Patent Publication Number: US-2023159933-A1

Title: Compositions and methods for silencing scn9a expression

Description:
RELATED APPLICATIONS 
     This application claims priority to U.S. provisional application No. 63/006,328, filed on Apr. 7, 2020, and U.S. provisional application No. 63/161,313, filed on Mar. 15, 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 Apr. 2, 2021, is named A2038-7235WO_SL.txt and is 1,514,568 bytes in size. 
     FIELD OF THE DISCLOSURE 
     The disclosure relates to the specific inhibition of the expression of the SCN9A gene. 
     BACKGROUND 
     Pain, e.g., chronic pain is a prevalent symptom and major cause of disability. Chronic pain can result from inflammatory pain or neuropathic pain, or it can be associated with a disease or disorder, e.g., cancer, arthritis, diabetes, traumatic injury and/or viral infections. Hypersensitivity or hyposensitivity to pain can also result from pain-related disorders, including but not limited to an inability to sense pain, primary erythromelalgia (PE), and paroxysmal extreme pain disorder (PEPD). Current therapies for pain are non-selective for their targets and result in unwanted, off-target effects involving the central nervous system (CNS). New treatments for pain, e.g., chronic pain and pain-related disorders are needed. 
     SUMMARY 
     The present disclosure describes methods and iRNA compositions for modulating the expression of SCN9A. In certain embodiments, expression of SCN9A is reduced or inhibited using an SCN9A-specific iRNA. Such inhibition can be useful in treating disorders related to SCN9A expression, such as pain, e.g., acute pain or chronic pain (e.g., inflammatory pain, neuropathic pain, pain hypersensitivity, pain hyposensitivity, inability to sense pain, primary erythromelalgia (PE), paroxysmal extreme pain disorder (PEPD), small fiber neuropathy (SFN), trigeminal neuralgia (TN) and pain associated with e.g., cancer, arthritis, diabetes, traumatic injury and viral infections). 
     Accordingly, described herein are compositions and methods that effect the RNA-induced silencing complex (RISC)-mediated cleavage of RNA transcripts of SCN9A, 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 SCN9A, such as pain (e.g., acute pain or chronic pain, e.g., inflammatory pain, neuropathic pain, pain hypersensitivity, pain hyposensitivity, inability to sense pain, primary erythromelalgia (PE), paroxysmal extreme pain disorder (PEPD), small fiber neuropathy (SFN), trigeminal neuralgia (TN) and pain associated with, e.g., cancer, arthritis, diabetes, traumatic injury and viral infections). 
     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 SCN9A (e.g., a human SCN9A) (also referred to herein as an “SCN9A-specific iRNA”). In some embodiments, the SCN9A mRNA transcript is a human SCN9A 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 SCN9A mRNA. In some embodiments, the human SCN9A mRNA has the sequence NM_002977.3 (SEQ ID NO: 1) or NM_001365536.1 (SEQ ID NO: 4001). In some embodiments, the human SCN9A mRNA has the sequence NM_002977.3 (SEQ ID NO: 1). The sequence of NM_002977.3 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 embodiments, the human SCN9A mRNA has the sequence NM_001365536.1 (SEQ ID NO: 4001). The sequence of NM_001365536.1 is also herein incorporated by reference in its entirety. The reverse complement of SEQ ID NO: 4001 is provided as SEQ ID NO: 4002 herein. 
     In some aspects, the present disclosure provides a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of sodium channel, voltage gated, type IX alpha subunit (SCN9A), 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 SCN9A 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 SCN9A 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 SCN9A, 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 SCN9A mRNA or a level of SCN9A 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., SCN9A), 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 human peripheral sensory neuron (e.g., a peripheral sensory neuron in a dorsal root ganglion, or a nociceptive neuron, e.g., an A-delta fiber or a C-type fiber). 
     The present disclosure also provides, in some aspects, a cell containing the dsRNA agent described herein. 
     In some aspects, the present disclosure also provides a pharmaceutical composition for inhibiting expression of a gene encoding SCN9A, comprising a dsRNA agent described herein. 
     The present disclosure also provides, in some aspects, a method of inhibiting expression of SCN9A 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 SCN9A, thereby inhibiting expression of the SCN9A in the cell. 
     The present disclosure also provides, in some aspects, a method of inhibiting expression of SCN9A 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 SCN9A mRNA, SCN9A protein, or both of SCN9A mRNA and protein, thereby inhibiting expression of the SCN9A in the cell. 
     The present disclosure also provides, in some aspects, a method of inhibiting expression of SCN9A in a cell or a tissue of the central nervous system (CNS), the method comprising: 
     (a) contacting the cell or tissue with a dsRNA agent that binds SCN9A; and 
     (b) maintaining the cell or tissue produced in step (a) for a time sufficient to reduce levels of SCN9A mRNA, SCN9A protein, or both of SCN9A mRNA and protein, thereby inhibiting expression of SCN9A in the cell or tissue. 
     The present disclosure also provides, in some aspects, a method of treating a subject diagnosed with SCN9A-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 SCN9A has the sequence of SEQ ID NO: 1. In some embodiments, the non-coding strand of human SCN9A has the sequence of SEQ ID NO: 2. In some embodiments, the coding strand of human SCN9A has the sequence of SEQ ID NO: 4001. In some embodiments, the non-coding strand of human SCN9A has the sequence of SEQ ID NO: 4002. 
     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 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: 4001. 
     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 17 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of nucleotide sequence of SEQ ID NO: 4002 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: 4001. 
     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 19 contiguous nucleotides, with 0, 1, 2, or 3 mismatches, of a portion of nucleotide sequence of SEQ ID NO: 4002 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: 4001. 
     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 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: 4002 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: 4001. 
     In some embodiments, the portion of the sense strand is a portion within nucleotides 581-601, 760-780, or 8498-8518 of SEQ ID NO: 4001. In some embodiments, the portion of the sense strand is a portion corresponding to SEQ ID NO: 4827, 5026, or 4822. 
     In some embodiments, the portion of the sense strand is a portion within a sense strand in any one of Tables 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 
     In some embodiments, the portion of the antisense strand is a portion within an antisense strand in any one of Tables 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 
     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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20 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-1251284 (UGUCGAGUACACUUUUACUGA (SEQ ID NO:4827)), AD-961334 (CAACACAATUTCUUCUUAGCA (SEQ ID NO: 5026)), or AD-1251325 (AAAACAAUCUUCCGUUUCAAA (SEQ ID NO: 4822)). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 5A, 13A, 14A, 15A, and 16. 
     In some embodiments, the portion of the sense strand is a sense strand chosen from the sense strands of AD-1251284 (UGUCGAGUACACUUUUACUGA (SEQ ID NO:4827)), AD-961334 (CAACACAATUTCUUCUUAGCA (SEQ ID NO: 5026)), or AD-1251325 (AAAACAAUCUUCCGUUUCAAA (SEQ ID NO: 4822)). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 5A, 13A, 14A, 15A, and 16. 
     In some embodiments, the portion of the antisense strand is a portion within an antisense strand from a duplex chosen from AD-1251284 (UCAGTAAAAGUGUACTCGACAUU (SEQ ID NO: 5093)), AD-961334 (UGCUAAGAAGAAATUGUGUUGUU (SEQ ID NO: 5292)), or AD-1251325 (UUUGAAACGGAAGAUUGUUUUCC (SEQ ID NO: 5088)). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 5A, 13A, 14A, 15A, and 16. 
     In some embodiments, the portion of the antisense strand is an antisense strand chosen from the antisense strands of AD-1251284 (UCAGTAAAAGUGUACTCGACAUU (SEQ ID NO: 5093)), AD-961334 (UGCUAAGAAGAAATUGUGUUGUU (SEQ ID NO: 5292)), or AD-1251325 (UUUGAAACGGAAGAUUGUUUUCC (SEQ ID NO: 5088)). In some embodiments, the portion is a portion of a corresponding chemically modified sequence provided in Tables 5A, 13A, 14A, 15A, and 16. 
     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-1251284 (SEQ ID NO: 4827 and 5093), AD-961334 (SEQ ID NO: 5026 and 5292), or AD-1251325 (SEQ ID NO: 4822 and 5088). In some embodiments, the sense strand and antisense strand comprises the corresponding chemically modified sense sequence and antisense sequence provided in Tables 5A, 13A, 14A, 15A, and 16. 
     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 logKow, 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 deoxythimidine (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 a CNS tissue or a liver tissue. In some embodiments, the CNS tissue is a brain tissue or a spinal tissue, e.g., a dorsal root ganglion. 
     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 SCN9A mRNA is inhibited by at least 50%. In some embodiments, the level of SCN9A protein is inhibited by at least 50%. In some embodiments, the expression of SCN9A is inhibited by at least 50%. In some embodiments, inhibiting expression of SCN9A decreases the SCN9A protein level in a biological sample (e.g., a cerebral spinal fluid (CSF) sample, or a CNS biopsy sample) from the subject by at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%. In some embodiments, inhibiting expression of SCN9A gene decreases the SCN9A mRNA level in a biological sample (e.g., a cerebral spinal fluid (CSF) sample, or a CNS biopsy sample) from the subject by at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%. 
     In some embodiments, the subject has or has been diagnosed with having a SCN9A-associated disorder. In some embodiments, the subject meets at least one diagnostic criterion for a SCN9A-associated disorder. In some embodiments, the SCN9A associated disorder is pain, e.g., chronic pain e.g., inflammatory pain, neuropathic pain, pain hypersensitivity, pain hyposensitivity, inability to sense pain, primary erythromelalgia (PE), paroxysmal extreme pain disorder (PEPD), small fiber neuropathy (SFN), trigeminal neuralgia (TN), and pain associated with, e.g., cancer, arthritis, diabetes, traumatic injury and viral infections. 
     In some embodiments, the neuronal cell or tissue is a peripheral sensory neuron, e.g., a peripheral sensory neuron in a dorsal root ganglion, or a nociceptive neuron, e.g., an A-delta fiber or a C-type fiber. 
     In some embodiments, the SCN9A-associated disorder is pain, e.g., chronic pain. In some embodiments, the chronic pain is caused by or associated with pain hypersensitivity, pain hyposensitivity, inability to sense pain, primary erythromelalgia (PE), paroxysmal extreme pain disorder (PEPD), small fiber neuropathy (SFN), trigeminal neuralgia (TN), and pain associated with, e.g., cancer, arthritis, diabetes, traumatic injury or viral infections 
     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 pain sensitivity, pain threshold, pain level, pain disability level presence, level, or activity of SCN9A (e.g., SCN9A gene, SCN9A mRNA, or SCN9A protein). 
     In some embodiments, a level of the SCN9A that is higher than a reference level is indicative that the subject has pain, e.g., chronic pain or a pain-related disorder. In some embodiments, treating comprises prevention of progression of the disorder. In some embodiments, the treating comprises one or more of (a) reducing pain; or (b) inhibiting or reducing the expression or activity of SCN9A. 
     In some embodiments, the treating results in at least a 30% mean reduction from baseline of SCN9A mRNA in the dorsal root ganglion. In some embodiments, the treating results in at least a 60% mean reduction from baseline of SCN9A mRNA in the dorsal root ganglion. In some embodiments, the treating results in at least a 90% mean reduction from baseline of SCN9A mRNA in the dorsal root ganglion. 
     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 SCN9A protein in the cerebral spinal fluid (CSF) or the CNS tissue, e.g., the dorsal root ganglion. In some embodiments, treating results in at least a 12-week duration of knockdown following a single dose of dsRNA as assessed by SCN9A protein in the cerebral spinal fluid (CSF) or the CNS tissue, e.g., the dorsal root ganglion. In some embodiments, treating results in at least a 16-week duration of knockdown following a single dose of dsRNA as assessed by SCN9A protein in the cerebral spinal fluid (CSF) or the CNS tissue, e.g., the dorsal root ganglion. 
     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 intracranially or intrathecally. 
     In some embodiments, the dsRNA agent is administered to the subject intrathecally, intraventricularly, or intracerebrally. 
     In some embodiments, a method described herein further comprises measuring a level of SCN9A (e.g., SCN9A gene, SCN9A mRNA, or SCN9A protein) in the subject. In some embodiments, measuring the level of SCN9A in the subject comprises measuring the level of SCN9A protein in a biological sample from the subject (e.g., a cerebral spinal fluid (CSF) sample or a CNS biopsy sample). In some embodiments, a method described herein further comprises performing a blood test, an imaging test, or, a CNS biopsy, or an aqueous cerebral spinal fluid biopsy. 
     In some embodiments, a method described herein further measuring level of SCN9A (e.g., SCN9A gene, SCN9A mRNA, or SCN9A 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 SCN9A 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 SCN9A 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 SCN9A-associated disorder, e.g., wherein the therapy comprises non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids, or corticosteroids, acupuncture, therapeutic massage, dorsal root ganglion stimulation, spinal cord stimulation, or topical pain relievers. In some embodiments, a method described herein further comprises administering to the subject an additional agent suitable for treatment or prevention of a SCN9A-associated disorder. In some embodiments, the additional agent comprises a steroid, or a non-steroidal anti-inflammatory agent. 
     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 
       The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. 
         FIG.  1 A  depicts the sequences and chemistry of exemplary SCN9A siRNAs including AD-795305, AD-1251249, AD-1251251, AD-1010663, AD-1251301, and AD-961179.  FIG.  1 B  depicts the sequences and chemistry of exemplary SCN9A siRNAs including AD-1251317, AD-1251318, AD-1251323, AD-1251325, AD-795634, AD-1251363.  FIG.  1 C  depicts the sequences and chemistry of exemplary SCN9A siRNAs including AD-1251364, AD-1251373, AD-1251385, AD-1251391, and AD-795913. 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, “(G2p)” refers to guanosine 2′-phosphate, “DNA” refers to a DNA base, 2-C16 refers to the targeting ligand, and PS refers to the phosphorothioate linkage.  FIGS.  1 A- 1 C  disclose SEQ ID NOS 5996-6029, respectively, in order of appearance. 
         FIG.  2    is a graph depicting the percent SCN9A message remaining relative to PBS in mice on day 14 post-treatment with the exemplary duplexes indicated on the X-axis (from left to right: PBS, AD-795305 (parent), AD-1251249, AD-1251251, AD-1010663 (parent), AD-1251301, AD-961179 (parent), AD-1251317, AD-1251318, AD-1251323, AD-1251325, AD-795634 (parent), AD-1251363, AD-1251364, AD-1251373, AD-1251385, and AD-1251391). 
         FIG.  3 A  depicts the sequences and chemistry of exemplary SCN9A siRNAs including AD-802471, AD-1251492, AD-961334, AD-1251279, and AD-1251284.  FIG.  3 B  depicts the sequences and chemistry of exemplary SCN9A siRNAs including AD-1251334, AD-1251377, AD-1251398, AD-1251399, AD-961188, and AD-1251274.  FIGS.  3 A- 3 B  disclose SEQ ID NOS 6030-6051, respectively, in order of appearance.  FIG.  3 C  depicts the sequences and chemistry of exemplary SCN9A siRNAs including AD-796825, AD-1251411, AD-1251419, AD-797564, AD-1251428, and AD-1251434.  FIG.  3 D  depicts the sequences and chemistry of exemplary SCN9A siRNAs including AD-1010661, AD-795366, AD-795634, and AD-795913. 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, “(G2p)” refers to guanosine 2′-phosphate, “DNA” refers to a DNA base, 2-C16 refers to the targeting ligand, and PS refers to the phosphorothioate linkage.  FIGS.  3 C- 3 D  disclose SEQ ID NOS 6052-6071, respectively, in order of appearance. 
         FIGS.  4 A- 4 C  present a series of graphs depicting the percent SCN9A message remaining versus the starting position in the target mRNA (NM_001365536.1) of the sense strand of the duplex grouped by those tested in screens 1 and 2 (targeting ORF-1, ORF-2, and the 3′ UTR).  FIG.  4 A  depicts the percent SCN9A message remaining with the duplexes tested at a final concentration of 0.1 nM.  FIG.  4 B  depicts the percent SCN9A message remaining with the duplexes tested at a final concentration of 1 nM.  FIG.  4 C  depicts the percent SCN9A message remaining with the duplexes tested at a final concentration of 10 nM. In  FIGS.  4 A- 4 C , screen 1 includes the following duplexes: AD-1010663.3, AD-1251301.1, AD-1251249.1, AD-1251251.1, AD-795305.3, AD-1251363.1, AD-1251364.1, AD-1251373.1, AD-795634.4, AD-1251385.1, AD-1251391.1, AD-1251317.1, AD-1251318.1, AD-1251323.1, AD-1251325.1, and AD-961179.3; screen 2 included the following duplexes: AD-1251492.1, AD-1251279.1, AD-961334.3, AD-1251284.1, AD-1251334.1, AD-1251377.1, AD-1251398.1, AD-1251399.1, AD-1251274.2, AD-961188.3, AD-1251411.1, AD-1251419.1, AD-796825.3, AD-1251428.1, AD-797564.4, and AD-1251434.1. 
         FIG.  5    is a graph depicting the percent SCN9A message remaining relative to PBS in mice on day 14 post-treatment with the exemplary duplexes indicated on the X-axis (from left to right: PBS, AD-1251492.2*, AD-961334.2 (parent), AD-1251279.2, PBS, AD-1251284.2*, AD-1251334.2*, AD-1251377.2*, AD-1251398.2*, AD-1251399.2*, AD-961188.2 (parent), AD-1251274.2, PBS, AD-796825.2 (parent), AD-1251411.2, AD-1251419.2, AD-797564.3 (parent), AD-1251428.2, and AD-1251434.2. The graph is divided into subsections for those duplexes that target the 3′UTR2 (AD-1251492.2*, AD-961334.2 (parent), AD-1251279.2), ORF1 (AD-1251284.2*, AD-1251334.2*, AD-1251377.2*, AD-1251398.2*, AD-1251399.2*, AD-961188.2 (parent), AD-1251274.2), and ORF2 (AD-796825.2 (parent), AD-1251411.2, AD-1251419.2, AD-797564.3 (parent), AD-1251428.2, AD-1251434.2). 
         FIG.  6 A  depicts the sequences and chemistry of exemplary SCN9A siRNAs including AD-1251284, AD-961334, and AD-1251325.  FIG.  6 A  discloses SEQ ID NOS 6072-6077, respectively, in order of appearance.  FIG.  6 B  depicts the sequences and CNS chemistry of exemplary SCN9A duplexes AD-1331352, AD-1209344, and AD-1331350.  FIG.  6 B  discloses SEQ ID NOS 6078-6083, respectively, in order of appearance. 
     
    
    
     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 SCN9A. Also provided are compositions and methods for treatment of disorders related to SCN9A expression, such as pain, e.g., acute pain or chronic pain (e.g., inflammatory (nociceptive), neuropathic pain, pain hypersensitivity, pain hyposensitivity, inability to sense pain, primary erythromelalgia (PE), paroxysmal extreme pain disorder (PEPD), small fiber neuropathy (SFN), trigeminal neuralgia (TN), and pain associated with, e.g., cancer, arthritis, diabetes, traumatic injury and viral infections). 
     Human SCN9A is approximately a 226 kDa protein and is a voltage gated sodium channel (Nav1.7 channel) that mediates the voltage-dependent sodium ion permeability of excitable membranes and also plays a role in nociception signaling. These channels are preferentially expressed in peripheral sensory neurons of the dorsal root ganglia, which are involved in the perception of pain. Mutations in the SCN9A gene have been associated with predispositions to pain hyper- or hyposensitivity. For example, gain-of-function mutations in the SCN9A gene can be the etiological basis of inherited pain syndromes such as primary erythermalgia (PE) and paroxysmal extreme pain disorder (PEPD). Moreover, loss-of-function mutations of the SCN9A gene result in a complete inability of an otherwise healthy individual to sense any form of pain. Without wishing to be bound by theory, increased levels of the SCN9A expression could enhance pain sensitivity; whereas decreased levels of the SCN9A expression could reduce pain sensitivity, and modulating SCN9A expression and Nav1.7 channel levels in peripheral sensory neurons of the dorsal root ganglia could provide an effective pain treatment. 
     The following description discloses how to make and use compositions containing iRNAs to modulate (e.g., inhibit) the expression of SCN9A, as well as compositions and methods for treating disorders related to expression of SCN9A. 
     In some aspects, pharmaceutical compositions containing SCN9A iRNA and a pharmaceutically acceptable carrier, methods of using the compositions to inhibit expression of SCN9A, and methods of using the pharmaceutical compositions to treat disorders related to expression of SCN9A (e.g., pain, e.g., chronic pain and/or pain related 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 terms “or more” and “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, “or less” and “no more than” are understood as including 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, “less than” is understood as not including the value adjacent to the phrase and including logical lower values or integers, as logical from context, to zero. For example, a duplex with mismatches to a target site of “less than 3 nucleotides” has 2, 1, or 0 mismatches. When “less than” is present before a series of numbers or a range, it is understood that “less than” can modify each of the numbers in the series or range. 
     As used herein, “more than” is understood as not including the value adjacent to the phrase and including logical higher values or integers, as logical from context, to infinity. For example, a duplex with mismatches to a target site of “more than 3 nucleotides” has 4, 5, 6, or more mismatches. When “more than” is present before a series of numbers or a range, it is understood that “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 SCN9A gene, herein refer to the at least partial activation of the expression of a SCN9A gene, as manifested by an increase in the amount of SCN9A mRNA, which may be isolated from or detected in a first cell or group of cells in which a SCN9A gene is transcribed and which has or have been treated such that the expression of a SCN9A 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 SCN9A 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 SCN9A 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 SCN9A 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 SCN9A 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 SCN9A, herein refer to the at least partial suppression of the expression of SCN9A, as assessed, e.g., based on SCN9A mRNA expression, SCN9A protein expression, or another parameter functionally linked to SCN9A expression. For example, inhibition of SCN9A expression may be manifested by a reduction of the amount of SCN9A mRNA which may be isolated from or detected in a first cell or group of cells in which SCN9A is transcribed and which has or have been treated such that the expression of SCN9A 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., 
     
       
         
           
             
               
                 
                   
                     ( 
                     
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                       cells 
                     
                     ) 
                   
                   - 
                   
                     ( 
                     
                       mRNA 
                       ⁢ 
                           
                       in 
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                       treated 
                       ⁢ 
                           
                       cells 
                     
                     ) 
                   
                 
                 
                   ( 
                   
                     mRNA 
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                     in 
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                     control 
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                     cells 
                   
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               · 
               100 
             
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     Alternatively, the degree of inhibition may be given in terms of a reduction of a parameter that is functionally linked to SCN9A expression, e.g., the amount of protein encoded by a SCN9A gene. The reduction of a parameter functionally linked to SCN9A expression may similarly be expressed as a percentage of a control level. In principle, SCN9A silencing may be determined in any cell expressing SCN9A, either constitutively or by genomic engineering, and by any appropriate assay. 
     For example, in certain instances, expression of SCN9A 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, SCN9A is suppressed by at least about 60%, 65%, 70%, 75%, or 80% by administration of an iRNA disclosed herein. In some embodiments, SCN9A 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 be, for example, “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 Hoogsteen base pairing. 
     The terms “complementary,” “fully complementary” and “substantially complementary” herein may be used with respect to the base matching between two oligonucleotides or polynucleotides, such as 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 SCN9A protein). For example, a polynucleotide is complementary to at least a part of a SCN9A mRNA if the sequence is substantially complementary to a non-interrupted portion of an mRNA encoding SCN9A. 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 SCN9A 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., intrathecally, intracranially, intracerebrally, or intraventricularly) 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 SCN9A expression,” a “disease related to SCN9A expression,” a “pathological process related to SCN9A expression,” “a SCN9A-associated disorder,” “a SCN9A-associated disease,” or the like includes any condition, disorder, or disease in which SCN9A 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, SCN9A expression is decreased. In some embodiments, SCN9A expression is increased. In some embodiments, the decrease or increase in SCN9A expression is detectable in a tissue sample from the subject (e.g., in a cerebral spinal fluid (CSF) sample or a CNS biopsy 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 brain or the spine). SCN9A-A-associated disorders include, but are not limited to, pain, e.g., chronic pain or pain-related disorders. 
     “Pain” as defined herein includes acute pain and chronic pain. Chronic pain includes inflammatory (nociceptive) and neuropathic pain associated with disorders including, but not limited to, cancer, arthritis, diabetes, traumatic injury and viral infections. Also included is pain due to inherited pain syndromes including, but not limited to primary erythermalgia (PE) and paroxysmal extreme pain disorder (PEPD). 
     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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20) 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 SCN9A expression, e.g., in a cell or mammal. Inhibition of SCN9A expression may be assessed based on a reduction in the level of SCN9A mRNA or a reduction in the level of the SCN9A 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, logK 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 logK ow  exceeds 0. Typically, the lipophilic moiety possesses a logK ow  exceeding 1, exceeding 1.5, exceeding 2, exceeding 3, exceeding 4, exceeding 5, or exceeding 10. For instance, the logK ow  of 6-amino hexanol, for instance, is predicted to be approximately 0.7. Using the same method, the logK 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., logK 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., SCN9A 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 SCN9A expression (e.g., pain, e.g., chronic pain or pain-related 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 pain or (b) inhibit or reduces the expression or activity of SCN9A) 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 SCN9A can reduce a level of SCN9A mRNA or a level of SCN9A 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 SCN9A expression, e.g., overexpression (e.g., pain, e.g., chronic pain or a pain-related disorder). In some embodiments, the subject has, or is suspected of having, a disorder related to SCN9A expression or overexpression. In some embodiments, the subject is at risk of developing a disorder related to SCN9A 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., SCN9A, 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 SCN9A expression (e.g., pain, e.g., chronic pain or a pain-related 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 SCN9A 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 pain, e.g., chronic pain or a pain-related disorder, may serve to reduce or prevent one or more symptoms of the pain, e.g., chronic pain, 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 SCN9A 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, “SCN9A” refers to “sodium channel, voltage gated, type IX alpha subunit” gene (“SCN9A gene”), the corresponding mRNA (“SCN9A mRNA”), or the corresponding protein (“SCN9A protein”). The sequence of a human SCN9A mRNA transcript can be found at SEQ ID NO: 1 or SEQ ID NO: 4001. 
     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. 
     II. iRNA Agents 
     Described herein are iRNA agents that modulate (e.g., inhibit) the expression of SCN9A. 
     In some embodiments, the iRNA agent activates the expression of SCN9A in a cell or mammal. 
     In some embodiments, the iRNA agent includes double-stranded ribonucleic acid (dsRNA) molecules for inhibiting the expression of SCN9A 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 SCN9A, 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 SCN9A, inhibits the expression of SCN9A, e.g., by at least 10%, 20%, 30%, 40%, or 50%. 
     The modulation (e.g., inhibition) of expression of SCN9A 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 SCN9A 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 SCN9A 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 SCN9A. 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 SCN9A 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, SCN9A is a human SCN9A. 
     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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20 and an antisense strand that comprises or consists of an antisense sequence selected from the antisense sequences provided in Tables 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20. 
     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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20 and the corresponding antisense strand is selected from the sequences provided in Tables 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20. 
     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 SCN9A. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20, 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20. 
     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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20. 
     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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20. 
     In some such embodiments, the dsRNA, although it comprises only a portion of the sequences provided in Tables 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20 is equally effective in inhibiting a level of SCN9A expression as is a dsRNA that comprises the full-length sequences provided in Tables 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20. In some embodiments, the dsRNA differs in its inhibition of a level of expression of SCN9A 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. 
     In some embodiments, an iRNA of Table 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20 decreases SCN9A protein or SCN9A 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, SCN9A protein or SCN9A mRNA levels are reduced by at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%. In some embodiments, the iRNA of Table 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, or 20 that inhibits SCN9A in a human cell has less than 5, 4, 3, 2, or 1 mismatches to the corresponding portion of human SCN9A. In some embodiments, the iRNA of Table 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20 that inhibits SCN9A in a human cell has no mismatches to the corresponding portion of human SCN9A. 
     iRNAs designed based on human sequences can have utility, e.g., for inhibiting SCN9A in human cells, e.g., for therapeutic purposes, or for inhibiting SCN9A in rodent cells, e.g., for research characterizing SCN9A 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 SCN9A mRNA may have the sequence of SEQ ID NO: 1 provided herein. 
       Homo sapiens  Sodium Channel, Voltage Gated, Type IX Alpha Subunit (SCN9A), Transcript Variant 1, mRNA 
     
       
         
           
               
               
            
               
                 (SEQ ID NO: 1) 
                   
               
               
                 CGGGGCUGCUACCUCCACGGGCGCGCCCUGGCAGGAGGGGCGCAGUCUGCUUGCAGGCGGUCGCCAGCGC 
                   
               
               
                   
               
               
                 UCCAGCGGCGGCUGUCGGCUUUCCAAUUCCGCCAGCUCGGCUGAGGCUGGGCUAGCCUGGGUGCCAGUGG 
               
               
                   
               
               
                 CUGCUAGCGGCAGGCGUCCCCUGAGCAACAGGAGCCCAGAGAAAAAGAAGCAGCCCUGAGAGAGCGCCGG 
               
               
                   
               
               
                 GGAAGGAGAGGCCCGCGCCCUCUCCUGGAGCCAGAUUCUGCAGGUGCACUGGGUGGGGAUGAUCGGCGGG 
               
               
                   
               
               
                 CUAGGUUGCAAGCCUCUUAUGUGAGGAGCUGAAGAGGAAUUAAAAUAUACAGGAUGAAAAGAUGGCAAUG 
               
               
                   
               
               
                 UUGCCUCCCCCAGGACCUCAGAGCUUUGUCCAUUUCACAAAACAGUCUCUUGCCCUCAUUGAACAACGCA 
               
               
                   
               
               
                 UUGCUGAAAGAAAAUCAAAGGAACCCAAAGAAGAAAAGAAAGAUGAUGAUGAAGAAGCCCCAAAGCCAAG 
               
               
                   
               
               
                 CAGUGACUUGGAAGCUGGCAAACAGCUGCCCUUCAUCUAUGGGGACAUUCCUCCCGGCAUGGUGUCAGAG 
               
               
                   
               
               
                 CCCCUGGAGGACUUGGACCCCUACUAUGCAGACAAAAAGACUUUCAUAGUAUUGAACAAAGGGAAAACAA 
               
               
                   
               
               
                 UCUUCCGUUUCAAUGCCACACCUGCUUUAUAUAUGCUUUCUCCUUUCAGUCCUCUAAGAAGAAUAUCUAU 
               
               
                   
               
               
                 UAAGAUUUUAGUACACUCCUUAUUCAGCAUGCUCAUCAUGUGCACUAUUCUGACAAACUGCAUAUUUAUG 
               
               
                   
               
               
                 ACCAUGAAUAACCCACCGGACUGGACCAAAAAUGUCGAGUACACUUUUACUGGAAUAUAUACUUUUGAAU 
               
               
                   
               
               
                 CACUUGUAAAAAUCCUUGCAAGAGGCUUCUGUGUAGGAGAAUUCACUUUUCUUCGUGACCCGUGGAACUG 
               
               
                   
               
               
                 GCUGGAUUUUGUCGUCAUUGUUUUUGCGUAUUUAACAGAAUUUGUAAACCUAGGCAAUGUUUCAGCUCUU 
               
               
                   
               
               
                 CGAACUUUCAGAGUAUUGAGAGCUUUGAAAACUAUUUCUGUAAUCCCAGGCCUGAAGACAAUUGUAGGGG 
               
               
                   
               
               
                 CUUUGAUCCAGUCAGUGAAGAAGCUUUCUGAUGUCAUGAUCCUGACUGUGUUCUGUCUGAGUGUGUUUGC 
               
               
                   
               
               
                 ACUAAUUGGACUACAGCUGUUCAUGGGAAACCUGAAGCAUAAAUGUUUUCGAAAUUCACUUGAAAAUAAU 
               
               
                   
               
               
                 GAAACAUUAGAAAGCAUAAUGAAUACCCUAGAGAGUGAAGAAGACUUUAGAAAAUAUUUUUAUUACUUGG 
               
               
                   
               
               
                 AAGGAUCCAAAGAUGCUCUCCUUUGUGGUUUCAGCACAGAUUCAGGUCAGUGUCCAGAGGGGUACACCUG 
               
               
                   
               
               
                 UGUGAAAAUUGGCAGAAACCCUGAUUAUGGCUACACGAGCUUUGACACUUUCAGCUGGGCCUUCUUAGCC 
               
               
                   
               
               
                 UUGUUUAGGCUAAUGACCCAAGAUUACUGGGAAAACCUUUACCAACAGACGCUGCGUGCUGCUGGCAAAA 
               
               
                   
               
               
                 CCUACAUGAUCUUCUUUGUCGUAGUGAUUUUCCUGGGCUCCUUUUAUCUAAUAAACUUGAUCCUGGCUGU 
               
               
                   
               
               
                 GGUUGCCAUGGCAUAUGAAGAACAGAACCAGGCAAACAUUGAAGAAGCUAAACAGAAAGAAUUAGAAUUU 
               
               
                   
               
               
                 CAACAGAUGUUAGACCGUCUUAAAAAAGAGCAAGAAGAAGCUGAGGCAAUUGCAGCGGCAGCGGCUGAAU 
               
               
                   
               
               
                 AUACAAGUAUUAGGAGAAGCAGAAUUAUGGGCCUCUCAGAGAGUUCUUCUGAAACAUCCAAACUGAGCUC 
               
               
                   
               
               
                 UAAAAGUGCUAAAGAAAGAAGAAACAGAAGAAAGAAAAAGAAUCAAAAGAAGCUCUCCAGUGGAGAGGAA 
               
               
                   
               
               
                 AAGGGAGAUGCUGAGAAAUUGUCGAAAUCAGAAUCAGAGGACAGCAUCAGAAGAAAAAGUUUCCACCUUG 
               
               
                   
               
               
                 GUGUCGAAGGGCAUAGGCGAGCACAUGAAAAGAGGUUGUCUACCCCCAAUCAGUCACCACUCAGCAUUCG 
               
               
                   
               
               
                 UGGCUCCUUGUUUUCUGCAAGGCGAAGCAGCAGAACAAGUCUUUUUAGUUUCAAAGGCAGAGGAAGAGAU 
               
               
                   
               
               
                 AUAGGAUCUGAGACUGAAUUUGCCGAUGAUGAGCACAGCAUUUUUGGAGACAAUGAGAGCAGAAGGGGCU 
               
               
                   
               
               
                 CACUGUUUGUGCCCCACAGACCCCAGGAGCGACGCAGCAGUAACAUCAGCCAAGCCAGUAGGUCCCCACC 
               
               
                   
               
               
                 AAUGCUGCCGGUGAACGGGAAAAUGCACAGUGCUGUGGACUGCAACGGUGUGGUCUCCCUGGUUGAUGGA 
               
               
                   
               
               
                 CGCUCAGCCCUCAUGCUCCCCAAUGGACAGCUUCUGCCAGAGGGCACGACCAAUCAAAUACACAAGAAAA 
               
               
                   
               
               
                 GGCGUUGUAGUUCCUAUCUCCUUUCAGAGGAUAUGCUGAAUGAUCCCAACCUCAGACAGAGAGCAAUGAG 
               
               
                   
               
               
                 UAGAGCAAGCAUAUUAACAAACACUGUGGAAGAACUUGAAGAGUCCAGACAAAAAUGUCCACCUUGGUGG 
               
               
                   
               
               
                 UACAGAUUUGCACACAAAUUCUUGAUCUGGAAUUGCUCUCCAUAUUGGAUAAAAUUCAAAAAGUGUAUCU 
               
               
                   
               
               
                 AUUUUAUUGUAAUGGAUCCUUUUGUAGAUCUUGCAAUUACCAUUUGCAUAGUUUUAAACACAUUAUUUAU 
               
               
                   
               
               
                 GGCUAUGGAACACCACCCAAUGACUGAGGAAUUCAAAAAUGUACUUGCUAUAGGAAAUUUGGUCUUUACU 
               
               
                   
               
               
                 GGAAUCUUUGCAGCUGAAAUGGUAUUAAAACUGAUUGCCAUGGAUCCAUAUGAGUAUUUCCAAGUAGGCU 
               
               
                   
               
               
                 GGAAUAUUUUUGACAGCCUUAUUGUGACUUUAAGUUUAGUGGAGCUCUUUCUAGCAGAUGUGGAAGGAUU 
               
               
                   
               
               
                 GUCAGUUCUGCGAUCAUUCAGACUGCUCCGAGUCUUCAAGUUGGCAAAAUCCUGGCCAACAUUGAACAUG 
               
               
                   
               
               
                 CUGAUUAAGAUCAUUGGUAACUCAGUAGGGGCUCUAGGUAACCUCACCUUAGUGUUGGCCAUCAUCGUCU 
               
               
                   
               
               
                 UCAUUUUUGCUGUGGUCGGCAUGCAGCUCUUUGGUAAGAGCUACAAAGAAUGUGUCUGCAAGAUCAAUGA 
               
               
                   
               
               
                 UGACUGUACGCUCCCACGGUGGCACAUGAACGACUUCUUCCACUCCUUCCUGAUUGUGUUCCGCGUGCUG 
               
               
                   
               
               
                 UGUGGAGAGUGGAUAGAGACCAUGUGGGACUGUAUGGAGGUCGCUGGUCAAGCUAUGUGCCUUAUUGUUU 
               
               
                   
               
               
                 ACAUGAUGGUCAUGGUCAUUGGAAACCUGGUGGUCCUAAACCUAUUUCUGGCCUUAUUAUUGAGCUCAUU 
               
               
                   
               
               
                 UAGUUCAGACAAUCUUACAGCAAUUGAAGAAGACCCUGAUGCAAACAACCUCCAGAUUGCAGUGACUAGA 
               
               
                   
               
               
                 AUUAAAAAGGGAAUAAAUUAUGUGAAACAAACCUUACGUGAAUUUAUUCUAAAAGCAUUUUCCAAAAAGC 
               
               
                   
               
               
                 CAAAGAUUUCCAGGGAGAUAAGACAAGCAGAAGAUCUGAAUACUAAGAAGGAAAACUAUAUUUCUAACCA 
               
               
                   
               
               
                 UACACUUGCUGAAAUGAGCAAAGGUCACAAUUUCCUCAAGGAAAAAGAUAAAAUCAGUGGUUUUGGAAGC 
               
               
                   
               
               
                 AGCGUGGACAAACACUUGAUGGAAGACAGUGAUGGUCAAUCAUUUAUUCACAAUCCCAGCCUCACAGUGA 
               
               
                   
               
               
                 CAGUGCCAAUUGCACCUGGGGAAUCCGAUUUGGAAAAUAUGAAUGCUGAGGAACUUAGCAGUGAUUCGGA 
               
               
                   
               
               
                 UAGUGAAUACAGCAAAGUGAGAUUAAACCGGUCAAGCUCCUCAGAGUGCAGCACAGUUGAUAACCCUUUG 
               
               
                   
               
               
                 CCUGGAGAAGGAGAAGAAGCAGAGGCUGAACCUAUGAAUUCCGAUGAGCCAGAGGCCUGUUUCACAGAUG 
               
               
                   
               
               
                 GUUGUGUACGGAGGUUCUCAUGCUGCCAAGUUAACAUAGAGUCAGGGAAAGGAAAAAUCUGGUGGAACAU 
               
               
                   
               
               
                 CAGGAAAACCUGCUACAAGAUUGUUGAACACAGUUGGUUUGAAAGCUUCAUUGUCCUCAUGAUCCUGCUC 
               
               
                   
               
               
                 AGCAGUGGUGCCCUGGCUUUUGAAGAUAUUUAUAUUGAAAGGAAAAAGACCAUUAAGAUUAUCCUGGAGU 
               
               
                   
               
               
                 AUGCAGACAAGAUCUUCACUUACAUCUUCAUUCUGGAAAUGCUUCUAAAAUGGAUAGCAUAUGGUUAUAA 
               
               
                   
               
               
                 AACAUAUUUCACCAAUGCCUGGUGUUGGCUGGAUUUCCUAAUUGUUGAUGUUUCUUUGGUUACUUUAGUG 
               
               
                   
               
               
                 GCAAACACUCUUGGCUACUCAGAUCUUGGCCCCAUUAAAUCCCUUCGGACACUGAGAGCUUUAAGACCUC 
               
               
                   
               
               
                 UAAGAGCCUUAUCUAGAUUUGAAGGAAUGAGGGUCGUUGUGAAUGCACUCAUAGGAGCAAUUCCUUCCAU 
               
               
                   
               
               
                 CAUGAAUGUGCUACUUGUGUGUCUUAUAUUCUGGCUGAUAUUCAGCAUCAUGGGAGUAAAUUUGUUUGCU 
               
               
                   
               
               
                 GGCAAGUUCUAUGAGUGUAUUAACACCACAGAUGGGUCACGGUUUCCUGCAAGUCAAGUUCCAAAUCGUU 
               
               
                   
               
               
                 CCGAAUGUUUUGCCCUUAUGAAUGUUAGUCAAAAUGUGCGAUGGAAAAACCUGAAAGUGAACUUUGAUAA 
               
               
                   
               
               
                 UGUCGGACUUGGUUACCUAUCUCUGCUUCAAGUUGCAACUUUUAAGGGAUGGACGAUUAUUAUGUAUGCA 
               
               
                   
               
               
                 GCAGUGGAUUCUGUUAAUGUAGACAAGCAGCCCAAAUAUGAAUAUAGCCUCUACAUGUAUAUUUAUUUUG 
               
               
                   
               
               
                 UCGUCUUUAUCAUCUUUGGGUCAUUCUUCACUUUGAACUUGUUCAUUGGUGUCAUCAUAGAUAAUUUCAA 
               
               
                   
               
               
                 CCAACAGAAAAAGAAGCUUGGAGGUCAAGACAUCUUUAUGACAGAAGAACAGAAGAAAUACUAUAAUGCA 
               
               
                   
               
               
                 AUGAAAAAGCUGGGGUCCAAGAAGCCACAAAAGCCAAUUCCUCGACCAGGGAACAAAAUCCAAGGAUGUA 
               
               
                   
               
               
                 UAUUUGACCUAGUGACAAAUCAAGCCUUUGAUAUUAGUAUCAUGGUUCUUAUCUGUCUCAACAUGGUAAC 
               
               
                   
               
               
                 CAUGAUGGUAGAAAAGGAGGGUCAAAGUCAACAUAUGACUGAAGUUUUAUAUUGGAUAAAUGUGGUUUUU 
               
               
                   
               
               
                 AUAAUCCUUUUCACUGGAGAAUGUGUGCUAAAACUGAUCUCCCUCAGACACUACUACUUCACUGUAGGAU 
               
               
                   
               
               
                 GGAAUAUUUUUGAUUUUGUGGUUGUGAUUAUCUCCAUUGUAGGUAUGUUUCUAGCUGAUUUGAUUGAAAC 
               
               
                   
               
               
                 GUAUUUUGUGUCCCCUACCCUGUUCCGAGUGAUCCGUCUUGCCAGGAUUGGCCGAAUCCUACGUCUAGUC 
               
               
                   
               
               
                 AAAGGAGCAAAGGGGAUCCGCACGCUGCUCUUUGCUUUGAUGAUGUCCCUUCCUGCGUUGUUUAACAUCG 
               
               
                   
               
               
                 GCCUCCUGCUCUUCCUGGUCAUGUUCAUCUACGCCAUCUUUGGAAUGUCCAACUUUGCCUAUGUUAAAAA 
               
               
                   
               
               
                 GGAAGAUGGAAUUAAUGACAUGUUCAAUUUUGAGACCUUUGGCAACAGUAUGAUUUGCCUGUUCCAAAUU 
               
               
                   
               
               
                 ACAACCUCUGCUGGCUGGGAUGGAUUGCUAGCACCUAUUCUUAACAGUAAGCCACCCGACUGUGACCCAA 
               
               
                   
               
               
                 AAAAAGUUCAUCCUGGAAGUUCAGUUGAAGGAGACUGUGGUAACCCAUCUGUUGGAAUAUUCUACUUUGU 
               
               
                   
               
               
                 UAGUUAUAUCAUCAUAUCCUUCCUGGUUGUGGUGAACAUGUACAUUGCAGUCAUACUGGAGAAUUUUAGU 
               
               
                   
               
               
                 GUUGCCACUGAAGAAAGUACUGAACCUCUGAGUGAGGAUGACUUUGAGAUGUUCUAUGAGGUUUGGGAGA 
               
               
                   
               
               
                 AGUUUGAUCCCGAUGCGACCCAGUUUAUAGAGUUCUCUAAACUCUCUGAUUUUGCAGCUGCCCUGGAUCC 
               
               
                   
               
               
                 UCCUCUUCUCAUAGCAAAACCCAACAAAGUCCAGCUCAUUGCCAUGGAUCUGCCCAUGGUUAGUGGUGAC 
               
               
                   
               
               
                 CGGAUCCAUUGUCUUGACAUCUUAUUUGCUUUUACAAAGCGUGUUUUGGGUGAGAGUGGGGAGAUGGAUU 
               
               
                   
               
               
                 CUCUUCGUUCACAGAUGGAAGAAAGGUUCAUGUCUGCAAAUCCUUCCAAAGUGUCCUAUGAACCCAUCAC 
               
               
                   
               
               
                 AACCACACUAAAACGGAAACAAGAGGAUGUGUCUGCUACUGUCAUUCAGCGUGCUUAUAGACGUUACCGC 
               
               
                   
               
               
                 UUAAGGCAAAAUGUCAAAAAUAUAUCAAGUAUAUACAUAAAAGAUGGAGACAGAGAUGAUGAUUUACUCA 
               
               
                   
               
               
                 AUAAAAAAGAUAUGGCUUUUGAUAAUGUUAAUGAGAACUCAAGUCCAGAAAAAACAGAUGCCACUUCAUC 
               
               
                   
               
               
                 CACCACCUCUCCACCUUCAUAUGAUAACAAAGCCAGACAAAGAGAAAUAUGAACAAGACAGAACAGAAAA 
               
               
                   
               
               
                 GGAAGACAAAGGGAAAGACAGCAAGGAAAGCAAAAAAUAGAGCUUCAUUUUUGAUAUAUUGUUUACAGCC 
               
               
                   
