 2600351 
                   
                 A 
                   
                 au(Uhd)uuucaL96 
                 UUUAUUUUUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3965 
                 VPusdGsaadAadAua 
                 UGAAAAAUAA 
                 4145 
               
               
                   
                 2521259 
                 sense 
                 A 
                   
                 aadAuGfgcgaaucscs 
                 AAUGGCGAAU 
                   
               
               
                   
                   
                   
                   
                   
                 g 
                 CCG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5018 
                 gsasgaa(Ahd)guGfUf 
                 GAGAAAGUGU 
                 5036 
               
               
                 1397066 
                 2600352 
                   
                 A 
                   
                 UfuuauauacgaL96 
                 UUUAUAUACG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3962 
                 VPusdCsgudAudAua 
                 UCGUAUAUAA 
                 4142 
               
               
                   
                 2521271 
                 sense 
                 A 
                   
                 aadAcAfcuuucucsus 
                 AACACUUUCU 
                   
               
               
                   
                   
                   
                   
                   
                 u 
                 CUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5019 
                 gsusguu(Uhd)uaUfA 
                 GUGUUUUAUA 
                 5037 
               
               
                 1397067 
                 2600353 
                   
                 A 
                   
                 fUfacgguacuuaL96 
                 UACGGUACUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3971 
                 VPusd AsagdT adCcgu 
                 UAAGTACCGU 
                 4151 
               
               
                   
                 2521275 
                 sense 
                 A 
                   
                 adTaUfaaaacacsusu 
                 ATAUAAAACAC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 UU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 sense 
                 VEGF- 
                 5020 
                 asgsauu(Ahd)gadGa 
                 AGAUUAGAGA 
                 5038 
               
               
                 1397069 
                 2600354 
                   
                 A 
                   
                 dGuuuuauuucaL96 
                 GUUUUAUUUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                 A- 
                 anti- 
                 VEGF- 
                 3928 
                 VPusdGsaadAudAaa 
                 UGAAAUAAAA 
                 4108 
               
               
                   
                 2521319 
                 sense 
                 A 
                   
                 acdTcdTcdTaaucusu 
                 CTCTCTAAUCU 
                   
               
               
                   
                   
                   
                   
                   
                 sc 
                 UC 
               
               
                   
               
            
           
         
       
     
     Experimental Methods 
     An AAV vector harboring  Homo sapiens  VEGF-A was injected in 6-8 week old C57BL/6 female mice (2×10 11  viral particles/mouse), and at 14 days post-AAV administration, a selected siRNA or a control agent were subcutaneously injected at 3 mg/kg in mice (n=3 per group). Mice were sacrificed and their livers were assessed for VEGF-A mRNA levels at 14 days post-injection of the siRNAs or control. 
     Results 
     Table 15 and  FIG.  2    demonstrate the results of the in vivo screen with the siRNA duplexes corresponding to the siRNA sequences in Table 12. Of the siRNA duplexes evaluated in vivo in Table 15, 2 achieved a knockdown of VEGF-A of ≥60%, 4 achieved a knockdown of VEGF-A of ≥50%, 9 achieved a knockdown of VEGF-A of ≥40%, 11 achieved a knockdown of VEGF-A of ≥30%, and 13 achieved a knockdown of VEGF-A of ≥15%. 
     
       
         
           
               
             
               
                 TABLE 15 
               
             
            
               
                   
               
               
                 Efficacy of exemplary VEGF-A siRNAs in mice. In this 
               
               
                 table the column “Duplex Name” provides the numerical  
               
               
                 part of the duplex name with a suffix (number following 
               
               
                 the decimal point in a duplex name) that merely refers 
               
               
                 to a batch production number. The suffix can be omitted 
               
               
                 from the duplex name without changing the chemical  
               
               
                 structure. For example, duplex AD-953504 in Table 12  
               
               
                 refers to the same duplex as AD-953504.2 in Table 15. 
               
            
           
           
               
               
            
               
                   
                 Day 14 post-treatment 
               
            
           
           
               
               
               
            
               
                 Duplex 
                 % VEGF-A 
                   
               
               
                 (Administered at 3 mg/kg) 
                 Message Remaining 
                 St Dev 
               
               
                   
               
            
           
           
               
               
               
            
               
                 PBS 
                 101.85 
                 21.59 
               
               
                 Naïve 
                 106.47 
                 14.34 
               
               
                 AD-64228.39 
                 62.99 
                 16.53 
               
               
                 AD-901376.2 
                 72.86 
                 10.62 
               
               
                 AD-953308.2 
                 81.89 
                 34.49 
               
               
                 AD-953336.2 
                 51.31 
                 16.11 
               
               
                 AD-953337.2 
                 44.93 
                  5.57 
               
               
                 AD-953339.2 
                 58.33 
                 25.29 
               
               
                 AD-953340.2 
                 33.05 
                 18.66 
               
               
                 AD-953342.2 
                 35.97 
                  8.19 
               
               
                 AD-953344.2 
                 56.71 
                 14.45 
               
               
                 AD-953351.2 
                 43.75 
                 29.11 
               
               
                 AD-953363.2 
                 52.28 
                 10.56 
               
               
                 AD-953364.2 
                 69.25 
                 10.87 
               
               
                 AD-953374.2 
                 59.51 
                 18.65 
               
               
                 AD-953504.2 
                 63.66 
                 10.61 
               
               
                   
               
            
           
         
       
     
     Table 16 and  FIG.  4    demonstrate the results of the in vivo screen with the siRNA duplexes corresponding to the siRNA sequences in Table 13. Of the siRNA duplexes evaluated in vivo in Table 16, 3 achieved a knockdown of VEGF-A of ≥70%, 6 achieved a knockdown of VEGF-A of ≥60%, 9 achieved a knockdown of VEGF-A of ≥50%, 12 achieved a knockdown of VEGF-A of ≥40%, and 13 achieved a knockdown of VEGF-A of ≥30%. 
     