               
               
                 UGUGAAAGUGAUUUAUUUGUGUUAAUAAAACUCUUUUGAGGAAGUCUAUGCCAAAAUCCUUUUUAUCAAA 
               
               
                   
               
               
                 AUAUUCUCGAAGGCAGUGCAGUCACUAACUCUGAUUUCCUAAGAAAGGUGGGCAGCAUUAGCAGAUGGUU 
               
               
                   
               
               
                 AUUUUUGCACUGAUGAUUCUUUAAGAAUCGUAAGAGAACUCUGUAGGAAUUAUUGAUUAUAGCAUACAAA 
               
               
                   
               
               
                 AGUGAUUCAGUUUUUUGGUUUUUAAUAAAUCAGAAGACCAUGUAGAAAACUUUUACAUCUGCCUUGUCAU 
               
               
                   
               
               
                 CUUUUCACAGGAUUGUAAUUAGUCUUGUUUCCCAUGUAAAUAAACAACACACGCAUACAGAAAAAUCUAU 
               
               
                   
               
               
                 UAUUUAUCUAUUAUUUGGAAAUCAACAAAAGUAUUUGCCUUGGCUUUGCAAUGAAAUGCUUGAUAGAAGU 
               
               
                   
               
               
                 AAUGGACAUUAGUUAUGAAUGUUUAGUUAAAAUGCAUUAUUAGGGAGCUUGACUUUUUAUCAAUGUACAG 
               
               
                   
               
               
                 AGGUUAUUCUAUAUUUUGAGGUGCUUAAAUUUAUUCUACAUUGCAUCAGAACCAAUUUAUAUGUGCCUAU 
               
               
                   
               
               
                 AAAAUGCCAUGGGAUUAAAAAUAUAUGUAGGCUAUUCAUUUCUACAAAUGUUUUUCAUUCAUCUUGACUC 
               
               
                   
               
               
                 ACAUGCCAACAAGGAUAAGACUUACCUUUAGAGUAUUGUGUUUCAUAGCCUUUCUUCUUUCAUAUCCCUU 
               
               
                   
               
               
                 UUUGUUCAUAGAAUAACCACAGAACUUGAAAAAUUAUUCUAAGUACAUAUUACACUCCUCAAAAAAAACA 
               
               
                   
               
               
                 AAGAUAACUGAGAAAAAAGUUAUUGACAGAAGUUCUAUUUGCUAUUAUUUACAUAGCCUAACAUUUGACU 
               
               
                   
               
               
                 GUGCUGCCCAAAAUACUGAUAAUAGUCUCUUAAACUCUUUUGUCAAAUUUUCCUGCUUUCUUAUGCAGUA 
               
               
                   
               
               
                 UUGUUUAGUCAUCCUUUCGCUGUAAGCAAAGUUGAUGAAAUCCUUCCUGAUAUGCAGUUAGUUGUUUGAC 
               
               
                   
               
               
                 CACGGUACAUACUUGAGCAGAUAAUAACUUGGGCACAGUAUUUAUUGCAUCACUUGUAUACAAUCCCGUG 
               
               
                   
               
               
                 UUUGGCAAGCUUUCAAAUCAUGUAAUAUGACAGACUUUACACAGAUAUGUGUUUAGUAUGAAUAAAAAAG 
               
               
                   
               
               
                 CAUUGAAAUAGGGAUUCUUGCCAACUUGCUCUCUUGCCACCAACUUACUUUCCUAAAUUAUGGAAGUAAU 
               
               
                   
               
               
                 CUUUUUUGGAUAUACUUCAAUGUAUACAAUGAGGAAGAUGUCACCUUCUCCUUAAAAUUCUAUGAUGUGA 
               
               
                   
               
               
                 AAUAUAUUUUGCCUCAAUCAACACAGUACCAUGGGCUUCUAAUUUAUCAAGCACAUAUUCAUUUUGCAUU 
               
               
                   
               
               
                 AGCUGUAGACAUCUAGUUUUUUGAAAACACCUAUUAAUAGUAAUUUGAAAAGAAAUAACCAUAAUGCUUU 
               
               
                   
               
               
                 UUUUCGUGAGUUUAUUUCAGGAAUAUGAGAUCUUUCUUCUAUAAAGUUAUUCAUGCACAGGCAAAAAUUG 
               
               
                   
               
               
                 AGCUACACAGGUAGAAUGUAGUUUUACUUAGAAGAUUUUUGUGGGAGGUUUUGAAGCAAAUAUAUAAAAC 
               
               
                   
               
               
                 AACUUUCACUAAUUUGCUUUCCAUAUUUAAAAAAUAAUAAAUUACAUUUAUAUAAUAAAUGUUUAAAGCA 
               
               
                   
               
               
                 CAUAUUUUUUGUUGUUCUGGCAAUUUAAAAAGAAAGAGGAUUUAAACGUACCUAUAGAAACAAAGAUUUA 
               
               
                   
               
               
                 UGGUUAAAGAAUGAGAUCAGAAGUCUAGAAUGUUUUUAAAUUGUGAUAUAUUUUACAACAUCCGUUAUUA 
               
               
                   
               
               
                 CUUUGAGACAUUUGUCCUAAUCUACGUAUAAAACUCAAUCUAGGGCUAAAGAUUCUUUAUACCAUCUUAG 
               
               
                   
               
               
                 GUUCAUUCAUCUUAGGCUAUUUGAACCACUUUUUAAUUUAAUAUGAAAGACACCAUGCAGUGUUUUCCGA 
               
               
                   
               
               
                 GACUACAUAGAUCAUUUUAUCACAUACCUACCAAGCCUGUUGGAAAUAGGUUUUGAUAAUUUAAGUAGGG 
               
               
                   
               
               
                 ACCUAUACAAAAUAUAUUACAUUUAUCAGAUUUUUAAAUACAUUCAAUUAAGAAUUUAACAUCACCUUAA 
               
               
                   
               
               
                 AUUUGAAUUCAAUCUACCGUUAUUUCAAACUCACAAAUAUAACUGCAUUAUGAAUACUUACAUAAUGUAG 
               
               
                   
               
               
                 UAAGACAAGAUGUUUGACAGGUUCGUGUGUAAUUUUCUAUUAAUGUUUUUACAUUGCCUUGUUUUUAUGU 
               
               
                   
               
               
                 AAAAUAAAAAAUAUGGGCAACUGGUUUGUUAACAACACAAUUUCUUCUUAGCAUUUCAAAAAUAUAUAUA 
               
               
                   
               
               
                 AAGUUGUUCUUUUUCCUAUUUCAUGAACUAUGUUUUUUUUUAAAAUAACAUGGUUAAGUUUUAUAUAUAU 
               
               
                   
               
               
                 UUACGUUUGUUUCAGGAAUGUCUACUUGUGACUUUUUAUCAAUUAAAAAUAAUAUUUGGAAGAAAGAGCU 
               
               
                   
               
               
                 UAUUAAGUAUAAGCUUGAAGUAAAAUUAGACCUCUCUUUCCAUGUAGAUUACUGUUUGUACUGAUGGUUU 
               
               
                   
               
               
                 CACCCUUCAGAAGGCACUGUCAUAUUAAUAUUUAAAUUUUAUAAUCGCUGAACUUAUUACACCCAACAAU 
               
               
                   
               
               
                 ACAGAAAGGCAGUUACACUGAAGAACUUAACUUAGAAUAAAAUGGAAGCAAACAGGUUUUCUAAAAACUU 
               
               
                   
               
               
                 UUUUAAGUGACCAGGUCUCGCUCUGUCACCCAGGCUAGAGUGCAAUGGCAUGAUCAUAGCUCUCUGCAGC 
               
               
                   
               
               
                 CUCAACUCUGGGCUCAAGCAACCCUCCUGCCUCAGCCUCCCAAGUAGCUAAGACUACAGGUACAUGCCAC 
               
               
                   
               
               
                 CAUGCCUGGCUAAUAUUUAAAUUUUUGUAGAUAAGGGGUCUUGCUAUGUUGCCCAGGCUAGUCUCAAACU 
               
               
                   
               
               
                 CCUGGCUUCAAGUGUUCCUACUGUCAUGACCUGCCAACAUGCUGGGGUUACAGGCAUGAGCCACCAUGCC 
               
               
                   
               
               
                 CCAAACAGGUUUGAACACAAAUCUUUCGGAUGAAAAUUAGAGAACCUAAUUUUAGCUUUUUGAUAGUUAC 
               
               
                   
               
               
                 CUAGUUUGCAAAAGAUUUGGGUGACUUGUGAGCUGUUUUUAAAUGCUGAUUGUUGAACAUCACAACCCAA 
               
               
                   
               
               
                 AAUACUUAGCAUGAUUUUAUAGAGUUUUGAUAGCUUUAUUAAAAAGAGUGAAAAUAAAAUGCAUAUGUAA 
               
               
                   
               
               
                 AUAAAGCAGUUCUAAAUAGCUAUUUCAGAGAAAUGUUAAUAGAAGUGCUGAAAGAAGGGCCAACUAAAUU 
               
               
                   
               
               
                 AGGAUGGCCAGGGAAUUGGCCUGGGUUUAGGACCUAUGUAUGAAGGCCACCAAUUUUUUAAAAAUAUCUG 
               
               
                   
               
               
                 UGGUUUAUUAUGUUAUUAUCUUCUUGAGGAAAACAAUCAAGAAUUGCUUCAUGAAAAUAAAUAAAUAGCC 
               
               
                   
               
               
                 AUGAAUAUCAUAAAGCUGUUUACAUAGGAUUCUUUACAAAUUUCAUAGAUCUAUGAAUGCUCAAAAUGUU 
               
               
                   
               
               
                 UGAGUUUGCCAUAAAUUAUAUUGUAGUUAUAUUGUAGUUAUACUUGAGACUGACACAUUGUAAUAUAAUC 
               
               
                   
               
               
                 UAAGAAUAAAAGUUAUACAAAAUAAAAAAAAAAAAA 
               
            
           
         
       
     
     The reverse complement of SEQ ID NO: 1 is provided as SEQ ID NO: 2 herein: 
     
       
         
           
               
               
            
               
                 (SEQ ID NO: 2) 
                   
               
               
                 UUUUUUUUUUUUUAUUUUGUAUAACUUUUAUUCUUAGAUUAUAUUACAAUGUGUCAGUCUCAAGUAUAAC 
                   
               
               
                   
               
               
                 UACAAUAUAACUACAAUAUAAUUUAUGGCAAACUCAAACAUUUUGAGCAUUCAUAGAUCUAUGAAAUUUG 
               
               
                   
               
               
                 UAAAGAAUCCUAUGUAAACAGCUUUAUGAUAUUCAUGGCUAUUUAUUUAUUUUCAUGAAGCAAUUCUUGA 
               
               
                   
               
               
                 UUGUUUUCCUCAAGAAGAUAAUAACAUAAUAAACCACAGAUAUUUUUAAAAAAUUGGUGGCCUUCAUACA 
               
               
                   
               
               
                 UAGGUCCUAAACCCAGGCCAAUUCCCUGGCCAUCCUAAUUUAGUUGGCCCUUCUUUCAGCACUUCUAUUA 
               
               
                   
               
               
                 ACAUUUCUCUGAAAUAGCUAUUUAGAACUGCUUUAUUUACAUAUGCAUUUUAUUUUCACUCUUUUUAAUA 
               
               
                   
               
               
                 AAGCUAUCAAAACUCUAUAAAAUCAUGCUAAGUAUUUUGGGUUGUGAUGUUCAACAAUCAGCAUUUAAAA 
               
               
                   
               
               
                 ACAGCUCACAAGUCACCCAAAUCUUUUGCAAACUAGGUAACUAUCAAAAAGCUAAAAUUAGGUUCUCUAA 
               
               
                   
               
               
                 UUUUCAUCCGAAAGAUUUGUGUUCAAACCUGUUUGGGGCAUGGUGGCUCAUGCCUGUAACCCCAGCAUGU 
               
               
                   
               
               
                 UGGCAGGUCAUGACAGUAGGAACACUUGAAGCCAGGAGUUUGAGACUAGCCUGGGCAACAUAGCAAGACC 
               
               
                   
               
               
                 CCUUAUCUACAAAAAUUUAAAUAUUAGCCAGGCAUGGUGGCAUGUACCUGUAGUCUUAGCUACUUGGGAG 
               
               
                   
               
               
                 GCUGAGGCAGGAGGGUUGCUUGAGCCCAGAGUUGAGGCUGCAGAGAGCUAUGAUCAUGCCAUUGCACUCU 
               
               
                   
               
               
                 AGCCUGGGUGACAGAGCGAGACCUGGUCACUUAAAAAAGUUUUUAGAAAACCUGUUUGCUUCCAUUUUAU 
               
               
                   
               
               
                 UCUAAGUUAAGUUCUUCAGUGUAACUGCCUUUCUGUAUUGUUGGGUGUAAUAAGUUCAGCGAUUAUAAAA 
               
               
                   
               
               
                 UUUAAAUAUUAAUAUGACAGUGCCUUCUGAAGGGUGAAACCAUCAGUACAAACAGUAAUCUACAUGGAAA 
               
               
                   
               
               
                 GAGAGGUCUAAUUUUACUUCAAGCUUAUACUUAAUAAGCUCUUUCUUCCAAAUAUUAUUUUUAAUUGAUA 
               
               
                   
               
               
                 AAAAGUCACAAGUAGACAUUCCUGAAACAAACGUAAAUAUAUAUAAAACUUAACCAUGUUAUUUUAAAAA 
               
               
                   
               
               
                 AAAACAUAGUUCAUGAAAUAGGAAAAAGAACAACUUUAUAUAUAUUUUUGAAAUGCUAAGAAGAAAUUGU 
               
               
                   
               
               
                 GUUGUUAACAAACCAGUUGCCCAUAUUUUUUAUUUUACAUAAAAACAAGGCAAUGUAAAAACAUUAAUAG 
               
               
                   
               
               
                 AAAAUUACACACGAACCUGUCAAACAUCUUGUCUUACUACAUUAUGUAAGUAUUCAUAAUGCAGUUAUAU 
               
               
                   
               
               
                 UUGUGAGUUUGAAAUAACGGUAGAUUGAAUUCAAAUUUAAGGUGAUGUUAAAUUCUUAAUUGAAUGUAUU 
               
               
                   
               
               
                 UAAAAAUCUGAUAAAUGUAAUAUAUUUUGUAUAGGUCCCUACUUAAAUUAUCAAAACCUAUUUCCAACAG 
               
               
                   
               
               
                 GCUUGGUAGGUAUGUGAUAAAAUGAUCUAUGUAGUCUCGGAAAACACUGCAUGGUGUCUUUCAUAUUAAA 
               
               
                   
               
               
                 UUAAAAAGUGGUUCAAAUAGCCUAAGAUGAAUGAACCUAAGAUGGUAUAAAGAAUCUUUAGCCCUAGAUU 
               
               
                   
               
               
                 GAGUUUUAUACGUAGAUUAGGACAAAUGUCUCAAAGUAAUAACGGAUGUUGUAAAAUAUAUCACAAUUUA 
               
               
                   
               
               
                 AAAACAUUCUAGACUUCUGAUCUCAUUCUUUAACCAUAAAUCUUUGUUUCUAUAGGUACGUUUAAAUCCU 
               
               
                   
               
               
                 CUUUCUUUUUAAAUUGCCAGAACAACAAAAAAUAUGUGCUUUAAACAUUUAUUAUAUAAAUGUAAUUUAU 
               
               
                   
               
               
                 UAUUUUUUAAAUAUGGAAAGCAAAUUAGUGAAAGUUGUUUUAUAUAUUUGCUUCAAAACCUCCCACAAAA 
               
               
                   
               
               
                 AUCUUCUAAGUAAAACUACAUUCUACCUGUGUAGCUCAAUUUUUGCCUGUGCAUGAAUAACUUUAUAGAA 
               
               
                   
               
               
                 GAAAGAUCUCAUAUUCCUGAAAUAAACUCACGAAAAAAAGCAUUAUGGUUAUUUCUUUUCAAAUUACUAU 
               
               
                   
               
               
                 UAAUAGGUGUUUUCAAAAAACUAGAUGUCUACAGCUAAUGCAAAAUGAAUAUGUGCUUGAUAAAUUAGAA 
               
               
                   
               
               
                 GCCCAUGGUACUGUGUUGAUUGAGGCAAAAUAUAUUUCACAUCAUAGAAUUUUAAGGAGAAGGUGACAUC 
               
               
                   
               
               
                 UUCCUCAUUGUAUACAUUGAAGUAUAUCCAAAAAAGAUUACUUCCAUAAUUUAGGAAAGUAAGUUGGUGG 
               
               
                   
               
               
                 CAAGAGAGCAAGUUGGCAAGAAUCCCUAUUUCAAUGCUUUUUUAUUCAUACUAAACACAUAUCUGUGUAA 
               
               
                   
               
               
                 AGUCUGUCAUAUUACAUGAUUUGAAAGCUUGCCAAACACGGGAUUGUAUACAAGUGAUGCAAUAAAUACU 
               
               
                   
               
               
                 GUGCCCAAGUUAUUAUCUGCUCAAGUAUGUACCGUGGUCAAACAACUAACUGCAUAUCAGGAAGGAUUUC 
               
               
                   
               
               
                 AUCAACUUUGCUUACAGCGAAAGGAUGACUAAACAAUACUGCAUAAGAAAGCAGGAAAAUUUGACAAAAG 
               
               
                   
               
               
                 AGUUUAAGAGACUAUUAUCAGUAUUUUGGGCAGCACAGUCAAAUGUUAGGCUAUGUAAAUAAUAGCAAAU 
               
               
                   
               
               
                 AGAACUUCUGUCAAUAACUUUUUUCUCAGUUAUCUUUGUUUUUUUUGAGGAGUGUAAUAUGUACUUAGAA 
               
               
                   
               
               
                 UAAUUUUUCAAGUUCUGUGGUUAUUCUAUGAACAAAAAGGGAUAUGAAAGAAGAAAGGCUAUGAAACACA 
               
               
                   
               
               
                 AUACUCUAAAGGUAAGUCUUAUCCUUGUUGGCAUGUGAGUCAAGAUGAAUGAAAAACAUUUGUAGAAAUG 
               
               
                   
               
               
                 AAUAGCCUACAUAUAUUUUUAAUCCCAUGGCAUUUUAUAGGCACAUAUAAAUUGGUUCUGAUGCAAUGUA 
               
               
                   
               
               
                 GAAUAAAUUUAAGCACCUCAAAAUAUAGAAUAACCUCUGUACAUUGAUAAAAAGUCAAGCUCCCUAAUAA 
               
               
                   
               
               
                 UGCAUUUUAACUAAACAUUCAUAACUAAUGUCCAUUACUUCUAUCAAGCAUUUCAUUGCAAAGCCAAGGC 
               
               
                   
               
               
                 AAAUACUUUUGUUGAUUUCCAAAUAAUAGAUAAAUAAUAGAUUUUUCUGUAUGCGUGUGUUGUUUAUUUA 
               
               
                   
               
               
                 CAUGGGAAACAAGACUAAUUACAAUCCUGUGAAAAGAUGACAAGGCAGAUGUAAAAGUUUUCUACAUGGU 
               
               
                   
               
               
                 CUUCUGAUUUAUUAAAAACCAAAAAACUGAAUCACUUUUGUAUGCUAUAAUCAAUAAUUCCUACAGAGUU 
               
               
                   
               
               
                 CUCUUACGAUUCUUAAAGAAUCAUCAGUGCAAAAAUAACCAUCUGCUAAUGCUGCCCACCUUUCUUAGGA 
               
               
                   
               
               
                 AAUCAGAGUUAGUGACUGCACUGCCUUCGAGAAUAUUUUGAUAAAAAGGAUUUUGGCAUAGACUUCCUCA 
               
               
                   
               
               
                 AAAGAGUUUUAUUAACACAAAUAAAUCACUUUCACAGGCUGUAAACAAUAUAUCAAAAAUGAAGCUCUAU 
               
               
                   
               
               
                 UUUUUGCUUUCCUUGCUGUCUUUCCCUUUGUCUUCCUUUUCUGUUCUGUCUUGUUCAUAUUUCUCUUUGU 
               
               
                   
               
               
                 CUGGCUUUGUUACACUAUCAUAUGAAGGUGGAGAGGUGGUGGAUGAAGUGGCAUCUGUUUUUUCUGGACU 
               
               
                   
               
               
                 UGAGUUCUCAUUAACAUUAUCAAAAGCCAUAUCUUUUUUAUUGAGUAAAUCAUCAUCUCUGUCUCCAUCU 
               
               
                   
               
               
                 UUUAUGUAUAUACUUGAUAUAUUUUUGACAUUUUGCCUUAAGCGGUAACGUCUAUAAGCACGCUGAAUGA 
               
               
                   
               
               
                 CAGUAGCAGACACAUCCUCUUGUUUCCGUUUUAGUGUGGUUGUGAUGGGUUCAUAGGACACUUUGGAAGG 
               
               
                   
               
               
                 AUUUGCAGACAUGAACCUUUCUUCCAUCUGUGAACGAAGAGAAUCCAUCUCCCCACUCUCACCCAAAACA 
               
               
                   
               
               
                 CGCUUUGUAAAAGCAAAUAAGAUGUCAAGACAAUGGAUCCGGUCACCACUAACCAUGGGCAGAUCCAUGG 
               
               
                   
               
               
                 CAAUGAGCUGGACUUUGUUGGGUUUUGCUAUGAGAAGAGGAGGAUCCAGGGCAGCUGCAAAAUCAGAGAG 
               
               
                   
               
               
                 UUUAGAGAACUCUAUAAACUGGGUCGCAUCGGGAUCAAACUUCUCCCAAACCUCAUAGAACAUCUCAAAG 
               
               
                   
               
               
                 UCAUCCUCACUCAGAGGUUCAGUACUUUCUUCAGUGGCAACACUAAAAUUCUCCAGUAUGACUGCAAUGU 
               
               
                   
               
               
                 ACAUGUUCACCACAACCAGGAAGGAUAUGAUGAUAUAACUAACAAAGUAGAAUAUUCCAACAGAUGGGUU 
               
               
                   
               
               
                 ACCACAGUCUCCUUCAACUGAACUUCCAGGAUGAACUUUUUUUGGGUCACAGUCGGGUGGCUUACUGUUA 
               
               
                   
               
               
                 AGAAUAGGUGCUAGCAAUCCAUCCCAGCCAGCAGAGGUUGUAAUUUGGAACAGGCAAAUCAUACUGUUGC 
               
               
                   
               
               
                 CAAAGGUCUCAAAAUUGAACAUGUCAUUAAUUCCAUCUUCCUUUUUAACAUAGGCAAAGUUGGACAUUCC 
               
               
                   
               
               
                 AAAGAUGGCGUAGAUGAACAUGACCAGGAAGAGCAGGAGGCCGAUGUUAAACAACGCAGGAAGGGACAUC 
               
               
                   
               
               
                 AUCAAAGCAAAGAGCAGCGUGCGGAUCCCCUUUGCUCCUUUGACUAGACGUAGGAUUCGGCCAAUCCUGG 
               
               
                   
               
               
                 CAAGACGGAUCACUCGGAACAGGGUAGGGGACACAAAAUACGUUUCAAUCAAAUCAGCUAGAAACAUACC 
               
               
                   
               
               
                 UACAAUGGAGAUAAUCACAACCACAAAAUCAAAAAUAUUCCAUCCUACAGUGAAGUAGUAGUGUCUGAGG 
               
               
                   
               
               
                 GAGAUCAGUUUUAGCACACAUUCUCCAGUGAAAAGGAUUAUAAAAACCACAUUUAUCCAAUAUAAAACUU 
               
               
                   
               
               
                 CAGUCAUAUGUUGACUUUGACCCUCCUUUUCUACCAUCAUGGUUACCAUGUUGAGACAGAUAAGAACCAU 
               
               
                   
               
               
                 GAUACUAAUAUCAAAGGCUUGAUUUGUCACUAGGUCAAAUAUACAUCCUUGGAUUUUGUUCCCUGGUCGA 
               
               
                   
               
               
                 GGAAUUGGCUUUUGUGGCUUCUUGGACCCCAGCUUUUUCAUUGCAUUAUAGUAUUUCUUCUGUUCUUCUG 
               
               
                   
               
               
                 UCAUAAAGAUGUCUUGACCUCCAAGCUUCUUUUUCUGUUGGUUGAAAUUAUCUAUGAUGACACCAAUGAA 
               
               
                   
               
               
                 CAAGUUCAAAGUGAAGAAUGACCCAAAGAUGAUAAAGACGACAAAAUAAAUAUACAUGUAGAGGCUAUAU 
               
               
                   
               
               
                 UCAUAUUUGGGCUGCUUGUCUACAUUAACAGAAUCCACUGCUGCAUACAUAAUAAUCGUCCAUCCCUUAA 
               
               
                   
               
               
                 AAGUUGCAACUUGAAGCAGAGAUAGGUAACCAAGUCCGACAUUAUCAAAGUUCACUUUCAGGUUUUUCCA 
               
               
                   
               
               
                 UCGCACAUUUUGACUAACAUUCAUAAGGGCAAAACAUUCGGAACGAUUUGGAACUUGACUUGCAGGAAAC 
               
               
                   
               
               
                 CGUGACCCAUCUGUGGUGUUAAUACACUCAUAGAACUUGCCAGCAAACAAAUUUACUCCCAUGAUGCUGA 
               
               
                   
               
               
                 AUAUCAGCCAGAAUAUAAGACACACAAGUAGCACAUUCAUGAUGGAAGGAAUUGCUCCUAUGAGUGCAUU 
               
               
                   
               
               
                 CACAACGACCCUCAUUCCUUCAAAUCUAGAUAAGGCUCUUAGAGGUCUUAAAGCUCUCAGUGUCCGAAGG 
               
               
                   
               
               
                 GAUUUAAUGGGGCCAAGAUCUGAGUAGCCAAGAGUGUUUGCCACUAAAGUAACCAAAGAAACAUCAACAA 
               
               
                   
               
               
                 UUAGGAAAUCCAGCCAACACCAGGCAUUGGUGAAAUAUGUUUUAUAACCAUAUGCUAUCCAUUUUAGAAG 
               
               
                   
               
               
                 CAUUUCCAGAAUGAAGAUGUAAGUGAAGAUCUUGUCUGCAUACUCCAGGAUAAUCUUAAUGGUCUUUUUC 
               
               
                   
               
               
                 CUUUCAAUAUAAAUAUCUUCAAAAGCCAGGGCACCACUGCUGAGCAGGAUCAUGAGGACAAUGAAGCUUU 
               
               
                   
               
               
                 CAAACCAACUGUGUUCAACAAUCUUGUAGCAGGUUUUCCUGAUGUUCCACCAGAUUUUUCCUUUCCCUGA 
               
               
                   
               
               
                 CUCUAUGUUAACUUGGCAGCAUGAGAACCUCCGUACACAACCAUCUGUGAAACAGGCCUCUGGCUCAUCG 
               
               
                   
               
               
                 GAAUUCAUAGGUUCAGCCUCUGCUUCUUCUCCUUCUCCAGGCAAAGGGUUAUCAACUGUGCUGCACUCUG 
               
               
                   
               
               
                 AGGAGCUUGACCGGUUUAAUCUCACUUUGCUGUAUUCACUAUCCGAAUCACUGCUAAGUUCCUCAGCAUU 
               
               
                   
               
               
                 CAUAUUUUCCAAAUCGGAUUCCCCAGGUGCAAUUGGCACUGUCACUGUGAGGCUGGGAUUGUGAAUAAAU 
               
               
                   
               
               
                 GAUUGACCAUCACUGUCUUCCAUCAAGUGUUUGUCCACGCUGCUUCCAAAACCACUGAUUUUAUCUUUUU 
               
               
                   
               
               
                 CCUUGAGGAAAUUGUGACCUUUGCUCAUUUCAGCAAGUGUAUGGUUAGAAAUAUAGUUUUCCUUCUUAGU 
               
               
                   
               
               
                 AUUCAGAUCUUCUGCUUGUCUUAUCUCCCUGGAAAUCUUUGGCUUUUUGGAAAAUGCUUUUAGAAUAAAU 
               
               
                   
               
               
                 UCACGUAAGGUUUGUUUCACAUAAUUUAUUCCCUUUUUAAUUCUAGUCACUGCAAUCUGGAGGUUGUUUG 
               
               
                   
               
               
                 CAUCAGGGUCUUCUUCAAUUGCUGUAAGAUUGUCUGAACUAAAUGAGCUCAAUAAUAAGGCCAGAAAUAG 
               
               
                   
               
               
                 GUUUAGGACCACCAGGUUUCCAAUGACCAUGACCAUCAUGUAAACAAUAAGGCACAUAGCUUGACCAGCG 
               
               
                   
               
               
                 ACCUCCAUACAGUCCCACAUGGUCUCUAUCCACUCUCCACACAGCACGCGGAACACAAUCAGGAAGGAGU 
               
               
                   
               
               
                 GGAAGAAGUCGUUCAUGUGCCACCGUGGGAGCGUACAGUCAUCAUUGAUCUUGCAGACACAUUCUUUGUA 
               
               
                   
               
               
                 GCUCUUACCAAAGAGCUGCAUGCCGACCACAGCAAAAAUGAAGACGAUGAUGGCCAACACUAAGGUGAGG 
               
               
                   
               
               
                 UUACCUAGAGCCCCUACUGAGUUACCAAUGAUCUUAAUCAGCAUGUUCAAUGUUGGCCAGGAUUUUGCCA 
               
               
                   
               
               
                 ACUUGAAGACUCGGAGCAGUCUGAAUGAUCGCAGAACUGACAAUCCUUCCACAUCUGCUAGAAAGAGCUC 
               
               
                   
               
               
                 CACUAAACUUAAAGUCACAAUAAGGCUGUCAAAAAUAUUCCAGCCUACUUGGAAAUACUCAUAUGGAUCC 
               
               
                   
               
               
                 AUGGCAAUCAGUUUUAAUACCAUUUCAGCUGCAAAGAUUCCAGUAAAGACCAAAUUUCCUAUAGCAAGUA 
               
               
                   
               
               
                 CAUUUUUGAAUUCCUCAGUCAUUGGGUGGUGUUCCAUAGCCAUAAAUAAUGUGUUUAAAACUAUGCAAAU 
               
               
                   
               
               
                 GGUAAUUGCAAGAUCUACAAAAGGAUCCAUUACAAUAAAAUAGAUACACUUUUUGAAUUUUAUCCAAUAU 
               
               
                   
               
               
                 GGAGAGCAAUUCCAGAUCAAGAAUUUGUGUGCAAAUCUGUACCACCAAGGUGGACAUUUUUGUCUGGACU 
               
               
                   
               
               
                 CUUCAAGUUCUUCCACAGUGUUUGUUAAUAUGCUUGCUCUACUCAUUGCUCUCUGUCUGAGGUUGGGAUC 
               
               
                   
               
               
                 AUUCAGCAUAUCCUCUGAAAGGAGAUAGGAACUACAACGCCUUUUCUUGUGUAUUUGAUUGGUCGUGCCC 
               
               
                   
               
               
                 UCUGGCAGAAGCUGUCCAUUGGGGAGCAUGAGGGCUGAGCGUCCAUCAACCAGGGAGACCACACCGUUGC 
               
               
                   
               
               
                 AGUCCACAGCACUGUGCAUUUUCCCGUUCACCGGCAGCAUUGGUGGGGACCUACUGGCUUGGCUGAUGUU 
               
               
                   
               
               
                 ACUGCUGCGUCGCUCCUGGGGUCUGUGGGGCACAAACAGUGAGCCCCUUCUGCUCUCAUUGUCUCCAAAA 
               
               
                   
               
               
                 AUGCUGUGCUCAUCAUCGGCAAAUUCAGUCUCAGAUCCUAUAUCUCUUCCUCUGCCUUUGAAACUAAAAA 
               
               
                   
               
               
                 GACUUGUUCUGCUGCUUCGCCUUGCAGAAAACAAGGAGCCACGAAUGCUGAGUGGUGACUGAUUGGGGGU 
               
               
                   
               
               
                 AGACAACCUCUUUUCAUGUGCUCGCCUAUGCCCUUCGACACCAAGGUGGAAACUUUUUCUUCUGAUGCUG 
               
               
                   
               
               
                 UCCUCUGAUUCUGAUUUCGACAAUUUCUCAGCAUCUCCCUUUUCCUCUCCACUGGAGAGCUUCUUUUGAU 
               
               
                   
               
               
                 UCUUUUUCUUUCUUCUGUUUCUUCUUUCUUUAGCACUUUUAGAGCUCAGUUUGGAUGUUUCAGAAGAACU 
               
               
                   
               
               
                 CUCUGAGAGGCCCAUAAUUCUGCUUCUCCUAAUACUUGUAUAUUCAGCCGCUGCCGCUGCAAUUGCCUCA 
               
               
                   
               
               
                 GCUUCUUCUUGCUCUUUUUUAAGACGGUCUAACAUCUGUUGAAAUUCUAAUUCUUUCUGUUUAGCUUCUU 
               
               
                   
               
               
                 CAAUGUUUGCCUGGUUCUGUUCUUCAUAUGCCAUGGCAACCACAGCCAGGAUCAAGUUUAUUAGAUAAAA 
               
               
                   
               
               
                 GGAGCCCAGGAAAAUCACUACGACAAAGAAGAUCAUGUAGGUUUUGCCAGCAGCACGCAGCGUCUGUUGG 
               
               
                   
               
               
                 UAAAGGUUUUCCCAGUAAUCUUGGGUCAUUAGCCUAAACAAGGCUAAGAAGGCCCAGCUGAAAGUGUCAA 
               
               
                   
               
               
                 AGCUCGUGUAGCCAUAAUCAGGGUUUCUGCCAAUUUUCACACAGGUGUACCCCUCUGGACACUGACCUGA 
               
               
                   
               
               
                 AUCUGUGCUGAAACCACAAAGGAGAGCAUCUUUGGAUCCUUCCAAGUAAUAAAAAUAUUUUCUAAAGUCU 
               
               
                   
               
               
                 UCUUCACUCUCUAGGGUAUUCAUUAUGCUUUCUAAUGUUUCAUUAUUUUCAAGUGAAUUUCGAAAACAUU 
               
               
                   
               
               
                 UAUGCUUCAGGUUUCCCAUGAACAGCUGUAGUCCAAUUAGUGCAAACACACUCAGACAGAACACAGUCAG 
               
               
                   
               
               
                 GAUCAUGACAUCAGAAAGCUUCUUCACUGACUGGAUCAAAGCCCCUACAAUUGUCUUCAGGCCUGGGAUU 
               
               
                   
               
               
                 ACAGAAAUAGUUUUCAAAGCUCUCAAUACUCUGAAAGUUCGAAGAGCUGAAACAUUGCCUAGGUUUACAA 
               
               
                   
               
               
                 AUUCUGUUAAAUACGCAAAAACAAUGACGACAAAAUCCAGCCAGUUCCACGGGUCACGAAGAAAAGUGAA 
               
               
                   
               
               
                 UUCUCCUACACAGAAGCCUCUUGCAAGGAUUUUUACAAGUGAUUCAAAAGUAUAUAUUCCAGUAAAAGUG 
               
               
                   
               
               
                 UACUCGACAUUUUUGGUCCAGUCCGGUGGGUUAUUCAUGGUCAUAAAUAUGCAGUUUGUCAGAAUAGUGC 
               
               
                   
               
               
                 ACAUGAUGAGCAUGCUGAAUAAGGAGUGUACUAAAAUCUUAAUAGAUAUUCUUCUUAGAGGACUGAAAGG 
               
               
                   
               
               
                 AGAAAGCAUAUAUAAAGCAGGUGUGGCAUUGAAACGGAAGAUUGUUUUCCCUUUGUUCAAUACUAUGAAA 
               
               
                   
               
               
                 GUCUUUUUGUCUGCAUAGUAGGGGUCCAAGUCCUCCAGGGGCUCUGACACCAUGCCGGGAGGAAUGUCCC 
               
               
                   
               
               
                 CAUAGAUGAAGGGCAGCUGUUUGCCAGCUUCCAAGUCACUGCUUGGCUUUGGGGCUUCUUCAUCAUCAUC 
               
               
                   
               
               
                 UUUCUUUUCUUCUUUGGGUUCCUUUGAUUUUCUUUCAGCAAUGCGUUGUUCAAUGAGGGCAAGAGACUGU 
               
               
                   
               
               
                 UUUGUGAAAUGGACAAAGCUCUGAGGUCCUGGGGGAGGCAACAUUGCCAUCUUUUCAUCCUGUAUAUUUU 
               
               
                   
               
               
                 AAUUCCUCUUCAGCUCCUCACAUAAGAGGCUUGCAACCUAGCCCGCCGAUCAUCCCCACCCAGUGCACCU 
               
               
                   
               
               
                 GCAGAAUCUGGCUCCAGGAGAGGGCGCGGGCCUCUCCUUCCCCGGCGCUCUCUCAGGGCUGCUUCUUUUU 
               
               
                   
               
               
                 CUCUGGGCUCCUGUUGCUCAGGGGACGCCUGCCGCUAGCAGCCACUGGCACCCAGGCUAGCCCAGCCUCA 
               
               
                   
               
               
                 GCCGAGCUGGCGGAAUUGGAAAGCCGACAGCCGCCGCUGGAGCGCUGGCGACCGCCUGCAAGCAGACUGC 
               
               
                   
               
               
                 GCCCCUCCUGCCAGGGCGCGCCCGUGGAGGUAGCAGCCCCG 
               
            
           
         
       
     
     A human SCN9A mRNA may have the sequence of SEQ ID NO: 4001 provided herein. 
       Homo sapiens  Sodium Channel, Voltage Gated, Type IX Alpha Subunit (SCN9A), Transcript Variant 2, mRNA 
     
       
         
           
               
               
            
               
                 (SEQ ID NO: 4001) 
                   
               
               
                 AGTCTGCTTGCAGGCGGTCGCCAGCGCTCCAGCGGCGGCTGTCGGCTTTCCAATTCCGCCAGCTCGGCTG 
                   
               
               
                   
               
               
                 AGGCTGGGCTAGCCTGGGTGCCAGTGGCTGCTAGCGGCAGGCGTCCCCTGAGCAACAGGAGCCCAGAGAA 
               
               
                   
               
               
                 AAAGAAGCAGCCCTGAGAGAGCGCCGGGGAAGGAGAGGCCCGCGCCCTCTCCTGGAGCCAGATTCTGCAG 
               
               
                   
               
               
                 GTGCACTGGGTGGGGATGATCGGCGGGCTAGGTTGCAAGCCTCTTATGTGAGGAGCTGAAGAGGAATTAA 
               
               
                   
               
               
                 AATATACAGGATGAAAAGATGGCAATGTTGCCTCCCCCAGGACCTCAGAGCTTTGTCCATTTCACAAAAC 
               
               
                   
               
               
                 AGTCTCTTGCCCTCATTGAACAACGCATTGCTGAAAGAAAATCAAAGGAACCCAAAGAAGAAAAGAAAGA 
               
               
                   
               
               
                 TGATGATGAAGAAGCCCCAAAGCCAAGCAGTGACTTGGAAGCTGGCAAACAGCTGCCCTTCATCTATGGG 
               
               
                   
               
               
                 GACATTCCTCCCGGCATGGTGTCAGAGCCCCTGGAGGACTTGGACCCCTACTATGCAGACAAAAAGACTT 
               
               
                   
               
               
                 TCATAGTATTGAACAAAGGGAAAACAATCTTCCGTTTCAATGCCACACCTGCTTTATATATGCTTTCTCC 
               
               
                   
               
               
                 TTTCAGTCCTCTAAGAAGAATATCTATTAAGATTTTAGTACACTCCTTATTCAGCATGCTCATCATGTGC 
               
               
                   
               
               
                 ACTATTCTGACAAACTGCATATTTATGACCATGAATAACCCACCGGACTGGACCAAAAATGTCGAGTACA 
               
               
                   
               
               
                 CTTTTACTGGAATATATACTTTTGAATCACTTGTAAAAATCCTTGCAAGAGGCTTCTGTGTAGGAGAATT 
               
               
                   
               
               
                 CACTTTTCTTCGTGACCCGTGGAACTGGCTGGATTTTGTCGTCATTGTTTTTGCGTATTTAACAGAATTT 
               
               
                   
               
               
                 GTAAACCTAGGCAATGTTTCAGCTCTTCGAACTTTCAGAGTATTGAGAGCTTTGAAAACTATTTCTGTAA 
               
               
                   
               
               
                 TCCCAGGCCTGAAGACAATTGTAGGGGCTTTGATCCAGTCAGTGAAGAAGCTTTCTGATGTCATGATCCT 
               
               
                   
               
               
                 GACTGTGTTCTGTCTGAGTGTGTTTGCACTAATTGGACTACAGCTGTTCATGGGAAACCTGAAGCATAAA 
               
               
                   
               
               
                 TGTTTTCGAAATTCACTTGAAAATAATGAAACATTAGAAAGCATAATGAATACCCTAGAGAGTGAAGAAG 
               
               
                   
               
               
                 ACTTTAGAAAATATTTTTATTACTTGGAAGGATCCAAAGATGCTCTCCTTTGTGGTTTCAGCACAGATTC 
               
               
                   
               
               
                 AGGTCAGTGTCCAGAGGGGTACACCTGTGTGAAAATTGGCAGAAACCCTGATTATGGCTACACGAGCTTT 
               
               
                   
               
               
                 GACACTTTCAGCTGGGCCTTCTTAGCCTTGTTTAGGCTAATGACCCAAGATTACTGGGAAAACCTTTACC 
               
               
                   
               
               
                 AACAGACGCTGCGTGCTGCTGGCAAAACCTACATGATCTTCTTTGTCGTAGTGATTTTCCTGGGCTCCTT 
               
               
                   
               
               
                 TTATCTAATAAACTTGATCCTGGCTGTGGTTGCCATGGCATATGAAGAACAGAACCAGGCAAACATTGAA 
               
               
                   
               
               
                 GAAGCTAAACAGAAAGAATTAGAATTTCAACAGATGTTAGACCGTCTTAAAAAAGAGCAAGAAGAAGCTG 
               
               
                   
               
               
                 AGGCAATTGCAGCGGCAGCGGCTGAATATACAAGTATTAGGAGAAGCAGAATTATGGGCCTCTCAGAGAG 
               
               
                   
               
               
                 TTCTTCTGAAACATCCAAACTGAGCTCTAAAAGTGCTAAAGAAAGAAGAAACAGAAGAAAGAAAAAGAAT 
               
               
                   
               
               
                 CAAAAGAAGCTCTCCAGTGGAGAGGAAAAGGGAGATGCTGAGAAATTGTCGAAATCAGAATCAGAGGACA 
               
               
                   
               
               
                 GCATCAGAAGAAAAAGTTTCCACCTTGGTGTCGAAGGGCATAGGCGAGCACATGAAAAGAGGTTGTCTAC 
               
               
                   
               
               
                 CCCCAATCAGTCACCACTCAGCATTCGTGGCTCCTTGTTTTCTGCAAGGCGAAGCAGCAGAACAAGTCTT 
               
               
                   
               
               
                 TTTAGTTTCAAAGGCAGAGGAAGAGATATAGGATCTGAGACTGAATTTGCCGATGATGAGCACAGCATTT 
               
               
                   
               
               
                 TTGGAGACAATGAGAGCAGAAGGGGCTCACTGTTTGTGCCCCACAGACCCCAGGAGCGACGCAGCAGTAA 
               
               
                   
               
               
                 CATCAGCCAAGCCAGTAGGTCCCCACCAATGCTGCCGGTGAACGGGAAAATGCACAGTGCTGTGGACTGC 
               
               
                   
               
               
                 AACGGTGTGGTCTCCCTGGTTGATGGACGCTCAGCCCTCATGCTCCCCAATGGACAGCTTCTGCCAGAGG 
               
               
                   
               
               
                 TGATAATAGATAAGGCAACTTCTGATGACAGCGGCACGACCAATCAAATACACAAGAAAAGGCGTTGTAG 
               
               
                   
               
               
                 TTCCTATCTCCTTTCAGAGGATATGCTGAATGATCCCAACCTCAGACAGAGAGCAATGAGTAGAGCAAGC 
               
               
                   
               
               
                 ATATTAACAAACACTGTGGAAGAACTTGAAGAGTCCAGACAAAAATGTCCACCTTGGTGGTACAGATTTG 
               
               
                   
               
               
                 CACACAAATTCTTGATCTGGAATTGCTCTCCATATTGGATAAAATTCAAAAAGTGTATCTATTTTATTGT 
               
               
                   
               
               
                 AATGGATCCTTTTGTAGATCTTGCAATTACCATTTGCATAGTTTTAAACACATTATTTATGGCTATGGAA 
               
               
                   
               
               
                 CACCACCCAATGACTGAGGAATTCAAAAATGTACTTGCTATAGGAAATTTGGTCTTTACTGGAATCTTTG 
               
               
                   
               
               
                 CAGCTGAAATGGTATTAAAACTGATTGCCATGGATCCATATGAGTATTTCCAAGTAGGCTGGAATATTTT 
               
               
                   
               
               
                 TGACAGCCTTATTGTGACTTTAAGTTTAGTGGAGCTCTTTCTAGCAGATGTGGAAGGATTGTCAGTTCTG 
               
               
                   
               
               
                 CGATCATTCAGACTGCTCCGAGTCTTCAAGTTGGCAAAATCCTGGCCAACATTGAACATGCTGATTAAGA 
               
               
                   
               
               
                 TCATTGGTAACTCAGTAGGGGCTCTAGGTAACCTCACCTTAGTGTTGGCCATCATCGTCTTCATTTTTGC 
               
               
                   
               
               
                 TGTGGTCGGCATGCAGCTCTTTGGTAAGAGCTACAAAGAATGTGTCTGCAAGATCAATGATGACTGTACG 
               
               
                   
               
               
                 CTCCCACGGTGGCACATGAACGACTTCTTCCACTCCTTCCTGATTGTGTTCCGCGTGCTGTGTGGAGAGT 
               
               
                   
               
               
                 GGATAGAGACCATGTGGGACTGTATGGAGGTCGCTGGTCAAGCTATGTGCCTTATTGTTTACATGATGGT 
               
               
                   
               
               
                 CATGGTCATTGGAAACCTGGTGGTCCTAAACCTATTTCTGGCCTTATTATTGAGCTCATTTAGTTCAGAC 
               
               
                   
               
               
                 AATCTTACAGCAATTGAAGAAGACCCTGATGCAAACAACCTCCAGATTGCAGTGACTAGAATTAAAAAGG 
               
               
                   
               
               
                 GAATAAATTATGTGAAACAAACCTTACGTGAATTTATTCTAAAAGCATTTTCCAAAAAGCCAAAGATTTC 
               
               
                   
               
               
                 CAGGGAGATAAGACAAGCAGAAGATCTGAATACTAAGAAGGAAAACTATATTTCTAACCATACACTTGCT 
               
               
                   
               
               
                 GAAATGAGCAAAGGTCACAATTTCCTCAAGGAAAAAGATAAAATCAGTGGTTTTGGAAGCAGCGTGGACA 
               
               
                   
               
               
                 AACACTTGATGGAAGACAGTGATGGTCAATCATTTATTCACAATCCCAGCCTCACAGTGACAGTGCCAAT 
               
               
                   
               
               
                 TGCACCTGGGGAATCCGATTTGGAAAATATGAATGCTGAGGAACTTAGCAGTGATTCGGATAGTGAATAC 
               
               
                   
               
               
                 AGCAAAGTGAGATTAAACCGGTCAAGCTCCTCAGAGTGCAGCACAGTTGATAACCCTTTGCCTGGAGAAG 
               
               
                   
               
               
                 GAGAAGAAGCAGAGGCTGAACCTATGAATTCCGATGAGCCAGAGGCCTGTTTCACAGATGGTTGTGTATG 
               
               
                   
               
               
                 GAGGTTCTCATGCTGCCAAGTTAACATAGAGTCAGGGAAAGGAAAAATCTGGTGGAACATCAGGAAAACC 
               
               
                   
               
               
                 TGCTACAAGATTGTTGAACACAGTTGGTTTGAAAGCTTCATTGTCCTCATGATCCTGCTCAGCAGTGGTG 
               
               
                   
               
               
                 CCCTGGCTTTTGAAGATATTTATATTGAAAGGAAAAAGACCATTAAGATTATCCTGGAGTATGCAGACAA 
               
               
                   
               
               
                 GATCTTCACTTACATCTTCATTCTGGAAATGCTTCTAAAATGGATAGCATATGGTTATAAAACATATTTC 
               
               
                   
               
               
                 ACCAATGCCTGGTGTTGGCTGGATTTCCTAATTGTTGATGTTTCTTTGGTTACTTTAGTGGCAAACACTC 
               
               
                   
               
               
                 TTGGCTACTCAGATCTTGGCCCCATTAAATCCCTTCGGACACTGAGAGCTTTAAGACCTCTAAGAGCCTT 
               
               
                   
               
               
                 ATCTAGATTTGAAGGAATGAGGGTCGTTGTGAATGCACTCATAGGAGCAATTCCTTCCATCATGAATGTG 
               
               
                   
               
               
                 CTACTTGTGTGTCTTATATTCTGGCTGATATTCAGCATCATGGGAGTAAATTTGTTTGCTGGCAAGTTCT 
               
               
                   
               
               
                 ATGAGTGTATTAACACCACAGATGGGTCACGGTTTCCTGCAAGTCAAGTTCCAAATCGTTCCGAATGTTT 
               
               
                   
               
               
                 TGCCCTTATGAATGTTAGTCAAAATGTGCGATGGAAAAACCTGAAAGTGAACTTTGATAATGTCGGACTT 
               
               
                   
               
               
                 GGTTACCTATCTCTGCTTCAAGTTGCAACTTTTAAGGGATGGACGATTATTATGTATGCAGCAGTGGATT 
               
               
                   
               
               
                 CTGTTAATGTAGACAAGCAGCCCAAATATGAATATAGCCTCTACATGTATATTTATTTTGTCGTCTTTAT 
               
               
                   
               
               
                 CATCTTTGGGTCATTCTTCACTTTGAACTTGTTCATTGGTGTCATCATAGATAATTTCAACCAACAGAAA 
               
               
                   
               
               
                 AAGAAGCTTGGAGGTCAAGACATCTTTATGACAGAAGAACAGAAGAAATACTATAATGCAATGAAAAAGC 
               
               
                   
               
               
                 TGGGGTCCAAGAAGCCACAAAAGCCAATTCCTCGACCAGGGAACAAAATCCAAGGATGTATATTTGACCT 
               
               
                   
               
               
                 AGTGACAAATCAAGCCTTTGATATTAGTATCATGGTTCTTATCTGTCTCAACATGGTAACCATGATGGTA 
               
               
                   
               
               
                 GAAAAGGAGGGTCAAAGTCAACATATGACTGAAGTTTTATATTGGATAAATGTGGTTTTTATAATCCTTT 
               
               
                   
               
               
                 TCACTGGAGAATGTGTGCTAAAACTGATCTCCCTCAGACACTACTACTTCACTGTAGGATGGAATATTTT 
               
               
                   
               
               
                 TGATTTTGTGGTTGTGATTATCTCCATTGTAGGTATGTTTCTAGCTGATTTGATTGAAACGTATTTTGTG 
               
               
                   
               
               
                 TCCCCTACCCTGTTCCGAGTGATCCGTCTTGCCAGGATTGGCCGAATCCTACGTCTAGTCAAAGGAGCAA 
               
               
                   
               
               
                 AGGGGATCCGCACGCTGCTCTTTGCTTTGATGATGTCCCTTCCTGCGTTGTTTAACATCGGCCTCCTGCT 
               
               
                   
               
               
                 CTTCCTGGTCATGTTCATCTACGCCATCTTTGGAATGTCCAACTTTGCCTATGTTAAAAAGGAAGATGGA 
               
               
                   
               
               
                 ATTAATGACATGTTCAATTTTGAGACCTTTGGCAACAGTATGATTTGCCTGTTCCAAATTACAACCTCTG 
               
               
                   
               
               
                 CTGGCTGGGATGGATTGCTAGCACCTATTCTTAACAGTAAGCCACCCGACTGTGACCCAAAAAAAGTTCA 
               
               
                   
               
               
                 TCCTGGAAGTTCAGTTGAAGGAGACTGTGGTAACCCATCTGTTGGAATATTCTACTTTGTTAGTTATATC 
               
               
                   
               
               
                 ATCATATCCTTCCTGGTTGTGGTGAACATGTACATTGCAGTCATACTGGAGAATTTTAGTGTTGCCACTG 
               
               
                   
               
               
                 AAGAAAGTACTGAACCTCTGAGTGAGGATGACTTTGAGATGTTCTATGAGGTTTGGGAGAAGTTTGATCC 
               
               
                   
               
               
                 CGATGCGACCCAGTTTATAGAGTTCTCTAAACTCTCTGATTTTGCAGCTGCCCTGGATCCTCCTCTTCTC 
               
               
                   
               
               
                 ATAGCAAAACCCAACAAAGTCCAGCTCATTGCCATGGATCTGCCCATGGTTAGTGGTGACCGGATCCATT 
               
               
                   
               
               
                 GTCTTGACATCTTATTTGCTTTTACAAAGCGTGTTTTGGGTGAGAGTGGGGAGATGGATTCTCTTCGTTC 
               
               
                   
               
               
                 ACAGATGGAAGAAAGGTTCATGTCTGCAAATCCTTCCAAAGTGTCCTATGAACCCATCACAACCACACTA 
               
               
                   
               
               
                 AAACGGAAACAAGAGGATGTGTCTGCTACTGTCATTCAGCGTGCTTATAGACGTTACCGCTTAAGGCAAA 
               
               
                   
               
               
                 ATGTCAAAAATATATCAAGTATATACATAAAAGATGGAGACAGAGATGATGATTTACTCAATAAAAAAGA 
               
               
                   
               
               
                 TATGGCTTTTGATAATGTTAATGAGAACTCAAGTCCAGAAAAAACAGATGCCACTTCATCCACCACCTCT 
               
               
                   
               
               
                 CCACCTTCATATGATAGTGTAACAAAGCCAGACAAAGAGAAATATGAACAAGACAGAACAGAAAAGGAAG 
               
               
                   
               
               
                 ACAAAGGGAAAGACAGCAAGGAAAGCAAAAAATAGAGCTTCATTTTTGATATATTGTTTACAGCCTGTGA 
               
               
                   
               
               
                 AAGTGATTTATTTGTGTTAATAAAACTCTTTTGAGGAAGTCTATGCCAAAATCCTTTTTATCAAAATATT 
               
               
                   
               
               
                 CTCGAAGGCAGTGCAGTCACTAACTCTGATTTCCTAAGAAAGGTGGGCAGCATTAGCAGATGGTTATTTT 
               
               
                   
               
               
                 TGCACTGATGATTCTTTAAGAATCGTAAGAGAACTCTGTAGGAATTATTGATTATAGCATACAAAAGTGA 
               
               
                   
               
               
                 TTCAGTTTTTTGGTTTTTAATAAATCAGAAGACCATGTAGAAAACTTTTACATCTGCCTTGTCATCTTTT 
               
               
                   
               
               
                 CACAGGATTGTAATTAGTCTTGTTTCCCATGTAAATAAACAACACACGCATACAGAAAAATCTATTATTT 
               
               
                   
               
               
                 ATCTATTATTTGGAAATCAACAAAAGTATTTGCCTTGGCTTTGCAATGAAATGCTTGATAGAAGTAATGG 
               
               
                   
               
               
                 ACATTAGTTATGAATGTTTAGTTAAAATGCATTATTAGGGAGCTTGACTTTTTATCAATGTACAGAGGTT 
               
               
                   
               
               
                 ATTCTATATTTTGAGGTGCTTAAATTTATTCTACATTGCATCAGAACCAATTTATATGTGCCTATAAAAT 
               
               
                   
               
               
                 GCCATGGGATTAAAAATATATGTAGGCTATTCATTTCTACAAATGTTTTTCATTCATCTTGACTCACATG 
               
               
                   
               
               
                 CCAACAAGGATAAGACTTACCTTTAGAGTATTGTGTTTCATAGCCTTTCTTCTTTCATATCCCTTTTTGT 
               
               
                   
               
               
                 TCATAGAATAACCACAGAACTTGAAAAATTATTCTAAGTACATATTACACTCCTCAAAAAAAACAAAGAT 
               
               
                   
               
               
                 AACTGAGAAAAAAGTTATTGACAGAAGTTCTATTTGCTATTATTTACATAGCCTAACATTTGACTGTGCT 
               
               
                   
               
               
                 GCCCAAAATACTGATAATAGTCTCTTAAACTCTTTTGTCAAATTTTCCTGCTTTCTTATGCAGTATTGTT 
               
               
                   
               
               
                 TAGTCATCCTTTCGCTGTAAGCAAAGTTGATGAAATCCTTCCTGATATGCAGTTAGTTGTTTGACCACGG 
               
               
                   
               
               
                 TACATACTTGAGCAGATAATAACTTGGGCACAGTATTTATTGCATCACTTGTATACAATCCCGTGTTTGG 
               
               
                   
               
               
                 CAAGCTTTCAAATCATGTAATATGACAGACTTTACACAGATATGTGTTTAGTATGAATAAAAAAGCATTG 
               
               
                   
               
               
                 AAATAGGGATTCTTGCCAACTTGCTCTCTTGCCACCAACTTACTTTCCTAAATTATGGAAGTAATCTTTT 
               
               
                   
               
               
                 TTGGATATACTTCAATGTATACAATGAGGAAGATGTCACCTTCTCCTTAAAATTCTATGATGTGAAATAT 
               
               
                   
               
               
                 ATTTTGCCTCAATCAACACAGTACCATGGGCTTCTAATTTATCAAGCACATATTCATTTTGCATTAGCTG 
               
               
                   
               
               
                 TAGACATCTAGTTTTTTGAAAACACCTATTAATAGTAATTTGAAAAGAAATAACCATAATGCTTTTTTTC 
               
               
                   
               
               
                 GTGAGTTTATTTCAGGAATATGAGATCTTTCTTCTATAAAGTTATTCATGCACAGGCAAAAATTGAGCTA 
               
               
                   
               
               
                 CACAGGTAGAATGTAGTTTTACTTAGAAGATTTTTGTGGGAGGTTTTGAAGCAAATATATAAAACAACTT 
               
               
                   
               
               
                 TCACTAATTTGCTTTCCATATTTAAAAAATAATAAATTACATTTATATAATAAATGTTTAAAGCACATAT 
               
               
                   
               
               
                 TTTTTGTTGTTCTGGCAATTTAAAAAGAAAGAGGATTTAAACGTACCTATAGAAACAAAGATTTATGGTT 
               
               
                   
               
               
                 AAAGAATGAGATCAGAAGTCTAGAATGTTTTTAAATTGTGATATATTTTACAACATCCGTTATTACTTTG 
               
               
                   
               
               
                 AGACATTTGTCCTAATCTACGTATAAAACTCAATCTAGGGCTAAAGATTCTTTATACCATCTTAGGTTCA 
               
               
                   
               
               
                 TTCATCTTAGGCTATTTGAACCACTTTTTAATTTAATATGAAAGACACCATGCAGTGTTTTCCGAGACTA 
               
               
                   
               
               
                 CATAGATCATTTTATCACATACCTACCAAGCCTGTTGGAAATAGGTTTTGATAATTTAAGTAGGGACCTA 
               
               
                   
               
               
                 TACAAAATATATTACATTTATCAGATTTTTAAATACATTCAATTAAGAATTTAACATCACCTTAAATTTG 
               
               
                   
               
               
                 AATTCAATCTACCGTTATTTCAAACTCACAAATATAACTGCATTATGAATACTTACATAATGTAGTAAGA 
               
               
                   
               
               
                 CAAGATGTTTGACAGGTTCGTGTGTAATTTTCTATTAATGTTTTTACATTGCCTTGTTTTTATGTAAAAT 
               
               
                   
               
               
                 AAAAAATATGGGCAACTGGTTTGTTAACAACACAATTTCTTCTTAGCATTTCAAAAATATATATAAAGTT 
               
               
                   
               
               
                 GTTCTTTTTCCTATTTCATGAACTATGTTTTTTTTTAAAATAACATGGTTAAGTTTTATATATATTTACG 
               
               
                   
               
               
                 TTTGTTTCAGGAATGTCTACTTGTGACTTTTTATCAATTAAAAATAATATTTGGAAGAAAGAGCTTATTA 
               
               
                   
               
               
                 AGTATAAGCTTGAAGTAAAATTAGACCTCTCTTTCCATGTAGATTACTGTTTGTACTGATGGTTTCACCC 
               
               
                   
               
               
                 TTCAGAAGGCACTGTCATATTAATATTTAAATTTTATAATCGCTGAACTTATTACACCCAACAATACAGA 
               
               
                   
               
               
                 AAGGCAGTTACACTGAAGAACTTAACTTAGAATAAAATGGAAGCAAACAGGTTTTCTAAAAACTTTTTTA 
               
               
                   
               
               
                 AGTGACCAGGTCTCGCTCTGTCACCCAGGCTAGAGTGCAATGGCATGATCATAGCTCTCTGCAGCCTCAA 
               
               
                   
               
               
                 CTCTGGGCTCAAGCAACCCTCCTGCCTCAGCCTCCCAAGTAGCTAAGACTACAGGTACATGCCACCATGC 
               
               
                   
               
               
                 CTGGCTAATATTTAAATTTTTGTAGATAAGGGGTCTTGCTATGTTGCCCAGGCTAGTCTCAAACTCCTGG 
               
               
                   
               
               
                 CTTCAAGTGTTCCTACTGTCATGACCTGCCAACATGCTGGGGTTACAGGCATGAGCCACCATGCCCCAAA 
               
               
                   
               
               
                 CAGGTTTGAACACAAATCTTTCGGATGAAAATTAGAGAACCTAATTTTAGCTTTTTGATAGTTACCTAGT 
               
               
                   
               
               
                 TTGCAAAAGATTTGGGTGACTTGTGAGCTGTTTTTAAATGCTGATTGTTGAACATCACAACCCAAAATAC 
               
               
                   
               
               
                 TTAGCATGATTTTATAGAGTTTTGATAGCTTTATTAAAAAGAGTGAAAATAAAATGCATATGTAAATAAA 
               
               
                   
               
               
                 GCAGTTCTAAATAGCTATTTCAGAGAAATGTTAATAGAAGTGCTGAAAGAAGGGCCAACTAAATTAGGAT 
               
               
                   
               
               
                 GGCCAGGGAATTGGCCTGGGTTTAGGACCTATGTATGAAGGCCACCAATTTTTTAAAAATATCTGTGGTT 
               
               
                   
               
               
                 TATTATGTTATTATCTTCTTGAGGAAAACAATCAAGAATTGCTTCATGAAAATAAATAAATAGCCATGAA 
               
               
                   
               
               
                 TATCATAAAGCTGTTTACATAGGATTCTTTACAAATTTCATAGATCTATGAATGCTCAAAATGTTTGAGT 
               
               
                   
               
               
                 TTGCCATAAATTATATTGTAGTTATATTGTAGTTATACTTGAGACTGACACATTGTAATATAATCTAAGA 
               
               
                   
               
               
                 ATAAAAGTTATACAAAATAAAA 
               
            
           
         
       
     
     The reverse complement of SEQ ID NO: 4001 is provided as SEQ ID NO: 4002 herein: 
     
       
         
           
               
               
            
               
                 (SEQ ID NO: 4002) 
                   
               
               
                 TTTTATTTTGTATAACTTTTATTCTTAGATTATATTACAATGTGTCAGTCTCAAGTATAACTACAATATA 
                   
               
               
                   
               
               
                 ACTACAATATAATTTATGGCAAACTCAAACATTTTGAGCATTCATAGATCTATGAAATTTGTAAAGAATC 
               
               
                   
               
               
                 CTATGTAAACAGCTTTATGATATTCATGGCTATTTATTTATTTTCATGAAGCAATTCTTGATTGTTTTCC 
               
               
                   
               
               
                 TCAAGAAGATAATAACATAATAAACCACAGATATTTTTAAAAAATTGGTGGCCTTCATACATAGGTCCTA 
               
               
                   
               
               
                 AACCCAGGCCAATTCCCTGGCCATCCTAATTTAGTTGGCCCTTCTTTCAGCACTTCTATTAACATTTCTC 
               
               
                   
               
               
                 TGAAATAGCTATTTAGAACTGCTTTATTTACATATGCATTTTATTTTCACTCTTTTTAATAAAGCTATCA 
               
               
                   
               
               
                 AAACTCTATAAAATCATGCTAAGTATTTTGGGTTGTGATGTTCAACAATCAGCATTTAAAAACAGCTCAC 
               
               
                   
               
               
                 AAGTCACCCAAATCTTTTGCAAACTAGGTAACTATCAAAAAGCTAAAATTAGGTTCTCTAATTTTCATCC 
               
               
                   
               
               
                 GAAAGATTTGTGTTCAAACCTGTTTGGGGCATGGTGGCTCATGCCTGTAACCCCAGCATGTTGGCAGGTC 
               
               
                   
               
               
                 ATGACAGTAGGAACACTTGAAGCCAGGAGTTTGAGACTAGCCTGGGCAACATAGCAAGACCCCTTATCTA 
               
               
                   
               
               
                 CAAAAATTTAAATATTAGCCAGGCATGGTGGCATGTACCTGTAGTCTTAGCTACTTGGGAGGCTGAGGCA 
               
               
                   
               
               
                 GGAGGGTTGCTTGAGCCCAGAGTTGAGGCTGCAGAGAGCTATGATCATGCCATTGCACTCTAGCCTGGGT 
               
               
                   
               
               
                 GACAGAGCGAGACCTGGTCACTTAAAAAAGTTTTTAGAAAACCTGTTTGCTTCCATTTTATTCTAAGTTA 
               
               
                   
               
               
                 AGTTCTTCAGTGTAACTGCCTTTCTGTATTGTTGGGTGTAATAAGTTCAGCGATTATAAAATTTAAATAT 
               
               
                   
               
               
                 TAATATGACAGTGCCTTCTGAAGGGTGAAACCATCAGTACAAACAGTAATCTACATGGAAAGAGAGGTCT 
               
               
                   
               
               
                 AATTTTACTTCAAGCTTATACTTAATAAGCTCTTTCTTCCAAATATTATTTTTAATTGATAAAAAGTCAC 
               
               
                   
               
               
                 AAGTAGACATTCCTGAAACAAACGTAAATATATATAAAACTTAACCATGTTATTTTAAAAAAAAACATAG 
               
               
                   
               
               
                 TTCATGAAATAGGAAAAAGAACAACTTTATATATATTTTTGAAATGCTAAGAAGAAATTGTGTTGTTAAC 
               
               
                   
               
               
                 AAACCAGTTGCCCATATTTTTTATTTTACATAAAAACAAGGCAATGTAAAAACATTAATAGAAAATTACA 
               
               
                   
               
               
                 CACGAACCTGTCAAACATCTTGTCTTACTACATTATGTAAGTATTCATAATGCAGTTATATTTGTGAGTT 
               
               
                   
               
               
                 TGAAATAACGGTAGATTGAATTCAAATTTAAGGTGATGTTAAATTCTTAATTGAATGTATTTAAAAATCT 
               
               
                   
               
               
                 GATAAATGTAATATATTTTGTATAGGTCCCTACTTAAATTATCAAAACCTATTTCCAACAGGCTTGGTAG 
               
               
                   
               
               
                 GTATGTGATAAAATGATCTATGTAGTCTCGGAAAACACTGCATGGTGTCTTTCATATTAAATTAAAAAGT 
               
               
                   
               
               
                 GGTTCAAATAGCCTAAGATGAATGAACCTAAGATGGTATAAAGAATCTTTAGCCCTAGATTGAGTTTTAT 
               
               
                   
               
               
                 ACGTAGATTAGGACAAATGTCTCAAAGTAATAACGGATGTTGTAAAATATATCACAATTTAAAAACATTC 
               
               
                   
               
               
                 TAGACTTCTGATCTCATTCTTTAACCATAAATCTTTGTTTCTATAGGTACGTTTAAATCCTCTTTCTTTT 
               
               
                   
               
               
                 TAAATTGCCAGAACAACAAAAAATATGTGCTTTAAACATTTATTATATAAATGTAATTTATTATTTTTTA 
               
               
                   
               
               
                 AATATGGAAAGCAAATTAGTGAAAGTTGTTTTATATATTTGCTTCAAAACCTCCCACAAAAATCTTCTAA 
               
               
                   
               
               
                 GTAAAACTACATTCTACCTGTGTAGCTCAATTTTTGCCTGTGCATGAATAACTTTATAGAAGAAAGATCT 
               
               
                   
               
               
                 CATATTCCTGAAATAAACTCACGAAAAAAAGCATTATGGTTATTTCTTTTCAAATTACTATTAATAGGTG 
               
               
                   
               
               
                 TTTTCAAAAAACTAGATGTCTACAGCTAATGCAAAATGAATATGTGCTTGATAAATTAGAAGCCCATGGT 
               
               
                   
               
               
                 ACTGTGTTGATTGAGGCAAAATATATTTCACATCATAGAATTTTAAGGAGAAGGTGACATCTTCCTCATT 
               
               
                   
               
               
                 GTATACATTGAAGTATATCCAAAAAAGATTACTTCCATAATTTAGGAAAGTAAGTTGGTGGCAAGAGAGC 
               
               
                   
               
               
                 AAGTTGGCAAGAATCCCTATTTCAATGCTTTTTTATTCATACTAAACACATATCTGTGTAAAGTCTGTCA 
               
               
                   
               
               
                 TATTACATGATTTGAAAGCTTGCCAAACACGGGATTGTATACAAGTGATGCAATAAATACTGTGCCCAAG 
               
               
                   
               
               
                 TTATTATCTGCTCAAGTATGTACCGTGGTCAAACAACTAACTGCATATCAGGAAGGATTTCATCAACTTT 
               
               
                   
               
               
                 GCTTACAGCGAAAGGATGACTAAACAATACTGCATAAGAAAGCAGGAAAATTTGACAAAAGAGTTTAAGA 
               
               
                   
               
               
                 GACTATTATCAGTATTTTGGGCAGCACAGTCAAATGTTAGGCTATGTAAATAATAGCAAATAGAACTTCT 
               
               
                   
               
               
                 GTCAATAACTTTTTTCTCAGTTATCTTTGTTTTTTTTGAGGAGTGTAATATGTACTTAGAATAATTTTTC 
               
               
                   
               
               
                 AAGTTCTGTGGTTATTCTATGAACAAAAAGGGATATGAAAGAAGAAAGGCTATGAAACACAATACTCTAA 
               
               
                   
               
               
                 AGGTAAGTCTTATCCTTGTTGGCATGTGAGTCAAGATGAATGAAAAACATTTGTAGAAATGAATAGCCTA 
               
               
                   
               
               
                 CATATATTTTTAATCCCATGGCATTTTATAGGCACATATAAATTGGTTCTGATGCAATGTAGAATAAATT 
               
               
                   
               
               
                 TAAGCACCTCAAAATATAGAATAACCTCTGTACATTGATAAAAAGTCAAGCTCCCTAATAATGCATTTTA 
               
               
                   
               
               
                 ACTAAACATTCATAACTAATGTCCATTACTTCTATCAAGCATTTCATTGCAAAGCCAAGGCAAATACTTT 
               
               
                   
               
               
                 TGTTGATTTCCAAATAATAGATAAATAATAGATTTTTCTGTATGCGTGTGTTGTTTATTTACATGGGAAA 
               
               
                   
               
               
                 CAAGACTAATTACAATCCTGTGAAAAGATGACAAGGCAGATGTAAAAGTTTTCTACATGGTCTTCTGATT 
               
               
                   
               
               
                 TATTAAAAACCAAAAAACTGAATCACTTTTGTATGCTATAATCAATAATTCCTACAGAGTTCTCTTACGA 
               
               
                   
               
               
                 TTCTTAAAGAATCATCAGTGCAAAAATAACCATCTGCTAATGCTGCCCACCTTTCTTAGGAAATCAGAGT 
               
               
                   
               
               
                 TAGTGACTGCACTGCCTTCGAGAATATTTTGATAAAAAGGATTTTGGCATAGACTTCCTCAAAAGAGTTT 
               
               
                   
               
               
                 TATTAACACAAATAAATCACTTTCACAGGCTGTAAACAATATATCAAAAATGAAGCTCTATTTTTTGCTT 
               
               
                   
               
               
                 TCCTTGCTGTCTTTCCCTTTGTCTTCCTTTTCTGTTCTGTCTTGTTCATATTTCTCTTTGTCTGGCTTTG 
               
               
                   
               
               
                 TTACACTATCATATGAAGGTGGAGAGGTGGTGGATGAAGTGGCATCTGTTTTTTCTGGACTTGAGTTCTC 
               
               
                   
               
               
                 ATTAACATTATCAAAAGCCATATCTTTTTTATTGAGTAAATCATCATCTCTGTCTCCATCTTTTATGTAT 
               
               
                   
               
               
                 ATACTTGATATATTTTTGACATTTTGCCTTAAGCGGTAACGTCTATAAGCACGCTGAATGACAGTAGCAG 
               
               
                   
               
               
                 ACACATCCTCTTGTTTCCGTTTTAGTGTGGTTGTGATGGGTTCATAGGACACTTTGGAAGGATTTGCAGA 
               
               
                   
               
               
                 CATGAACCTTTCTTCCATCTGTGAACGAAGAGAATCCATCTCCCCACTCTCACCCAAAACACGCTTTGTA 
               
               
                   
               
               
                 AAAGCAAATAAGATGTCAAGACAATGGATCCGGTCACCACTAACCATGGGCAGATCCATGGCAATGAGCT 
               
               
                   
               
               
                 GGACTTTGTTGGGTTTTGCTATGAGAAGAGGAGGATCCAGGGCAGCTGCAAAATCAGAGAGTTTAGAGAA 
               
               
                   
               
               
                 CTCTATAAACTGGGTCGCATCGGGATCAAACTTCTCCCAAACCTCATAGAACATCTCAAAGTCATCCTCA 
               
               
                   
               
               
                 CTCAGAGGTTCAGTACTTTCTTCAGTGGCAACACTAAAATTCTCCAGTATGACTGCAATGTACATGTTCA 
               
               
                   
               
               
                 CCACAACCAGGAAGGATATGATGATATAACTAACAAAGTAGAATATTCCAACAGATGGGTTACCACAGTC 
               
               
                   
               
               
                 TCCTTCAACTGAACTTCCAGGATGAACTTTTTTTGGGTCACAGTCGGGTGGCTTACTGTTAAGAATAGGT 
               
               
                   
               
               
                 GCTAGCAATCCATCCCAGCCAGCAGAGGTTGTAATTTGGAACAGGCAAATCATACTGTTGCCAAAGGTCT 
               
               
                   
               
               
                 CAAAATTGAACATGTCATTAATTCCATCTTCCTTTTTAACATAGGCAAAGTTGGACATTCCAAAGATGGC 
               
               
                   
               
               
                 GTAGATGAACATGACCAGGAAGAGCAGGAGGCCGATGTTAAACAACGCAGGAAGGGACATCATCAAAGCA 
               
               
                   
               
               
                 AAGAGCAGCGTGCGGATCCCCTTTGCTCCTTTGACTAGACGTAGGATTCGGCCAATCCTGGCAAGACGGA 
               
               
                   
               
               
                 TCACTCGGAACAGGGTAGGGGACACAAAATACGTTTCAATCAAATCAGCTAGAAACATACCTACAATGGA 
               
               
                   
               
               
                 GATAATCACAACCACAAAATCAAAAATATTCCATCCTACAGTGAAGTAGTAGTGTCTGAGGGAGATCAGT 
               
               
                   
               
               
                 TTTAGCACACATTCTCCAGTGAAAAGGATTATAAAAACCACATTTATCCAATATAAAACTTCAGTCATAT 
               
               
                   
               
               
                 GTTGACTTTGACCCTCCTTTTCTACCATCATGGTTACCATGTTGAGACAGATAAGAACCATGATACTAAT 
               
               
                   
               
               
                 ATCAAAGGCTTGATTTGTCACTAGGTCAAATATACATCCTTGGATTTTGTTCCCTGGTCGAGGAATTGGC 
               
               
                   
               
               
                 TTTTGTGGCTTCTTGGACCCCAGCTTTTTCATTGCATTATAGTATTTCTTCTGTTCTTCTGTCATAAAGA 
               
               
                   
               
               
                 TGTCTTGACCTCCAAGCTTCTTTTTCTGTTGGTTGAAATTATCTATGATGACACCAATGAACAAGTTCAA 
               
               
                   
               
               
                 AGTGAAGAATGACCCAAAGATGATAAAGACGACAAAATAAATATACATGTAGAGGCTATATTCATATTTG 
               
               
                   
               
               
                 GGCTGCTTGTCTACATTAACAGAATCCACTGCTGCATACATAATAATCGTCCATCCCTTAAAAGTTGCAA 
               
               
                   
               
               
                 CTTGAAGCAGAGATAGGTAACCAAGTCCGACATTATCAAAGTTCACTTTCAGGTTTTTCCATCGCACATT 
               
               
                   
               
               
                 TTGACTAACATTCATAAGGGCAAAACATTCGGAACGATTTGGAACTTGACTTGCAGGAAACCGTGACCCA 
               
               
                   
               
               
                 TCTGTGGTGTTAATACACTCATAGAACTTGCCAGCAAACAAATTTACTCCCATGATGCTGAATATCAGCC 
               
               
                   
               
               
                 AGAATATAAGACACACAAGTAGCACATTCATGATGGAAGGAATTGCTCCTATGAGTGCATTCACAACGAC 
               
               
                   
               
               
                 CCTCATTCCTTCAAATCTAGATAAGGCTCTTAGAGGTCTTAAAGCTCTCAGTGTCCGAAGGGATTTAATG 
               
               
                   
               
               
                 GGGCCAAGATCTGAGTAGCCAAGAGTGTTTGCCACTAAAGTAACCAAAGAAACATCAACAATTAGGAAAT 
               
               
                   
               
               
                 CCAGCCAACACCAGGCATTGGTGAAATATGTTTTATAACCATATGCTATCCATTTTAGAAGCATTTCCAG 
               
               
                   
               
               
                 AATGAAGATGTAAGTGAAGATCTTGTCTGCATACTCCAGGATAATCTTAATGGTCTTTTTCCTTTCAATA 
               
               
                   
               
               
                 TAAATATCTTCAAAAGCCAGGGCACCACTGCTGAGCAGGATCATGAGGACAATGAAGCTTTCAAACCAAC 
               
               
                   
               
               
                 TGTGTTCAACAATCTTGTAGCAGGTTTTCCTGATGTTCCACCAGATTTTTCCTTTCCCTGACTCTATGTT 
               
               
                   
               
               
                 AACTTGGCAGCATGAGAACCTCCATACACAACCATCTGTGAAACAGGCCTCTGGCTCATCGGAATTCATA 
               
               
                   
               
               
                 GGTTCAGCCTCTGCTTCTTCTCCTTCTCCAGGCAAAGGGTTATCAACTGTGCTGCACTCTGAGGAGCTTG 
               
               
                   
               
               
                 ACCGGTTTAATCTCACTTTGCTGTATTCACTATCCGAATCACTGCTAAGTTCCTCAGCATTCATATTTTC 
               
               
                   
               
               
                 CAAATCGGATTCCCCAGGTGCAATTGGCACTGTCACTGTGAGGCTGGGATTGTGAATAAATGATTGACCA 
               
               
                   
               
               
                 TCACTGTCTTCCATCAAGTGTTTGTCCACGCTGCTTCCAAAACCACTGATTTTATCTTTTTCCTTGAGGA 
               
               
                   
               
               
                 AATTGTGACCTTTGCTCATTTCAGCAAGTGTATGGTTAGAAATATAGTTTTCCTTCTTAGTATTCAGATC 
               
               
                   
               
               
                 TTCTGCTTGTCTTATCTCCCTGGAAATCTTTGGCTTTTTGGAAAATGCTTTTAGAATAAATTCACGTAAG 
               
               
                   
               
               
                 GTTTGTTTCACATAATTTATTCCCTTTTTAATTCTAGTCACTGCAATCTGGAGGTTGTTTGCATCAGGGT 
               
               
                   
               
               
                 CTTCTTCAATTGCTGTAAGATTGTCTGAACTAAATGAGCTCAATAATAAGGCCAGAAATAGGTTTAGGAC 
               
               
                   
               
               
                 CACCAGGTTTCCAATGACCATGACCATCATGTAAACAATAAGGCACATAGCTTGACCAGCGACCTCCATA 
               
               
                   
               
               
                 CAGTCCCACATGGTCTCTATCCACTCTCCACACAGCACGCGGAACACAATCAGGAAGGAGTGGAAGAAGT 
               
               
                   
               
               
                 CGTTCATGTGCCACCGTGGGAGCGTACAGTCATCATTGATCTTGCAGACACATTCTTTGTAGCTCTTACC 
               
               
                   
               
               
                 AAAGAGCTGCATGCCGACCACAGCAAAAATGAAGACGATGATGGCCAACACTAAGGTGAGGTTACCTAGA 
               
               
                   
               
               
                 GCCCCTACTGAGTTACCAATGATCTTAATCAGCATGTTCAATGTTGGCCAGGATTTTGCCAACTTGAAGA 
               
               
                   
               
               
                 CTCGGAGCAGTCTGAATGATCGCAGAACTGACAATCCTTCCACATCTGCTAGAAAGAGCTCCACTAAACT 
               
               
                   
               
               
                 TAAAGTCACAATAAGGCTGTCAAAAATATTCCAGCCTACTTGGAAATACTCATATGGATCCATGGCAATC 
               
               
                   
               
               
                 AGTTTTAATACCATTTCAGCTGCAAAGATTCCAGTAAAGACCAAATTTCCTATAGCAAGTACATTTTTGA 
               
               
                   
               
               
                 ATTCCTCAGTCATTGGGTGGTGTTCCATAGCCATAAATAATGTGTTTAAAACTATGCAAATGGTAATTGC 
               
               
                   
               
               
                 AAGATCTACAAAAGGATCCATTACAATAAAATAGATACACTTTTTGAATTTTATCCAATATGGAGAGCAA 
               
               
                   
               
               
                 TTCCAGATCAAGAATTTGTGTGCAAATCTGTACCACCAAGGTGGACATTTTTGTCTGGACTCTTCAAGTT 
               
               
                   
               
               
                 CTTCCACAGTGTTTGTTAATATGCTTGCTCTACTCATTGCTCTCTGTCTGAGGTTGGGATCATTCAGCAT 
               
               
                   
               
               
                 ATCCTCTGAAAGGAGATAGGAACTACAACGCCTTTTCTTGTGTATTTGATTGGTCGTGCCGCTGTCATCA 
               
               
                   
               
               
                 GAAGTTGCCTTATCTATTATCACCTCTGGCAGAAGCTGTCCATTGGGGAGCATGAGGGCTGAGCGTCCAT 
               
               
                   
               
               
                 CAACCAGGGAGACCACACCGTTGCAGTCCACAGCACTGTGCATTTTCCCGTTCACCGGCAGCATTGGTGG 
               
               
                   
               
               
                 GGACCTACTGGCTTGGCTGATGTTACTGCTGCGTCGCTCCTGGGGTCTGTGGGGCACAAACAGTGAGCCC 
               
               
                   
               
               
                 CTTCTGCTCTCATTGTCTCCAAAAATGCTGTGCTCATCATCGGCAAATTCAGTCTCAGATCCTATATCTC 
               
               
                   
               
               
                 TTCCTCTGCCTTTGAAACTAAAAAGACTTGTTCTGCTGCTTCGCCTTGCAGAAAACAAGGAGCCACGAAT 
               
               
                   
               
               
                 GCTGAGTGGTGACTGATTGGGGGTAGACAACCTCTTTTCATGTGCTCGCCTATGCCCTTCGACACCAAGG 
               
               
                   
               
               
                 TGGAAACTTTTTCTTCTGATGCTGTCCTCTGATTCTGATTTCGACAATTTCTCAGCATCTCCCTTTTCCT 
               
               
                   
               
               
                 CTCCACTGGAGAGCTTCTTTTGATTCTTTTTCTTTCTTCTGTTTCTTCTTTCTTTAGCACTTTTAGAGCT 
               
               
                   
               
               
                 CAGTTTGGATGTTTCAGAAGAACTCTCTGAGAGGCCCATAATTCTGCTTCTCCTAATACTTGTATATTCA 
               
               
                   
               
               
                 GCCGCTGCCGCTGCAATTGCCTCAGCTTCTTCTTGCTCTTTTTTAAGACGGTCTAACATCTGTTGAAATT 
               
               
                   
               
               
                 CTAATTCTTTCTGTTTAGCTTCTTCAATGTTTGCCTGGTTCTGTTCTTCATATGCCATGGCAACCACAGC 
               
               
                   
               
               
                 CAGGATCAAGTTTATTAGATAAAAGGAGCCCAGGAAAATCACTACGACAAAGAAGATCATGTAGGTTTTG 
               
               
                   
               
               
                 CCAGCAGCACGCAGCGTCTGTTGGTAAAGGTTTTCCCAGTAATCTTGGGTCATTAGCCTAAACAAGGCTA 
               
               
                   
               
               
                 AGAAGGCCCAGCTGAAAGTGTCAAAGCTCGTGTAGCCATAATCAGGGTTTCTGCCAATTTTCACACAGGT 
               
               
                   
               
               
                 GTACCCCTCTGGACACTGACCTGAATCTGTGCTGAAACCACAAAGGAGAGCATCTTTGGATCCTTCCAAG 
               
               
                   
               
               
                 TAATAAAAATATTTTCTAAAGTCTTCTTCACTCTCTAGGGTATTCATTATGCTTTCTAATGTTTCATTAT 
               
               
                   
               
               
                 TTTCAAGTGAATTTCGAAAACATTTATGCTTCAGGTTTCCCATGAACAGCTGTAGTCCAATTAGTGCAAA 
               
               
                   
               
               
                 CACACTCAGACAGAACACAGTCAGGATCATGACATCAGAAAGCTTCTTCACTGACTGGATCAAAGCCCCT 
               
               
                   
               
               
                 ACAATTGTCTTCAGGCCTGGGATTACAGAAATAGTTTTCAAAGCTCTCAATACTCTGAAAGTTCGAAGAG 
               
               
                   
               
               
                 CTGAAACATTGCCTAGGTTTACAAATTCTGTTAAATACGCAAAAACAATGACGACAAAATCCAGCCAGTT 
               
               
                   
               
               
                 CCACGGGTCACGAAGAAAAGTGAATTCTCCTACACAGAAGCCTCTTGCAAGGATTTTTACAAGTGATTCA 
               
               
                   
               
               
                 AAAGTATATATTCCAGTAAAAGTGTACTCGACATTTTTGGTCCAGTCCGGTGGGTTATTCATGGTCATAA 
               
               
                   
               
               
                 ATATGCAGTTTGTCAGAATAGTGCACATGATGAGCATGCTGAATAAGGAGTGTACTAAAATCTTAATAGA 
               
               
                   
               
               
                 TATTCTTCTTAGAGGACTGAAAGGAGAAAGCATATATAAAGCAGGTGTGGCATTGAAACGGAAGATTGTT 
               
               
                   
               
               
                 TTCCCTTTGTTCAATACTATGAAAGTCTTTTTGTCTGCATAGTAGGGGTCCAAGTCCTCCAGGGGCTCTG 
               
               
                   
               
               
                 ACACCATGCCGGGAGGAATGTCCCCATAGATGAAGGGCAGCTGTTTGCCAGCTTCCAAGTCACTGCTTGG 
               
               
                   
               
               
                 CTTTGGGGCTTCTTCATCATCATCTTTCTTTTCTTCTTTGGGTTCCTTTGATTTTCTTTCAGCAATGCGT 
               
               
                   
               
               
                 TGTTCAATGAGGGCAAGAGACTGTTTTGTGAAATGGACAAAGCTCTGAGGTCCTGGGGGAGGCAACATTG 
               
               
                   
               
               
                 CCATCTTTTCATCCTGTATATTTTAATTCCTCTTCAGCTCCTCACATAAGAGGCTTGCAACCTAGCCCGC 
               
               
                   
               
               
                 CGATCATCCCCACCCAGTGCACCTGCAGAATCTGGCTCCAGGAGAGGGCGCGGGCCTCTCCTTCCCCGGC 
               
               
                   
               
               
                 GCTCTCTCAGGGCTGCTTCTTTTTCTCTGGGCTCCTGTTGCTCAGGGGACGCCTGCCGCTAGCAGCCACT 
               
               
                   
               
               
                 GGCACCCAGGCTAGCCCAGCCTCAGCCGAGCTGGCGGAATTGGAAAGCCGACAGCCGCCGCTGGAGCGCT 
               
               
                   
               
               
                 GGCGACCGCCTGCAAGCAGACT 
               
            
           
         
       
     
     In some embodiments, an iRNA described herein includes at least 15 contiguous nucleotides from 50 one of the sequences provided in Tables 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20, and may optionally be coupled to additional nucleotide sequences taken from the region contiguous to the selected sequence in SCN9A. 
     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, 4A, 5A, 6A, 13A, 14A, 15A, 16, 18, and 20, 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, e.g., in Tables 2B, 4B, 5B, 6B, 13B, 14B, an 15B, that is 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, 4A, 5A, 6A, 13A, 14A, 15A, 16, 18, or 20, 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 SCN9A, 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 SCN9A. Consideration of the efficacy of iRNAs with mismatches in inhibiting expression of SCN9A is important, especially if the particular region of complementarity in a SCN9A 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 U.S. Pat. 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 — 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. The native phosphodiester backbone can be represented as O—P(O)(OH)—OCH 2 —. 
     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 3 ) 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-C5 is absent (e.g., a l′-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′-OCH3), 2′-5 aminopropoxy (2′-OCH2CH2CH2NH2) 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 modified 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 modified 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 O-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; 5,130,302; 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(H2)-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)-0-2′ 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′ np-Na-(X X X)i-Nb-Y Y Y-Nb-(Z Z Z)j-Na-nq 3′  (I)
 
     wherein: 
     i and j are each independently 0 or 1; 
     p and q are each independently 0-6; 
     each Na independently represents an oligonucleotide sequence comprising 0-25 modified nucleotides, each sequence comprising at least two differently modified nucleotides; 
     each Nb independently represents an oligonucleotide sequence comprising 0-10 modified nucleotides; 
     each np and nq independently represent an overhang nucleotide; 
     wherein Nb 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 Na and/or Nb 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 1st 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′ np-Na-YYY-Nb-ZZZ-Na-nq 3′  (Ib);
 
       5′ np-Na-XXX-Nb-YYY-Na-nq 3′  (Ic); or
 
       5′ np-Na-XXX-Nb-YYY-Nb-ZZZ-Na-nq 3′  (Id).
 
     When the sense strand is represented by formula (Ib), Nb represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. Each Na 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), Nb represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. Each Na 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 Nb independently represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. In some embodiments, Nb is 0, 1, 2, 3, 4, 5 or 6. Each Na 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 Na′ independently represents an oligonucleotide sequence comprising 0-25 modified nucleotides, each sequence comprising at least two differently modified nucleotides; 
     each Nb′ 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′-Nb′-Y′Y′Y′-N a ′-n p ′ 3′  (IIb);
 
       5′ n q ′-N a ′-Y′Y′Y′-Nb′-X′X′X′-n p ′ 3′  (IIc); or
 
       5′ n q ′-Na′-Z′Z′Z′-Ne′-Y′Y′Y′-Nb′-X′X′X′-N a ′-n p ′ 3′  (IId).
 