       
         
           
               
             
               
                 TABLE 16 
               
             
            
               
                   
               
               
                 Efficacy of exemplary VEGF-A siRNAs in mice. In this 
               
               
                 table the column “Duplex Name” provides the numerical 
               
               
                 part of the duplex name with a suffix (number following  
               
               
                 the decimal point in a duplex name) that merely refers 
               
               
                 to a batch production number. The suffix can be omitted 
               
               
                 from the duplex name without changing the chemical 
               
               
                 structure. For example, duplex AD-901349 in Table 13 
               
               
                 refers to the same duplex as AD-901349.1 in Table 16. 
               
            
           
           
               
               
            
               
                   
                 Day 14 post-treatment 
               
            
           
           
               
               
               
            
               
                 Duplex 
                 % VEGF-A  
                   
               
               
                 (Administered at 3 mg/kg) 
                 Message Remaining 
                 St Dev 
               
               
                   
               
            
           
           
               
               
               
            
               
                 PBS 
                 102.2 
                 24.0 
               
               
                 Naïve 
                 56.8 
                  8.9 
               
               
                 AD-901349.1 
                 26.4 
                 14.1 
               
               
                 AD-953481.1 
                 22.6 
                 26.2 
               
               
                 AD-901356.1 
                 34.5 
                  6.4 
               
               
                 AD-901355.1 
                 43.0 
                  4.4 
               
               
                 AD-953365.1 
                 60.5 
                  3.3 
               
               
                 AD-953410.1 
                 38.8 
                 16.4 
               
               
                 AD-953411.1 
                 56.2 
                 10.5 
               
               
                 AD-953338.1 
                 58.1 
                  5.6 
               
               
                 AD-953350.1 
                 42.0 
                  2.5 
               
               
                 AD-953375.1 
                 45.6 
                  6.1 
               
               
                 AD-953341.1 
                 30.1 
                 12.4 
               
               
                 AD-953370.1 
                 28.3 
                  8.5 
               
               
                 AD-953386.1 
                 52.9 
                 13.3 
               
               
                 AD-64958  
                 57.1 
                  6.1 
               
               
                 (ELF8 TTR control) 
                   
                   
               
               
                   
               
            
           
         
       
     
     Table 17 and  FIG.  6    demonstrate the results of the in vivo screen with the siRNA duplexes corresponding to the siRNA sequences in Table 14. Of the siRNA duplexes evaluated in vivo in Table 17, 5 achieved a knockdown of VEGF-A of ≥40%, 10 achieved a knockdown of VEGF-A of ≥30%, 15 achieved a knockdown of VEGF-A of ≥20%, and 17 achieved a knockdown of VEGF-A of ≥10%. 
     
       
         
           
               
             
               
                 TABLE 17 
               
             
            
               
                   
               
               
                 Efficacy of exemplary VEGF-A siRNAs in mice. In this  
               
               
                 table the column “Duplex Name” provides the numerical  
               
               
                 part of the duplex name with a suffix (number following  
               
               
                 the decimal point in a duplex name) that merely refers 
               
               
                 to a batch production number. The suffix can be omitted 
               
               
                 from the duplex name without changing the chemical 
               
               
                 structure. For example, duplex AD-1397050 in Table 14 
               
               
                 refers to the same duplex as AD-1397050.2 in Table 17. 
               
            
           
           
               
               
            
               
                   
                 Day 14 post-treatment 
               
            
           
           
               
               
               
            
               
                 Duplex 
                 % VEGF-A  
                   
               
               
                 (Administered at 3 mg/kg) 
                 Message Remaining 
                 St Dev 
               
               
                   
               
            
           
           
               
               
               
            
               
                 PBS 
                 89.7 
                 45.3 
               
               
                 Naïve 
                 100.0 
                 17.4 
               
               
                 AD-1397050.2 
                 50.1 
                 15.3 
               
               
                 AD-1397051.2 
                 76.7 
                 28.9 
               
               
                 AD-1397052.2 
                 63.6 
                 19.6 
               
               
                 AD-1397053.2 
                 50.9 
                 15.6 
               
               
                 AD-1397054.2 
                 53.0 
                 12.1 
               
               
                 AD-1397055.2 
                 84.4 
                 32.4 
               
               
                 AD-1397056.2 
                 59.2 
                 23.8 
               
               
                 AD-1397058.2 
                 77.5 
                 20.7 
               
               
                 AD-1397059.2 
                 77.1 
                 13.4 
               
               
                 AD-1397060.2 
                 68.9 
                  6.8 
               
               
                 AD-1397061.2 
                 58.2 
                 12.9 
               
               
                 AD-1397062.2 
                 68.7 
                 12.0 
               
               
                 AD-1397064.2 
                 62.9 
                  6.7 
               
               
                 AD-1397065.2 
                 85.2 
                 29.9 
               
               
                 AD-1397066.2 
                 77.7 
                  8.7 
               
               
                 AD-1397067.2 
                 93.5 
                 37.3 
               
               
                 AD-1397068.2 
                 62.0 
                 15.7 
               
               
                 AD-1397069.2 
                 76.9 
                 26.1 
               
               
                 AD-64958.100 
                 66.0 
                  2.6