     When the antisense strand is represented by formula (IIb), Nb′ represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. Each Na′ 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 Nb′ independently represents an oligonucleotide sequence comprising 0-10, 0-7, 0-5, 0-4, 0-2 or 0 modified nucleotides. Each Na′ independently represents an oligonucleotide sequence comprising 2-20, 2-15, or 2-10 modified nucleotides. In some embodiments, Nb 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′ np′-Na′-Y′Y′Y′-Na′-nq′ 3′  (Ia).
 
     When the antisense strand is represented as formula (IIa), each Na′ 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 ′-Na′-(X′X′X′)k-N b ′-Y′Y′Y′-N b ′-(Z′Z′Z′) l -N a ′-n q ′ 5′   (III)
 
     wherein, 
     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 -Y Y Y-N a -n q  3′
 
       3′ n p ′-N a ′-Y′Y′Y′-N a ′n q ′ 5′   (IIIa)
 
       5′ n p -N a ′-Y Y Y-N b -ZZZ-N a -n q  3′
 
       3′ n p -N a ′-Y′Y′Y′-Nb′-Z′Z′Z′-Na′-nq′ 5′   (IIIb)
 
       5′ n p -N a -X X X-N b -Y Y Y-N a -n q  3′
 
       3′ n p -N a ′-X′X′X′-N b ′-Y′Y′Y′-Na′-n q ′ 5′   (IIIc)
 
       5′ n p -N a -XXX-N b -Y Y Y-N b -Z Z Z-N a -n q  3′
 
       3′ n p -N a ′-X′X′X′-N b ′-Y′Y′Y′-N b ′-Z′Z′Z′-Na′-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 Nb 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 Nb, Nb′ 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 Nb, Nb′ 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 Na modifications are 2′-O-methyl or 2′-fluoro modifications. In some embodiments, when the RNAi agent is represented by formula (IIId), the Na modifications are 2′-O-methyl or 2′-fluoro modifications and np′ &gt;0 and at least one np′ is linked to a neighboring nucleotide a via phosphorothioate linkage. In some embodiments, when the RNAi agent is represented by formula (IIId), the Na modifications are 2′-O-methyl or 2′-fluoro modifications, np′&gt;0 and at least one np′ 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 Na modifications are 2′-O-methyl or 2′-fluoro modifications, np′&gt;0 and at least one np′ 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 Na modifications are 2′-O-methyl or 2′-fluoro modifications, np′&gt;0 and at least one np′ 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) 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,” or 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. In some embodiments, 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 and decalin. In some embodiments, 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 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-glycolied) copolymer, divinyl ether-maleic anhydride copolymer, N-(2-hydroxypropyl)methacrylamide copolymer (HMPA), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyurethane, poly(2-ethylacryllic 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 a neuron. 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 C16 hydrocarbon chain (e.g., a linear C16 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 other embodiments, 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 other embodiments, 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, C 6 -C 14  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, e.g., 5, 6, 9, or 10 ring atoms; having 6, 10, or 14π 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, one to about three, or 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 other embodiments, 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 central nervous system (CNS), e.g., brain and/or the spine, e.g., the dorsal root ganglion. 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 other embodiments, 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 other embodiments, 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: 3699). An RFGF analogue (e.g., amino acid sequence AALLPVLLAAP (SEQ ID NO: 3700)) 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:3701)) and the  Drosophila  Antennapedia protein (RQIKIWFQNRRMKWKK (SEQ ID NO: 3702)) 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 an 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 exemplary embodiments, the C16 ligand of the disclosure can be conjugated to a ribonucleotide residue according to the following structure: 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: 
     
       
         
         
             
             
         
       
     
     where * denotes a bond to an adjacent nucleotide, and B is a nucleobase or a nucleobase analog, for example, where B is adenine, guanine, cytosine, thymine or uracil. 
     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 5′-vinyl phosponate (VP) modification of an RNAi agent as described herein. In exemplary embodiments, a 5′-vinyl phosphonate modified nucleotide of the disclosure has the structure of formula: 
     
       
         
         
             
             
         
       
     
     wherein X is O or S; 
     R is hydrogen, hydroxy, methoxy, fluoro, or C 1-20 alkoxy (e.g., methoxy or n-hexadecyloxy); 
     R 5′  is ═C(H)—P(O)(OH) 2  and the double bond between the C5′ carbon and R5′ is in the E or Z orientation (e.g., E orientation); and B is a nucleobase or a modified nucleobase, optionally where B is adenine, guanine, cytosine, thymine, or uracil. 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 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: 
     
       
         
         
             
             
         
       
     
     for example, including the preceding structure where R 5′  is ═C(H)—OP(O)(OH) 2  and the double bond between the C5′ carbon and R5′ is in the E or Z orientation (e.g., E orientation). 
     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 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) (e.g., 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′-C4′, or C1′-C4′) is absent or at least one of ribose carbons or oxygen (e.g., C1′, C2′, C3′, C4′, or C4′) 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. In some embodiments, 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. In some embodiments, 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 other embodiments, 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)(NH2)(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′-CH2-), 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″), CEC 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 5 , 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—, wherein Rk at each occurrence can be, independently, C1-C20 alkyl, C1-C20 haloalkyl, C6-C10 aryl, or C7-C12 aralkyl. 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 alkynelene. 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: (1) 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 spine) 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 some embodiments, iRNA targeting SCN9A 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 SCN9A (e.g., pain, e.g., chronic pain or pain-related 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 CNS delivery (e.g., intrathecal, intracranial, intracerebral, intraventricular, epidural, or intraganglionic routes of injection, optionally by infusion into the brain or spine, e.g., by continuous pump infusion). In another example, compositions can be formulated for systemic administration via parenteral delivery, e.g., by intravenous (IV) delivery, intramuscular (IM), or subcutaneous delivery (subQ). 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 SCN9A. 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, generally in the range of 1 to 50 mg per kilogram body weight per day. For example, the dsRNA can be administered at 0.05 mg/kg, 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, 2 mg/kg, 3 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg, or 50 mg/kg per single dose. 
     In some embodiments, a repeat-dose regimen may include administration of a therapeutic amount of a RNAi agent on a regular basis, such as monthly to once every six months. In certain embodiments, the RNAi agent is administered about once per quarter (i.e., about once every three months) to about twice per year. 
     After an initial treatment regimen (e.g., loading dose), the treatments can be administered on a less frequent basis. 
     In other embodiments, 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 SCN9A 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 SCN9A, can be used to determine the therapeutically effective dose and/or an effective dosage regimen administration of SCN9A siRNA. 
     In some embodiments, the iRNA compounds described herein can be delivered in a manner to target a particular tissue, such as the CNS (e.g., optionally the brain or spine tissue, e.g., cortex, cerebellum, dorsal root ganglia, substantia nigra, cerebellar dentate nucleus, pallidum, striatum, brainstem, thalamus, subthalamic, red, and pontine nuclei, cranial nerve nuclei and the anterior horn; and Clarke&#39;s column of the spinal cord cervical spine, lumbar spine, or thoracic spine). 
     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 intrathecal, intraventricular, intracranial, epidural, or intraganglionic injection), topical (e.g., buccal and sublingual administration), oral, intravitreal, transdermal, airway (aerosol), nasal, rectal, 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. 
     In some embodiments, the administration is via a bolus injection. In some embodiments, the administration is via a depot injection. A depot injection may release the RNAi agent in a consistent way over a prolonged time period. Thus, a depot injection may reduce the frequency of dosing needed to obtain a desired effect, e.g., a desired inhibition of SCN9A, or a therapeutic or prophylactic effect. 
     In some embodiments, the administration is via a pump. The pump may be an external pump or a surgically implanted pump. In other embodiments, the pump is an infusion pump. An infusion pump may be used for intracranial, intravenous, or epidural infusions. In certain embodiments, the pump is a surgically implanted pump that delivers the RNAi agent to the CNS. 
     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 C 1-20  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, 2C 1215G , that contains a PEG moiety. Ilium 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, an SCN9A 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-4-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 ND98.4HCl (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 7 
               
             
            
               
                   
               
               
                 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-[1,3]- 
                 XTC/DPPC/Cholesterol/PEG-cDMA 
               
               
                   
                 dioxolane (XTC) 
                 57.1/7.1/34.4/1.4 
               
               
                   
                   
                 lipid:siRNA ~7:1 
               
               
                 LNP05 
                 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]- 
                 XTC/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 dioxolane (XTC) 
                 57.5/7.5/31.5/3.5 
               
               
                   
                   
                 lipid:siRNA ~6:1 
               
               
                 LNP06 
                 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]- 
                 XTC/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 dioxolane (XTC) 
                 57.5/7.5/31.5/3.5 
               
               
                   
                   
                 lipid:siRNA ~11:1 
               
               
                 LNP07 
                 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]- 
                 XTC/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 dioxolane (XTC) 
                 60/7.5/31/1.5, 
               
               
                   
                   
                 lipid:siRNA ~6:1 
               
               
                 LNP08 
                 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]- 
                 XTC/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 dioxolane (XTC) 
                 60/7.5/31/1.5, 
               
               
                   
                   
                 lipid:siRNA ~11:1 
               
               
                 LNP09 
                 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]- 
                 XTC/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 dioxolane (XTC) 
                 50/10/38.5/1.5 
               
               
                   
                   
                 Lipid:siRNA 10:1 
               
               
                 LNP10 
                 (3aR,5s,6aS)-N,N-dimethyl-2,2-di((9Z,12Z)- 
                 ALN100/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 octadeca-9,12-dienyl)tetrahydro-3aH- 
                 50/10/38.5/1.5 
               
               
                   
                 cyclopenta[d][1,3]dioxol-5-amine (ALN100) 
                 Lipid:siRNA 10:1 
               
               
                 LNP11 
                 (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31- 
                 MC-3/DSPC/Cholesterol/PEG-DMG 
               
               
                   
                 tetraen-19-yl 4-(dimethylamino)butanoate 
                 50/10/38.5/1.5 
               
               
                   
                 (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-1- 
                 Lipid:siRNA 10:1 
               
               
                   
                 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, tetrahydroprimidinyl, 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 (0.61 g) 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 (1 L), was added a solution of 514 (10 g, 0.04926 mol) in 70 mL of THF slowly at 0° C. 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, 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, 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; 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, 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). 
     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 (P0310), 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.), Lipofectamine2000™ (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 SCN9A and at least one SCN9A 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 SCN9A expression (e.g., pain, e.g., chronic pain or pain-related 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 SCN9A 
     The present disclosure relates to the use of an iRNA targeting SCN9A to inhibit SCN9A expression and/or to treat a disease, disorder, or pathological process that is related to SCN9A expression (e.g., pain, e.g., chronic pain or pain-related disorder). 
     In some aspects, a method of treatment of a disorder related to expression of SCN9A 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) SCN9A expression. 
     In some embodiments, the subject is an animal that serves as a model for a disorder related to SCN9A expression, e.g., pain, e.g., chronic pain or pain-related disorder, e.g., inflammatory pain, neuropathic pain, pain hypersensitivity, pain hyposensitivity, inability to sense pain, primary erythromelalgia (PE), paroxysmal extreme pain disorder (PEPD), small fiber neuropathy (SFN), trigeminal neuralgia (TN), and pain associated with, e.g., cancer, arthritis, diabetes, traumatic injury and viral infections. 
     Chronic Pain and Pain-Related Disorders 
     In some embodiments, the disorder related to SCN9A expression is pain, e.g., chronic pain or pain related disorders, e.g., pain hypersensitivity or hyposensitivity. Non-limiting examples of pain-related disorders that are treatable using the methods described herein include inflammatory pain, neuropathic pain, pain insensitivity, primary erythromelalgia (PE), paroxysmal extreme pain disorder (PEPD), small fiber neuropathy (SFN), trigeminal neuralgia (TN), and pain associated with cancer, arthritis, diabetes, traumatic injury, and viral infections. In some embodiments, the pain-related disorder is an inherited pain-related disorder, e.g., PE and PEPD. 
     Clinical and pathological features of pain-related disorders include, but are not limited to, burning pain, redness of skin, flushing, warmth of extremities, joint pain, severe pain, e.g., periods of severe pain in the lower body, upper body (e.g., pain in the eyes or jaw), or extremities (e.g., hands and feet), inability to sense pain, fatigue, and/or insomnia. 
     In some embodiments, the subject with the pain, e.g., chronic pain, or pain-related disorder is less than 18 years old. In some embodiments, the subject with the pain, e.g., chronic pain, or pain-related disorder is an adult. In some embodiments, the subject has, or is identified as having, elevated levels of SCN9A mRNA or protein relative to a reference level (e.g., a level of SCN9A that is greater than a reference level). 
     In some embodiments, the pain, e.g., chronic pain, or the pain-related disorder is diagnosed using analysis of a sample from the subject (e.g., an aqueous cerebral spinal fluid (CSF) sample). In some embodiments, the sample is analyzed using a method selected from one or more of: fluorescent in situ hybridization (FISH), immunohistochemistry, SCN9A immunoassay, electron microscopy, laser microdissection, and mass spectrometry. In some embodiments, pain, e.g., chronic pain, or pain-related disorder is diagnosed using any suitable diagnostic test or technique, e.g., SCN9A mutation testing, a measure of pain sensitivity, a measure of pain threshold, a measure of pain level, and/or a measure of pain disability level (Dansie and Turk 2013  Br J Anaesth  111(1):19-25). 
     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 SCN9A expression (e.g., pain, e.g., chronic pain or pain-related 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, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids, or corticosteroids, acupuncture, therapeutic massage, dorsal root ganglion stimulation, spinal cord stimulation, or topical pain relievers. 
     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. For example, the therapeutic amount can be 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.5, 2.0, or 2.5, 3.0, 3.5, 4.0, 4.5, 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mg/kg dsRNA. 
     In some embodiments, the iRNA is formulated for delivery to a target organ, e.g., to the brain or spinal chord. 
     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, e.g., 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, or 5.0 mg/kg dsRNA. In some embodiments, the lipid formulation, e.g., LNP formulation, is administered intravenously. In some embodiments, the iRNA (e.g., dsRNA) is formulated as an LNP formulation and is administered (e.g., intravenously, intrathecally, intracerebrally, intracranially, or intraventricularly administered) at a dose of 0.1 to 1 mg/kg. 
     In some embodiments, the iRNA is administered by intravenous infusion over a period of time, such as over a 5 minute, 10 minute, 15 minute, 20 minute, or 25 minute period. 
     In some embodiments, the iRNA is in the form of a lipophilic conjugate (e.g., a C16 conjugate) as described herein. In some such embodiments, the therapeutic amount is 0.5-50 mg, e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mg/kg dsRNA. In some embodiments, the lipophilic conjugate (e.g., a C16 conjugate) is administered subcutaneously. In some embodiments, the iRNA (e.g., dsRNA) is in the form of a lipophilic conjugate and is administered (e.g., subcutaneously administered) at a dose of 1 to 10 mg/kg. 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, e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mg/kg 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) reduce pain; (b) inhibit or reduce the expression or activity of SCN9A 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 SCN9A 
     In some aspects, the disclosure provides a method for modulating (e.g., inhibiting or activating) the expression of SCN9A, 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 central nervous system (e.g., brain or spine tissue, e.g., cortex, cerebellum, dorsal root ganglia, substantia nigra, cerebellar dentate nucleus, pallidum, striatum, brainstem, thalamus, subthalamic, red, and pontine nuclei, cranial nerve nuclei and the anterior horn; and Clarke&#39;s column of the spinal cord cervical spine, lumbar spine, or thoracic spine). 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 SCN9A 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 SCN9A 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., a CNS 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 SCN9A may be assessed based on the level of expression of SCN9A mRNA, SCN9A protein, or the level of another parameter functionally linked to the level of expression of SCN9A. In some embodiments, the expression of SCN9A 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 IC 50  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 SCN9A, thereby inhibiting the expression of SCN9A 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 SCN9A, to the mammal such that expression of the target SCN9A 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 SCN9A 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 SCN9A is increased by e.g., at least 10% compared to an untreated animal. In some embodiments, the activation of SCN9A 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 SCN9A expression by stabilizing the SCN9A mRNA transcript, interacting with a promoter in the genome, or inhibiting an inhibitor of SCN9A expression. 
     The iRNAs useful for the methods and compositions featured in the disclosure specifically target RNAs (primary or processed) of SCN9A. Compositions and methods for inhibiting the expression of SCN9A 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 SCN9A 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 intracranial, intrathecal, intraventricular, topical, and intravenous administration. 
     In certain embodiments, the composition is administered, e.g., using oral, intraperitoneal, or parenteral routes, including intracranial (e.g., intraventricular, intraparenchymal, intracranial, and intrathecal), intravenous, intramuscular, intravitreal, subcutaneous, transdermal, airway (aerosol), nasal, or rectal. In other embodiments, the composition is administered topically (e.g., buccal and sublingual administration). In other embodiments, the composition is administered by intravenous infusion or injection. In certain embodiments, the compositions are administered by intrathecal injection. In certain embodiments, the compositions are administered by intraventricular injection. In certain embodiments, the compositions are administered by intracranial injection. In certain embodiments, the compositions are administered by epidural injection. In certain embodiments, the compositions are administered by intraganglionic 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 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 sodium channel, voltage gated, type IX alpha subunit (SCN9A), 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 SCN9A 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 SCN9A 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 SCN9A comprises the sequence SEQ ID NO: 1. 
     3. The dsRNA agent of embodiment 1 or 2, wherein the non-coding strand of human SCN9A comprises the sequence of SEQ ID NO: 2. 
     4 The dsRNA agent of embodiment 1, wherein the coding strand of human SCN9A comprises the sequence SEQ ID NO: 4001. 
     5. The dsRNA agent of embodiment 1 or 4, wherein the non-coding strand of human SCN9A comprises the sequence of SEQ ID NO: 4002. 
     6. A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of SCN9A, 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. 
     7. The dsRNA agent of embodiment 6, 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. 
     8. A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of SCN9A, 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: 4002 such that the sense strand is complementary to the at least 15 contiguous nucleotides in the antisense strand. 
     9. The dsRNA agent of embodiment 8, 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: 4001. 
     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 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. 
     11. The dsRNA of embodiment 10, 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. 
     12. 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: 4002 such that the sense strand is complementary to the at least 17 contiguous nucleotides in the antisense strand. 
     13. The dsRNA of embodiment 12, 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: 4001. 
     14. 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. 
     15. The dsRNA of embodiment 14, 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. 
     16. 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: 4002 such that the sense strand is complementary to the at least 19 contiguous nucleotides in the antisense strand. 
     17. The dsRNA of embodiment 16, 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: 4001. 
     18. 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. 
     19. The dsRNA of embodiment 18, 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. 
     20. 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: 4002 such that the sense strand is complementary to the at least 21 contiguous nucleotides in the antisense strand. 
     21. The dsRNA of embodiment 20, 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: 4001. 
     22. The dsRNA agent of any one of embodiments 1-21, wherein the portion of the sense strand is a portion within nucleotides 581-601, 760-780, or 8498-8518 of SEQ ID NO: 4001. 
     23. The dsRNA agent of any one of embodiments 1-22, wherein the portion of the sense strand is a portion within a sense strand from a duplex chosen from AD-1251284 (UGUCGAGUACACUUUUACUGA (SEQ ID NO:4827)), AD-961334 (CAACACAATUTCUUCUUAGCA (SEQ ID NO: 5026)), or AD-1251325 (AAAACAAUCUUCCGUUUCAAA (SEQ ID NO: 4822)). 
     24. The dsRNA agent of any one of embodiments 1-23, wherein the portion of the sense strand is a sense strand chosen from the sense strands of AD-1251284 (UGUCGAGUACACUUUUACUGA (SEQ ID NO:4827)), AD-961334 (CAACACAATUTCUUCUUAGCA (SEQ ID NO: 5026)), or AD-1251325 (AAAACAAUCUUCCGUUUCAAA (SEQ ID NO: 4822)). 
     25. The dsRNA of any one of embodiments 1-24, wherein the portion of the antisense strand is a portion within an antisense strand from a duplex chosen from AD-1251284 (UCAGTAAAAGUGUACTCGACAUU (SEQ ID NO: 5093)), AD-961334 (UGCUAAGAAGAAATUGUGUUGUU (SEQ ID NO: 5292)), or AD-1251325 (UUUGAAACGGAAGAUUGUUUUCC (SEQ ID NO: 5088)). 
     26. The dsRNA of any one of embodiments 1-25, wherein the portion of the antisense strand is an antisense strand chosen the antisense strands of AD-1251284 (UCAGTAAAAGUGUACTCGACAUU (SEQ ID NO: 5093)), AD-961334 (UGCUAAGAAGAAATUGUGUUGUU (SEQ ID NO: 5292)), or AD-1251325 (UUUGAAACGGAAGAUUGUUUUCC (SEQ ID NO: 5088)). 
     27. The dsRNA of any one of embodiments 1-26, 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-1251284 (SEQ ID NO: 4827 and 5093), AD-961334 (SEQ ID NO: 5026 and 5292), or AD-1251325 (SEQ ID NO: 4822 and 5088). 
     28. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 
     29. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 
     30. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 
     31. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20 that corresponds to the antisense sequence. 
     32. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 
     33. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20 that corresponds to the antisense sequence. 
     34. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 
     35. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20 that corresponds to the antisense sequence. 
     36. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20. 
     37. 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20 that corresponds to the antisense sequence. 
     38. A double-stranded ribonucleic acid (dsRNA) agent for inhibiting expression of SCN9A, 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, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20, and the sense strand comprises a nucleotide sequence of a sense sequence listed in any one of Tables 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, 16, 18, and 20 that corresponds to the antisense sequence. 
     39. The dsRNA agent of embodiment 38, wherein the antisense strand comprises a nucleotide sequence of an antisense sequence listed in Table 5A, and the sense strand comprises a nucleotide sequence of a sense sequence listed in Table 5A that corresponds to the antisense sequence. 
     40. The dsRNA agent of embodiment 38, wherein the antisense strand comprises a nucleotide sequence of an antisense sequence listed in Table 13A, and the sense strand comprises a nucleotide sequence of a sense sequence listed in Table 13A that corresponds to the antisense sequence. 
     41. The dsRNA agent of embodiment 38, wherein the antisense strand comprises a nucleotide sequence of an antisense sequence listed in Table 14A, and the sense strand comprises a nucleotide sequence of a sense sequence listed in Table 14A that corresponds to the antisense sequence. 
     42. The dsRNA agent of embodiment 38, wherein the antisense strand comprises a nucleotide sequence of an antisense sequence listed in Table 15A, and the sense strand comprises a nucleotide sequence of a sense sequence listed in Table 15A that corresponds to the antisense sequence. 
     43. The dsRNA agent of embodiment 38, wherein the antisense strand comprises a nucleotide sequence of an antisense sequence listed in Table 16, and the sense strand comprises a nucleotide sequence of a sense sequence listed in Table 16 that corresponds to the antisense sequence. 
     44. The dsRNA agent of any one of embodiments 38, wherein the dsRNA agent is AD-1251284, AD-961334, AD-1251325, AD-1331352, AD-1209344, or AD-1331350. 
     45. The dsRNA of any one of embodiments 38-44, wherein: 
     (i) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 4029, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4295; 
     (ii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 4228, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 4494; 
     (iii) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 5339, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 5355; 
     (iv) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 5800, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 5801; 
     (v) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 5526, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 5681; or 
     (vi) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 5542, and the antisense strand comprises the sequence and all the modifications of SEQ ID NO: 5697. 
     46. 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. 
     47. 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. 
     48. The dsRNA agent of embodiment 47, wherein the lipophilic moiety is conjugated to one or more positions in the double stranded region of the dsRNA agent. 
     49. The dsRNA agent of embodiment 47 or 48, wherein the lipophilic moiety is conjugated via a linker or carrier. 
     50. The dsRNA agent of any one of embodiments 47-49, wherein lipophilicity of the lipophilic moiety, measured by logKow, exceeds 0. 
     51. 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. 
     52. The dsRNA agent of embodiment 51, wherein the plasma protein binding assay is an electrophoretic mobility shift assay using human serum albumin protein. 
     53. The dsRNA agent of any of the preceding embodiments, wherein the dsRNA agent comprises at least one modified nucleotide. 
     54. The dsRNA agent of embodiment 53, 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. 
     55. The dsRNA agent of embodiment 53, wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand comprise a modification. 
     56. The dsRNA agent of any one of embodiments 53-55, wherein at least one of the modified nucleotides is selected from the group consisting of a deoxy-nucleotide, a 3′-terminal deoxythimidine (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. 
     57. The dsRNA agent of any of embodiments 53-42, 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). 
     58. 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. 
     59. The dsRNA agent of any of the preceding embodiments, wherein each strand is no more than 30 nucleotides in length. 
     60. The dsRNA agent of any of the preceding embodiments, wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide. 
     61. The dsRNA agent of any of the preceding embodiments, wherein at least one strand comprises a 3′ overhang of at least 2 nucleotides. 
     62. The dsRNA agent of any of the preceding embodiments, wherein the double stranded region is 15-30 nucleotide pairs in length. 
     63. The dsRNA agent of embodiment 62, wherein the double stranded region is 17-23 nucleotide pairs in length. 
     64. The dsRNA agent of embodiment 62, wherein the double stranded region is 17-25 nucleotide pairs in length. 
     65. The dsRNA agent of embodiment 62, wherein the double stranded region is 23-27 nucleotide pairs in length. 
     66. The dsRNA agent of embodiment 62, wherein the double stranded region is 19-21 nucleotide pairs in length. 
     67. The dsRNA agent of embodiment 62, wherein the double stranded region is 21-23 nucleotide pairs in length. 
     68. The dsRNA agent of any of the preceding embodiments, wherein each strand has 19-30 nucleotides. 
     69. The dsRNA agent of any of the preceding embodiments, wherein each strand has 19-23 nucleotides. 
     70. The dsRNA agent of any of the preceding embodiments, wherein each strand has 21-23 nucleotides. 
     71. The dsRNA agent of any of the preceding embodiments, wherein the agent comprises at least one phosphorothioate or methylphosphonate internucleotide linkage. 
     72. The dsRNA agent of embodiment 71, wherein the phosphorothioate or methylphosphonate internucleotide linkage is at the 3′-terminus of one strand. 
     73. The dsRNA agent of embodiment 72, wherein the strand is the antisense strand. 
     74. The dsRNA agent of embodiment 72, wherein the strand is the sense strand. 
     75. The dsRNA agent of embodiment 71, wherein the phosphorothioate or methylphosphonate internucleotide linkage is at the 5′-terminus of one strand. 
     76. The dsRNA agent of embodiment 75, wherein the strand is the antisense strand. 
     77. The dsRNA agent of embodiment 75, wherein the strand is the sense strand. 
     78. The dsRNA agent of embodiment 71, wherein each of the 5′- and 3′-terminus of one strand comprises a phosphorothioate or methylphosphonate internucleotide linkage. 
     79. The dsRNA agent of embodiment 78, wherein the strand is the antisense strand. 
     80. 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. 
     81. The dsRNA agent of embodiment 78, wherein the sense strand has a total of 21 nucleotides and the antisense strand has a total of 23 nucleotides. 
     82. The dsRNA agent of any one of embodiments 47-81, wherein one or more lipophilic moieties are conjugated to one or more internal positions on at least one strand. 
     83. The dsRNA agent of embodiment 82, 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. 
     84. The dsRNA agent of embodiment 83, wherein the internal positions include all positions except the terminal two positions from each end of the at least one strand. 
     85. The dsRNA agent of embodiment 83, wherein the internal positions include all positions except the terminal three positions from each end of the at least one strand. 
     86. The dsRNA agent of any one of embodiments 83-85, wherein the internal positions exclude a cleavage site region of the sense strand. 
     87. The dsRNA agent of embodiment 86, wherein the internal positions include all positions except positions 9-12, counting from the 5′-end of the sense strand. 
     88. The dsRNA agent of embodiment 86, wherein the internal positions include all positions except positions 11-13, counting from the 3′-end of the sense strand. 
     89. The dsRNA agent of any one of embodiments 83-85, wherein the internal positions exclude a cleavage site region of the antisense strand. 
     90. The dsRNA agent of embodiment 89, wherein the internal positions include all positions except positions 12-14, counting from the 5′-end of the antisense strand. 
     91. The dsRNA agent of any one of embodiments 83-85, 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. 
     92. The dsRNA agent of any one of embodiments 47-91, 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. 
     93. The dsRNA agent of embodiment 92, 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. 
     94. The dsRNA agent of embodiment 48, wherein the positions in the double stranded region exclude a cleavage site region of the sense strand. 
     95. The dsRNA agent of any one of embodiments 47-80, 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. 
     96. The dsRNA agent of embodiment 95, wherein the lipophilic moiety is conjugated to position 21, position 20, position 15, position 1, or position 7 of the sense strand. 
     97. The dsRNA agent of embodiment 95, wherein the lipophilic moiety is conjugated to position 21, position 20, or position 15 of the sense strand. 
     98. The dsRNA agent of embodiment 95, wherein the lipophilic moiety is conjugated to position 20 or position 15 of the sense strand. 
     99. The dsRNA agent of embodiment 95, wherein the lipophilic moiety is conjugated to position 16 of the antisense strand. 
     100. The dsRNA agent of embodiment 95, wherein the lipophilic moiety is conjugated to position 6, counting from the 5′-end of the sense strand. 
     101. The dsRNA agent of any one of embodiments 47-100, wherein the lipophilic moiety is an aliphatic, alicyclic, or polyalicyclic compound. 
     102. The dsRNA agent of embodiment 101, 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. 
     103. The dsRNA agent of embodiment 102, 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. 
     104. The dsRNA agent of embodiment 103, wherein the lipophilic moiety contains a saturated or unsaturated C6-C18 hydrocarbon chain. 
     105. The dsRNA agent of embodiment 103, wherein the lipophilic moiety contains a saturated or unsaturated C16 hydrocarbon chain. 
     106. The dsRNA agent of any one of embodiments 47-105, 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. 
     107. The dsRNA agent of embodiment 106, 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. 
     108. The dsRNA agent of any one of embodiments 47-105, 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. 
     109. The double-stranded iRNA agent of any one of embodiments 47-108, wherein the lipophilic moiety is conjugated to a nucleobase, sugar moiety, or internucleosidic linkage. 
     110. The dsRNA agent of any one of embodiments 47-109, wherein 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. 
     111. The dsRNA agent of any one of embodiments 47-110, 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. 
     112. The dsRNA agent of any one of embodiments 47-111, further comprising a targeting ligand, e.g., a ligand that targets a CNS tissue or a liver tissue. 
     113. The dsRNA agent of embodiment 112, wherein the CNS tissue is a brain tissue or a spinal tissue. 
     114. The dsRNA agent of embodiment 112, wherein the targeting ligand is a GalNAc conjugate. 
     115. The dsRNA agent of any one of embodiments 1-114, 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. 
     116. The dsRNA agent of any one of embodiments 1-114, 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. 
     117. The dsRNA agent of any one of embodiments 1-114, 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. 
     118. The dsRNA agent of any one of embodiments 1-114, 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. 
     119. The dsRNA agent of any one of embodiments 1-114, 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. 
     120. The dsRNA agent of any one of embodiments 1-119, further comprising a phosphate or phosphate mimic at the 5′-end of the antisense strand. 
     121. The dsRNA agent of embodiment 120, wherein the phosphate mimic is a 5′-vinyl phosphonate (VP). 
     122. A cell containing the dsRNA agent of any one of embodiments 1-121. 
     123. A human peripheral sensory neuron, e.g., (a peripheral sensory neuron in a dorsal root ganglion, or a nociceptive neuron, e.g., an A-delta fiber or a C-type fiber) comprising a reduced level of SCN9A mRNA or a level of SCN9A protein as compared to an otherwise similar untreated peripheral sensory neuron, 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%. 
     124. The human peripheral sensory neuron of embodiment 123, which was produced by a process comprising contacting a peripheral sensory neuron with the dsRNA agent of any one of embodiments 1-121. 
     125. A pharmaceutical composition for inhibiting expression of SCN9A, comprising the dsRNA agent of any one of embodiments 1-121. 
     126. A pharmaceutical composition comprising the dsRNA agent of any one of embodiments 1-121 and a lipid formulation. 
     127. A method of inhibiting expression of SCN9A in a cell, the method comprising: 
     (a) contacting the cell with the dsRNA agent of any one of embodiments 1-121, or a pharmaceutical composition of embodiment 125 or 126; and 
     (b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of SCN9A thereby inhibiting expression of SCN9A in the cell. 
     128. A method of inhibiting expression of SCN9A in a cell, the method comprising: 
     (a) contacting the cell with the dsRNA agent of any one of embodiments 1-121, or a pharmaceutical composition of embodiment 125 or 126; and 
     (b) maintaining the cell produced in step (a) for a time sufficient to reduce levels of SCN9A mRNA, SCN9A protein, or both of SCN9A mRNA and protein, thereby inhibiting expression of SCN9A in the cell. 
     129. The method of embodiment 127 or 128, wherein the cell is within a subject. 
     130. The method of embodiment 129, wherein the subject is a human. 
     131. The method of any one of embodiments 127-130, wherein the level of SCN9A mRNA is inhibited by at least 50%. 
     132. The method of any one of embodiments 127-130, wherein the level of SCN9A protein is inhibited by at least 50%. 
     133. The method of embodiment 130-132, wherein inhibiting expression of SCN9A decreases a SCN9A protein level in a biological sample (e.g., a a cerebral spinal fluid (CSF) sample, or a CNS biopsy sample) from the subject by at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%. 
     134. The method of any one of embodiments 130-133, wherein the subject has been diagnosed with a SCN9A-associated disorder, e.g., pain, e.g., chronic pain e.g., inflammatory pain, neuropathic pain, pain hypersensitivity, pain hyposensitivity, inability to sense pain, primary erythromelalgia (PE), paroxysmal extreme pain disorder (PEPD), small fiber neuropathy (SFN), trigeminal neuralgia (TN), and pain associated with, e.g., cancer, arthritis, diabetes, traumatic injury and viral infections. 
     135. A method of inhibiting expression of SCN9A in an neuronal cell or tissue, the method comprising: 
     (a) contacting the cell or tissue with a dsRNA agent that binds SCN9A; and 
     (b) maintaining the cell or tissue produced in step (a) for a time sufficient to reduce levels of SCN9A mRNA, SCN9A protein, or both of SCN9A mRNA and protein, thereby inhibiting expression of SCN9A in the cell or tissue. 
     136. The method of embodiment 135, wherein the neuronal cell or tissue comprises a peripheral sensory neuron, e.g., a peripheral sensory neuron in a dorsal root ganglion, or a nociceptive neuron, e.g., an A-delta fiber or a C-type fiber. 
     137. A method of treating a subject having or diagnosed with having a SCN9A-associated disorder comprising administering to the subject a therapeutically effective amount of the dsRNA agent of any one of embodiments 1-121 or a pharmaceutical composition of embodiment 125 or 126, thereby treating the disorder. 
     138. The method of embodiment 134 or 137, wherein the SCN9A-associated disorder is pain, e.g., chronic pain. 
     139. The method of embodiment 138, wherein the chronic pain is associated with one or more of the disorders in the group consisting of pain hypersensitivity, pain hyposensitivity, inability to sense pain, primary erythromelalgia (PE), paroxysmal extreme pain disorder (PEPD), small fiber neuropathy (SFN), trigeminal neuralgia (TN), or pain associated with, e.g., cancer, arthritis, diabetes, traumatic injury or viral infections. 
     140. The method of any one of embodiments 137-139, wherein treating comprises amelioration of at least one sign or symptom of the disorder. 
     141. The method of embodiment 140, wherein at least one sign or symptom of pain, e.g., chronic pain comprises a measure of one or more of pain sensitivity, pain threshold, pain level, pain disability level presence, level, or activity of SCN9A (e.g., SCN9A gene, SCN9A mRNA, or SCN9A protein). 
     142. The method of any one of embodiments 137-139, where treating comprises prevention of progression of the disorder. 
     143. The method of any one of embodiments 137-142, wherein the treating comprises one or more of (a) reducing pain; or (b) inhibiting or reducing the expression or activity of SCN9A. 
     144. The method of embodiment 143, wherein the treating results in at least a 30% mean reduction from baseline of SCN9A mRNA in the dorsal root ganglion. 
     145. The method of embodiment 144, wherein the treating results in at least a 60% mean reduction from baseline of SCN9A mRNA in dorsal root ganglion. 
     146. The method of embodiment 145, wherein the treating results in at least a 90% mean reduction from baseline of SCN9 mRNA in the dorsal root ganglion. 
     147. The method of any one of embodiments 137-146, wherein after treatment the subject experiences at least an 8-week duration of knockdown following a single dose of dsRNA as assessed by SCN9A protein in a cerebral spinal fluid (CSF) sample or a CNS biopsy sample. 
     148. The method of embodiment 147, wherein treating results in at least a 12-week duration of knockdown following a single dose of dsRNA as assessed by SCN9A protein in a cerebral spinal fluid (CSF) sample or a CNS biopsy sample. 
     149. The method of embodiment 148, wherein treating results in at least a 16-week duration of knockdown following a single dose of dsRNA as assessed by SCN9A protein in a cerebral spinal fluid (CSF) sample or a CNS biopsy sample. 
     150. The method of any of embodiments 129-149, wherein the subject is human. 
     151. The method of any one of embodiments 130-150, wherein the dsRNA agent is administered at a dose of about 0.01 mg/kg to about 50 mg/kg. 
     152. The method of any one of embodiments 130-151, wherein the dsRNA agent is administered to the subject intracranially or intrathecally, 
     153. The method of any one of embodiments 130-151, wherein the dsRNA agent is administered to the subject intrathecally, intraventricularly, or intracerebrally. 
     154. The method of any one of embodiments 130-153, further comprising measuring level of SCN9A (e.g., SCN9A gene, SCN9A mRNA, or SCN9A protein) in the subject. 
     155. The method of embodiment 154, where measuring the level of SCN9A in the subject comprises measuring the level of SCN9A gene, SCN9A protein or SCN9A mRNA in a biological sample from the subject (e.g., a cerebral spinal fluid (CSF) sample or a CNS biopsy sample). 
     156. The method of any one of embodiments 130-155, further comprising performing a blood test, an imaging test, a CNS biopsy sample, or an aqueous cerebral spinal fluid biopsy. 
     157. The method of any one of embodiments 154-156, wherein measuring level of SCN9A (e.g., SCN9A gene, SCN9A mRNA, or SCN9A protein) in the subject is performed prior to treatment with the dsRNA agent or the pharmaceutical composition. 
     158. The method of embodiment 157, wherein, upon determination that a subject has a level of SCN9A (e.g., SCN9A gene, SCN9A mRNA, or SCN9A protein) that is greater than a reference level, the dsRNA agent or the pharmaceutical composition is administered to the subject. 
     159. The method of any one of embodiments 155-158, wherein measuring level of SCN9A (e.g., SCN9A gene, SCN9A mRNA, or SCN9A protein) in the subject is performed after treatment with the dsRNA agent or the pharmaceutical composition. 
     160. The method of any one of embodiments 137-159, further comprising administering to the subject an additional agent and/or therapy suitable for treatment or prevention of an SCN9A-associated disorder. 
     161. The method of embodiment 160, wherein the additional agent and/or therapy comprises one or more of a non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids, or corticosteroids, acupuncture, therapeutic massage, dorsal root ganglion stimulation, spinal cord stimulation, or topical pain relievers. 
     EXAMPLES 
     Example 1. SCN9A 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; and  
               
               
                 it is understood that when the nucleotide contains a 2′-fluoro modification, then the fluoro replaces the hydroxy at that position  
               
               
                 in the parent nucleotide (i.e., it is a 2′-deoxy-2′-fluoronucleotide). . . 
               
            
           
           
               
               
            
               
                 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 
               
               
                 (G2p) 
                 guanosine 2′-phosphate 
               
               
                 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 
               
               
                 (T2p) 
                 thymidine 2′-phosphate 
               
               
                 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 
     A set of siRNAs targeting the human SCN9A, “sodium channel, voltage gated, type IX alpha subunit” (human NCBI refseqID NM_002977.3; NCBI GeneID: 6335 or human: NCBI refseqID NM_001365536.1; NCBI GeneID: 6335) were generated. The human NM_002977.3 REFSEQ mRNA, has a length of 9771 bases. The human NM_001365536.1 REFSEQ mRNA, has a length of 9752 bases. Pairs of oligos were generated using bioinformatic methods and ranked, and exemplary pairs of oligos are shown in Table 2A, Table 2B, Table 4A, Table 4B, Table 5A, Table 5B, Table 6A, Table 6B, Table 13A, Table 13B, Table 14A, Table 14B, Table 15A, Table 15B, and Table 16. Modified sequences are presented in Table 2A, Table 4A, Table 5A, Table 6A, Table 13A, Table 14A, Table 15A, and Table 16. Unmodified sequences are presented in Table 2B, Table 4B, Table 5B, Table 6B, Table 13B, Table 14B, and Table 15B. The target mRNA source for each exemplary set of duplexes is in Tables 2A, 2B, 4A, 4B, 5A, 5B, 6A, 6B, 13A, 13B, 14A, 14B, 15A, 15B, and 16 are denoted in the tables. The number following the decimal point in a duplex name as indicated in the tables merely refers to a batch production number. 
     
       
         
           
               
             
               
                 TABLE 2A 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A siRNA Modified Single Strands and Duplex Sequences 
               
               
                 Column 1 indicates duplex name. Column 2 indicates the name of the sense sequence. Column 3 indicates the sequence ID for the sequence of 
               
               
                 column 4. Column 4 provides the modified sequence of a sense strand suitable for use in a duplex described herein. Column 5 indicates the 
               
               
                 antisense sequence name. Column 6 indicates the sequence ID for the sequence of column 7. Column 7 provides the sequence of a modified 
               
               
                 antisense strand suitable for use in a duplex described herein, e.g., a duplex comprising the sense sequence in the same row of the table. 
               
               
                 Column 8 indicates the position in the target mRNA (NM_002977.3) that is complementary to the antisense strand of Column 7. Column9  
               
               
                 indicated the sequence ID for the sequence of column 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 Sense 
                 Seq ID 
                   
                 Antisense 
                 Seq ID 
                   
                 mRNA target 
                   
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 sequence 
                 NO: 
                 Antisense sequence 
                 sequence in 
                 Seq ID NO: 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 name 
                 (antisense) 
                 (5′-3′) 
                 NM_002977.3 
                 (mRNA target) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 AD- 
                 A- 
                 3 
                 UCACAAAACAGU 
                 A-1683739.1 
                 4 
                 GCAAGAGACUGUUU 
                 UCACAAAACAGUCUC 
                 3039 
               
               
                 887232 
                 1683738. 
                   
                 CUCUUGCdTdT 
                   
                   
                 UGUGAdTdT 
                 UUGC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5 
                 GGAAAACAAUCU 
                 A-1683741.1 
                 6 
                 AAACGGAAGAUUGU 
                 GGAAAACAAUCUUCC 
                 3040 
               
               
                 887233 
                 1683740. 
                   
                 UCCGUUUdTdT 
                   
                   
                 UUUCCdTdT 
                 GUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 7 
                 GAAAACAAUCUU 
                 A-1683743.1 
                 8 
                 GAAACGGAAGAUUG 
                 GAAAACAAUCUUCCG 
                 3041 
               
               
                 887234 
                 1683742. 
                   
                 CCGUUUCdTdT 
                   
                   
                 UUUUCdTdT 
                 UUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 9 
                 AAAACAAUCUUC 
                 A-1683745.1 
                 10 
                 UGAAACGGAAGAUU 
                 AAAACAAUCUUCCGU 
                 3042 
               
               
                 887235 
                 1683744. 
                   
                 CGUUUCAdTdT 
                   
                   
                 GUUUUdTdT 
                 UUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 11 
                 AAACAAUCUUCC 
                 A-1683747.1 
                 12 
                 UUGAAACGGAAGAU 
                 AAACAAUCUUCCGUU 
                 3043 
               
               
                 887236 
                 1683746. 
                   
                 GUUUCAAdTdT 
                   
                   
                 UGUUUdTdT 
                 UCAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 13 
                 AACAAUCUUCCG 
                 A-1683749.1 
                 14 
                 AUUGAAACGGAAGA 
                 AACAAUCUUCCGUUU 
                 3044 
               
               
                 887237 
                 1683748. 
                   
                 UUUCAAUdTdT 
                   
                   
                 UUGUUdTdT 
                 CAAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 15 
                 CAAUCUUCCGUU 
                 A-1683751.1 
                 16 
                 GCAUUGAAACGGAA 
                 CAAUCUUCCGUUUCA 
                 3045 
               
               
                 887238 
                 1683750. 
                   
                 UCAAUGCdTdT 
                   
                   
                 GAUUGdTdT 
                 AUGC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 17 
                 CCUGCUUUAUAU 
                 A-1683753.1 
                 18 
                 AAAGCAUAUAUAAA 
                 CCUGCUUUAUAUAUG 
                 3046 
               
               
                 887239 
                 1683752. 
                   
                 AUGCUUUdTdT 
                   
                   
                 GCAGGdTdT 
                 CUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 19 
                 CUGCUUUAUAUA 
                 A-1683755.1 
                 20 
                 GAAAGCAUAUAUAA 
                 CUGCUUUAUAUAUGC 
                 3047 
               
               
                 887240 
                 1683754. 
                   
                 UGCUUUCdTdT 
                   
                   
                 AGCAGdTdT 
                 UUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 21 
                 UAUGCUUUCUCC 
                 A-1683757.1 
                 22 
                 ACUGAAAGGAGAAA 
                 UAUGCUUUCUCCUUU 
                 3048 
               
               
                 887241 
                 1683756. 
                   
                 UUUCAGUdTdT 
                   
                   
                 GCAUAdTdT 
                 CAGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 23 
                 AUGCUUUCUCCU 
                 A-1683759.1 
                 24 
                 GACUGAAAGGAGAA 
                 AUGCUUUCUCCUUUC 
                 3049 
               
               
                 887242 
                 1683758. 
                   
                 UUCAGUCdTdT 
                   
                   
                 AGCAUdTdT 
                 AGUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 25 
                 UGCUUUCUCCUU 
                 A-1683761.1 
                 26 
                 GGACUGAAAGGAGA 
                 UGCUUUCUCCUUUCA 
                 3050 
               
               
                 887243 
                 1683760. 
                   
                 UCAGUCCdTdT 
                   
                   
                 AAGCAdTdT 
                 GUCC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 27 
                 cuuucuccuuuc 
                 A-1683763.1 
                 28 
                 GAGGACUGAAAGGA 
                 CUUUCUCCUUUCAGU 
                 3051 
               
               
                 887244 
                 1683762. 
                   
                 AGUCCUCdTdT 
                   
                   
                 GAAAGdTdT 
                 CCUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 29 
                 UCUCCUUUCAGU 
                 A-1683765.1 
                 30 
                 UUAGAGGACUGAAA 
                 UCUCCUUUCAGUCCU 
                 3052 
               
               
                 887245 
                 1683764. 
                   
                 CCUCUAAdTdT 
                   
                   
                 GGAGAdTdT 
                 CUAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 31 
                 CUCCUUUCAGUC 
                 A-1683767.1 
                 32 
                 CUUAGAGGACUGAA 
                 CUCCUUUCAGUCCUC 
                 3053 
               
               
                 887246 
                 1683766. 
                   
                 CUCUAAGdTdT 
                   
                   
                 AGGAGdTdT 
                 UAAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 33 
                 UCCUUUCAGUCC 
                 A-1683769.1 
                 34 
                 UCUUAGAGGACUGA 
                 UCCUUUCAGUCCUCU 
                 3054 
               
               
                 887247 
                 1683768. 
                   
                 UCUAAGAdTdT 
                   
                   
                 AAGGAdTdT 
                 AAGA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 35 
                 CCUUUCAGUCCU 
                 A-1683771.1 
                 36 
                 UUCUUAGAGGACUG 
                 CCUUUCAGUCCUCUA 
                 3055 
               
               
                 887248 
                 1683770. 
                   
                 CUAAGAAdTdT 
                   
                   
                 AAAGGdTdT 
                 AGAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 37 
                 CUUUCAGUCCUC 
                 A-1683773.1 
                 38 
                 CUUCUUAGAGGACU 
                 CUUUCAGUCCUCUAA 
                 3056 
               
               
                 887249 
                 1683772. 
                   
                 UAAGAAGdTdT 
                   
                   
                 GAAAGdTdT 
                 GAAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 39 
                 AGUCCUCUAAGA 
                 A-1683775.1 
                 40 
                 AUAUUCUUCUUAGA 
                 AGUCCUCUAAGAAGA 
                 3057 
               
               
                 887250 
                 1683774. 
                   
                 AGAAUAUdTdT 
                   
                   
                 GGACUdTdT 
                 AUAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 41 
                 UCCUCUAAGAAG 
                 A-1683777.1 
                 42 
                 AGAUAUUCUUCUUA 
                 UCCUCUAAGAAGAAU 
                 3058 
               
               
                 887251 
                 1683776. 
                   
                 AAUAUCUdTdT 
                   
                   
                 GAGGAdTdT 
                 AUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 43 
                 CCUCUAAGAAGA 
                 A-1683779.1 
                 44 
                 UAGAUAUUCUUCUU 
                 CCUCUAAGAAGAAUA 
                 3059 
               
               
                 887252 
                 1683778. 
                   
                 AUAUCUAdTdT 
                   
                   
                 AGAGGdTdT 
                 UCUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 45 
                 CUCUAAGAAGAA 
                 A-1683781.1 
                 46 
                 AUAGAUAUUCUUCU 
                 CUCUAAGAAGAAUAU 
                 3060 
               
               
                 887253 
                 1683780. 
                   
                 UAUCUAUdTdT 
                   
                   
                 UAGAGdTdT 
                 CUAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 47 
                 AUUUUAGUACAC 
                 A-1683783.1 
                 48 
                 AUAAGGAGUGUACU 
                 AUUUUAGUACACUCC 
                 3061 
               
               
                 887254 
                 1683782. 
                   
                 UCCUUAUdTdT 
                   
                   
                 AAAAUdTdT 
                 UUAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 49 
                 UAGUACACUCCU 
                 A-1683785.1 
                 50 
                 CUGAAUAAGGAGUG 
                 UAGUACACUCCUUAU 
                 3062 
               
               
                 887255 
                 1683784. 
                   
                 UAUUCAGdTdT 
                   
                   
                 UACUAdTdT 
                 UCAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 51 
                 AGUACACUCCUU 
                 A-1683787.1 
                 52 
                 GCUGAAUAAGGAGU 
                 AGUACACUCCUUAUU 
                 3063 
               
               
                 887256 
                 1683786. 
                   
                 AUUCAGCdTdT 
                   
                   
                 GUACUdTdT 
                 CAGC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 53 
                 CCUUAUUCAGCA 
                 A-1683789.1 
                 54 
                 AUGAGCAUGCUGAA 
                 CCUUAUUCAGCAUGC 
                 3064 
               
               
                 887257 
                 1683788. 
                   
                 UGCUCAUdTdT 
                   
                   
                 UAAGGdTdT 
                 UCAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 55 
                 UCAUCAUGUGCA 
                 A-1683791.1 
                 56 
                 AGAAUAGUGCACAU 
                 UCAUCAUGUGCACUA 
                 3065 
               
               
                 887258 
                 1683790. 
                   
                 CUAUUCUdTdT 
                   
                   
                 GAUGAdTdT 
                 UUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 57 
                 CAUCAUGUGCAC 
                 A-1683793.1 
                 58 
                 CAGAAUAGUGCACAU 
                 CAUCAUGUGCACUAU 
                 3066 
               
               
                 887259 
                 1683792. 
                   
                 UAUUCUGdTdT 
                   
                   
                 GAUGdTdT 
                 UCUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 59 
                 UGUCGAGUACAC 
                 A-1683795.1 
                 60 
                 AGUAAAAGUGUACU 
                 UGUCGAGUACACUUU 
                 3067 
               
               
                 887260 
                 1683794. 
                   
                 UUUUACUdTdT 
                   
                   
                 CGACAdTdT 
                 UACU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 61 
                 GUCGAGUACACU 
                 A-1683797.1 
                 62 
                 CAGUAAAAGUGUAC 
                 GUCGAGUACACUUUU 
                 3068 
               
               
                 887261 
                 1683796. 
                   
                 UUUACUGdTdT 
                   
                   
                 UCGACdTdT 
                 ACUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 63 
                 CUUCUGUGUAG 
                 A-1683799.1 
                 64 
                 GAAUUCUCCUACACA 
                 CUUCUGUGUAGGAGA 
                 3069 
               
               
                 887262 
                 1683798. 
                   
                 GAGAAUUCdTdT 
                   
                   
                 GAAGdTdT 
                 AUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 65 
                 UAGGAGAAUUCA 
                 A-1683801.1 
                 66 
                 AGAAAAGUGAAUUC 
                 UAGGAGAAUUCACUU 
                 3070 
               
               
                 887263 
                 1683800. 
                   
                 CUUUUCUdTdT 
                   
                   
                 UCCUAdTdT 
                 UUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 67 
                 AGGAGAAUUCAC 
                 A-1683803.1 
                 68 
                 AAGAAAAGUGAAUU 
                 AGGAGAAUUCACUUU 
                 3071 
               
               
                 887264 
                 1683802. 
                   
                 UUUUCUUdTdT 
                   
                   
                 CUCCUdTdT 
                 UCUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 69 
                 GGAGAAUUCACU 
                 A-1683805.1 
                 70 
                 GAAGAAAAGUGAAU 
                 GGAGAAUUCACUUUU 
                 3072 
               
               
                 887265 
                 1683804. 
                   
                 UUUCUUCdTdT 
                   
                   
                 UCUCCdTdT 
                 CUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 71 
                 GGCAAUGUUUCA 
                 A-1683807.1 
                 72 
                 GAAGAGCUGAAACA 
                 GGCAAUGUUUCAGCU 
                 3073 
               
               
                 887266 
                 1683806. 
                   
                 GCUCUUCdTdT 
                   
                   
                 UUGCCdTdT 
                 CUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 73 
                 AAUGUUUCAGCU 
                 A-1683809.1 
                 74 
                 UUCGAAGAGCUGAA 
                 AAUGUUUCAGCUCUU 
                 3074 
               
               
                 887267 
                 1683808. 
                   
                 CUUCGAAdTdT 
                   
                   
                 ACAUUdTdT 
                 CGAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 75 
                 GUUUCAGCUCUU 
                 A-1683811.1 
                 76 
                 AAGUUCGAAGAGCU 
                 GUUUCAGCUCUUCGA 
                 3075 
               
               
                 887268 
                 1683810. 
                   
                 CGAACUUdTdT 
                   
                   
                 GAAACdTdT 
                 ACUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 77 
                 UCAGCUCUUCGA 
                 A-1683813.1 
                 78 
                 UGAAAGUUCGAAGA 
                 UCAGCUCUUCGAACU 
                 3076 
               
               
                 887269 
                 1683812. 
                   
                 ACUUUCAdTdT 
                   
                   
                 GCUGAdTdT 
                 UUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 79 
                 AGCUCUUCGAAC 
                 A-1683815.1 
                 80 
                 UCUGAAAGUUCGAA 
                 AGCUCUUCGAACUUU 
                 3077 
               
               
                 887270 
                 1683814. 
                   
                 UUUCAGAdTdT 
                   
                   
                 GAGCUdTdT 
                 CAGA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 81 
                 CUCUUCGAACUU 
                 A-1683817.1 
                 82 
                 ACUCUGAAAGUUCG 
                 CUCUUCGAACUUUCA 
                 3078 
               
               
                 887271 
                 1683816. 
                   
                 UCAGAGUdTdT 
                   
                   
                 AAGAGdTdT 
                 GAGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 83 
                 CUUCGAACUUUC 
                 A-1683819.1 
                 84 
                 AUACUCUGAAAGUU 
                 CUUCGAACUUUCAGA 
                 3079 
               
               
                 887272 
                 1683818. 
                   
                 AGAGUAUdTdT 
                   
                   
                 CGAAGdTdT 
                 GUAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 85 
                 UCCUGACUGUGU 
                 A-1683821.1 
                 86 
                 AGACAGAACACAGUC 
                 UCCUGACUGUGUUCU 
                 3080 
               
               
                 887273 
                 1683820. 
                   
                 UCUGUCUdTdT 
                   
                   
                 AGGAdTdT 
                 GUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 87 
                 CUGACUGUGUUC 
                 A-1683823.1 
                 88 
                 UCAGACAGAACACAG 
                 CUGACUGUGUUCUGU 
                 3081 
               
               
                 887274 
                 1683822. 
                   
                 UGUCUGAdTdT 
                   
                   
                 UCAGdTdT 
                 CUGA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 89 
                 UGACUGUGUUC 
                 A-1683825.1 
                 90 
                 CUCAGACAGAACACA 
                 UGACUGUGUUCUGUC 
                 3082 
               
               
                 887275 
                 1683824. 
                   
                 UGUCUGAGdTdT 
                   
                   
                 GUCAdTdT 
                 UGAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 91 
                 GACUGUGUUCU 
                 A-1683827.1 
                 92 
                 ACUCAGACAGAACAC 
                 GACUGUGUUCUGUCU 
                 3083 
               
               
                 887276 
                 1683826. 
                   
                 GUCUGAGUdTdT 
                   
                   
                 AGUCdTdT 
                 GAGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 93 
                 ACUGUGUUCUG 
                 A-1683829.1 
                 94 
                 CACUCAGACAGAACA 
                 ACUGUGUUCUGUCUG 
                 3084 
               
               
                 887277 
                 1683828. 
                   
                 UCUGAGUGdTdT 
                   
                   
                 CAGUdTdT 
                 AGUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 95 
                 CUGUGUUCUGUC 
                 A-1683831.1 
                 96 
                 ACACUCAGACAGAAC 
                 CUGUGUUCUGUCUGA 
                 3085 
               
               
                 887278 
                 1683830. 
                   
                 UGAGUGUdTdT 
                   
                   
                 ACAGdTdT 
                 GUGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 97 
                 UGUGUUCUGUC 
                 A-1683833.1 
                 98 
                 CACACUCAGACAGAA 
                 UGUGUUCUGUCUGA 
                 3086 
               
               
                 887279 
                 1683832. 
                   
                 UGAGUGUGdTdT 
                   
                   
                 CACAdTdT 
                 GUGUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 99 
                 UGUUCUGUCUG 
                 A-1683835.1 
                 100 
                 AACACACUCAGACAG 
                 UGUUCUGUCUGAGU 
                 3087 
               
               
                 887280 
                 1683834. 
                   
                 AGUGUGUUdTdT 
                   
                   
                 AACAdTdT 
                 GUGUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 101 
                 GUUCUGUCUGA 
                 A-1683837.1 
                 102 
                 AAACACACUCAGACA 
                 GUUCUGUCUGAGUG 
                 3088 
               
               
                 887281 
                 1683836. 
                   
                 GUGUGUUUdTdT 
                   
                   
                 GAACdTdT 
                 UGUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 103 
                 UUCUGUCUGAG 
                 A-1683839.1 
                 104 
                 CAAACACACUCAGAC 
                 UUCUGUCUGAGUGU 
                 3089 
               
               
                 887282 
                 1683838. 
                   
                 UGUGUUUGdTdT 
                   
                   
                 AGAAdTdT 
                 GUUUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 105 
                 UCUGUCUGAGU 
                 A-1683841.1 
                 106 
                 GCAAACACACUCAGA 
                 UCUGUCUGAGUGUG 
                 3090 
               
               
                 887283 
                 1683840. 
                   
                 GUGUUUGCdTdT 
                   
                   
                 CAGAdTdT 
                 UUUGC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 107 
                 UGCUCUCCUUUG 
                 A-1683843.1 
                 108 
                 GAAACCACAAAGGAG 
                 UGCUCUCCUUUGUGG 
                 3091 
               
               
                 887284 
                 1683842. 
                   
                 UGGUUUCdTdT 
                   
                   
                 AGCAdTdT 
                 UUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 109 
                 CUCUCCUUUGUG 
                 A-1683845.1 
                 110 
                 CUGAAACCACAAAGG 
                 CUCUCCUUUGUGGUU 
                 3092 
               
               
                 887285 
                 1683844. 
                   
                 GUUUCAGdTdT 
                   
                   
                 AGAGdTdT 
                 UCAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 111 
                 UCUCCUUUGUGG 
                 A-1683847.1 
                 112 
                 GCUGAAACCACAAAG 
                 UCUCCUUUGUGGUU 
                 3093 
               
               
                 887286 
                 1683846. 
                   
                 UUUCAGCdTdT 
                   
                   
                 GAGAdTdT 
                 UCAGC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 113 
                 CUCCUUUGUGGU 
                 A-1683849.1 
                 114 
                 UGCUGAAACCACAAA 
                 CUCCUUUGUGGUUUC 
                 3094 
               
               
                 887287 
                 1683848. 
                   
                 UUCAGCAdTdT 
                   
                   
                 GGAGdTdT 
                 AGCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 115 
                 CGAGCUUUGACA 
                 A-1683851.1 
                 116 
                 CUGAAAGUGUCAAA 
                 CGAGCUUUGACACUU 
                 3095 
               
               
                 887288 
                 1683850. 
                   
                 CUUUCAGdTdT 
                   
                   
                 GCUCGdTdT 
                 UCAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 117 
                 ACAUGAUCUUCU 
                 A-1683853.1 
                 118 
                 ACGACAAAGAAGAUC 
                 ACAUGAUCUUCUUUG 
                 3096 
               
               
                 887289 
                 1683852. 
                   
                 UUGUCGUdTdT 
                   
                   
                 AUGUdTdT 
                 UCGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 119 
                 CAUGAUCUUCUU 
                 A-1683855.1 
                 120 
                 UACGACAAAGAAGAU 
                 CAUGAUCUUCUUUGU 
                 3097 
               
               
                 887290 
                 1683854. 
                   
                 UGUCGUAdTdT 
                   
                   
                 CAUGdTdT 
                 CGUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 121 
                 GAUCUUCUUUG 
                 A-1683857.1 
                 122 
                 CACUACGACAAAGAA 
                 GAUCUUCUUUGUCGU 
                 3098 
               
               
                 887291 
                 1683856. 
                   
                 UCGUAGUGdTdT 
                   
                   
                 GAUCdTdT 
                 AGUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 123 
                 UCUUCUUUGUCG 
                 A-1683859.1 
                 124 
                 AUCACUACGACAAAG 
                 UCUUCUUUGUCGUAG 
                 3099 
               
               
                 887292 
                 1683858. 
                   
                 UAGUGAUdTdT 
                   
                   
                 AAGAdTdT 
                 UGAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 125 
                 CUUCUUUGUCGU 
                 A-1683861.1 
                 126 
                 AAUCACUACGACAAA 
                 CUUCUUUGUCGUAGU 
                 3100 
               
               
                 887293 
                 1683860. 
                   
                 AGUGAUUdTdT 
                   
                   
                 GAAGdTdT 
                 GAUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 127 
                 UUGUCGUAGUG 
                 A-1683863.1 
                 128 
                 AGGAAAAUCACUACG 
                 UUGUCGUAGUGAUU 
                 3101 
               
               
                 887294 
                 1683862. 
                   
                 AUUUUCCUdTdT 
                   
                   
                 ACAAdTdT 
                 UUCCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 129 
                 GCUCCUUUUAUC 
                 A-1683865.1 
                 130 
                 UUUAUUAGAUAAAA 
                 GCUCCUUUUAUCUAA 
                 3102 
               
               
                 887295 
                 1683864. 
                   
                 UAAUAAAdTdT 
                   
                   
                 GGAGCdTdT 
                 UAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 131 
                 CUCCUUUUAUCU 
                 A-1683867.1 
                 132 
                 GUUUAUUAGAUAAA 
                 CUCCUUUUAUCUAAU 
                 3103 
               
               
                 887296 
                 1683866. 
                   
                 AAUAAACdTdT 
                   
                   
                 AGGAGdTdT 
                 AAAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 133 
                 CCUCUCAGAGAG 
                 A-1683869.1 
                 134 
                 AGAAGAACUCUCUGA 
                 CCUCUCAGAGAGUUC 
                 3104 
               
               
                 887297 
                 1683868. 
                   
                 UUCUUCUdTdT 
                   
                   
                 GAGGdTdT 
                 UUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 135 
                 CUCUCAGAGAGU 
                 A-1683871.1 
                 136 
                 CAGAAGAACUCUCUG 
                 CUCUCAGAGAGUUCU 
                 3105 
               
               
                 887298 
                 1683870. 
                   
                 UCUUCUGdTdT 
                   
                   
                 AGAGdTdT 
                 UCUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 137 
                 UCUCAGAGAGUU 
                 A-1683873.1 
                 138 
                 UCAGAAGAACUCUCU 
                 UCUCAGAGAGUUCUU 
                 3106 
               
               
                 887299 
                 1683872. 
                   
                 CUUCUGAdTdT 
                   
                   
                 GAGAdTdT 
                 CUGA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 139 
                 CUCAGAGAGUUC 
                 A-1683875.1 
                 140 
                 UUCAGAAGAACUCUC 
                 CUCAGAGAGUUCUUC 
                 3107 
               
               
                 887300 
                 1683874. 
                   
                 UUCUGAAdTdT 
                   
                   
                 UGAGdTdT 
                 UGAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 141 
                 UCAGAGAGUUCU 
                 A-1683877.1 
                 142 
                 UUUCAGAAGAACUC 
                 UCAGAGAGUUCUUCU 
                 3108 
               
               
                 887301 
                 1683876. 
                   
                 UCUGAAAdTdT 
                   
                   
                 UCUGAdTdT 
                 GAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 143 
                 CAGAGAGUUCUU 
                 A-1683879.1 
                 144 
                 GUUUCAGAAGAACU 
                 CAGAGAGUUCUUCUG 
                 3109 
               
               
                 887302 
                 1683878. 
                   
                 CUGAAACdTdT 
                   
                   
                 CUCUGdTdT 
                 AAAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 145 
                 GAGAGUUCUUCU 
                 A-1683881.1 
                 146 
                 AUGUUUCAGAAGAA 
                 GAGAGUUCUUCUGAA 
                 3110 
               
               
                 887303 
                 1683880. 
                   
                 GAAACAUdTdT 
                   
                   
                 CUCUCdTdT 
                 ACAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 147 
                 AGAGUUCUUCUG 
                 A-1683883.1 
                 148 
                 GAUGUUUCAGAAGA 
                 AGAGUUCUUCUGAAA 
                 3111 
               
               
                 887304 
                 1683882. 
                   
                 AAACAUCdTdT 
                   
                   
                 ACUCUdTdT 
                 CAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 149 
                 GAGUUCUUCUGA 
                 A-1683885.1 
                 150 
                 GGAUGUUUCAGAAG 
                 GAGUUCUUCUGAAAC 
                 3112 
               
               
                 887305 
                 1683884. 
                   
                 AACAUCCdTdT 
                   
                   
                 AACUCdTdT 
                 AUCC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 151 
                 AGUUCUUCUGAA 
                 A-1683887.1 
                 152 
                 UGGAUGUUUCAGAA 
                 AGUUCUUCUGAAACA 
                 3113 
               
               
                 887306 
                 1683886. 
                   
                 ACAUCCAdTdT 
                   
                   
                 GAACUdTdT 
                 UCCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 153 
                 GUUCUUCUGAAA 
                 A-1683889.1 
                 154 
                 UUGGAUGUUUCAGA 
                 GUUCUUCUGAAACAU 
                 3114 
               
               
                 887307 
                 1683888. 
                   
                 CAUCCAAdTdT 
                   
                   
                 AGAACdTdT 
                 CCAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 155 
                 UCUUCUGAAACA 
                 A-1683891.1 
                 156 
                 GUUUGGAUGUUUCA 
                 UCUUCUGAAACAUCC 
                 3115 
               
               
                 887308 
                 1683890. 
                   
                 UCCAAACdTdT 
                   
                   
                 GAAGAdTdT 
                 AAAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 157 
                 CUUCUGAAACAU 
                 A-1683893.1 
                 158 
                 AGUUUGGAUGUUUC 
                 CUUCUGAAACAUCCA 
                 3116 
               
               
                 887309 
                 1683892. 
                   
                 CCAAACUdTdT 
                   
                   
                 AGAAGdTdT 
                 AACU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 159 
                 UCUGAAACAUCC 
                 A-1683895.1 
                 160 
                 UCAGUUUGGAUGUU 
                 UCUGAAACAUCCAAA 
                 3117 
               
               
                 887310 
                 1683894. 
                   
                 AAACUGAdTdT 
                   
                   
                 UCAGAdTdT 
                 CUGA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 161 
                 UCCAAACUGAGC 
                 A-1683897.1 
                 162 
                 UUUUAGAGCUCAGU 
                 UCCAAACUGAGCUCU 
                 3118 
               
               
                 887311 
                 1683896. 
                   
                 UCUAAAAdTdT 
                   
                   
                 UUGGAdTdT 
                 AAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 163 
                 AGGCGUUGUAG 
                 A-1683899.1 
                 164 
                 GAUAGGAACUACAAC 
                 AGGCGUUGUAGUUCC 
                 3119 
               
               
                 887312 
                 1683898. 
                   
                 UUCCUAUCdTdT 
                   
                   
                 GCCUdTdT 
                 UAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 165 
                 GCGUUGUAGUU 
                 A-1683901.1 
                 166 
                 GAGAUAGGAACUAC 
                 GCGUUGUAGUUCCUA 
                 3120 
               
               
                 887313 
                 1683900. 
                   
                 CCUAUCUCdTdT 
                   
                   
                 AACGCdTdT 
                 UCUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 167 
                 CGUUGUAGUUCC 
                 A-1683903.1 
                 168 
                 GGAGAUAGGAACUA 
                 CGUUGUAGUUCCUAU 
                 3121 
               
               
                 887314 
                 1683902. 
                   
                 UAUCUCCdTdT 
                   
                   
                 CAACGdTdT 
                 CUCC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 169 
                 GUUGUAGUUCC 
                 A-1683905.1 
                 170 
                 AGGAGAUAGGAACU 
                 GUUGUAGUUCCUAUC 
                 3122 
               
               
                 887315 
                 1683904. 
                   
                 UAUCUCCUdTdT 
                   
                   
                 ACAACdTdT 
                 uccu 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 171 
                 UUGUAGUUCCUA 
                 A-1683907.1 
                 172 
                 AAGGAGAUAGGAAC 
                 UUGUAGUUCCUAUCU 
                 3123 
               
               
                 887316 
                 1683906. 
                   
                 UCUCCUUdTdT 
                   
                   
                 UACAAdTdT 
                 CCUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 173 
                 UGUAGUUCCUAU 
                 A-1683909.1 
                 174 
                 AAAGGAGAUAGGAA 
                 UGUAGUUCCUAUCUC 
                 3124 
               
               
                 887317 
                 1683908. 
                   
                 CUCCUUUdTdT 
                   
                   
                 CUACAdTdT 
                 CUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 175 
                 GUAGUUCCUAUC 
                 A-1683911.1 
                 176 
                 GAAAGGAGAUAGGA 
                 GUAGUUCCUAUCUCC 
                 3125 
               
               
                 887318 
                 1683910. 
                   
                 UCCUUUCdTdT 
                   
                   
                 ACUACdTdT 
                 UUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 177 
                 UAGUUCCUAUCU 
                 A-1683913.1 
                 178 
                 UGAAAGGAGAUAGG 
                 UAGUUCCUAUCUCCU 
                 3126 
               
               
                 887319 
                 1683912. 
                   
                 CCUUUCAdTdT 
                   
                   
                 AACUAdTdT 
                 UUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 179 
                 AGUUCCUAUCUC 
                 A-1683915.1 
                 180 
                 CUGAAAGGAGAUAG 
                 AGUUCCUAUCUCCUU 
                 3127 
               
               
                 887320 
                 1683914. 
                   
                 CUUUCAGdTdT 
                   
                   
                 GAACUdTdT 
                 UCAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 181 
                 GUUCCUAUCUCC 
                 A-1683917.1 
                 182 
                 UCUGAAAGGAGAUA 
                 GUUCCUAUCUCCUUU 
                 3128 
               
               
                 887321 
                 1683916. 
                   
                 UUUCAGAdTdT 
                   
                   
                 GGAACdTdT 
                 CAGA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 183 
                 UUCCUAUCUCCU 
                 A-1683919.1 
                 184 
                 CUCUGAAAGGAGAU 
                 UUCCUAUCUCCUUUC 
                 3129 
               
               
                 887322 
                 1683918. 
                   
                 UUCAGAGdTdT 
                   
                   
                 AGGAAdTdT 
                 AGAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 185 
                 UCCUAUCUCCUU 
                 A-1683921.1 
                 186 
                 CCUCUGAAAGGAGA 
                 UCCUAUCUCCUUUCA 
                 3130 
               
               
                 887323 
                 1683920. 
                   
                 UCAGAGGdTdT 
                   
                   
                 UAGGAdTdT 
                 GAGG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 187 
                 UCUCCUUUCAGA 
                 A-1683923.1 
                 188 
                 CAUAUCCUCUGAAAG 
                 UCUCCUUUCAGAGGA 
                 3131 
               
               
                 887324 
                 1683922. 
                   
                 GGAUAUGdTdT 
                   
                   
                 GAGAdTdT 
                 UAUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 189 
                 GCAUAUUAACAA 
                 A-1683925.1 
                 190 
                 ACAGUGUUUGUUAA 
                 GCAUAUUAACAAACA 
                 3132 
               
               
                 887325 
                 1683924. 
                   
                 ACACUGUdTdT 
                   
                   
                 UAUGCdTdT 
                 CUGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 191 
                 CUUGAUCUGGAA 
                 A-1683927.1 
                 192 
                 AGAGCAAUUCCAGAU 
                 CUUGAUCUGGAAUUG 
                 3133 
               
               
                 887326 
                 1683926. 
                   
                 UUGCUCUdTdT 
                   
                   
                 CAAGdTdT 
                 CUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 193 
                 CUCUCCAUAUUG 
                 A-1683929.1 
                 194 
                 UUUUAUCCAAUAUG 
                 CUCUCCAUAUUGGAU 
                 3134 
               
               
                 887327 
                 1683928. 
                   
                 GAUAAAAdTdT 
                   
                   
                 GAGAGdTdT 
                 AAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 195 
                 UCUCCAUAUUGG 
                 A-1683931.1 
                 196 
                 AUUUUAUCCAAUAU 
                 UCUCCAUAUUGGAUA 
                 3135 
               
               
                 887328 
                 1683930. 
                   
                 AUAAAAUdTdT 
                   
                   
                 GGAGAdTdT 
                 AAAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 197 
                 CUCCAUAUUGGA 
                 A-1683933.1 
                 198 
                 AAUUUUAUCCAAUA 
                 CUCCAUAUUGGAUAA 
                 3136 
               
               
                 887329 
                 1683932. 
                   
                 UAAAAUUdTdT 
                   
                   
                 UGGAGdTdT 
                 AAUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 199 
                 GAUCUUGCAAUU 
                 A-1683935.1 
                 200 
                 AAAUGGUAAUUGCA 
                 GAUCUUGCAAUUACC 
                 3137 
               
               
                 887330 
                 1683934. 
                   
                 ACCAUUUdTdT 
                   
                   
                 AGAUCdTdT 
                 AUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 201 
                 UUGGUCUUUAC 
                 A-1683937.1 
                 202 
                 AGAUUCCAGUAAAG 
                 UUGGUCUUUACUGGA 
                 3138 
               
               
                 887331 
                 1683936. 
                   
                 UGGAAUCUdTdT 
                   
                   
                 ACCAAdTdT 
                 AUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 203 
                 GGUCUUUACUG 
                 A-1683939.1 
                 204 
                 AAAGAUUCCAGUAAA 
                 GGUCUUUACUGGAAU 
                 3139 
               
               
                 887332 
                 1683938. 
                   
                 GAAUCUUUdTdT 
                   
                   
                 GACCdTdT 
                 CUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 205 
                 GUCUUUACUGGA 
                 A-1683941.1 
                 206 
                 CAAAGAUUCCAGUAA 
                 GUCUUUACUGGAAUC 
                 3140 
               
               
                 887333 
                 1683940. 
                   
                 AUCUUUGdTdT 
                   
                   
                 AGACdTdT 
                 UUUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 207 
                 GCCUUAUUGUGA 
                 A-1683943.1 
                 208 
                 CUUAAAGUCACAAUA 
                 GCCUUAUUGUGACUU 
                 3141 
               
               
                 887334 
                 1683942. 
                   
                 CUUUAAGdTdT 
                   
                   
                 AGGCdTdT 
                 UAAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 209 
                 GCUCUUUCUAGC 
                 A-1683945.1 
                 210 
                 CACAUCUGCUAGAAA 
                 GCUCUUUCUAGCAGA 
                 3142 
               
               
                 887335 
                 1683944. 
                   
                 AGAUGUGdTdT 
                   
                   
                 GAGCdTdT 
                 UGUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 211 
                 CUCUUUCUAGCA 
                 A-1683947.1 
                 212 
                 CCACAUCUGCUAGAA 
                 CUCUUUCUAGCAGAU 
                 3143 
               
               
                 887336 
                 1683946. 
                   
                 GAUGUGGdTdT 
                   
                   
                 AGAGdTdT 
                 GUGG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 213 
                 GUCAGUUCUGCG 
                 A-1683949.1 
                 214 
                 GAAUGAUCGCAGAAC 
                 GUCAGUUCUGCGAUC 
                 3144 
               
               
                 887337 
                 1683948. 
                   
                 AUCAUUCdTdT 
                   
                   
                 UGACdTdT 
                 AUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 215 
                 UCAGUUCUGCGA 
                 A-1683951.1 
                 216 
                 UGAAUGAUCGCAGA 
                 UCAGUUCUGCGAUCA 
                 3145 
               
               
                 887338 
                 1683950. 
                   
                 UCAUUCAdTdT 
                   
                   
                 ACUGAdTdT 
                 UUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 217 
                 AGUCUUCAAGUU 
                 A-1683953.1 
                 218 
                 UUUUGCCAACUUGA 
                 AGUCUUCAAGUUGGC 
                 3146 
               
               
                 887339 
                 1683952. 
                   
                 GGCAAAAdTdT 
                   
                   
                 AGACUdTdT 
                 AAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 219 
                 UCUUCAAGUUGG 
                 A-1683955.1 
                 220 
                 GAUUUUGCCAACUU 
                 UCUUCAAGUUGGCAA 
                 3147 
               
               
                 887340 
                 1683954. 
                   
                 CAAAAUCdTdT 
                   
                   
                 GAAGAdTdT 
                 AAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 221 
                 CUUCAAGUUGGC 
                 A-1683957.1 
                 222 
                 GGAUUUUGCCAACU 
                 CUUCAAGUUGGCAAA 
                 3148 
               
               
                 887341 
                 1683956. 
                   
                 AAAAUCCdTdT 
                   
                   
                 UGAAGdTdT 
                 AUCC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 223 
                 CCAUCAUCGUCU 
                 A-1683959.1 
                 224 
                 AAAAUGAAGACGAU 
                 CCAUCAUCGUCUUCA 
                 3149 
               
               
                 887342 
                 1683958. 
                   
                 UCAUUUUdTdT 
                   
                   
                 GAUGGdTdT 
                 UUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 225 
                 CAUCAUCGUCUU 
                 A-1683961.1 
                 226 
                 AAAAAUGAAGACGAU 
                 CAUCAUCGUCUUCAU 
                 3150 
               
               
                 887343 
                 1683960. 
                   
                 CAUUUUUdTdT 
                   
                   
                 GAUGdTdT 
                 UUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 227 
                 GCACAUGAACGA 
                 A-1683963.1 
                 228 
                 GAAGAAGUCGUUCA 
                 GCACAUGAACGACUU 
                 3151 
               
               
                 887344 
                 1683962. 
                   
                 CUUCUUCdTdT 
                   
                   
                 UGUGCdTdT 
                 CUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 229 
                 CACAUGAACGAC 
                 A-1683965.1 
                 230 
                 GGAAGAAGUCGUUC 
                 CACAUGAACGACUUC 
                 3152 
               
               
                 887345 
                 1683964. 
                   
                 UUCUUCCdTdT 
                   
                   
                 AUGUGdTdT 
                 UUCC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 231 
                 ACAUGAACGACU 
                 A-1683967.1 
                 232 
                 UGGAAGAAGUCGUU 
                 ACAUGAACGACUUCU 
                 3153 
               
               
                 887346 
                 1683966. 
                   
                 UCUUCCAdTdT 
                   
                   
                 CAUGUdTdT 
                 UCCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 233 
                 CAUGAACGACUU 
                 A-1683969.1 
                 234 
                 GUGGAAGAAGUCGU 
                 CAUGAACGACUUCUU 
                 3154 
               
               
                 887347 
                 1683968. 
                   
                 CUUCCACdTdT 
                   
                   
                 UCAUGdTdT 
                 CCAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 235 
                 UGAACGACUUCU 
                 A-1683971.1 
                 236 
                 GAGUGGAAGAAGUC 
                 UGAACGACUUCUUCC 
                 3155 
               
               
                 887348 
                 1683970. 
                   
                 UCCACUCdTdT 
                   
                   
                 GUUCAdTdT 
                 ACUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 237 
                 CGACUUCUUCCA 
                 A-1683973.1 
                 238 
                 GAAGGAGUGGAAGA 
                 CGACUUCUUCCACUC 
                 3156 
               
               
                 887349 
                 1683972. 
                   
                 CUCCUUCdTdT 
                   
                   
                 AGUCGdTdT 
                 CUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 239 
                 UCCACUCCUUCC 
                 A-1683975.1 
                 240 
                 ACAAUCAGGAAGGAG 
                 UCCACUCCUUCCUGA 
                 3157 
               
               
                 887350 
                 1683974. 
                   
                 UGAUUGUdTdT 
                   
                   
                 UGGAdTdT 
                 UUGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 241 
                 ACUCCUUCCUGA 
                 A-1683977.1 
                 242 
                 AACACAAUCAGGAAG 
                 ACUCCUUCCUGAUUG 
                 3158 
               
               
                 887351 
                 1683976. 
                   
                 UUGUGUUdTdT 
                   
                   
                 GAGUdTdT 
                 UGUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 243 
                 CUCCUUCCUGAU 
                 A-1683979.1 
                 244 
                 GAACACAAUCAGGAA 
                 CUCCUUCCUGAUUGU 
                 3159 
               
               
                 887352 
                 1683978. 
                   
                 UGUGUUCdTdT 
                   
                   
                 GGAGdTdT 
                 GUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 245 
                 UCCUUCCUGAUU 
                 A-1683981.1 
                 246 
                 GGAACACAAUCAGGA 
                 UCCUUCCUGAUUGUG 
                 3160 
               
               
                 887353 
                 1683980. 
                   
                 GUGUUCCdTdT 
                   
                   
                 AGGAdTdT 
                 UUCC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 247 
                 CUAUGUGCCUUA 
                 A-1683983.1 
                 248 
                 UAAACAAUAAGGCAC 
                 CUAUGUGCCUUAUUG 
                 3161 
               
               
                 887354 
                 1683982. 
                   
                 UUGUUUAdTdT 
                   
                   
                 AUAGdTdT 
                 UUUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 249 
                 UGGUCCUAAACC 
                 A-1683985.1 
                 250 
                 AGAAAUAGGUUUAG 
                 UGGUCCUAAACCUAU 
                 3162 
               
               
                 887355 
                 1683984. 
                   
                 UAUUUCUdTdT 
                   
                   
                 GACCAdTdT 
                 UUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 251 
                 GGUCCUAAACCU 
                 A-1683987.1 
                 252 
                 CAGAAAUAGGUUUA 
                 GGUCCUAAACCUAUU 
                 3163 
               
               
                 887356 
                 1683986. 
                   
                 AUUUCUGdTdT 
                   
                   
                 GGACCdTdT 
                 UCUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 253 
                 GUCCUAAACCUA 
                 A-1683989.1 
                 254 
                 CCAGAAAUAGGUUU 
                 GUCCUAAACCUAUUU 
                 3164 
               
               
                 887357 
                 1683988. 
                   
                 UUUCUGGdTdT 
                   
                   
                 AGGACdTdT 
                 CUGG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 255 
                 CCUUACGUGAAU 
                 A-1683991.1 
                 256 
                 AGAAUAAAUUCACG 
                 CCUUACGUGAAUUUA 
                 3165 
               
               
                 887358 
                 1683990. 
                   
                 UUAUUCUdTdT 
                   
                   
                 UAAGGdTdT 
                 UUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 257 
                 CAAAGGUCACAA 
                 A-1683993.1 
                 258 
                 GAGGAAAUUGUGAC 
                 CAAAGGUCACAAUUU 
                 3166 
               
               
                 887359 
                 1683992. 
                   
                 UUUCCUCdTdT 
                   
                   
                 CUUUGdTdT 
                 CCUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 259 
                 UCACAAUUUCCU 
                 A-1683995.1 
                 260 
                 UUCCUUGAGGAAAU 
                 UCACAAUUUCCUCAA 
                 3167 
               
               
                 887360 
                 1683994. 
                   
                 CAAGGAAdTdT 
                   
                   
                 UGUGAdTdT 
                 GGAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 261 
                 CCUCAAGGAAAA 
                 A-1683997.1 
                 262 
                 UUUAUCUUUUUCCU 
                 CCUCAAGGAAAAAGA 
                 3168 
               
               
                 887361 
                 1683996. 
                   
                 AGAUAAAdTdT 
                   
                   
                 UGAGGdTdT 
                 UAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 263 
                 GCUUCAUUGUCC 
                 A-1683999.1 
                 264 
                 AUCAUGAGGACAAU 
                 GCUUCAUUGUCCUCA 
                 3169 
               
               
                 887362 
                 1683998. 
                   
                 UCAUGAUdTdT 
                   
                   
                 GAAGCdTdT 
                 UGAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 265 
                 CUUCAUUGUCCU 
                 A-1684001.1 
                 266 
                 GAUCAUGAGGACAA 
                 CUUCAUUGUCCUCAU 
                 3170 
               
               
                 887363 
                 1684000. 
                   
                 CAUGAUCdTdT 
                   
                   
                 UGAAGdTdT 
                 GAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 267 
                 UGCAGACAAGAU 
                 A-1684003.1 
                 268 
                 AGUGAAGAUCUUGU 
                 UGCAGACAAGAUCUU 
                 3171 
               
               
                 887364 
                 1684002. 
                   
                 CUUCACUdTdT 
                   
                   
                 CUGCAdTdT 
                 CACU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 269 
                 CAGACAAGAUCU 
                 A-1684005.1 
                 270 
                 UAAGUGAAGAUCUU 
                 CAGACAAGAUCUUCA 
                 3172 
               
               
                 887365 
                 1684004. 
                   
                 UCACUUAdTdT 
                   
                   
                 GUCUGdTdT 
                 CUUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 271 
                 AGACAAGAUCUU 
                 A-1684007.1 
                 272 
                 GUAAGUGAAGAUCU 
                 AGACAAGAUCUUCAC 
                 3173 
               
               
                 887366 
                 1684006. 
                   
                 CACUUACdTdT 
                   
                   
                 UGUCUdTdT 
                 UUAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 273 
                 GACAAGAUCUUC 
                 A-1684009.1 
                 274 
                 UGUAAGUGAAGAUC 
                 GACAAGAUCUUCACU 
                 3174 
               
               
                 887367 
                 1684008. 
                   
                 ACUUACAdTdT 
                   
                   
                 UUGUCdTdT 
                 UACA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 275 
                 ACAAGAUCUUCA 
                 A-1684011.1 
                 276 
                 AUGUAAGUGAAGAU 
                 ACAAGAUCUUCACUU 
                 3175 
               
               
                 887368 
                 1684010. 
                   
                 CUUACAUdTdT 
                   
                   
                 CUUGUdTdT 
                 ACAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 277 
                 CAAGAUCUUCAC 
                 A-1684013.1 
                 278 
                 GAUGUAAGUGAAGA 
                 CAAGAUCUUCACUUA 
                 3176 
               
               
                 887369 
                 1684012. 
                   
                 UUACAUCdTdT 
                   
                   
                 UCUUGdTdT 
                 CAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 279 
                 AGAUCUUCACUU 
                 A-1684015.1 
                 280 
                 AAGAUGUAAGUGAA 
                 AGAUCUUCACUUACA 
                 3177 
               
               
                 887370 
                 1684014. 
                   
                 ACAUCUUdTdT 
                   
                   
                 GAUCUdTdT 
                 UCUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 281 
                 GAUCUUCACUUA 
                 A-1684017.1 
                 282 
                 GAAGAUGUAAGUGA 
                 GAUCUUCACUUACAU 
                 3178 
               
               
                 887371 
                 1684016. 
                   
                 CAUCUUCdTdT 
                   
                   
                 AGAUCdTdT 
                 CUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 283 
                 UCUUCACUUACA 
                 A-1684019.1 
                 284 
                 AUGAAGAUGUAAGU 
                 UCUUCACUUACAUCU 
                 3179 
               
               
                 887372 
                 1684018. 
                   
                 UCUUCAUdTdT 
                   
                   
                 GAAGAdTdT 
                 UCAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 285 
                 CUUCACUUACAU 
                 A-1684021.1 
                 286 
                 AAUGAAGAUGUAAG 
                 CUUCACUUACAUCUU 
                 3180 
               
               
                 887373 
                 1684020. 
                   
                 CUUCAUUdTdT 
                   
                   
                 UGAAGdTdT 
                 CAUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 287 
                 UUCACUUACAUC 
                 A-1684023.1 
                 288 
                 GAAUGAAGAUGUAA 
                 UUCACUUACAUCUUC 
                 3181 
               
               
                 887374 
                 1684022. 
                   
                 UUCAUUCdTdT 
                   
                   
                 GUGAAdTdT 
                 AUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 289 
                 UCACUUACAUCU 
                 A-1684025.1 
                 290 
                 AGAAUGAAGAUGUA 
                 UCACUUACAUCUUCA 
                 3182 
               
               
                 887375 
                 1684024. 
                   
                 UCAUUCUdTdT 
                   
                   
                 AGUGAdTdT 
                 UUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 291 
                 CACUUACAUCUU 
                 A-1684027.1 
                 292 
                 CAGAAUGAAGAUGU 
                 CACUUACAUCUUCAU 
                 3183 
               
               
                 887376 
                 1684026. 
                   
                 CAUUCUGdTdT 
                   
                   
                 AAGUGdTdT 
                 UCUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 293 
                 CUUACAUCUUCA 
                 A-1684029.1 
                 294 
                 UCCAGAAUGAAGAU 
                 CUUACAUCUUCAUUC 
                 3184 
               
               
                 887377 
                 1684028. 
                   
                 UUCUGGAdTdT 
                   
                   
                 GUAAGdTdT 
                 UGGA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 295 
                 ACAUCUUCAUUC 
                 A-1684031.1 
                 296 
                 AUUUCCAGAAUGAA 
                 ACAUCUUCAUUCUGG 
                 3185 
               
               
                 887378 
                 1684030. 
                   
                 UGGAAAUdTdT 
                   
                   
                 GAUGUdTdT 
                 AAAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 297 
                 CAUCUUCAUUCU 
                 A-1684033.1 
                 298 
                 CAUUUCCAGAAUGAA 
                 CAUCUUCAUUCUGGA 
                 3186 
               
               
                 887379 
                 1684032. 
                   
                 GGAAAUGdTdT 
                   
                   
                 GAUGdTdT 
                 AAUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 299 
                 UCUUCAUUCUGG 
                 A-1684035.1 
                 300 
                 AGCAUUUCCAGAAU 
                 UCUUCAUUCUGGAAA 
                 3187 
               
               
                 887380 
                 1684034. 
                   
                 AAAUGCUdTdT 
                   
                   
                 GAAGAdTdT 
                 UGCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 301 
                 CUUCAUUCUGGA 
                 A-1684037.1 
                 302 
                 AAGCAUUUCCAGAAU 
                 CUUCAUUCUGGAAAU 
                 3188 
               
               
                 887381 
                 1684036. 
                   
                 AAUGCUUdTdT 
                   
                   
                 GAAGdTdT 
                 GCUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 303 
                 UCUGGAAAUGCU 
                 A-1684039.1 
                 304 
                 UUUUAGAAGCAUUU 
                 UCUGGAAAUGCUUCU 
                 3189 
               
               
                 887382 
                 1684038. 
                   
                 UCUAAAAdTdT 
                   
                   
                 CCAGAdTdT 
                 AAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 305 
                 GCUGGAUUUCCU 
                 A-1684041.1 
                 306 
                 AACAAUUAGGAAAUC 
                 GCUGGAUUUCCUAAU 
                 3190 
               
               
                 887383 
                 1684040. 
                   
                 AAUUGUUdTdT 
                   
                   
                 CAGCdTdT 
                 UGUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 307 
                 CUGGAUUUCCUA 
                 A-1684043.1 
                 308 
                 CAACAAUUAGGAAAU 
                 CUGGAUUUCCUAAUU 
                 3191 
               
               
                 887384 
                 1684042. 
                   
                 AUUGUUGdTdT 
                   
                   
                 CCAGdTdT 
                 GUUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 309 
                 CCUCUAAGAGCC 
                 A-1684045.1 
                 310 
                 UAGAUAAGGCUCUU 
                 CCUCUAAGAGCCUUA 
                 3192 
               
               
                 887385 
                 1684044. 
                   
                 UUAUCUAdTdT 
                   
                   
                 AGAGGdTdT 
                 UCUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 311 
                 CUCUAAGAGCCU 
                 A-1684047.1 
                 312 
                 CUAGAUAAGGCUCU 
                 CUCUAAGAGCCUUAU 
                 3193 
               
               
                 887386 
                 1684046. 
                   
                 UAUCUAGdTdT 
                   
                   
                 UAGAGdTdT 
                 CUAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 313 
                 CUUCCAUCAUGA 
                 A-1684049.1 
                 314 
                 AGCACAUUCAUGAU 
                 CUUCCAUCAUGAAUG 
                 3194 
               
               
                 887387 
                 1684048. 
                   
                 AUGUGCUdTdT 
                   
                   
                 GGAAGdTdT 
                 UGCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 315 
                 UUUCCUGCAAGU 
                 A-1684051.1 
                 316 
                 GAACUUGACUUGCA 
                 UUUCCUGCAAGUCAA 
                 3195 
               
               
                 887388 
                 1684050. 
                   
                 CAAGUUCdTdT 
                   
                   
                 GGAAAdTdT 
                 GUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 317 
                 CUGCAAGUCAAG 
                 A-1684053.1 
                 318 
                 UUUGGAACUUGACU 
                 CUGCAAGUCAAGUUC 
                 3196 
               
               
                 887389 
                 1684052. 
                   
                 UUCCAAAdTdT 
                   
                   
                 UGCAGdTdT 
                 CAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 319 
                 AGUCAAGUUCCA 
                 A-1684055.1 
                 320 
                 AACGAUUUGGAACU 
                 AGUCAAGUUCCAAAU 
                 3197 
               
               
                 887390 
                 1684054. 
                   
                 AAUCGUUdTdT 
                   
                   
                 UGACUdTdT 
                 CGUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 321 
                 ACUUGGUUACCU 
                 A-1684057.1 
                 322 
                 CAGAGAUAGGUAACC 
                 ACUUGGUUACCUAUC 
                 3198 
               
               
                 887391 
                 1684056. 
                   
                 AUCUCUGdTdT 
                   
                   
                 AAGUdTdT 
                 UCUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 323 
                 CUUGGUUACCUA 
                 A-1684059.1 
                 324 
                 GCAGAGAUAGGUAA 
                 CUUGGUUACCUAUCU 
                 3199 
               
               
                 887392 
                 1684058. 
                   
                 UCUCUGCdTdT 
                   
                   
                 CCAAGdTdT 
                 CUGC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 325 
                 GGUUACCUAUCU 
                 A-1684061.1 
                 326 
                 GAAGCAGAGAUAGG 
                 GGUUACCUAUCUCUG 
                 3200 
               
               
                 887393 
                 1684060. 
                   
                 CUGCUUCdTdT 
                   
                   
                 UAACCdTdT 
                 CUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 327 
                 GUUACCUAUCUC 
                 A-1684063.1 
                 328 
                 UGAAGCAGAGAUAG 
                 GUUACCUAUCUCUGC 
                 3201 
               
               
                 887394 
                 1684062. 
                   
                 UGCUUCAdTdT 
                   
                   
                 GUAACdTdT 
                 UUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 329 
                 UUACCUAUCUCU 
                 A-1684065.1 
                 330 
                 UUGAAGCAGAGAUA 
                 UUACCUAUCUCUGCU 
                 3202 
               
               
                 887395 
                 1684064. 
                   
                 GCUUCAAdTdT 
                   
                   
                 GGUAAdTdT 
                 UCAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 331 
                 UACCUAUCUCUG 
                 A-1684067.1 
                 332 
                 CUUGAAGCAGAGAU 
                 UACCUAUCUCUGCUU 
                 3203 
               
               
                 887396 
                 1684066. 
                   
                 CUUCAAGdTdT 
                   
                   
                 AGGUAdTdT 
                 CAAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 333 
                 ACCUAUCUCUGC 
                 A-1684069.1 
                 334 
                 ACUUGAAGCAGAGA 
                 ACCUAUCUCUGCUUC 
                 3204 
               
               
                 887397 
                 1684068. 
                   
                 UUCAAGUdTdT 
                   
                   
                 UAGGUdTdT 
                 AAGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 335 
                 CCUAUCUCUGCU 
                 A-1684071.1 
                 336 
                 AACUUGAAGCAGAG 
                 CCUAUCUCUGCUUCA 
                 3205 
               
               
                 887398 
                 1684070. 
                   
                 UCAAGUUdTdT 
                   
                   
                 AUAGGdTdT 
                 AGUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 337 
                 CUAUCUCUGCUU 
                 A-1684073.1 
                 338 
                 CAACUUGAAGCAGAG 
                 CUAUCUCUGCUUCAA 
                 3206 
               
               
                 887399 
                 1684072. 
                   
                 CAAGUUGdTdT 
                   
                   
                 AUAGdTdT 
                 GUUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 339 
                 AUCUCUGCUUCA 
                 A-1684075.1 
                 340 
                 UGCAACUUGAAGCA 
                 AUCUCUGCUUCAAGU 
                 3207 
               
               
                 887400 
                 1684074. 
                   
                 AGUUGCAdTdT 
                   
                   
                 GAGAUdTdT 
                 UGCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 341 
                 UCUCUGCUUCAA 
                 A-1684077.1 
                 342 
                 UUGCAACUUGAAGC 
                 UCUCUGCUUCAAGUU 
                 3208 
               
               
                 887401 
                 1684076. 
                   
                 GUUGCAAdTdT 
                   
                   
                 AGAGAdTdT 
                 GCAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 343 
                 CUCUGCUUCAAG 
                 A-1684079.1 
                 344 
                 GUUGCAACUUGAAG 
                 CUCUGCUUCAAGUUG 
                 3209 
               
               
                 887402 
                 1684078. 
                   
                 UUGCAACdTdT 
                   
                   
                 CAGAGdTdT 
                 CAAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 345 
                 UCUGCUUCAAGU 
                 A-1684081.1 
                 346 
                 AGUUGCAACUUGAA 
                 UCUGCUUCAAGUUGC 
                 3210 
               
               
                 887403 
                 1684080. 
                   
                 UGCAACUdTdT 
                   
                   
                 GCAGAdTdT 
                 AACU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 347 
                 UAUCAUCUUUGG 
                 A-1684083.1 
                 348 
                 GAAUGACCCAAAGAU 
                 UAUCAUCUUUGGGUC 
                 3211 
               
               
                 887404 
                 1684082. 
                   
                 GUCAUUCdTdT 
                   
                   
                 GAUAdTdT 
                 AUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 349 
                 AUCAUCUUUGGG 
                 A-1684085.1 
                 350 
                 AGAAUGACCCAAAGA 
                 AUCAUCUUUGGGUCA 
                 3212 
               
               
                 887405 
                 1684084. 
                   
                 UCAUUCUdTdT 
                   
                   
                 UGAUdTdT 
                 UUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 351 
                 UCAUCUUUGGG 
                 A-1684087.1 
                 352 
                 AAGAAUGACCCAAAG 
                 UCAUCUUUGGGUCAU 
                 3213 
               
               
                 887406 
                 1684086. 
                   
                 UCAUUCUUdTdT 
                   
                   
                 AUGAdTdT 
                 UCUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 353 
                 CAUCUUUGGGUC 
                 A-1684089.1 
                 354 
                 GAAGAAUGACCCAAA 
                 CAUCUUUGGGUCAUU 
                 3214 
               
               
                 887407 
                 1684088. 
                   
                 AUUCUUCdTdT 
                   
                   
                 GAUGdTdT 
                 CUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 355 
                 CUUUGGGUCAU 
                 A-1684091.1 
                 356 
                 AGUGAAGAAUGACCC 
                 CUUUGGGUCAUUCUU 
                 3215 
               
               
                 887408 
                 1684090. 
                   
                 UCUUCACUdTdT 
                   
                   
                 AAAGdTdT 
                 CACU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 357 
                 UUGGGUCAUUC 
                 A-1684093.1 
                 358 
                 AAAGUGAAGAAUGA 
                 UUGGGUCAUUCUUCA 
                 3216 
               
               
                 887409 
                 1684092. 
                   
                 UUCACUUUdTdT 
                   
                   
                 CCCAAdTdT 
                 CUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 359 
                 UGGGUCAUUCU 
                 A-1684095.1 
                 360 
                 CAAAGUGAAGAAUG 
                 UGGGUCAUUCUUCAC 
                 3217 
               
               
                 887410 
                 1684094. 
                   
                 UCACUUUGdTdT 
                   
                   
                 ACCCAdTdT 
                 UUUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 361 
                 GGGUCAUUCUUC 
                 A-1684097.1 
                 362 
                 UCAAAGUGAAGAAU 
                 GGGUCAUUCUUCACU 
                 3218 
               
               
                 887411 
                 1684096. 
                   
                 ACUUUGAdTdT 
                   
                   
                 GACCCdTdT 
                 UUGA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 363 
                 GGUCAUUCUUCA 
                 A-1684099.1 
                 364 
                 UUCAAAGUGAAGAA 
                 GGUCAUUCUUCACUU 
                 3219 
               
               
                 887412 
                 1684098. 
                   
                 CUUUGAAdTdT 
                   
                   
                 UGACCdTdT 
                 UGAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 365 
                 GUCAUUCUUCAC 
                 A-1684101.1 
                 366 
                 GUUCAAAGUGAAGA 
                 GUCAUUCUUCACUUU 
                 3220 
               
               
                 887413 
                 1684100. 
                   
                 UUUGAACdTdT 
                   
                   
                 AUGACdTdT 
                 GAAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 367 
                 CAUUCUUCACUU 
                 A-1684103.1 
                 368 
                 AAGUUCAAAGUGAA 
                 CAUUCUUCACUUUGA 
                 3221 
               
               
                 887414 
                 1684102. 
                   
                 UGAACUUdTdT 
                   
                   
                 GAAUGdTdT 
                 ACUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 369 
                 UCACUUUGAACU 
                 A-1684105.1 
                 370 
                 AUGAACAAGUUCAAA 
                 UCACUUUGAACUUGU 
                 3222 
               
               
                 887415 
                 1684104. 
                   
                 UGUUCAUdTdT 
                   
                   
                 GUGAdTdT 
                 UCAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 371 
                 CUUGUUCAUUG 
                 A-1684107.1 
                 372 
                 GAUGACACCAAUGAA 
                 CUUGUUCAUUGGUG 
                 3223 
               
               
                 887416 
                 1684106. 
                   
                 GUGUCAUCdTdT 
                   
                   
                 CAAGdTdT 
                 UCAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 373 
                 GUGUCAUCAUAG 
                 A-1684109.1 
                 374 
                 AAAUUAUCUAUGAU 
                 GUGUCAUCAUAGAUA 
                 3224 
               
               
                 887417 
                 1684108. 
                   
                 AUAAUUUdTdT 
                   
                   
                 GACACdTdT 
                 AUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 375 
                 UGUCAUCAUAGA 
                 A-1684111.1 
                 376 
                 GAAAUUAUCUAUGA 
                 UGUCAUCAUAGAUAA 
                 3225 
               
               
                 887418 
                 1684110. 
                   
                 UAAUUUCdTdT 
                   
                   
                 UGACAdTdT 
                 UUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 377 
                 GAGGUCAAGACA 
                 A-1684113.1 
                 378 
                 AUAAAGAUGUCUUG 
                 GAGGUCAAGACAUCU 
                 3226 
               
               
                 887419 
                 1684112. 
                   
                 UCUUUAUdTdT 
                   
                   
                 ACCUCdTdT 
                 UUAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 379 
                 AGGUCAAGACAU 
                 A-1684115.1 
                 380 
                 CAUAAAGAUGUCUU 
                 AGGUCAAGACAUCUU 
                 3227 
               
               
                 887420 
                 1684114. 
                   
                 CUUUAUGdTdT 
                   
                   
                 GACCUdTdT 
                 UAUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 381 
                 GGUCAAGACAUC 
                 A-1684117.1 
                 382 
                 UCAUAAAGAUGUCU 
                 GGUCAAGACAUCUUU 
                 3228 
               
               
                 887421 
                 1684116. 
                   
                 UUUAUGAdTdT 
                   
                   
                 UGACCdTdT 
                 AUGA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 383 
                 CCACAAAAGCCAA 
                 A-1684119.1 
                 384 
                 GAGGAAUUGGCUUU 
                 CCACAAAAGCCAAUUC 
                 3229 
               
               
                 887422 
                 1684118. 
                   
                 UUCCUCdTdT 
                   
                   
                 UGUGGdTdT 
                 cue 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 385 
                 GACCUAGUGACA 
                 A-1684121.1 
                 386 
                 CUUGAUUUGUCACU 
                 GACCUAGUGACAAAU 
                 3230 
               
               
                 887423 
                 1684120. 
                   
                 AAUCAAGdTdT 
                   
                   
                 AGGUCdTdT 
                 CAAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 387 
                 GUAUCAUGGUUC 
                 A-1684123.1 
                 388 
                 CAGAUAAGAACCAUG 
                 GUAUCAUGGUUCUUA 
                 3231 
               
               
                 887424 
                 1684122. 
                   
                 UUAUCUGdTdT 
                   
                   
                 AUACdTdT 
                 UCUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 389 
                 UAUCAUGGUUCU 
                 A-1684125.1 
                 390 
                 ACAGAUAAGAACCAU 
                 UAUCAUGGUUCUUAU 
                 3232 
               
               
                 887425 
                 1684124. 
                   
                 UAUCUGUdTdT 
                   
                   
                 GAUAdTdT 
                 CUGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 391 
                 UCAUGGUUCUUA 
                 A-1684127.1 
                 392 
                 AGACAGAUAAGAACC 
                 UCAUGGUUCUUAUCU 
                 3233 
               
               
                 887426 
                 1684126. 
                   
                 UCUGUCUdTdT 
                   
                   
                 AUGAdTdT 
                 GUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 393 
                 CAUGGUUCUUAU 
                 A-1684129.1 
                 394 
                 GAGACAGAUAAGAAC 
                 CAUGGUUCUUAUCUG 
                 3234 
               
               
                 887427 
                 1684128. 
                   
                 CUGUCUCdTdT 
                   
                   
                 CAUGdTdT 
                 UCUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 395 
                 AUGGUUCUUAUC 
                 A-1684131.1 
                 396 
                 UGAGACAGAUAAGA 
                 AUGGUUCUUAUCUGU 
                 3235 
               
               
                 887428 
                 1684130. 
                   
                 UGUCUCAdTdT 
                   
                   
                 ACCAUdTdT 
                 CUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 397 
                 UGGUUCUUAUC 
                 A-1684133.1 
                 398 
                 UUGAGACAGAUAAG 
                 UGGUUCUUAUCUGUC 
                 3236 
               
               
                 887429 
                 1684132. 
                   
                 UGUCUCAAdTdT 
                   
                   
                 AACCAdTdT 
                 UCAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 399 
                 GGUUCUUAUCU 
                 A-1684135.1 
                 400 
                 GUUGAGACAGAUAA 
                 GGUUCUUAUCUGUCU 
                 3237 
               
               
                 887430 
                 1684134. 
                   
                 GUCUCAACdTdT 
                   
                   
                 GAACCdTdT 
                 CAAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 401 
                 GUUCUUAUCUG 
                 A-1684137.1 
                 402 
                 UGUUGAGACAGAUA 
                 GUUCUUAUCUGUCUC 
                 3238 
               
               
                 887431 
                 1684136. 
                   
                 UCUCAACAdTdT 
                   
                   
                 AGAACdTdT 
                 AACA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 403 
                 UCUUAUCUGUCU 
                 A-1684139.1 
                 404 
                 CAUGUUGAGACAGA 
                 UCUUAUCUGUCUCAA 
                 3239 
               
               
                 887432 
                 1684138. 
                   
                 CAACAUGdTdT 
                   
                   
                 UAAGAdTdT 
                 CAUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 405 
                 AUCUGUCUCAAC 
                 A-1684141.1 
                 406 
                 UUACCAUGUUGAGA 
                 AUCUGUCUCAACAUG 
                 3240 
               
               
                 887433 
                 1684140. 
                   
                 AUGGUAAdTdT 
                   
                   
                 CAGAUdTdT 
                 GUAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 407 
                 UCUGUCUCAACA 
                 A-1684143.1 
                 408 
                 GUUACCAUGUUGAG 
                 UCUGUCUCAACAUGG 
                 3241 
               
               
                 887434 
                 1684142. 
                   
                 UGGUAACdTdT 
                   
                   
                 ACAGAdTdT 
                 UAAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 409 
                 CUGUCUCAACAU 
                 A-1684145.1 
                 410 
                 GGUUACCAUGUUGA 
                 CUGUCUCAACAUGGU 
                 3242 
               
               
                 887435 
                 1684144. 
                   
                 GGUAACCdTdT 
                   
                   
                 GACAGdTdT 
                 AACC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 411 
                 UCCUGGUCAUGU 
                 A-1684147.1 
                 412 
                 UAGAUGAACAUGACC 
                 UCCUGGUCAUGUUCA 
                 3243 
               
               
                 887436 
                 1684146. 
                   
                 UCAUCUAdTdT 
                   
                   
                 AGGAdTdT 
                 UCUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 413 
                 AGUUCAUCCUGG 
                 A-1684149.1 
                 414 
                 UGAACUUCCAGGAU 
                 AGUUCAUCCUGGAAG 
                 3244 
               
               
                 887437 
                 1684148. 
                   
                 AAGUUCAdTdT 
                   
                   
                 GAACUdTdT 
                 UUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 415 
                 CCAUCUGUUGGA 
                 A-1684151.1 
                 416 
                 AGAAUAUUCCAACAG 
                 CCAUCUGUUGGAAUA 
                 3245 
               
               
                 887438 
                 1684150. 
                   
                 AUAUUCUdTdT 
                   
                   
                 AUGGdTdT 
                 UUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 417 
                 CAUCUGUUGGAA 
                 A-1684153.1 
                 418 
                 UAGAAUAUUCCAACA 
                 CAUCUGUUGGAAUAU 
                 3246 
               
               
                 887439 
                 1684152. 
                   
                 UAUUCUAdTdT 
                   
                   
                 GAUGdTdT 
                 UCUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 419 
                 UCUGUUGGAAU 
                 A-1684155.1 
                 420 
                 AGUAGAAUAUUCCA 
                 UCUGUUGGAAUAUUC 
                 3247 
               
               
                 887440 
                 1684154. 
                   
                 AUUCUACUdTdT 
                   
                   
                 ACAGAdTdT 
                 UACU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 421 
                 CAUACUGGAGAA 
                 A-1684157.1 
                 422 
                 ACUAAAAUUCUCCAG 
                 CAUACUGGAGAAUUU 
                 3248 
               
               
                 887441 
                 1684156. 
                   
                 UUUUAGUdTdT 
                   
                   
                 UAUGdTdT 
                 UAGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 423 
                 CUCCUCUUCUCA 
                 A-1684159.1 
                 424 
                 UUUGCUAUGAGAAG 
                 CUCCUCUUCUCAUAG 
                 3249 
               
               
                 887442 
                 1684158. 
                   
                 UAGCAAAdTdT 
                   
                   
                 AGGAGdTdT 
                 CAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 425 
                 UCCUCUUCUCAU 
                 A-1684161.1 
                 426 
                 UUUUGCUAUGAGAA 
                 UCCUCUUCUCAUAGC 
                 3250 
               
               
                 887443 
                 1684160. 
                   
                 AGCAAAAdTdT 
                   
                   
                 GAGGAdTdT 
                 AAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 427 
                 CCUCUUCUCAUA 
                 A-1684163.1 
                 428 
                 GUUUUGCUAUGAGA 
                 CCUCUUCUCAUAGCA 
                 3251 
               
               
                 887444 
                 1684162. 
                   
                 GCAAAACdTdT 
                   
                   
                 AGAGGdTdT 
                 AAAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 429 
                 CUCUUCUCAUAG 
                 A-1684165.1 
                 430 
                 GGUUUUGCUAUGAG 
                 CUCUUCUCAUAGCAA 
                 3252 
               
               
                 887445 
                 1684164. 
                   
                 CAAAACCdTdT 
                   
                   
                 AAGAGdTdT 
                 AACC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 431 
                 GAUCCAUUGUCU 
                 A-1684167.1 
                 432 
                 GAUGUCAAGACAAU 
                 GAUCCAUUGUCUUGA 
                 3253 
               
               
                 887446 
                 1684166. 
                   
                 UGACAUCdTdT 
                   
                   
                 GGAUCdTdT 
                 CAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 433 
                 AUCCAUUGUCUU 
                 A-1684169.1 
                 434 
                 AGAUGUCAAGACAA 
                 AUCCAUUGUCUUGAC 
                 3254 
               
               
                 887447 
                 1684168. 
                   
                 GACAUCUdTdT 
                   
                   
                 UGGAUdTdT 
                 AUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 435 
                 UCCAUUGUCUUG 
                 A-1684171.1 
                 436 
                 AAGAUGUCAAGACAA 
                 UCCAUUGUCUUGACA 
                 3255 
               
               
                 887448 
                 1684170. 
                   
                 ACAUCUUdTdT 
                   
                   
                 UGGAdTdT 
                 UCUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 437 
                 CAUUGUCUUGAC 
                 A-1684173.1 
                 438 
                 AUAAGAUGUCAAGA 
                 CAUUGUCUUGACAUC 
                 3256 
               
               
                 887449 
                 1684172. 
                   
                 AUCUUAUdTdT 
                   
                   
                 CAAUGdTdT 
                 UUAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 439 
                 UUGUCUUGACAU 
                 A-1684175.1 
                 440 
                 AAAUAAGAUGUCAA 
                 UUGUCUUGACAUCUU 
                 3257 
               
               
                 887450 
                 1684174. 
                   
                 CUUAUUUdTdT 
                   
                   
                 GACAAdTdT 
                 AUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 441 
                 UGUCUUGACAUC 
                 A-1684177.1 
                 442 
                 CAAAUAAGAUGUCAA 
                 UGUCUUGACAUCUUA 
                 3258 
               
               
                 887451 
                 1684176. 
                   
                 UUAUUUGdTdT 
                   
                   
                 GACAdTdT 
                 UUUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 443 
                 GUCUUGACAUCU 
                 A-1684179.1 
                 444 
                 GCAAAUAAGAUGUC 
                 GUCUUGACAUCUUAU 
                 3259 
               
               
                 887452 
                 1684178. 
                   
                 UAUUUGCdTdT 
                   
                   
                 AAGACdTdT 
                 UUGC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 445 
                 GGAGAUGGAUUC 
                 A-1684181.1 
                 446 
                 ACGAAGAGAAUCCAU 
                 GGAGAUGGAUUCUCU 
                 3260 
               
               
                 887453 
                 1684180. 
                   
                 UCUUCGUdTdT 
                   
                   
                 CUCCdTdT 
                 UCGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 447 
                 GAGAUGGAUUCU 
                 A-1684183.1 
                 448 
                 AACGAAGAGAAUCCA 
                 GAGAUGGAUUCUCUU 
                 3261 
               
               
                 887454 
                 1684182. 
                   
                 CUUCGUUdTdT 
                   
                   
                 UCUCdTdT 
                 CGUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 449 
                 AGAUGGAUUCUC 
                 A-1684185.1 
                 450 
                 GAACGAAGAGAAUCC 
                 AGAUGGAUUCUCUUC 
                 3262 
               
               
                 887455 
                 1684184. 
                   
                 UUCGUUCdTdT 
                   
                   
                 AUCUdTdT 
                 GUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 451 
                 GAUGGAUUCUCU 
                 A-1684187.1 
                 452 
                 UGAACGAAGAGAAU 
                 GAUGGAUUCUCUUCG 
                 3263 
               
               
                 887456 
                 1684186. 
                   
                 UCGUUCAdTdT 
                   
                   
                 CCAUCdTdT 
                 UUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 453 
                 AUGGAUUCUCUU 
                 A-1684189.1 
                 454 
                 GUGAACGAAGAGAA 
                 AUGGAUUCUCUUCGU 
                 3264 
               
               
                 887457 
                 1684188. 
                   
                 CGUUCACdTdT 
                   
                   
                 UCCAUdTdT 
                 UCAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 455 
                 UGGAUUCUCUUC 
                 A-1684191.1 
                 456 
                 UGUGAACGAAGAGA 
                 UGGAUUCUCUUCGUU 
                 3265 
               
               
                 887458 
                 1684190. 
                   
                 GUUCACAdTdT 
                   
                   
                 AUCCAdTdT 
                 CACA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 457 
                 GGAUUCUCUUCG 
                 A-1684193.1 
                 458 
                 CUGUGAACGAAGAG 
                 GGAUUCUCUUCGUUC 
                 3266 
               
               
                 887459 
                 1684192. 
                   
                 UUCACAGdTdT 
                   
                   
                 AAUCCdTdT 
                 ACAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 459 
                 GAUUCUCUUCGU 
                 A-1684195.1 
                 460 
                 UCUGUGAACGAAGA 
                 GAUUCUCUUCGUUCA 
                 3267 
               
               
                 887460 
                 1684194. 
                   
                 UCACAGAdTdT 
                   
                   
                 GAAUCdTdT 
                 CAGA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 461 
                 UUCUCUUCGUUC 
                 A-1684197.1 
                 462 
                 CAUCUGUGAACGAA 
                 UUCUCUUCGUUCACA 
                 3268 
               
               
                 887461 
                 1684196. 
                   
                 ACAGAUGdTdT 
                   
                   
                 GAGAAdTdT 
                 GAUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 463 
                 UCUCUUCGUUCA 
                 A-1684199.1 
                 464 
                 CCAUCUGUGAACGAA 
                 UCUCUUCGUUCACAG 
                 3269 
               
               
                 887462 
                 1684198. 
                   
                 CAGAUGGdTdT 
                   
                   
                 GAGAdTdT 
                 AUGG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 465 
                 CUCUUCGUUCAC 
                 A-1684201.1 
                 466 
                 UCCAUCUGUGAACGA 
                 CUCUUCGUUCACAGA 
                 3270 
               
               
                 887463 
                 1684200. 
                   
                 AGAUGGAdTdT 
                   
                   
                 AGAGdTdT 
                 UGGA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 467 
                 UCUUCGUUCACA 
                 A-1684203.1 
                 468 
                 UUCCAUCUGUGAAC 
                 UCUUCGUUCACAGAU 
                 3271 
               
               
                 887464 
                 1684202. 
                   
                 GAUGGAAdTdT 
                   
                   
                 GAAGAdTdT 
                 GGAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 469 
                 AGGUUCAUGUCU 
                 A-1684205.1 
                 470 
                 GAUUUGCAGACAUG 
                 AGGUUCAUGUCUGCA 
                 3272 
               
               
                 887465 
                 1684204. 
                   
                 GCAAAUCdTdT 
                   
                   
                 AACCUdTdT 
                 AAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 471 
                 UCUGCAAAUCCU 
                 A-1684207.1 
                 472 
                 CUUUGGAAGGAUUU 
                 UCUGCAAAUCCUUCC 
                 3273 
               
               
                 887466 
                 1684206. 
                   
                 UCCAAAGdTdT 
                   
                   
                 GCAGAdTdT 
                 AAAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 473 
                 CUGCAAAUCCUU 
                 A-1684209.1 
                 474 
                 ACUUUGGAAGGAUU 
                 CUGCAAAUCCUUCCA 
                 3274 
               
               
                 887467 
                 1684208. 
                   
                 CCAAAGUdTdT 
                   
                   
                 UGCAGdTdT 
                 AAGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 475 
                 GUGUCUGCUACU 
                 A-1684211.1 
                 476 
                 GAAUGACAGUAGCA 
                 GUGUCUGCUACUGUC 
                 3275 
               
               
                 887468 
                 1684210. 
                   
                 GUCAUUCdTdT 
                   
                   
                 GACACdTdT 
                 AUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 477 
                 UGUCUGCUACUG 
                 A-1684213.1 
                 478 
                 UGAAUGACAGUAGC 
                 UGUCUGCUACUGUCA 
                 3276 
               
               
                 887469 
                 1684212. 
                   
                 UCAUUCAdTdT 
                   
                   
                 AGACAdTdT 
                 UUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 479 
                 GUCUGCUACUGU 
                 A-1684215.1 
                 480 
                 CUGAAUGACAGUAG 
                 GUCUGCUACUGUCAU 
                 3277 
               
               
                 887470 
                 1684214. 
                   
                 CAUUCAGdTdT 
                   
                   
                 CAGACdTdT 
                 UCAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 481 
                 ACCGCUUAAGGC 
                 A-1684217.1 
                 482 
                 ACAUUUUGCCUUAA 
                 ACCGCUUAAGGCAAA 
                 3278 
               
               
                 887471 
                 1684216. 
                   
                 AAAAUGUdTdT 
                   
                   
                 GCGGUdTdT 
                 AUGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 483 
                 CCGCUUAAGGCA 
                 A-1684219.1 
                 484 
                 GACAUUUUGCCUUA 
                 CCGCUUAAGGCAAAA 
                 3279 
               
               
                 887472 
                 1684218. 
                   
                 AAAUGUCdTdT 
                   
                   
                 AGCGGdTdT 
                 UGUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 485 
                 UCUCCACCUUCA 
                 A-1684221.1 
                 486 
                 UAUCAUAUGAAGGU 
                 UCUCCACCUUCAUAU 
                 3280 
               
               
                 887473 
                 1684220. 
                   
                 UAUGAUAdTdT 
                   
                   
                 GGAGAdTdT 
                 GAUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 487 
                 UGCCAAAAUCCU 
                 A-1684223.1 
                 488 
                 GAUAAAAAGGAUUU 
                 UGCCAAAAUCCUUUU 
                 3281 
               
               
                 887474 
                 1684222. 
                   
                 UUUUAUCdTdT 
                   
                   
                 UGGCAdTdT 
                 UAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 489 
                 GCCAAAAUCCUU 
                 A-1684225.1 
                 490 
                 UGAUAAAAAGGAUU 
                 GCCAAAAUCCUUUUU 
                 3282 
               
               
                 887475 
                 1684224. 
                   
                 UUUAUCAdTdT 
                   
                   
                 UUGGCdTdT 
                 AUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 491 
                 UCGUAAGAGAAC 
                 A-1684227.1 
                 492 
                 CUACAGAGUUCUCU 
                 UCGUAAGAGAACUCU 
                 3283 
               
               
                 887476 
                 1684226. 
                   
                 UCUGUAGdTdT 
                   
                   
                 UACGAdTdT 
                 GUAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 493 
                 UCUGCCUUGUCA 
                 A-1684229.1 
                 494 
                 GAAAAGAUGACAAG 
                 UCUGCCUUGUCAUCU 
                 3284 
               
               
                 887477 
                 1684228. 
                   
                 UCUUUUCdTdT 
                   
                   
                 GCAGAdTdT 
                 UUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 495 
                 CUGCCUUGUCAU 
                 A-1684231.1 
                 496 
                 UGAAAAGAUGACAA 
                 CUGCCUUGUCAUCUU 
                 3285 
               
               
                 887478 
                 1684230. 
                   
                 CUUUUCAdTdT 
                   
                   
                 GGCAGdTdT 
                 UUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 497 
                 UGCCUUGUCAUC 
                 A-1684233.1 
                 498 
                 GUGAAAAGAUGACA 
                 UGCCUUGUCAUCUUU 
                 3286 
               
               
                 887479 
                 1684232. 
                   
                 UUUUCACdTdT 
                   
                   
                 AGGCAdTdT 
                 UCAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 499 
                 GCCUUGUCAUCU 
                 A-1684235.1 
                 500 
                 UGUGAAAAGAUGAC 
                 GCCUUGUCAUCUUUU 
                 3287 
               
               
                 887480 
                 1684234. 
                   
                 UUUCACAdTdT 
                   
                   
                 AAGGCdTdT 
                 CACA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 501 
                 CCUUGUCAUCUU 
                 A-1684237.1 
                 502 
                 CUGUGAAAAGAUGA 
                 CCUUGUCAUCUUUUC 
                 3288 
               
               
                 887481 
                 1684236. 
                   
                 UUCACAGdTdT 
                   
                   
                 CAAGGdTdT 
                 ACAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 503 
                 CAUCUUUUCACA 
                 A-1684239.1 
                 504 
                 ACAAUCCUGUGAAAA 
                 CAUCUUUUCACAGGA 
                 3289 
               
               
                 887482 
                 1684238. 
                   
                 GGAUUGUdTdT 
                   
                   
                 GAUGdTdT 
                 UUGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 505 
                 CCCAUGUAAAUA 
                 A-1684241.1 
                 506 
                 UGUUGUUUAUUUAC 
                 CCCAUGUAAAUAAAC 
                 3290 
               
               
                 887483 
                 1684240. 
                   
                 AACAACAdTdT 
                   
                   
                 AUGGGdTdT 
                 AACA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 507 
                 CAUUCAUCUUGA 
                 A-1684243.1 
                 508 
                 AUGUGAGUCAAGAU 
                 CAUUCAUCUUGACUC 
                 3291 
               
               
                 887484 
                 1684242. 
                   
                 CUCACAUdTdT 
                   
                   
                 GAAUGdTdT 
                 ACAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 509 
                 ACAUAUUACACU 
                 A-1684245.1 
                 510 
                 UUUGAGGAGUGUAA 
                 ACAUAUUACACUCCU 
                 3292 
               
               
                 887485 
                 1684244. 
                   
                 CCUCAAAdTdT 
                   
                   
                 UAUGUdTdT 
                 CAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 511 
                 CAUAUUACACUC 
                 A-1684247.1 
                 512 
                 UUUUGAGGAGUGUA 
                 CAUAUUACACUCCUC 
                 3293 
               
               
                 887486 
                 1684246. 
                   
                 CUCAAAAdTdT 
                   
                   
                 AUAUGdTdT 
                 AAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 513 
                 UGCCCAAAAUAC 
                 A-1684249.1 
                 514 
                 AUUAUCAGUAUUUU 
                 UGCCCAAAAUACUGA 
                 3294 
               
               
                 887487 
                 1684248. 
                   
                 UGAUAAUdTdT 
                   
                   
                 GGGCAdTdT 
                 UAAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 515 
                 GCCCAAAAUACU 
                 A-1684251.1 
                 516 
                 UAUUAUCAGUAUUU 
                 GCCCAAAAUACUGAU 
                 3295 
               
               
                 887488 
                 1684250. 
                   
                 GAUAAUAdTdT 
                   
                   
                 UGGGCdTdT 
                 AAUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 517 
                 CUGAUAAUAGUC 
                 A-1684253.1 
                 518 
                 UUUAAGAGACUAUU 
                 CUGAUAAUAGUCUCU 
                 3296 
               
               
                 887489 
                 1684252. 
                   
                 UCUUAAAdTdT 
                   
                   
                 AUCAGdTdT 
                 UAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 519 
                 GUCAAAUUUUCC 
                 A-1684255.1 
                 520 
                 GAAAGCAGGAAAAU 
                 GUCAAAUUUUCCUGC 
                 3297 
               
               
                 887490 
                 1684254. 
                   
                 UGCUUUCdTdT 
                   
                   
                 UUGACdTdT 
                 UUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 521 
                 UCAAAUUUUCCU 
                 A-1684257.1 
                 522 
                 AGAAAGCAGGAAAAU 
                 UCAAAUUUUCCUGCU 
                 3298 
               
               
                 887491 
                 1684256. 
                   
                 GCUUUCUdTdT 
                   
                   
                 UUGAdTdT 
                 UUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 523 
                 CAAAUUUUCCUG 
                 A-1684259.1 
                 524 
                 AAGAAAGCAGGAAAA 
                 CAAAUUUUCCUGCUU 
                 3299 
               
               
                 887492 
                 1684258. 
                   
                 CUUUCUUdTdT 
                   
                   
                 UUUGdTdT 
                 UCUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 525 
                 AUUGUUUAGUC 
                 A-1684261.1 
                 526 
                 GAAAGGAUGACUAA 
                 AUUGUUUAGUCAUCC 
                 3300 
               
               
                 887493 
                 1684260. 
                   
                 AUCCUUUCdTdT 
                   
                   
                 ACAAUdTdT 
                 UUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 527 
                 GCAUCACUUGUA 
                 A-1684263.1 
                 528 
                 GAUUGUAUACAAGU 
                 GCAUCACUUGUAUAC 
                 3301 
               
               
                 887494 
                 1684262. 
                   
                 UACAAUCdTdT 
                   
                   
                 GAUGCdTdT 
                 AAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 529 
                 CACCAACUUACU 
                 A-1684265.1 
                 530 
                 UUAGGAAAGUAAGU 
                 CACCAACUUACUUUC 
                 3302 
               
               
                 887495 
                 1684264. 
                   
                 UUCCUAAdTdT 
                   
                   
                 UGGUGdTdT 
                 CUAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 531 
                 ACCAACUUACUU 
                 A-1684267.1 
                 532 
                 UUUAGGAAAGUAAG 
                 ACCAACUUACUUUCC 
                 3303 
               
               
                 887496 
                 1684266. 
                   
                 UCCUAAAdTdT 
                   
                   
                 UUGGUdTdT 
                 UAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 533 
                 CCAACUUACUUU 
                 A-1684269.1 
                 534 
                 AUUUAGGAAAGUAA 
                 CCAACUUACUUUCCU 
                 3304 
               
               
                 887497 
                 1684268. 
                   
                 CCUAAAUdTdT 
                   
                   
                 GUUGGdTdT 
                 AAAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 535 
                 CAACUUACUUUC 
                 A-1684271.1 
                 536 
                 AAUUUAGGAAAGUA 
                 CAACUUACUUUCCUA 
                 3305 
               
               
                 887498 
                 1684270. 
                   
                 CUAAAUUdTdT 
                   
                   
                 AGUUGdTdT 
                 AAUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 537 
                 AGGAAGAUGUCA 
                 A-1684273.1 
                 538 
                 GAGAAGGUGACAUC 
                 AGGAAGAUGUCACCU 
                 3306 
               
               
                 887499 
                 1684272. 
                   
                 CCUUCUCdTdT 
                   
                   
                 UUCCUdTdT 
                 UCUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 539 
                 GAAGAUGUCACC 
                 A-1684275.1 
                 540 
                 AGGAGAAGGUGACA 
                 GAAGAUGUCACCUUC 
                 3307 
               
               
                 887500 
                 1684274. 
                   
                 UUCUCCUdTdT 
                   
                   
                 UCUUCdTdT 
                 UCCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 541 
                 AGAUGUCACCUU 
                 A-1684277.1 
                 542 
                 UAAGGAGAAGGUGA 
                 AGAUGUCACCUUCUC 
                 3308 
               
               
                 887501 
                 1684276. 
                   
                 CUCCUUAdTdT 
                   
                   
                 CAUCUdTdT 
                 CUUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 543 
                 GAUGUCACCUUC 
                 A-1684279.1 
                 544 
                 UUAAGGAGAAGGUG 
                 GAUGUCACCUUCUCC 
                 3309 
               
               
                 887502 
                 1684278. 
                   
                 UCCUUAAdTdT 
                   
                   
                 ACAUCdTdT 
                 UUAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 545 
                 AUGUCACCUUCU 
                 A-1684281.1 
                 546 
                 UUUAAGGAGAAGGU 
                 AUGUCACCUUCUCCU 
                 3310 
               
               
                 887503 
                 1684280. 
                   
                 CCUUAAAdTdT 
                   
                   
                 GACAUdTdT 
                 UAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 547 
                 UGUCACCUUCUC 
                 A-1684283.1 
                 548 
                 UUUUAAGGAGAAGG 
                 UGUCACCUUCUCCUU 
                 3311 
               
               
                 887504 
                 1684282. 
                   
                 CUUAAAAdTdT 
                   
                   
                 UGACAdTdT 
                 AAAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 549 
                 GUCACCUUCUCC 
                 A-1684285.1 
                 550 
                 AUUUUAAGGAGAAG 
                 GUCACCUUCUCCUUA 
                 3312 
               
               
                 887505 
                 1684284. 
                   
                 UUAAAAUdTdT 
                   
                   
                 GUGACdTdT 
                 AAAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 551 
                 UCACCUUCUCCU 
                 A-1684287.1 
                 552 
                 AAUUUUAAGGAGAA 
                 UCACCUUCUCCUUAA 
                 3313 
               
               
                 887506 
                 1684286. 
                   
                 UAAAAUUdTdT 
                   
                   
                 GGUGAdTdT 
                 AAUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 553 
                 ACCUUCUCCUUA 
                 A-1684289.1 
                 554 
                 AGAAUUUUAAGGAG 
                 ACCUUCUCCUUAAAA 
                 3314 
               
               
                 887507 
                 1684288. 
                   
                 AAAUUCUdTdT 
                   
                   
                 AAGGUdTdT 
                 UUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 555 
                 CCUUCUCCUUAA 
                 A-1684291.1 
                 556 
                 UAGAAUUUUAAGGA 
                 CCUUCUCCUUAAAAU 
                 3315 
               
               
                 887508 
                 1684290. 
                   
                 AAUUCUAdTdT 
                   
                   
                 GAAGGdTdT 
                 UCUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 557 
                 CUUCUCCUUAAA 
                 A-1684293.1 
                 558 
                 AUAGAAUUUUAAGG 
                 CUUCUCCUUAAAAUU 
                 3316 
               
               
                 887509 
                 1684292. 
                   
                 AUUCUAUdTdT 
                   
                   
                 AGAAGdTdT 
                 CUAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 559 
                 UGAGAUCUUUCU 
                 A-1684295.1 
                 560 
                 UUAUAGAAGAAAGA 
                 UGAGAUCUUUCUUCU 
                 3317 
               
               
                 887510 
                 1684294. 
                   
                 UCUAUAAdTdT 
                   
                   
                 UCUCAdTdT 
                 AUAA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 561 
                 GAUCUUUCUUCU 
                 A-1684297.1 
                 562 
                 ACUUUAUAGAAGAA 
                 GAUCUUUCUUCUAUA 
                 3318 
               
               
                 887511 
                 1684296. 
                   
                 AUAAAGUdTdT 
                   
                   
                 AGAUCdTdT 
                 AAGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 563 
                 UACCAUCUUAGG 
                 A-1684299.1 
                 564 
                 GAAUGAACCUAAGA 
                 UACCAUCUUAGGUUC 
                 3319 
               
               
                 887512 
                 1684298. 
                   
                 UUCAUUCdTdT 
                   
                   
                 UGGUAdTdT 
                 AUUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 565 
                 ACCAUCUUAGGU 
                 A-1684301.1 
                 566 
                 UGAAUGAACCUAAG 
                 ACCAUCUUAGGUUCA 
                 3320 
               
               
                 887513 
                 1684300. 
                   
                 UCAUUCAdTdT 
                   
                   
                 AUGGUdTdT 
                 UUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 567 
                 CCAUCUUAGGUU 
                 A-1684303.1 
                 568 
                 AUGAAUGAACCUAA 
                 CCAUCUUAGGUUCAU 
                 3321 
               
               
                 887514 
                 1684302. 
                   
                 CAUUCAUdTdT 
                   
                   
                 GAUGGdTdT 
                 UCAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 569 
                 CAUCUUAGGUUC 
                 A-1684305.1 
                 570 
                 GAUGAAUGAACCUA 
                 CAUCUUAGGUUCAUU 
                 3322 
               
               
                 887515 
                 1684304. 
                   
                 AUUCAUCdTdT 
                   
                   
                 AGAUGdTdT 
                 CAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 571 
                 UCUUAGGUUCAU 
                 A-1684307.1 
                 572 
                 AAGAUGAAUGAACC 
                 UCUUAGGUUCAUUCA 
                 3323 
               
               
                 887516 
                 1684306. 
                   
                 UCAUCUUdTdT 
                   
                   
                 UAAGAdTdT 
                 UCUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 573 
                 CUUAGGUUCAUU 
                 A-1684309.1 
                 574 
                 UAAGAUGAAUGAAC 
                 CUUAGGUUCAUUCAU 
                 3324 
               
               
                 887517 
                 1684308. 
                   
                 CAUCUUAdTdT 
                   
                   
                 CUAAGdTdT 
                 CUUA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 575 
                 UUAGGUUCAUUC 
                 A-1684311.1 
                 576 
                 CUAAGAUGAAUGAA 
                 UUAGGUUCAUUCAUC 
                 3325 
               
               
                 887518 
                 1684310. 
                   
                 AUCUUAGdTdT 
                   
                   
                 CCUAAdTdT 
                 UUAG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 577 
                 UAGGUUCAUUCA 
                 A-1684313.1 
                 578 
                 CCUAAGAUGAAUGA 
                 UAGGUUCAUUCAUCU 
                 3326 
               
               
                 887519 
                 1684312. 
                   
                 UCUUAGGdTdT 
                   
                   
                 ACCUAdTdT 
                 UAGG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 579 
                 CUGCAUUAUGAA 
                 A-1684315.1 
                 580 
                 GUAAGUAUUCAUAA 
                 CUGCAUUAUGAAUAC 
                 3327 
               
               
                 887520 
                 1684314. 
                   
                 UACUUACdTdT 
                   
                   
                 UGCAGdTdT 
                 UUAC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 581 
                 ACACAAUUUCUU 
                 A-1684317.1 
                 582 
                 UGCUAAGAAGAAAU 
                 ACACAAUUUCUUCUU 
                 3328 
               
               
                 887521 
                 1684316. 
                   
                 CUUAGCAdTdT 
                   
                   
                 UGUGUdTdT 
                 AGCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 583 
                 GUUCUUUUUCC 
                 A-1684319.1 
                 584 
                 AUGAAAUAGGAAAA 
                 GUUCUUUUUCCUAUU 
                 3329 
               
               
                 887522 
                 1684318. 
                   
                 UAUUUCAUdTdT 
                   
                   
                 AGAACdTdT 
                 UCAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 585 
                 UCCUAUUUCAUG 
                 A-1684321.1 
                 586 
                 CAUAGUUCAUGAAA 
                 UCCUAUUUCAUGAAC 
                 3330 
               
               
                 887523 
                 1684320. 
                   
                 AACUAUGdTdT 
                   
                   
                 UAGGAdTdT 
                 UAUG 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 587 
                 CCUAUUUCAUGA 
                 A-1684323.1 
                 588 
                 ACAUAGUUCAUGAA 
                 CCUAUUUCAUGAACU 
                 3331 
               
               
                 887524 
                 1684322. 
                   
                 ACUAUGUdTdT 
                   
                   
                 AUAGGdTdT 
                 AUGU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 589 
                 AUGUCUACUUGU 
                 A-1684325.1 
                 590 
                 AAAAGUCACAAGUAG 
                 AUGUCUACUUGUGAC 
                 3332 
               
               
                 887525 
                 1684324. 
                   
                 GACUUUUdTdT 
                   
                   
                 ACAUdTdT 
                 UUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 591 
                 UGUCUACUUGU 
                 A-1684327.1 
                 592 
                 AAAAAGUCACAAGUA 
                 UGUCUACUUGUGACU 
                 3333 
               
               
                 887526 
                 1684326. 
                   
                 GACUUUUUdTdT 
                   
                   
                 GACAdTdT 
                 UUUU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 593 
                 UCUACUUGUGAC 
                 A-1684329.1 
                 594 
                 AUAAAAAGUCACAAG 
                 UCUACUUGUGACUUU 
                 3334 
               
               
                 887527 
                 1684328. 
                   
                 UUUUUAUdTdT 
                   
                   
                 UAGAdTdT 
                 UUAU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 595 
                 CUACUUGUGACU 
                 A-1684331.1 
                 596 
                 GAUAAAAAGUCACAA 
                 CUACUUGUGACUUUU 
                 3335 
               
               
                 887528 
                 1684330. 
                   
                 UUUUAUCdTdT 
                   
                   
                 GUAGdTdT 
                 UAUC 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 597 
                 GUUCUAAAUAGC 
                 A-1684333.1 
                 598 
                 UGAAAUAGCUAUUU 
                 GUUCUAAAUAGCUAU 
                 3336 
               
               
                 887529 
                 1684332. 
                   
                 UAUUUCAdTdT 
                   
                   
                 AGAACdTdT 
                 UUCA 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 599 
                 GCUGUUUACAUA 
                 A-1684335.1 
                 600 
                 AGAAUCCUAUGUAA 
                 GCUGUUUACAUAGGA 
                 3337 
               
               
                 887530 
                 1684334. 
                   
                 GGAUUCUdTdT 
                   
                   
                 ACAGCdTdT 
                 UUCU 
                   
               
               
                   
                 1 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 601 
                 GCUCAAAAUGUU 
                 A-1684337.1 
                 602 
                 AAACUCAAACAUUUU 
                 GCUCAAAAUGUUUGA 
                 3338 
               
               
                 887531 
                 1684336. 
                   
                 UGAGUUUdTdT 
                   
                   
                 GAGCdTdT 
                 GUUU 
                   
               
               
                   
                 1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2B 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A Unmodified Single Strands and Duplex Sequences. 
               
               
                 Column 1 indicates duplex name. Column 2 indicates the sense sequence name. Column 3 indicates the sequence ID for the sequence of column 
               
               
                 4. Column 4 provides the unmodified sequence of a sense strand suitable for use in a duplex described herein. Column 5 provides the position in 
               
               
                 the target mRNA (NM_002977.3) of the sense strand of Column 4. Column 6 indicates the antisense sequence name. Column 7 indicates the 
               
               
                 sequence ID for the sequence of column 8. Column 8 provides the sequence of an antisense strand suitable for use in a duplex described herein, 
               
               
                 without specifying chemical modifications. Column 9 indicates the position in the target mRNA (NM_002977.3) that is complementary to the 
               
               
                 antisense strand of Column 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 Anti 
                 Seq ID 
                   
                   
               
               
                   
                 Sense 
                 Seq ID 
                   
                 mRNA target 
                 sense 
                 NO: 
                   
                 mRNA target 
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 range in 
                 sequence 
                 (anti 
                 antisense sequence 
                 range in 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 NM_002977.3 
                 name 
                 sense) 
                 (5′-3′) 
                 NM_002977.3 
               
               
                   
               
               
                 AD-887232 
                 A-1683738.1 
                  603 
                 UCACAAAACAGUCUCU 
                  342-360 
                 A- 
                  604 
                 GCAAGAGACUGU 
                  342-360 
               
               
                   
                   
                   
                 UGC 
                   
                 1683739.1 
                   
                 UUUGUGA 
                   
               
               
                   
               
               
                 AD-887233 
                 A-1683740.1 
                  605 
                 GGAAAACAAUCUUCCG 
                  579-597 
                 A- 
                  606 
                 AAACGGAAGAUU 
                  579-597 
               
               
                   
                   
                   
                 UUU 
                   
                 1683741.1 
                   
                 GUUUUCC 
                   
               
               
                   
               
               
                 AD-887234 
                 A-1683742.1 
                  607 
                 GAAAACAAUCUUCCGU 
                  580-598 
                 A- 
                  608 
                 GAAACGGAAGAU 
                  580-598 
               
               
                   
                   
                   
                 UUC 
                   
                 1683743.1 
                   
                 UGUUUUC 
                   
               
               
                   
               
               
                 AD-887235 
                 A-1683744.1 
                  609 
                 AAAACAAUCUUCCGUU 
                  581-599 
                 A- 
                  610 
                 UGAAACGGAAGA 
                  581-599 
               
               
                   
                   
                   
                 UCA 
                   
                 1683745.1 
                   
                 UUGUUUU 
                   
               
               
                   
               
               
                 AD-887236 
                 A-1683746.1 
                  611 
                 AAACAAUCUUCCGUUU 
                  582-600 
                 A- 
                  612 
                 UUGAAACGGAAG 
                  582-600 
               
               
                   
                   
                   
                 CAA 
                   
                 1683747.1 
                   
                 AUUGUUU 
                   
               
               
                   
               
               
                 AD-887237 
                 A-1683748.1 
                  613 
                 AACAAUCUUCCGUUUC 
                  583-601 
                 A- 
                  614 
                 AUUGAAACGGAA 
                  583-601 
               
               
                   
                   
                   
                 AAU 
                   
                 1683749.1 
                   
                 GAUUGUU 
                   
               
               
                   
               
               
                 AD-887238 
                 A-1683750.1 
                  615 
                 CAAUCUUCCGUUUCAA 
                  585-603 
                 A- 
                  616 
                 GCAUUGAAACGG 
                  585-603 
               
               
                   
                   
                   
                 UGC 
                   
                 1683751.1 
                   
                 AAGAUUG 
                   
               
               
                   
               
               
                 AD-887239 
                 A-1683752.1 
                  617 
                 CCUGCUUUAUAUAUGC 
                  608-626 
                 A- 
                  618 
                 AAAGCAUAUAUA 
                  608-626 
               
               
                   
                   
                   
                 UUU 
                   
                 1683753.1 
                   
                 AAGCAGG 
                   
               
               
                   
               
               
                 AD-887240 
                 A-1683754.1 
                  619 
                 CUGCUUUAUAUAUGC 
                  609-627 
                 A- 
                  620 
                 GAAAGCAUAUAU 
                  609-627 
               
               
                   
                   
                   
                 UUUC 
                   
                 1683755.1 
                   
                 AAAGCAG 
                   
               
               
                   
               
               
                 AD-887241 
                 A-1683756.1 
                  621 
                 UAUGCUUUCUCCUUUC 
                  619-637 
                 A- 
                  622 
                 ACUGAAAGGAGA 
                  619-637 
               
               
                   
                   
                   
                 AGU 
                   
                 1683757.1 
                   
                 AAGCAUA 
                   
               
               
                   
               
               
                 AD-887242 
                 A-1683758.1 
                  623 
                 AUGCUUUCUCCUUUCA 
                  620-638 
                 A- 
                  624 
                 GACUGAAAGGAG 
                  620-638 
               
               
                   
                   
                   
                 GUC 
                   
                 1683759.1 
                   
                 AAAGCAU 
                   
               
               
                   
               
               
                 AD-887243 
                 A-1683760.1 
                  625 
                 UGCUUUCUCCUUUCAG 
                  621-639 
                 A- 
                  626 
                 GGACUGAAAGGA 
                  621-639 
               
               
                   
                   
                   
                 UCC 
                   
                 1683761.1 
                   
                 GAAAGCA 
                   
               
               
                   
               
               
                 AD-887244 
                 A-1683762.1 
                  627 
                 CUUUCUCCUUUCAGUC 
                  623-641 
                 A- 
                  628 
                 GAGGACUGAAAG 
                  623-641 
               
               
                   
                   
                   
                 CUC 
                   
                 1683763.1 
                   
                 GAGAAAG 
                   
               
               
                   
               
               
                 AD-887245 
                 A-1683764.1 
                  629 
                 UCUCCUUUCAGUCCUC 
                  626-644 
                 A- 
                  630 
                 UUAGAGGACUGA 
                  626-644 
               
               
                   
                   
                   
                 UAA 
                   
                 1683765.1 
                   
                 AAGGAGA 
                   
               
               
                   
               
               
                 AD-887246 
                 A-1683766.1 
                  631 
                 CUCCUUUCAGUCCUCU 
                  627-645 
                 A- 
                  632 
                 CUUAGAGGACUG 
                  627-645 
               
               
                   
                   
                   
                 AAG 
                   
                 1683767.1 
                   
                 AAAGGAG 
                   
               
               
                   
               
               
                 AD-887247 
                 A-1683768.1 
                  633 
                 UCCUUUCAGUCCUCUA 
                  628-646 
                 A- 
                  634 
                 UCUUAGAGGACU 
                  628-646 
               
               
                   
                   
                   
                 AGA 
                   
                 1683769.1 
                   
                 GAAAGGA 
                   
               
               
                   
               
               
                 AD-887248 
                 A-1683770.1 
                  635 
                 CCUUUCAGUCCUCUAA 
                  629-647 
                 A- 
                  636 
                 UUCUUAGAGGAC 
                  629-647 
               
               
                   
                   
                   
                 GAA 
                   
                 1683771.1 
                   
                 UGAAAGG 
                   
               
               
                   
               
               
                 AD-887249 
                 A-1683772.1 
                  637 
                 CUUUCAGUCCUCUAAG 
                  630-648 
                 A- 
                  638 
                 CUUCUUAGAGGA 
                  630-648 
               
               
                   
                   
                   
                 AAG 
                   
                 1683773.1 
                   
                 CUGAAAG 
                   
               
               
                   
               
               
                 AD-887250 
                 A-1683774.1 
                  639 
                 AGUCCUCUAAGAAGAA 
                  635-653 
                 A- 
                  640 
                 AUAUUCUUCUUA 
                  635-653 
               
               
                   
                   
                   
                 UAU 
                   
                 1683775.1 
                   
                 GAGGACU 
                   
               
               
                   
               
               
                 AD-887251 
                 A-1683776.1 
                  641 
                 UCCUCUAAGAAGAAUA 
                  637-655 
                 A- 
                  642 
                 AGAUAUUCUUCU 
                  637-655 
               
               
                   
                   
                   
                 UCU 
                   
                 1683777.1 
                   
                 UAGAGGA 
                   
               
               
                   
               
               
                 AD-887252 
                 A-1683778.1 
                  643 
                 CCUCUAAGAAGAAUAU 
                  638-656 
                 A- 
                  644 
                 UAGAUAUUCUUC 
                  638-656 
               
               
                   
                   
                   
                 CUA 
                   
                 1683779.1 
                   
                 UUAGAGG 
                   
               
               
                   
               
               
                 AD-887253 
                 A-1683780.1 
                  645 
                 CUCUAAGAAGAAUAUC 
                  639-657 
                 A- 
                  646 
                 AUAGAUAUUCUU 
                  639-657 
               
               
                   
                   
                   
                 UAU 
                   
                 1683781.1 
                   
                 CUUAGAG 
                   
               
               
                   
               
               
                 AD-887254 
                 A-1683782.1 
                  647 
                 AUUUUAGUACACUCCU 
                  662-680 
                 A- 
                  648 
                 AUAAGGAGUGUA 
                  662-680 
               
               
                   
                   
                   
                 UAU 
                   
                 1683783.1 
                   
                 CUAAAAU 
                   
               
               
                   
               
               
                 AD-887255 
                 A-1683784.1 
                  649 
                 UAGUACACUCCUUAUU 
                  666-684 
                 A- 
                  650 
                 CUGAAUAAGGAG 
                  666-684 
               
               
                   
                   
                   
                 CAG 
                   
                 1683785.1 
                   
                 UGUACUA 
                   
               
               
                   
               
               
                 AD-887256 
                 A-1683786.1 
                  651 
                 AGUACACUCCUUAUUC 
                  667-685 
                 A- 
                  652 
                 GCUGAAUAAGGA 
                  667-685 
               
               
                   
                   
                   
                 AGC 
                   
                 1683787.1 
                   
                 GUGUACU 
                   
               
               
                   
               
               
                 AD-887257 
                 A-1683788.1 
                  653 
                 CCUUAUUCAGCAUGCU 
                  675-693 
                 A- 
                  654 
                 AUGAGCAUGCUG 
                  675-693 
               
               
                   
                   
                   
                 CAU 
                   
                 1683789.1 
                   
                 AAUAAGG 
                   
               
               
                   
               
               
                 AD-887258 
                 A-1683790.1 
                  655 
                 UCAUCAUGUGCACUAU 
                  690-708 
                 A- 
                  656 
                 AGAAUAGUGCAC 
                  690-708 
               
               
                   
                   
                   
                 UCU 
                   
                 1683791.1 
                   
                 AUGAUGA 
                   
               
               
                   
               
               
                 AD-887259 
                 A-1683792.1 
                  657 
                 CAUCAUGUGCACUAUU 
                  691-709 
                 A- 
                  658 
                 CAGAAUAGUGCA 
                  691-709 
               
               
                   
                   
                   
                 CUG 
                   
                 1683793.1 
                   
                 CAUGAUG 
                   
               
               
                   
               
               
                 AD-887260 
                 A-1683794.1 
                  659 
                 UGUCGAGUACACUUU 
                  760-778 
                 A- 
                  660 
                 AGUAAAAGUGUA 
                  760-778 
               
               
                   
                   
                   
                 UACU 
                   
                 1683795.1 
                   
                 CUCGACA 
                   
               
               
                   
               
               
                 AD-887261 
                 A-1683796.1 
                  661 
                 GUCGAGUACACUUUUA 
                  761-779 
                 A- 
                  662 
                 CAGUAAAAGUGU 
                  761-779 
               
               
                   
                   
                   
                 CUG 
                   
                 1683797.1 
                   
                 ACUCGAC 
                   
               
               
                   
               
               
                 AD-887262 
                 A-1683798.1 
                  663 
                 CUUCUGUGUAGGAGA 
                  823-841 
                 A- 
                  664 
                 GAAUUCUCCUAC 
                  823-841 
               
               
                   
                   
                   
                 AUUC 
                   
                 1683799.1 
                   
                 ACAGAAG 
                   
               
               
                   
               
               
                 AD-887263 
                 A-1683800.1 
                  665 
                 UAGGAGAAUUCACUU 
                  831-849 
                 A- 
                  666 
                 AGAAAAGUGAAU 
                  831-849 
               
               
                   
                   
                   
                 UUCU 
                   
                 1683801.1 
                   
                 UCUCCUA 
                   
               
               
                   
               
               
                 AD-887264 
                 A-1683802.1 
                  667 
                 AGGAGAAUUCACUUU 
                  832-850 
                 A- 
                  668 
                 AAGAAAAGUGAA 
                  832-850 
               
               
                   
                   
                   
                 UCUU 
                   
                 1683803.1 
                   
                 UUCUCCU 
                   
               
               
                   
               
               
                 AD-887265 
                 A-1683804.1 
                  669 
                 GGAGAAUUCACUUUUC 
                  833-851 
                 A- 
                  670 
                 GAAGAAAAGUGA 
                  833-851 
               
               
                   
                   
                   
                 UUC 
                   
                 1683805.1 
                   
                 AUUCUCC 
                   
               
               
                   
               
               
                 AD-887266 
                 A-1683806.1 
                  671 
                 GGCAAUGUUUCAGCUC 
                  920-938 
                 A- 
                  672 
                 GAAGAGCUGAAA 
                  920-938 
               
               
                   
                   
                   
                 UUC 
                   
                 1683807.1 
                   
                 CAUUGCC 
                   
               
               
                   
               
               
                 AD-887267 
                 A-1683808.1 
                  673 
                 AAUGUUUCAGCUCUUC 
                  923-941 
                 A- 
                  674 
                 UUCGAAGAGCUG 
                  923-941 
               
               
                   
                   
                   
                 GAA 
                   
                 1683809.1 
                   
                 AAACAUU 
                   
               
               
                   
               
               
                 AD-887268 
                 A-1683810.1 
                  675 
                 GUUUCAGCUCUUCGAA 
                  926-944 
                 A- 
                  676 
                 AAGUUCGAAGAG 
                  926-944 
               
               
                   
                   
                   
                 CUU 
                   
                 1683811.1 
                   
                 CUGAAAC 
                   
               
               
                   
               
               
                 AD-887269 
                 A-1683812.1 
                  677 
                 UCAGCUCUUCGAACUU 
                  929-947 
                 A- 
                  678 
                 UGAAAGUUCGAA 
                  929-947 
               
               
                   
                   
                   
                 UCA 
                   
                 1683813.1 
                   
                 GAGCUGA 
                   
               
               
                   
               
               
                 AD-887270 
                 A-1683814.1 
                  679 
                 AGCUCUUCGAACUUUC 
                  931-949 
                 A- 
                 5804 
                 UCUGAAAGUUCG 
                  931-949 
               
               
                   
                   
                   
                 AGA 
                   
                 1683815.1 
                   
                 AAGAGCU 
                   
               
               
                   
               
               
                 AD-887271 
                 A-1683816.1 
                 5805 
                 CUCUUCGAACUUUCAG 
                  933-951 
                 A- 
                 5806 
                 ACUCUGAAAGUU 
                  933-951 
               
               
                   
                   
                   
                 AGU 
                   
                 1683817.1 
                   
                 CGAAGAG 
                   
               
               
                   
               
               
                 AD-887272 
                 A-1683818.1 
                 5807 
                 CUUCGAACUUUCAGAG 
                  935-953 
                 A- 
                 5808 
                 AUACUCUGAAAG 
                  935-953 
               
               
                   
                   
                   
                 UAU 
                   
                 1683819.1 
                   
                 UUCGAAG 
                   
               
               
                   
               
               
                 AD-887273 
                 A-1683820.1 
                 5809 
                 UCCUGACUGUGUUCU 
                 1047-1065 
                 A- 
                 5810 
                 AGACAGAACACAG 
                 1047-1065 
               
               
                   
                   
                   
                 GUCU 
                   
                 1683821.1 
                   
                 UCAGGA 
                   
               
               
                   
               
               
                 AD-887274 
                 A-1683822.1 
                 5811 
                 CUGACUGUGUUCUGU 
                 1049-1067 
                 A- 
                 5812 
                 UCAGACAGAACAC 
                 1049-1067 
               
               
                   
                   
                   
                 CUGA 
                   
                 1683823.1 
                   
                 AGUCAG 
                   
               
               
                   
               
               
                 AD-887275 
                 A-1683824.1 
                 5813 
                 UGACUGUGUUCUGUC 
                 1050-1068 
                 A- 
                  680 
                 CUCAGACAGAACA 
                 1050-1068 
               
               
                   
                   
                   
                 UGAG 
                   
                 1683825.1 
                   
                 CAGUCA 
                   
               
               
                   
               
               
                 AD-887276 
                 A-1683826.1 
                  681 
                 GACUGUGUUCUGUCU 
                 1051-1069 
                 A- 
                  682 
                 ACUCAGACAGAAC 
                 1051-1069 
               
               
                   
                   
                   
                 GAGU 
                   
                 1683827.1 
                   
                 ACAGUC 
                   
               
               
                   
               
               
                 AD-887277 
                 A-1683828.1 
                  683 
                 ACUGUGUUCUGUCUG 
                 1052-1070 
                 A- 
                  684 
                 CACUCAGACAGAA 
                 1052-1070 
               
               
                   
                   
                   
                 AGUG 
                   
                 1683829.1 
                   
                 CACAGU 
                   
               
               
                   
               
               
                 AD-887278 
                 A-1683830.1 
                  685 
                 CUGUGUUCUGUCUGA 
                 1053-1071 
                 A- 
                  686 
                 ACACUCAGACAGA 
                 1053-1071 
               
               
                   
                   
                   
                 GUGU 
                   
                 1683831.1 
                   
                 ACACAG 
                   
               
               
                   
               
               
                 AD-887279 
                 A-1683832.1 
                  687 
                 UGUGUUCUGUCUGAG 
                 1054-1072 
                 A- 
                  688 
                 CACACUCAGACAG 
                 1054-1072 
               
               
                   
                   
                   
                 UGUG 
                   
                 1683833.1 
                   
                 AACACA 
                   
               
               
                   
               
               
                 AD-887280 
                 A-1683834.1 
                  689 
                 UGUUCUGUCUGAGUG 
                 1056-1074 
                 A- 
                  690 
                 AACACACUCAGAC 
                 1056-1074 
               
               
                   
                   
                   
                 UGUU 
                   
                 1683835.1 
                   
                 AGAACA 
                   
               
               
                   
               
               
                 AD-887281 
                 A-1683836.1 
                  691 
                 GUUCUGUCUGAGUGU 
                 1057-1075 
                 A- 
                  692 
                 AAACACACUCAGA 
                 1057-1075 
               
               
                   
                   
                   
                 GUUU 
                   
                 1683837.1 
                   
                 CAGAAC 
                   
               
               
                   
               
               
                 AD-887282 
                 A-1683838.1 
                  693 
                 UUCUGUCUGAGUGUG 
                 1058-1076 
                 A- 
                  694 
                 CAAACACACUCAG 
                 1058-1076 
               
               
                   
                   
                   
                 UUUG 
                   
                 1683839.1 
                   
                 ACAGAA 
                   
               
               
                   
               
               
                 AD-887283 
                 A-1683840.1 
                  695 
                 UCUGUCUGAGUGUGU 
                 1059-1077 
                 A- 
                  696 
                 GCAAACACACUCA 
                 1059-1077 
               
               
                   
                   
                   
                 UUGC 
                   
                 1683841.1 
                   
                 GACAGA 
                   
               
               
                   
               
               
                 AD-887284 
                 A-1683842.1 
                  697 
                 UGCUCUCCUUUGUGG 
                 1231-1249 
                 A- 
                  698 
                 GAAACCACAAAGG 
                 1231-1249 
               
               
                   
                   
                   
                 UUUC 
                   
                 1683843.1 
                   
                 AGAGCA 
                   
               
               
                   
               
               
                 AD-887285 
                 A-1683844.1 
                  699 
                 CUCUCCUUUGUGGUU 
                 1233-1251 
                 A- 
                  700 
                 CUGAAACCACAAA 
                 1233-1251 
               
               
                   
                   
                   
                 UCAG 
                   
                 1683845.1 
                   
                 GGAGAG 
                   
               
               
                   
               
               
                 AD-887286 
                 A-1683846.1 
                  701 
                 UCUCCUUUGUGGUUU 
                 1234-1252 
                 A- 
                  702 
                 GCUGAAACCACAA 
                 1234-1252 
               
               
                   
                   
                   
                 CAGC 
                   
                 1683847.1 
                   
                 AGGAGA 
                   
               
               
                   
               
               
                 AD-887287 
                 A-1683848.1 
                  703 
                 CUCCUUUGUGGUUUC 
                 1235-1253 
                 A- 
                  704 
                 UGCUGAAACCACA 
                 1235-1253 
               
               
                   
                   
                   
                 AGCA 
                   
                 1683849.1 
                   
                 AAGGAG 
                   
               
               
                   
               
               
                 AD-887288 
                 A-1683850.1 
                  705 
                 CGAGCUUUGACACUUU 
                 1323-1341 
                 A- 
                  706 
                 CUGAAAGUGUCA 
                 1323-1341 
               
               
                   
                   
                   
                 CAG 
                   
                 1683851.1 
                   
                 AAGCUCG 
                   
               
               
                   
               
               
                 AD-887289 
                 A-1683852.1 
                  707 
                 ACAUGAUCUUCUUUG 
                 1431-1449 
                 A- 
                  708 
                 ACGACAAAGAAGA 
                 1431-1449 
               
               
                   
                   
                   
                 UCGU 
                   
                 1683853.1 
                   
                 UCAUGU 
                   
               
               
                   
               
               
                 AD-887290 
                 A-1683854.1 
                  709 
                 CAUGAUCUUCUUUGU 
                 1432-1450 
                 A- 
                  710 
                 UACGACAAAGAA 
                 1432-1450 
               
               
                   
                   
                   
                 CGUA 
                   
                 1683855.1 
                   
                 GAUCAUG 
                   
               
               
                   
               
               
                 AD-887291 
                 A-1683856.1 
                  711 
                 GAUCUUCUUUGUCGU 
                 1435-1453 
                 A- 
                  712 
                 CACUACGACAAAG 
                 1435-1453 
               
               
                   
                   
                   
                 AGUG 
                   
                 1683857.1 
                   
                 AAGAUC 
                   
               
               
                   
               
               
                 AD-887292 
                 A-1683858.1 
                  713 
                 UCUUCUUUGUCGUAG 
                 1437-1455 
                 A- 
                  714 
                 AUCACUACGACAA 
                 1437-1455 
               
               
                   
                   
                   
                 UGAU 
                   
                 1683859.1 
                   
                 AGAAGA 
                   
               
               
                   
               
               
                 AD-887293 
                 A-1683860.1 
                  715 
                 CUUCUUUGUCGUAGU 
                 1438-1456 
                 A- 
                  716 
                 AAUCACUACGACA 
                 1438-1456 
               
               
                   
                   
                   
                 GAUU 
                   
                 1683861.1 
                   
                 AAGAAG 
                   
               
               
                   
               
               
                 AD-887294 
                 A-1683862.1 
                  717 
                 UUGUCGUAGUGAUUU 
                 1443-1461 
                 A- 
                  718 
                 AGGAAAAUCACU 
                 1443-1461 
               
               
                   
                   
                   
                 UCCU 
                   
                 1683863.1 
                   
                 ACGACAA 
                   
               
               
                   
               
               
                 AD-887295 
                 A-1683864.1 
                  719 
                 GCUCCUUUUAUCUAAU 
                 1464-1482 
                 A- 
                  720 
                 UUUAUUAGAUAA 
                 1464-1482 
               
               
                   
                   
                   
                 AAA 
                   
                 1683865.1 
                   
                 AAGGAGC 
                   
               
               
                   
               
               
                 AD-887296 
                 A-1683866.1 
                  721 
                 CUCCUUUUAUCUAAUA 
                 1465-1483 
                 A- 
                  722 
                 GUUUAUUAGAUA 
                 1465-1483 
               
               
                   
                   
                   
                 AAC 
                   
                 1683867.1 
                   
                 AAAGGAG 
                   
               
               
                   
               
               
                 AD-887297 
                 A-1683868.1 
                  723 
                 CCUCUCAGAGAGUUCU 
                 1669-1687 
                 A- 
                  724 
                 AGAAGAACUCUC 
                 1669-1687 
               
               
                   
                   
                   
                 UCU 
                   
                 1683869.1 
                   
                 UGAGAGG 
                   
               
               
                   
               
               
                 AD-887298 
                 A-1683870.1 
                  725 
                 CUCUCAGAGAGUUCUU 
                 1670-1688 
                 A- 
                  726 
                 CAGAAGAACUCUC 
                 1670-1688 
               
               
                   
                   
                   
                 CUG 
                   
                 1683871.1 
                   
                 UGAGAG 
                   
               
               
                   
               
               
                 AD-887299 
                 A-1683872.1 
                  727 
                 UCUCAGAGAGUUCUUC 
                 1671-1689 
                 A- 
                  728 
                 UCAGAAGAACUC 
                 1671-1689 
               
               
                   
                   
                   
                 UGA 
                   
                 1683873.1 
                   
                 UCUGAGA 
                   
               
               
                   
               
               
                 AD-887300 
                 A-1683874.1 
                  729 
                 CUCAGAGAGUUCUUCU 
                 1672-1690 
                 A- 
                  730 
                 UUCAGAAGAACU 
                 1672-1690 
               
               
                   
                   
                   
                 GAA 
                   
                 1683875.1 
                   
                 CUCUGAG 
                   
               
               
                   
               
               
                 AD-887301 
                 A-1683876.1 
                  731 
                 UCAGAGAGUUCUUCU 
                 1673-1691 
                 A- 
                  732 
                 UUUCAGAAGAAC 
                 1673-1691 
               
               
                   
                   
                   
                 GAAA 
                   
                 1683877.1 
                   
                 UCUCUGA 
                   
               
               
                   
               
               
                 AD-887302 
                 A-1683878.1 
                  733 
                 CAGAGAGUUCUUCUGA 
                 1674-1692 
                 A- 
                  734 
                 GUUUCAGAAGAA 
                 1674-1692 
               
               
                   
                   
                   
                 AAC 
                   
                 1683879.1 
                   
                 CUCUCUG 
                   
               
               
                   
               
               
                 AD-887303 
                 A-1683880.1 
                  735 
                 GAGAGUUCUUCUGAA 
                 1676-1694 
                 A- 
                  736 
                 AUGUUUCAGAAG 
                 1676-1694 
               
               
                   
                   
                   
                 ACAU 
                   
                 1683881.1 
                   
                 AACUCUC 
                   
               
               
                   
               
               
                 AD-887304 
                 A-1683882.1 
                  737 
                 AGAGUUCUUCUGAAAC 
                 1677-1695 
                 A- 
                  738 
                 GAUGUUUCAGAA 
                 1677-1695 
               
               
                   
                   
                   
                 AUC 
                   
                 1683883.1 
                   
                 GAACUCU 
                   
               
               
                   
               
               
                 AD-887305 
                 A-1683884.1 
                  739 
                 GAGUUCUUCUGAAACA 
                 1678-1696 
                 A- 
                  740 
                 GGAUGUUUCAGA 
                 1678-1696 
               
               
                   
                   
                   
                 UCC 
                   
                 1683885.1 
                   
                 AGAACUC 
                   
               
               
                   
               
               
                 AD-887306 
                 A-1683886.1 
                  741 
                 AGUUCUUCUGAAACAU 
                 1679-1697 
                 A- 
                  742 
                 UGGAUGUUUCAG 
                 1679-1697 
               
               
                   
                   
                   
                 CCA 
                   
                 1683887.1 
                   
                 AAGAACU 
                   
               
               
                   
               
               
                 AD-887307 
                 A-1683888.1 
                  743 
                 GUUCUUCUGAAACAUC 
                 1680-1698 
                 A- 
                  744 
                 UUGGAUGUUUCA 
                 1680-1698 
               
               
                   
                   
                   
                 CAA 
                   
                 1683889.1 
                   
                 GAAGAAC 
                   
               
               
                   
               
               
                 AD-887308 
                 A-1683890.1 
                  745 
                 UCUUCUGAAACAUCCA 
                 1682-1700 
                 A- 
                  746 
                 GUUUGGAUGUUU 
                 1682-1700 
               
               
                   
                   
                   
                 AAC 
                   
                 1683891.1 
                   
                 CAGAAGA 
                   
               
               
                   
               
               
                 AD-887309 
                 A-1683892.1 
                  747 
                 CUUCUGAAACAUCCAA 
                 1683-1701 
                 A- 
                  748 
                 AGUUUGGAUGUU 
                 1683-1701 
               
               
                   
                   
                   
                 ACU 
                   
                 1683893.1 
                   
                 UCAGAAG 
                   
               
               
                   
               
               
                 AD-887310 
                 A-1683894.1 
                  749 
                 UCUGAAACAUCCAAAC 
                 1685-1703 
                 A- 
                  750 
                 UCAGUUUGGAUG 
                 1685-1703 
               
               
                   
                   
                   
                 UGA 
                   
                 1683895.1 
                   
                 UUUCAGA 
                   
               
               
                   
               
               
                 AD-887311 
                 A-1683896.1 
                  751 
                 UCCAAACUGAGCUCUA 
                 1694-1712 
                 A- 
                  752 
                 UUUUAGAGCUCA 
                 1694-1712 
               
               
                   
                   
                   
                 AAA 
                   
                 1683897.1 
                   
                 GUUUGGA 
                   
               
               
                   
               
               
                 AD-887312 
                 A-1683898.1 
                  753 
                 AGGCGUUGUAGUUCC 
                 2300-2318 
                 A- 
                  754 
                 GAUAGGAACUAC 
                 2300-2318 
               
               
                   
                   
                   
                 UAUC 
                   
                 1683899.1 
                   
                 AACGCCU 
                   
               
               
                   
               
               
                 AD-887313 
                 A-1683900.1 
                  755 
                 GCGUUGUAGUUCCUA 
                 2302-2320 
                 A- 
                  756 
                 GAGAUAGGAACU 
                 2302-2320 
               
               
                   
                   
                   
                 UCUC 
                   
                 1683901.1 
                   
                 ACAACGC 
                   
               
               
                   
               
               
                 AD-887314 
                 A-1683902.1 
                  757 
                 CGUUGUAGUUCCUAU 
                 2303-2321 
                 A- 
                  758 
                 GGAGAUAGGAAC 
                 2303-2321 
               
               
                   
                   
                   
                 CUCC 
                   
                 1683903.1 
                   
                 UACAACG 
                   
               
               
                   
               
               
                 AD-887315 
                 A-1683904.1 
                  759 
                 GUUGUAGUUCCUAUC 
                 2304-2322 
                 A- 
                  760 
                 AGGAGAUAGGAA 
                 2304-2322 
               
               
                   
                   
                   
                 UCCU 
                   
                 1683905.1 
                   
                 CUACAAC 
                   
               
               
                   
               
               
                 AD-887316 
                 A-1683906.1 
                  761 
                 UUGUAGUUCCUAUCU 
                 2305-2323 
                 A- 
                  762 
                 AAGGAGAUAGGA 
                 2305-2323 
               
               
                   
                   
                   
                 CCUU 
                   
                 1683907.1 
                   
                 ACUACAA 
                   
               
               
                   
               
               
                 AD-887317 
                 A-1683908.1 
                  763 
                 UGUAGUUCCUAUCUCC 
                 2306-2324 
                 A- 
                  764 
                 AAAGGAGAUAGG 
                 2306-2324 
               
               
                   
                   
                   
                 UUU 
                   
                 1683909.1 
                   
                 AACUACA 
                   
               
               
                   
               
               
                 AD-887318 
                 A-1683910.1 
                  765 
                 GUAGUUCCUAUCUCCU 
                 2307-2325 
                 A- 
                  766 
                 GAAAGGAGAUAG 
                 2307-2325 
               
               
                   
                   
                   
                 UUC 
                   
                 1683911.1 
                   
                 GAACUAC 
                   
               
               
                   
               
               
                 AD-887319 
                 A-1683912.1 
                  767 
                 UAGUUCCUAUCUCCUU 
                 2308-2326 
                 A- 
                  768 
                 UGAAAGGAGAUA 
                 2308-2326 
               
               
                   
                   
                   
                 UCA 
                   
                 1683913.1 
                   
                 GGAACUA 
                   
               
               
                   
               
               
                 AD-887320 
                 A-1683914.1 
                  769 
                 AGUUCCUAUCUCCUUU 
                 2309-2327 
                 A- 
                  770 
                 CUGAAAGGAGAU 
                 2309-2327 
               
               
                   
                   
                   
                 CAG 
                   
                 1683915.1 
                   
                 AGGAACU 
                   
               
               
                   
               
               
                 AD-887321 
                 A-1683916.1 
                  771 
                 GUUCCUAUCUCCUUUC 
                 2310-2328 
                 A- 
                  772 
                 UCUGAAAGGAGA 
                 2310-2328 
               
               
                   
                   
                   
                 AGA 
                   
                 1683917.1 
                   
                 UAGGAAC 
                   
               
               
                   
               
               
                 AD-887322 
                 A-1683918.1 
                  773 
                 UUCCUAUCUCCUUUCA 
                 2311-2329 
                 A- 
                  774 
                 CUCUGAAAGGAG 
                 2311-2329 
               
               
                   
                   
                   
                 GAG 
                   
                 1683919.1 
                   
                 AUAGGAA 
                   
               
               
                   
               
               
                 AD-887323 
                 A-1683920.1 
                  775 
                 UCCUAUCUCCUUUCAG 
                 2312-2330 
                 A- 
                  776 
                 CCUCUGAAAGGA 
                 2312-2330 
               
               
                   
                   
                   
                 AGG 
                   
                 1683921.1 
                   
                 GAUAGGA 
                   
               
               
                   
               
               
                 AD-887324 
                 A-1683922.1 
                  777 
                 UCUCCUUUCAGAGGAU 
                 2317-2335 
                 A- 
                  778 
                 CAUAUCCUCUGA 
                 2317-2335 
               
               
                   
                   
                   
                 AUG 
                   
                 1683923.1 
                   
                 AAGGAGA 
                   
               
               
                   
               
               
                 AD-887325 
                 A-1683924.1 
                  779 
                 GCAUAUUAACAAACAC 
                 2379-2397 
                 A- 
                  780 
                 ACAGUGUUUGUU 
                 2379-2397 
               
               
                   
                   
                   
                 UGU 
                   
                 1683925.1 
                   
                 AAUAUGC 
                   
               
               
                   
               
               
                 AD-887326 
                 A-1683926.1 
                  781 
                 CUUGAUCUGGAAUUG 
                 2461-2479 
                 A- 
                  782 
                 AGAGCAAUUCCA 
                 2461-2479 
               
               
                   
                   
                   
                 CUCU 
                   
                 1683927.1 
                   
                 GAUCAAG 
                   
               
               
                   
               
               
                 AD-887327 
                 A-1683928.1 
                  783 
                 CUCUCCAUAUUGGAUA 
                 2476-2494 
                 A- 
                  784 
                 UUUUAUCCAAUA 
                 2476-2494 
               
               
                   
                   
                   
                 AAA 
                   
                 1683929.1 
                   
                 UGGAGAG 
                   
               
               
                   
               
               
                 AD-887328 
                 A-1683930.1 
                  785 
                 UCUCCAUAUUGGAUAA 
                 2477-2495 
                 A- 
                  786 
                 AUUUUAUCCAAU 
                 2477-2495 
               
               
                   
                   
                   
                 AAU 
                   
                 1683931.1 
                   
                 AUGGAGA 
                   
               
               
                   
               
               
                 AD-887329 
                 A-1683932.1 
                  787 
                 CUCCAUAUUGGAUAAA 
                 2478-2496 
                 A- 
                  788 
                 AAUUUUAUCCAA 
                 2478-2496 
               
               
                   
                   
                   
                 AUU 
                   
                 1683933.1 
                   
                 UAUGGAG 
                   
               
               
                   
               
               
                 AD-887330 
                 A-1683934.1 
                  789 
                 GAUCUUGCAAUUACCA 
                 2537-2555 
                 A- 
                  790 
                 AAAUGGUAAUUG 
                 2537-2555 
               
               
                   
                   
                   
                 UUU 
                   
                 1683935.1 
                   
                 CAAGAUC 
                   
               
               
                   
               
               
                 AD-887331 
                 A-1683936.1 
                  791 
                 UUGGUCUUUACUGGA 
                 2639-2657 
                 A- 
                  792 
                 AGAUUCCAGUAA 
                 2639-2657 
               
               
                   
                   
                   
                 AUCU 
                   
                 1683937.1 
                   
                 AGACCAA 
                   
               
               
                   
               
               
                 AD-887332 
                 A-1683938.1 
                  793 
                 GGUCUUUACUGGAAU 
                 2641-2659 
                 A- 
                  794 
                 AAAGAUUCCAGU 
                 2641-2659 
               
               
                   
                   
                   
                 CUUU 
                   
                 1683939.1 
                   
                 AAAGACC 
                   
               
               
                   
               
               
                 AD-887333 
                 A-1683940.1 
                  795 
                 GUCUUUACUGGAAUC 
                 2642-2660 
                 A- 
                  796 
                 CAAAGAUUCCAG 
                 2642-2660 
               
               
                   
                   
                   
                 UUUG 
                   
                 1683941.1 
                   
                 UAAAGAC 
                   
               
               
                   
               
               
                 AD-887334 
                 A-1683942.1 
                  797 
                 GCCUUAUUGUGACUU 
                 2736-2754 
                 A- 
                  798 
                 CUUAAAGUCACA 
                 2736-2754 
               
               
                   
                   
                   
                 UAAG 
                   
                 1683943.1 
                   
                 AUAAGGC 
                   
               
               
                   
               
               
                 AD-887335 
                 A-1683944.1 
                  799 
                 GCUCUUUCUAGCAGAU 
                 2764-2782 
                 A- 
                  800 
                 CACAUCUGCUAG 
                 2764-2782 
               
               
                   
                   
                   
                 GUG 
                   
                 1683945.1 
                   
                 AAAGAGC 
                   
               
               
                   
               
               
                 AD-887336 
                 A-1683946.1 
                  801 
                 CUCUUUCUAGCAGAUG 
                 2765-2783 
                 A- 
                  802 
                 CCACAUCUGCUAG 
                 2765-2783 
               
               
                   
                   
                   
                 UGG 
                   
                 1683947.1 
                   
                 AAAGAG 
                   
               
               
                   
               
               
                 AD-887337 
                 A-1683948.1 
                  803 
                 GUCAGUUCUGCGAUCA 
                 2791-2809 
                 A- 
                  804 
                 GAAUGAUCGCAG 
                 2791-2809 
               
               
                   
                   
                   
                 UUC 
                   
                 1683949.1 
                   
                 AACUGAC 
                   
               
               
                   
               
               
                 AD-887338 
                 A-1683950.1 
                  805 
                 UCAGUUCUGCGAUCAU 
                 2792-2810 
                 A- 
                  806 
                 UGAAUGAUCGCA 
                 2792-2810 
               
               
                   
                   
                   
                 UCA 
                   
                 1683951.1 
                   
                 GAACUGA 
                   
               
               
                   
               
               
                 AD-887339 
                 A-1683952.1 
                  807 
                 AGUCUUCAAGUUGGCA 
                 2821-2839 
                 A- 
                  808 
                 UUUUGCCAACUU 
                 2821-2839 
               
               
                   
                   
                   
                 AAA 
                   
                 1683953.1 
                   
                 GAAGACU 
                   
               
               
                   
               
               
                 AD-887340 
                 A-1683954.1 
                  809 
                 UCUUCAAGUUGGCAAA 
                 2823-2841 
                 A- 
                  810 
                 GAUUUUGCCAAC 
                 2823-2841 
               
               
                   
                   
                   
                 AUC 
                   
                 1683955.1 
                   
                 UUGAAGA 
                   
               
               
                   
               
               
                 AD-887341 
                 A-1683956.1 
                  811 
                 CUUCAAGUUGGCAAAA 
                 2824-2842 
                 A- 
                  812 
                 GGAUUUUGCCAA 
                 2824-2842 
               
               
                   
                   
                   
                 UCC 
                   
                 1683957.1 
                   
                 CUUGAAG 
                   
               
               
                   
               
               
                 AD-887342 
                 A-1683958.1 
                  813 
                 CCAUCAUCGUCUUCAU 
                 2919-2937 
                 A- 
                  814 
                 AAAAUGAAGACG 
                 2919-2937 
               
               
                   
                   
                   
                 UUU 
                   
                 1683959.1 
                   
                 AUGAUGG 
                   
               
               
                   
               
               
                 AD-887343 
                 A-1683960.1 
                  815 
                 CAUCAUCGUCUUCAUU 
                 2920-2938 
                 A- 
                  816 
                 AAAAAUGAAGAC 
                 2920-2938 
               
               
                   
                   
                   
                 UUU 
                   
                 1683961.1 
                   
                 GAUGAUG 
                   
               
               
                   
               
               
                 AD-887344 
                 A-1683962.1 
                  817 
                 GCACAUGAACGACUUC 
                 3022-3040 
                 A- 
                  818 
                 GAAGAAGUCGUU 
                 3022-3040 
               
               
                   
                   
                   
                 UUC 
                   
                 1683963.1 
                   
                 CAUGUGC 
                   
               
               
                   
               
               
                 AD-887345 
                 A-1683964.1 
                  819 
                 CACAUGAACGACUUCU 
                 3023-3041 
                 A- 
                  820 
                 GGAAGAAGUCGU 
                 3023-3041 
               
               
                   
                   
                   
                 UCC 
                   
                 1683965.1 
                   
                 UCAUGUG 
                   
               
               
                   
               
               
                 AD-887346 
                 A-1683966.1 
                  821 
                 ACAUGAACGACUUCUU 
                 3024-3042 
                 A- 
                  822 
                 UGGAAGAAGUCG 
                 3024-3042 
               
               
                   
                   
                   
                 CCA 
                   
                 1683967.1 
                   
                 UUCAUGU 
                   
               
               
                   
               
               
                 AD-887347 
                 A-1683968.1 
                  823 
                 CAUGAACGACUUCUUC 
                 3025-3043 
                 A- 
                  824 
                 GUGGAAGAAGUC 
                 3025-3043 
               
               
                   
                   
                   
                 CAC 
                   
                 1683969.1 
                   
                 GUUCAUG 
                   
               
               
                   
               
               
                 AD-887348 
                 A-1683970.1 
                  825 
                 UGAACGACUUCUUCCA 
                 3027-3045 
                 A- 
                  826 
                 GAGUGGAAGAAG 
                 3027-3045 
               
               
                   
                   
                   
                 CUC 
                   
                 1683971.1 
                   
                 UCGUUCA 
                   
               
               
                   
               
               
                 AD-887349 
                 A-1683972.1 
                  827 
                 CGACUUCUUCCACUCC 
                 3031-3049 
                 A- 
                  828 
                 GAAGGAGUGGAA 
                 3031-3049 
               
               
                   
                   
                   
                 UUC 
                   
                 1683973.1 
                   
                 GAAGUCG 
                   
               
               
                   
               
               
                 AD-887350 
                 A-1683974.1 
                  829 
                 UCCACUCCUUCCUGAU 
                 3039-3057 
                 A- 
                  830 
                 ACAAUCAGGAAG 
                 3039-3057 
               
               
                   
                   
                   
                 UGU 
                   
                 1683975.1 
                   
                 GAGUGGA 
                   
               
               
                   
               
               
                 AD-887351 
                 A-1683976.1 
                  831 
                 ACUCCUUCCUGAUUGU 
                 3042-3060 
                 A- 
                  832 
                 AACACAAUCAGGA 
                 3042-3060 
               
               
                   
                   
                   
                 GUU 
                   
                 1683977.1 
                   
                 AGGAGU 
                   
               
               
                   
               
               
                 AD-887352 
                 A-1683978.1 
                  833 
                 CUCCUUCCUGAUUGUG 
                 3043-3061 
                 A- 
                  834 
                 GAACACAAUCAGG 
                 3043-3061 
               
               
                   
                   
                   
                 UUC 
                   
                 1683979.1 
                   
                 AAGGAG 
                   
               
               
                   
               
               
                 AD-887353 
                 A-1683980.1 
                  835 
                 UCCUUCCUGAUUGUG 
                 3044-3062 
                 A- 
                  836 
                 GGAACACAAUCAG 
                 3044-3062 
               
               
                   
                   
                   
                 UUCC 
                   
                 1683981.1 
                   
                 GAAGGA 
                   
               
               
                   
               
               
                 AD-887354 
                 A-1683982.1 
                  837 
                 CUAUGUGCCUUAUUG 
                 3123-3141 
                 A- 
                  838 
                 UAAACAAUAAGG 
                 3123-3141 
               
               
                   
                   
                   
                 UUUA 
                   
                 1683983.1 
                   
                 CACAUAG 
                   
               
               
                   
               
               
                 AD-887355 
                 A-1683984.1 
                  839 
                 UGGUCCUAAACCUAUU 
                 3171-3189 
                 A- 
                  840 
                 AGAAAUAGGUUU 
                 3171-3189 
               
               
                   
                   
                   
                 UCU 
                   
                 1683985.1 
                   
                 AGGACCA 
                   
               
               
                   
               
               
                 AD-887356 
                 A-1683986.1 
                  841 
                 GGUCCUAAACCUAUUU 
                 3172-3190 
                 A- 
                  842 
                 CAGAAAUAGGUU 
                 3172-3190 
               
               
                   
                   
                   
                 CUG 
                   
                 1683987.1 
                   
                 UAGGACC 
                   
               
               
                   
               
               
                 AD-887357 
                 A-1683988.1 
                  843 
                 GUCCUAAACCUAUUUC 
                 3173-3191 
                 A- 
                  844 
                 CCAGAAAUAGGU 
                 3173-3191 
               
               
                   
                   
                   
                 UGG 
                   
                 1683989.1 
                   
                 UUAGGAC 
                   
               
               
                   
               
               
                 AD-887358 
                 A-1683990.1 
                  845 
                 CCUUACGUGAAUUUA 
                 3312-3330 
                 A- 
                  846 
                 AGAAUAAAUUCA 
                 3312-3330 
               
               
                   
                   
                   
                 UUCU 
                   
                 1683991.1 
                   
                 CGUAAGG 
                   
               
               
                   
               
               
                 AD-887359 
                 A-1683992.1 
                  847 
                 CAAAGGUCACAAUUUC 
                 3439-3457 
                 A- 
                  848 
                 GAGGAAAUUGUG 
                 3439-3457 
               
               
                   
                   
                   
                 CUC 
                   
                 1683993.1 
                   
                 ACCUUUG 
                   
               
               
                   
               
               
                 AD-887360 
                 A-1683994.1 
                  849 
                 UCACAAUUUCCUCAAG 
                 3445-3463 
                 A- 
                  850 
                 UUCCUUGAGGAA 
                 3445-3463 
               
               
                   
                   
                   
                 GAA 
                   
                 1683995.1 
                   
                 AUUGUGA 
                   
               
               
                   
               
               
                 AD-887361 
                 A-1683996.1 
                  851 
                 CCUCAAGGAAAAAGAU 
                 3454-3472 
                 A- 
                  852 
                 UUUAUCUUUUUC 
                 3454-3472 
               
               
                   
                   
                   
                 AAA 
                   
                 1683997.1 
                   
                 CUUGAGG 
                   
               
               
                   
               
               
                 AD-887362 
                 A-1683998.1 
                  853 
                 GCUUCAUUGUCCUCAU 
                 3885-3903 
                 A- 
                  854 
                 AUCAUGAGGACA 
                 3885-3903 
               
               
                   
                   
                   
                 GAU 
                   
                 1683999.1 
                   
                 AUGAAGC 
                   
               
               
                   
               
               
                 AD-887363 
                 A-1684000.1 
                  855 
                 CUUCAUUGUCCUCAUG 
                 3886-3904 
                 A- 
                  856 
                 GAUCAUGAGGAC 
                 3886-3904 
               
               
                   
                   
                   
                 AUC 
                   
                 1684001.1 
                   
                 AAUGAAG 
                   
               
               
                   
               
               
                 AD-887364 
                 A-1684002.1 
                  857 
                 UGCAGACAAGAUCUUC 
                 3982-4000 
                 A- 
                  858 
                 AGUGAAGAUCUU 
                 3982-4000 
               
               
                   
                   
                   
                 ACU 
                   
                 1684003.1 
                   
                 GUCUGCA 
                   
               
               
                   
               
               
                 AD-887365 
                 A-1684004.1 
                  859 
                 CAGACAAGAUCUUCAC 
                 3984-4002 
                 A- 
                  860 
                 UAAGUGAAGAUC 
                 3984-4002 
               
               
                   
                   
                   
                 UUA 
                   
                 1684005.1 
                   
                 UUGUCUG 
                   
               
               
                   
               
               
                 AD-887366 
                 A-1684006.1 
                  861 
                 AGACAAGAUCUUCACU 
                 3985-4003 
                 A- 
                  862 
                 GUAAGUGAAGAU 
                 3985-4003 
               
               
                   
                   
                   
                 UAC 
                   
                 1684007.1 
                   
                 CUUGUCU 
                   
               
               
                   
               
               
                 AD-887367 
                 A-1684008.1 
                  863 
                 GACAAGAUCUUCACUU 
                 3986-4004 
                 A- 
                  864 
                 UGUAAGUGAAGA 
                 3986-4004 
               
               
                   
                   
                   
                 ACA 
                   
                 1684009.1 
                   
                 UCUUGUC 
                   
               
               
                   
               
               
                 AD-887368 
                 A-1684010.1 
                  865 
                 ACAAGAUCUUCACUUA 
                 3987-4005 
                 A- 
                  866 
                 AUGUAAGUGAAG 
                 3987-4005 
               
               
                   
                   
                   
                 CAU 
                   
                 1684011.1 
                   
                 AUCUUGU 
                   
               
               
                   
               
               
                 AD-887369 
                 A-1684012.1 
                  867 
                 CAAGAUCUUCACUUAC 
                 3988-4006 
                 A- 
                  868 
                 GAUGUAAGUGAA 
                 3988-4006 
               
               
                   
                   
                   
                 AUC 
                   
                 1684013.1 
                   
                 GAUCUUG 
                   
               
               
                   
               
               
                 AD-887370 
                 A-1684014.1 
                  869 
                 AGAUCUUCACUUACAU 
                 3990-4008 
                 A- 
                  870 
                 AAGAUGUAAGUG 
                 3990-4008 
               
               
                   
                   
                   
                 CUU 
                   
                 1684015.1 
                   
                 AAGAUCU 
                   
               
               
                   
               
               
                 AD-887371 
                 A-1684016.1 
                  871 
                 GAUCUUCACUUACAUC 
                 3991-4009 
                 A- 
                  872 
                 GAAGAUGUAAGU 
                 3991-4009 
               
               
                   
                   
                   
                 UUC 
                   
                 1684017.1 
                   
                 GAAGAUC 
                   
               
               
                   
               
               
                 AD-887372 
                 A-1684018.1 
                  873 
                 UCUUCACUUACAUCUU 
                 3993-4011 
                 A- 
                  874 
                 AUGAAGAUGUAA 
                 3993-4011 
               
               
                   
                   
                   
                 CAU 
                   
                 1684019.1 
                   
                 GUGAAGA 
                   
               
               
                   
               
               
                 AD-887373 
                 A-1684020.1 
                  875 
                 CUUCACUUACAUCUUC 
                 3994-4012 
                 A- 
                  876 
                 AAUGAAGAUGUA 
                 3994-4012 
               
               
                   
                   
                   
                 AUU 
                   
                 1684021.1 
                   
                 AGUGAAG 
                   
               
               
                   
               
               
                 AD-887374 
                 A-1684022.1 
                  877 
                 UUCACUUACAUCUUCA 
                 3995-4013 
                 A- 
                  878 
                 GAAUGAAGAUGU 
                 3995-4013 
               
               
                   
                   
                   
                 UUC 
                   
                 1684023.1 
                   
                 AAGUGAA 
                   
               
               
                   
               
               
                 AD-887375 
                 A-1684024.1 
                  879 
                 UCACUUACAUCUUCAU 
                 3996-4014 
                 A- 
                  880 
                 AGAAUGAAGAUG 
                 3996-4014 
               
               
                   
                   
                   
                 UCU 
                   
                 1684025.1 
                   
                 UAAGUGA 
                   
               
               
                   
               
               
                 AD-887376 
                 A-1684026.1 
                  881 
                 CACUUACAUCUUCAUU 
                 3997-4015 
                 A- 
                  882 
                 CAGAAUGAAGAU 
                 3997-4015 
               
               
                   
                   
                   
                 CUG 
                   
                 1684027.1 
                   
                 GUAAGUG 
                   
               
               
                   
               
               
                 AD-887377 
                 A-1684028.1 
                  883 
                 CUUACAUCUUCAUUCU 
                 3999-4017 
                 A- 
                  884 
                 UCCAGAAUGAAG 
                 3999-4017 
               
               
                   
                   
                   
                 GGA 
                   
                 1684029.1 
                   
                 AUGUAAG 
                   
               
               
                   
               
               
                 AD-887378 
                 A-1684030.1 
                  885 
                 ACAUCUUCAUUCUGGA 
                 4002-4020 
                 A- 
                  886 
                 AUUUCCAGAAUG 
                 4002-4020 
               
               
                   
                   
                   
                 AAU 
                   
                 1684031.1 
                   
                 AAGAUGU 
                   
               
               
                   
               
               
                 AD-887379 
                 A-1684032.1 
                  887 
                 CAUCUUCAUUCUGGAA 
                 4003-4021 
                 A- 
                  888 
                 CAUUUCCAGAAU 
                 4003-4021 
               
               
                   
                   
                   
                 AUG 
                   
                 1684033.1 
                   
                 GAAGAUG 
                   
               
               
                   
               
               
                 AD-887380 
                 A-1684034.1 
                  889 
                 UCUUCAUUCUGGAAA 
                 4005-4023 
                 A- 
                  890 
                 AGCAUUUCCAGA 
                 4005-4023 
               
               
                   
                   
                   
                 UGCU 
                   
                 1684035.1 
                   
                 AUGAAGA 
                   
               
               
                   
               
               
                 AD-887381 
                 A-1684036.1 
                  891 
                 CUUCAUUCUGGAAAUG 
                 4006-4024 
                 A- 
                  892 
                 AAGCAUUUCCAG 
                 4006-4024 
               
               
                   
                   
                   
                 CUU 
                   
                 1684037.1 
                   
                 AAUGAAG 
                   
               
               
                   
               
               
                 AD-887382 
                 A-1684038.1 
                  893 
                 UCUGGAAAUGCUUCUA 
                 4012-4030 
                 A- 
                  894 
                 UUUUAGAAGCAU 
                 4012-4030 
               
               
                   
                   
                   
                 AAA 
                   
                 1684039.1 
                   
                 UUCCAGA 
                   
               
               
                   
               
               
                 AD-887383 
                 A-1684040.1 
                  895 
                 GCUGGAUUUCCUAAU 
                 4078-4096 
                 A- 
                  896 
                 AACAAUUAGGAA 
                 4078-4096 
               
               
                   
                   
                   
                 UGUU 
                   
                 1684041.1 
                   
                 AUCCAGC 
                   
               
               
                   
               
               
                 AD-887384 
                 A-1684042.1 
                  897 
                 CUGGAUUUCCUAAUU 
                 4079-4097 
                 A- 
                  898 
                 CAACAAUUAGGA 
                 4079-4097 
               
               
                   
                   
                   
                 GUUG 
                   
                 1684043.1 
                   
                 AAUCCAG 
                   
               
               
                   
               
               
                 AD-887385 
                 A-1684044.1 
                  899 
                 CCUCUAAGAGCCUUAU 
                 4187-4205 
                 A- 
                  900 
                 UAGAUAAGGCUC 
                 4187-4205 
               
               
                   
                   
                   
                 CUA 
                   
                 1684045.1 
                   
                 UUAGAGG 
                   
               
               
                   
               
               
                 AD-887386 
                 A-1684046.1 
                  901 
                 CUCUAAGAGCCUUAUC 
                 4188-4206 
                 A- 
                  902 
                 CUAGAUAAGGCU 
                 4188-4206 
               
               
                   
                   
                   
                 UAG 
                   
                 1684047.1 
                   
                 CUUAGAG 
                   
               
               
                   
               
               
                 AD-887387 
                 A-1684048.1 
                  903 
                 CUUCCAUCAUGAAUGU 
                 4254-4272 
                 A- 
                  904 
                 AGCACAUUCAUG 
                 4254-4272 
               
               
                   
                   
                   
                 GCU 
                   
                 1684049.1 
                   
                 AUGGAAG 
                   
               
               
                   
               
               
                 AD-887388 
                 A-1684050.1 
                  905 
                 UUUCCUGCAAGUCAAG 
                 4373-4391 
                 A- 
                  906 
                 GAACUUGACUUG 
                 4373-4391 
               
               
                   
                   
                   
                 UUC 
                   
                 1684051.1 
                   
                 CAGGAAA 
                   
               
               
                   
               
               
                 AD-887389 
                 A-1684052.1 
                  907 
                 CUGCAAGUCAAGUUCC 
                 4377-4395 
                 A- 
                  908 
                 UUUGGAACUUGA 
                 4377-4395 
               
               
                   
                   
                   
                 AAA 
                   
                 1684053.1 
                   
                 CUUGCAG 
                   
               
               
                   
               
               
                 AD-887390 
                 A-1684054.1 
                  909 
                 AGUCAAGUUCCAAAUC 
                 4382-4400 
                 A- 
                  910 
                 AACGAUUUGGAA 
                 4382-4400 
               
               
                   
                   
                   
                 GUU 
                   
                 1684055.1 
                   
                 CUUGACU 
                   
               
               
                   
               
               
                 AD-887391 
                 A-1684056.1 
                  911 
                 ACUUGGUUACCUAUCU 
                 4477-4495 
                 A- 
                  912 
                 CAGAGAUAGGUA 
                 4477-4495 
               
               
                   
                   
                   
                 CUG 
                   
                 1684057.1 
                   
                 ACCAAGU 
                   
               
               
                   
               
               
                 AD-887392 
                 A-1684058.1 
                  913 
                 CUUGGUUACCUAUCUC 
                 4478-4496 
                 A- 
                  914 
                 GCAGAGAUAGGU 
                 4478-4496 
               
               
                   
                   
                   
                 UGC 
                   
                 1684059.1 
                   
                 AACCAAG 
                   
               
               
                   
               
               
                 AD-887393 
                 A-1684060.1 
                  915 
                 GGUUACCUAUCUCUGC 
                 4481-4499 
                 A- 
                  916 
                 GAAGCAGAGAUA 
                 4481-4499 
               
               
                   
                   
                   
                 UUC 
                   
                 1684061.1 
                   
                 GGUAACC 
                   
               
               
                   
               
               
                 AD-887394 
                 A-1684062.1 
                  917 
                 GUUACCUAUCUCUGCU 
                 4482-4500 
                 A- 
                  918 
                 UGAAGCAGAGAU 
                 4482-4500 
               
               
                   
                   
                   
                 UCA 
                   
                 1684063.1 
                   
                 AGGUAAC 
                   
               
               
                   
               
               
                 AD-887395 
                 A-1684064.1 
                  919 
                 UUACCUAUCUCUGCUU 
                 4483-4501 
                 A- 
                  920 
                 UUGAAGCAGAGA 
                 4483-4501 
               
               
                   
                   
                   
                 CAA 
                   
                 1684065.1 
                   
                 UAGGUAA 
                   
               
               
                   
               
               
                 AD-887396 
                 A-1684066.1 
                  921 
                 UACCUAUCUCUGCUUC 
                 4484-4502 
                 A- 
                  922 
                 CUUGAAGCAGAG 
                 4484-4502 
               
               
                   
                   
                   
                 AAG 
                   
                 1684067.1 
                   
                 AUAGGUA 
                   
               
               
                   
               
               
                 AD-887397 
                 A-1684068.1 
                  923 
                 ACCUAUCUCUGCUUCA 
                 4485-4503 
                 A- 
                  924 
                 ACUUGAAGCAGA 
                 4485-4503 
               
               
                   
                   
                   
                 AGU 
                   
                 1684069.1 
                   
                 GAUAGGU 
                   
               
               
                   
               
               
                 AD-887398 
                 A-1684070.1 
                  925 
                 CCUAUCUCUGCUUCAA 
                 4486-4504 
                 A- 
                  926 
                 AACUUGAAGCAG 
                 4486-4504 
               
               
                   
                   
                   
                 GUU 
                   
                 1684071.1 
                   
                 AGAUAGG 
                   
               
               
                   
               
               
                 AD-887399 
                 A-1684072.1 
                  927 
                 CUAUCUCUGCUUCAAG 
                 4487-4505 
                 A- 
                  928 
                 CAACUUGAAGCA 
                 4487-4505 
               
               
                   
                   
                   
                 UUG 
                   
                 1684073.1 
                   
                 GAGAUAG 
                   
               
               
                   
               
               
                 AD-887400 
                 A-1684074.1 
                  929 
                 AUCUCUGCUUCAAGUU 
                 4489-4507 
                 A- 
                  930 
                 UGCAACUUGAAG 
                 4489-4507 
               
               
                   
                   
                   
                 GCA 
                   
                 1684075.1 
                   
                 CAGAGAU 
                   
               
               
                   
               
               
                 AD-887401 
                 A-1684076.1 
                  931 
                 UCUCUGCUUCAAGUU 
                 4490-4508 
                 A- 
                  932 
                 UUGCAACUUGAA 
                 4490-4508 
               
               
                   
                   
                   
                 GCAA 
                   
                 1684077.1 
                   
                 GCAGAGA 
                   
               
               
                   
               
               
                 AD-887402 
                 A-1684078.1 
                  933 
                 CUCUGCUUCAAGUUGC 
                 4491-4509 
                 A- 
                  934 
                 GUUGCAACUUGA 
                 4491-4509 
               
               
                   
                   
                   
                 AAC 
                   
                 1684079.1 
                   
                 AGCAGAG 
                   
               
               
                   
               
               
                 AD-887403 
                 A-1684080.1 
                  935 
                 UCUGCUUCAAGUUGCA 
                 4492-4510 
                 A- 
                  936 
                 AGUUGCAACUUG 
                 4492-4510 
               
               
                   
                   
                   
                 ACU 
                   
                 1684081.1 
                   
                 AAGCAGA 
                   
               
               
                   
               
               
                 AD-887404 
                 A-1684082.1 
                  937 
                 UAUCAUCUUUGGGUC 
                 4618-4636 
                 A- 
                  938 
                 GAAUGACCCAAAG 
                 4618-4636 
               
               
                   
                   
                   
                 AUUC 
                   
                 1684083.1 
                   
                 AUGAUA 
                   
               
               
                   
               
               
                 AD-887405 
                 A-1684084.1 
                  939 
                 AUCAUCUUUGGGUCA 
                 4619-4637 
                 A- 
                  940 
                 AGAAUGACCCAAA 
                 4619-4637 
               
               
                   
                   
                   
                 UUCU 
                   
                 1684085.1 
                   
                 GAUGAU 
                   
               
               
                   
               
               
                 AD-887406 
                 A-1684086.1 
                  941 
                 UCAUCUUUGGGUCAU 
                 4620-4638 
                 A- 
                  942 
                 AAGAAUGACCCAA 
                 4620-4638 
               
               
                   
                   
                   
                 UCUU 
                   
                 1684087.1 
                   
                 AGAUGA 
                   
               
               
                   
               
               
                 AD-887407 
                 A-1684088.1 
                  943 
                 CAUCUUUGGGUCAUU 
                 4621-4639 
                 A- 
                  944 
                 GAAGAAUGACCCA 
                 4621-4639 
               
               
                   
                   
                   
                 CUUC 
                   
                 1684089.1 
                   
                 AAGAUG 
                   
               
               
                   
               
               
                 AD-887408 
                 A-1684090.1 
                  945 
                 CUUUGGGUCAUUCUU 
                 4624-4642 
                 A- 
                  946 
                 AGUGAAGAAUGA 
                 4624-4642 
               
               
                   
                   
                   
                 CACU 
                   
                 1684091.1 
                   
                 CCCAAAG 
                   
               
               
                   
               
               
                 AD-887409 
                 A-1684092.1 
                  947 
                 UUGGGUCAUUCUUCA 
                 4626-4644 
                 A- 
                  948 
                 AAAGUGAAGAAU 
                 4626-4644 
               
               
                   
                   
                   
                 CUUU 
                   
                 1684093.1 
                   
                 GACCCAA 
                   
               
               
                   
               
               
                 AD-887410 
                 A-1684094.1 
                  949 
                 UGGGUCAUUCUUCAC 
                 4627-4645 
                 A- 
                  950 
                 CAAAGUGAAGAA 
                 4627-4645 
               
               
                   
                   
                   
                 UUUG 
                   
                 1684095.1 
                   
                 UGACCCA 
                   
               
               
                   
               
               
                 AD-887411 
                 A-1684096.1 
                  951 
                 GGGUCAUUCUUCACU 
                 4628-4646 
                 A- 
                  952 
                 UCAAAGUGAAGA 
                 4628-4646 
               
               
                   
                   
                   
                 UUGA 
                   
                 1684097.1 
                   
                 AUGACCC 
                   
               
               
                   
               
               
                 AD-887412 
                 A-1684098.1 
                  953 
                 GGUCAUUCUUCACUU 
                 4629-4647 
                 A- 
                  954 
                 UUCAAAGUGAAG 
                 4629-4647 
               
               
                   
                   
                   
                 UGAA 
                   
                 1684099.1 
                   
                 AAUGACC 
                   
               
               
                   
               
               
                 AD-887413 
                 A-1684100.1 
                  955 
                 GUCAUUCUUCACUUU 
                 4630-4648 
                 A- 
                  956 
                 GUUCAAAGUGAA 
                 4630-4648 
               
               
                   
                   
                   
                 GAAC 
                   
                 1684101.1 
                   
                 GAAUGAC 
                   
               
               
                   
               
               
                 AD-887414 
                 A-1684102.1 
                  957 
                 CAUUCUUCACUUUGAA 
                 4632-4650 
                 A- 
                  958 
                 AAGUUCAAAGUG 
                 4632-4650 
               
               
                   
                   
                   
                 CUU 
                   
                 1684103.1 
                   
                 AAGAAUG 
                   
               
               
                   
               
               
                 AD-887415 
                 A-1684104.1 
                  959 
                 UCACUUUGAACUUGU 
                 4638-4656 
                 A- 
                  960 
                 AUGAACAAGUUC 
                 4638-4656 
               
               
                   
                   
                   
                 UCAU 
                   
                 1684105.1 
                   
                 AAAGUGA 
                   
               
               
                   
               
               
                 AD-887416 
                 A-1684106.1 
                  961 
                 CUUGUUCAUUGGUGU 
                 4648-4666 
                 A- 
                  962 
                 GAUGACACCAAU 
                 4648-4666 
               
               
                   
                   
                   
                 CAUC 
                   
                 1684107.1 
                   
                 GAACAAG 
                   
               
               
                   
               
               
                 AD-887417 
                 A-1684108.1 
                  963 
                 GUGUCAUCAUAGAUAA 
                 4659-4677 
                 A- 
                  964 
                 AAAUUAUCUAUG 
                 4659-4677 
               
               
                   
                   
                   
                 UUU 
                   
                 1684109.1 
                   
                 AUGACAC 
                   
               
               
                   
               
               
                 AD-887418 
                 A-1684110.1 
                  965 
                 UGUCAUCAUAGAUAAU 
                 4660-4678 
                 A- 
                  966 
                 GAAAUUAUCUAU 
                 4660-4678 
               
               
                   
                   
                   
                 UUC 
                   
                 1684111.1 
                   
                 GAUGACA 
                   
               
               
                   
               
               
                 AD-887419 
                 A-1684112.1 
                  967 
                 GAGGUCAAGACAUCUU 
                 4701-4719 
                 A- 
                  968 
                 AUAAAGAUGUCU 
                 4701-4719 
               
               
                   
                   
                   
                 UAU 
                   
                 1684113.1 
                   
                 UGACCUC 
                   
               
               
                   
               
               
                 AD-887420 
                 A-1684114.1 
                  969 
                 AGGUCAAGACAUCUUU 
                 4702-4720 
                 A- 
                  970 
                 CAUAAAGAUGUC 
                 4702-4720 
               
               
                   
                   
                   
                 AUG 
                   
                 1684115.1 
                   
                 UUGACCU 
                   
               
               
                   
               
               
                 AD-887421 
                 A-1684116.1 
                  971 
                 GGUCAAGACAUCUUUA 
                 4703-4721 
                 A- 
                  972 
                 UCAUAAAGAUGU 
                 4703-4721 
               
               
                   
                   
                   
                 UGA 
                   
                 1684117.1 
                   
                 CUUGACC 
                   
               
               
                   
               
               
                 AD-887422 
                 A-1684118.1 
                  973 
                 CCACAAAAGCCAAUUC 
                 4775-4793 
                 A- 
                  974 
                 GAGGAAUUGGCU 
                 4775-4793 
               
               
                   
                   
                   
                 CUC 
                   
                 1684119.1 
                   
                 UUUGUGG 
                   
               
               
                   
               
               
                 AD-887423 
                 A-1684120.1 
                  975 
                 GACCUAGUGACAAAUC 
                 4826-4844 
                 A- 
                  976 
                 CUUGAUUUGUCA 
                 4826-4844 
               
               
                   
                   
                   
                 AAG 
                   
                 1684121.1 
                   
                 CUAGGUC 
                   
               
               
                   
               
               
                 AD-887424 
                 A-1684122.1 
                  977 
                 GUAUCAUGGUUCUUA 
                 4857-4875 
                 A- 
                  978 
                 CAGAUAAGAACCA 
                 4857-4875 
               
               
                   
                   
                   
                 UCUG 
                   
                 1684123.1 
                   
                 UGAUAC 
                   
               
               
                   
               
               
                 AD-887425 
                 A-1684124.1 
                  979 
                 UAUCAUGGUUCUUAU 
                 4858-4876 
                 A- 
                  980 
                 ACAGAUAAGAACC 
                 4858-4876 
               
               
                   
                   
                   
                 CUGU 
                   
                 1684125.1 
                   
                 AUGAUA 
                   
               
               
                   
               
               
                 AD-887426 
                 A-1684126.1 
                  981 
                 UCAUGGUUCUUAUCU 
                 4860-4878 
                 A- 
                  982 
                 AGACAGAUAAGA 
                 4860-4878 
               
               
                   
                   
                   
                 GUCU 
                   
                 1684127.1 
                   
                 ACCAUGA 
                   
               
               
                   
               
               
                 AD-887427 
                 A-1684128.1 
                  983 
                 CAUGGUUCUUAUCUG 
                 4861-4879 
                 A- 
                  984 
                 GAGACAGAUAAG 
                 4861-4879 
               
               
                   
                   
                   
                 UCUC 
                   
                 1684129.1 
                   
                 AACCAUG 
                   
               
               
                   
               
               
                 AD-887428 
                 A-1684130.1 
                  985 
                 AUGGUUCUUAUCUGU 
                 4862-4880 
                 A- 
                  986 
                 UGAGACAGAUAA 
                 4862-4880 
               
               
                   
                   
                   
                 CUCA 
                   
                 1684131.1 
                   
                 GAACCAU 
                   
               
               
                   
               
               
                 AD-887429 
                 A-1684132.1 
                  987 
                 UGGUUCUUAUCUGUC 
                 4863-4881 
                 A- 
                  988 
                 UUGAGACAGAUA 
                 4863-4881 
               
               
                   
                   
                   
                 UCAA 
                   
                 1684133.1 
                   
                 AGAACCA 
                   
               
               
                   
               
               
                 AD-887430 
                 A-1684134.1 
                  989 
                 GGUUCUUAUCUGUCU 
                 4864-4882 
                 A- 
                  990 
                 GUUGAGACAGAU 
                 4864-4882 
               
               
                   
                   
                   
                 CAAC 
                   
                 1684135.1 
                   
                 AAGAACC 
                   
               
               
                   
               
               
                 AD-887431 
                 A-1684136.1 
                  991 
                 GUUCUUAUCUGUCUC 
                 4865-4883 
                 A- 
                  992 
                 UGUUGAGACAGA 
                 4865-4883 
               
               
                   
                   
                   
                 AACA 
                   
                 1684137.1 
                   
                 UAAGAAC 
                   
               
               
                   
               
               
                 AD-887432 
                 A-1684138.1 
                  993 
                 UCUUAUCUGUCUCAAC 
                 4867-4885 
                 A- 
                  994 
                 CAUGUUGAGACA 
                 4867-4885 
               
               
                   
                   
                   
                 AUG 
                   
                 1684139.1 
                   
                 GAUAAGA 
                   
               
               
                   
               
               
                 AD-887433 
                 A-1684140.1 
                  995 
                 AUCUGUCUCAACAUGG 
                 4871-4889 
                 A- 
                  996 
                 UUACCAUGUUGA 
                 4871-4889 
               
               
                   
                   
                   
                 UAA 
                   
                 1684141.1 
                   
                 GACAGAU 
                   
               
               
                   
               
               
                 AD-887434 
                 A-1684142.1 
                  997 
                 UCUGUCUCAACAUGGU 
                 4872-4890 
                 A- 
                  998 
                 GUUACCAUGUUG 
                 4872-4890 
               
               
                   
                   
                   
                 AAC 
                   
                 1684143.1 
                   
                 AGACAGA 
                   
               
               
                   
               
               
                 AD-887435 
                 A-1684144.1 
                  999 
                 CUGUCUCAACAUGGUA 
                 4873-4891 
                 A- 
                 1000 
                 GGUUACCAUGUU 
                 4873-4891 
               
               
                   
                   
                   
                 ACC 
                   
                 1684145.1 
                   
                 GAGACAG 
                   
               
               
                   
               
               
                 AD-887436 
                 A-1684146.1 
                 1001 
                 UCCUGGUCAUGUUCA 
                 5253-5271 
                 A- 
                 1002 
                 UAGAUGAACAUG 
                 5253-5271 
               
               
                   
                   
                   
                 UCUA 
                   
                 1684147.1 
                   
                 ACCAGGA 
                   
               
               
                   
               
               
                 AD-887437 
                 A-1684148.1 
                 1003 
                 AGUUCAUCCUGGAAGU 
                 5455-5473 
                 A- 
                 1004 
                 UGAACUUCCAGG 
                 5455-5473 
               
               
                   
                   
                   
                 UCA 
                   
                 1684149.1 
                   
                 AUGAACU 
                   
               
               
                   
               
               
                 AD-887438 
                 A-1684150.1 
                 1005 
                 CCAUCUGUUGGAAUAU 
                 5495-5513 
                 A- 
                 1006 
                 AGAAUAUUCCAA 
                 5495-5513 
               
               
                   
                   
                   
                 UCU 
                   
                 1684151.1 
                   
                 CAGAUGG 
                   
               
               
                   
               
               
                 AD-887439 
                 A-1684152.1 
                 1007 
                 CAUCUGUUGGAAUAU 
                 5496-5514 
                 A- 
                 1008 
                 UAGAAUAUUCCA 
                 5496-5514 
               
               
                   
                   
                   
                 UCUA 
                   
                 1684153.1 
                   
                 ACAGAUG 
                   
               
               
                   
               
               
                 AD-887440 
                 A-1684154.1 
                 1009 
                 UCUGUUGGAAUAUUC 
                 5498-5516 
                 A- 
                 1010 
                 AGUAGAAUAUUC 
                 5498-5516 
               
               
                   
                   
                   
                 UACU 
                   
                 1684155.1 
                   
                 CAACAGA 
                   
               
               
                   
               
               
                 AD-887441 
                 A-1684156.1 
                 1011 
                 CAUACUGGAGAAUUU 
                 5572-5590 
                 A- 
                 1012 
                 ACUAAAAUUCUCC 
                 5572-5590 
               
               
                   
                   
                   
                 UAGU 
                   
                 1684157.1 
                   
                 AGUAUG 
                   
               
               
                   
               
               
                 AD-887442 
                 A-1684158.1 
                 1013 
                 CUCCUCUUCUCAUAGC 
                 5730-5748 
                 A- 
                 1014 
                 UUUGCUAUGAGA 
                 5730-5748 
               
               
                   
                   
                   
                 AAA 
                   
                 1684159.1 
                   
                 AGAGGAG 
                   
               
               
                   
               
               
                 AD-887443 
                 A-1684160.1 
                 1015 
                 UCCUCUUCUCAUAGCA 
                 5731-5749 
                 A- 
                 1016 
                 UUUUGCUAUGAG 
                 5731-5749 
               
               
                   
                   
                   
                 AAA 
                   
                 1684161.1 
                   
                 AAGAGGA 
                   
               
               
                   
               
               
                 AD-887444 
                 A-1684162.1 
                 1017 
                 CCUCUUCUCAUAGCAA 
                 5732-5750 
                 A- 
                 1018 
                 GUUUUGCUAUGA 
                 5732-5750 
               
               
                   
                   
                   
                 AAC 
                   
                 1684163.1 
                   
                 GAAGAGG 
                   
               
               
                   
               
               
                 AD-887445 
                 A-1684164.1 
                 1019 
                 CUCUUCUCAUAGCAAA 
                 5733-5751 
                 A- 
                 1020 
                 GGUUUUGCUAUG 
                 5733-5751 
               
               
                   
                   
                   
                 ACC 
                   
                 1684165.1 
                   
                 AGAAGAG 
                   
               
               
                   
               
               
                 AD-887446 
                 A-1684166.1 
                 1021 
                 GAUCCAUUGUCUUGAC 
                 5803-5821 
                 A- 
                 1022 
                 GAUGUCAAGACA 
                 5803-5821 
               
               
                   
                   
                   
                 AUC 
                   
                 1684167.1 
                   
                 AUGGAUC 
                   
               
               
                   
               
               
                 AD-887447 
                 A-1684168.1 
                 1023 
                 AUCCAUUGUCUUGACA 
                 5804-5822 
                 A- 
                 1024 
                 AGAUGUCAAGAC 
                 5804-5822 
               
               
                   
                   
                   
                 UCU 
                   
                 1684169.1 
                   
                 AAUGGAU 
                   
               
               
                   
               
               
                 AD-887448 
                 A-1684170.1 
                 1025 
                 UCCAUUGUCUUGACAU 
                 5805-5823 
                 A- 
                 1026 
                 AAGAUGUCAAGA 
                 5805-5823 
               
               
                   
                   
                   
                 CUU 
                   
                 1684171.1 
                   
                 CAAUGGA 
                   
               
               
                   
               
               
                 AD-887449 
                 A-1684172.1 
                 1027 
                 CAUUGUCUUGACAUCU 
                 5807-5825 
                 A- 
                 1028 
                 AUAAGAUGUCAA 
                 5807-5825 
               
               
                   
                   
                   
                 UAU 
                   
                 1684173.1 
                   
                 GACAAUG 
                   
               
               
                   
               
               
                 AD-887450 
                 A-1684174.1 
                 1029 
                 UUGUCUUGACAUCUU 
                 5809-5827 
                 A- 
                 1030 
                 AAAUAAGAUGUC 
                 5809-5827 
               
               
                   
                   
                   
                 AUUU 
                   
                 1684175.1 
                   
                 AAGACAA 
                   
               
               
                   
               
               
                 AD-887451 
                 A-1684176.1 
                 1031 
                 UGUCUUGACAUCUUA 
                 5810-5828 
                 A- 
                 1032 
                 CAAAUAAGAUGU 
                 5810-5828 
               
               
                   
                   
                   
                 UUUG 
                   
                 1684177.1 
                   
                 CAAGACA 
                   
               
               
                   
               
               
                 AD-887452 
                 A-1684178.1 
                 1033 
                 GUCUUGACAUCUUAU 
                 5811-5829 
                 A- 
                 1034 
                 GCAAAUAAGAUG 
                 5811-5829 
               
               
                   
                   
                   
                 UUGC 
                   
                 1684179.1 
                   
                 UCAAGAC 
                   
               
               
                   
               
               
                 AD-887453 
                 A-1684180.1 
                 1035 
                 GGAGAUGGAUUCUCU 
                 5860-5878 
                 A- 
                 1036 
                 ACGAAGAGAAUCC 
                 5860-5878 
               
               
                   
                   
                   
                 UCGU 
                   
                 1684181.1 
                   
                 AUCUCC 
                   
               
               
                   
               
               
                 AD-887454 
                 A-1684182.1 
                 1037 
                 GAGAUGGAUUCUCUU 
                 5861-5879 
                 A- 
                 1038 
                 AACGAAGAGAAU 
                 5861-5879 
               
               
                   
                   
                   
                 CGUU 
                   
                 1684183.1 
                   
                 CCAUCUC 
                   
               
               
                   
               
               
                 AD-887455 
                 A-1684184.1 
                 1039 
                 AGAUGGAUUCUCUUC 
                 5862-5880 
                 A- 
                 1040 
                 GAACGAAGAGAA 
                 5862-5880 
               
               
                   
                   
                   
                 GUUC 
                   
                 1684185.1 
                   
                 UCCAUCU 
                   
               
               
                   
               
               
                 AD-887456 
                 A-1684186.1 
                 1041 
                 GAUGGAUUCUCUUCG 
                 5863-5881 
                 A- 
                 1042 
                 UGAACGAAGAGA 
                 5863-5881 
               
               
                   
                   
                   
                 UUCA 
                   
                 1684187.1 
                   
                 AUCCAUC 
                   
               
               
                   
               
               
                 AD-887457 
                 A-1684188.1 
                 1043 
                 AUGGAUUCUCUUCGU 
                 5864-5882 
                 A- 
                 1044 
                 GUGAACGAAGAG 
                 5864-5882 
               
               
                   
                   
                   
                 UCAC 
                   
                 1684189.1 
                   
                 AAUCCAU 
                   
               
               
                   
               
               
                 AD-887458 
                 A-1684190.1 
                 1045 
                 UGGAUUCUCUUCGUU 
                 5865-5883 
                 A- 
                 1046 
                 UGUGAACGAAGA 
                 5865-5883 
               
               
                   
                   
                   
                 CACA 
                   
                 1684191.1 
                   
                 GAAUCCA 
                   
               
               
                   
               
               
                 AD-887459 
                 A-1684192.1 
                 1047 
                 GGAUUCUCUUCGUUC 
                 5866-5884 
                 A- 
                 1048 
                 CUGUGAACGAAG 
                 5866-5884 
               
               
                   
                   
                   
                 ACAG 
                   
                 1684193.1 
                   
                 AGAAUCC 
                   
               
               
                   
               
               
                 AD-887460 
                 A-1684194.1 
                 1049 
                 GAUUCUCUUCGUUCAC 
                 5867-5885 
                 A- 
                 1050 
                 UCUGUGAACGAA 
                 5867-5885 
               
               
                   
                   
                   
                 AGA 
                   
                 1684195.1 
                   
                 GAGAAUC 
                   
               
               
                   
               
               
                 AD-887461 
                 A-1684196.1 
                 1051 
                 UUCUCUUCGUUCACAG 
                 5869-5887 
                 A- 
                 1052 
                 CAUCUGUGAACG 
                 5869-5887 
               
               
                   
                   
                   
                 AUG 
                   
                 1684197.1 
                   
                 AAGAGAA 
                   
               
               
                   
               
               
                 AD-887462 
                 A-1684198.1 
                 1053 
                 UCUCUUCGUUCACAGA 
                 5870-5888 
                 A- 
                 1054 
                 CCAUCUGUGAAC 
                 5870-5888 
               
               
                   
                   
                   
                 UGG 
                   
                 1684199.1 
                   
                 GAAGAGA 
                   
               
               
                   
               
               
                 AD-887463 
                 A-1684200.1 
                 1055 
                 CUCUUCGUUCACAGAU 
                 5871-5889 
                 A- 
                 1056 
                 UCCAUCUGUGAA 
                 5871-5889 
               
               
                   
                   
                   
                 GGA 
                   
                 1684201.1 
                   
                 CGAAGAG 
                   
               
               
                   
               
               
                 AD-887464 
                 A-1684202.1 
                 1057 
                 UCUUCGUUCACAGAUG 
                 5872-5890 
                 A- 
                 1058 
                 UUCCAUCUGUGA 
                 5872-5890 
               
               
                   
                   
                   
                 GAA 
                   
                 1684203.1 
                   
                 ACGAAGA 
                   
               
               
                   
               
               
                 AD-887465 
                 A-1684204.1 
                 1059 
                 AGGUUCAUGUCUGCAA 
                 5894-5912 
                 A- 
                 1060 
                 GAUUUGCAGACA 
                 5894-5912 
               
               
                   
                   
                   
                 AUC 
                   
                 1684205.1 
                   
                 UGAACCU 
                   
               
               
                   
               
               
                 AD-887466 
                 A-1684206.1 
                 1061 
                 UCUGCAAAUCCUUCCA 
                 5903-5921 
                 A- 
                 1062 
                 CUUUGGAAGGAU 
                 5903-5921 
               
               
                   
                   
                   
                 AAG 
                   
                 1684207.1 
                   
                 UUGCAGA 
                   
               
               
                   
               
               
                 AD-887467 
                 A-1684208.1 
                 1063 
                 CUGCAAAUCCUUCCAA 
                 5904-5922 
                 A- 
                 1064 
                 ACUUUGGAAGGA 
                 5904-5922 
               
               
                   
                   
                   
                 AGU 
                   
                 1684209.1 
                   
                 UUUGCAG 
                   
               
               
                   
               
               
                 AD-887468 
                 A-1684210.1 
                 1065 
                 GUGUCUGCUACUGUC 
                 5969-5987 
                 A- 
                 1066 
                 GAAUGACAGUAG 
                 5969-5987 
               
               
                   
                   
                   
                 AUUC 
                   
                 1684211.1 
                   
                 CAGACAC 
                   
               
               
                   
               
               
                 AD-887469 
                 A-1684212.1 
                 1067 
                 UGUCUGCUACUGUCA 
                 5970-5988 
                 A- 
                 1068 
                 UGAAUGACAGUA 
                 5970-5988 
               
               
                   
                   
                   
                 UUCA 
                   
                 1684213.1 
                   
                 GCAGACA 
                   
               
               
                   
               
               
                 AD-887470 
                 A-1684214.1 
                 1069 
                 GUCUGCUACUGUCAU 
                 5971-5989 
                 A- 
                 1070 
                 CUGAAUGACAGU 
                 5971-5989 
               
               
                   
                   
                   
                 UCAG 
                   
                 1684215.1 
                   
                 AGCAGAC 
                   
               
               
                   
               
               
                 AD-887471 
                 A-1684216.1 
                 1071 
                 ACCGCUUAAGGCAAAA 
                 6006-6024 
                 A- 
                 1072 
                 ACAUUUUGCCUU 
                 6006-6024 
               
               
                   
                   
                   
                 UGU 
                   
                 1684217.1 
                   
                 AAGCGGU 
                   
               
               
                   
               
               
                 AD-887472 
                 A-1684218.1 
                 1073 
                 CCGCUUAAGGCAAAAU 
                 6007-6025 
                 A- 
                 1074 
                 GACAUUUUGCCU 
                 6007-6025 
               
               
                   
                   
                   
                 GUC 
                   
                 1684219.1 
                   
                 UAAGCGG 
                   
               
               
                   
               
               
                 AD-887473 
                 A-1684220.1 
                 1075 
                 UCUCCACCUUCAUAUG 
                 6158-6176 
                 A- 
                 1076 
                 UAUCAUAUGAAG 
                 6158-6176 
               
               
                   
                   
                   
                 AUA 
                   
                 1684221.1 
                   
                 GUGGAGA 
                   
               
               
                   
               
               
                 AD-887474 
                 A-1684222.1 
                 1077 
                 UGCCAAAAUCCUUUUU 
                 6344-6362 
                 A- 
                 1078 
                 GAUAAAAAGGAU 
                 6344-6362 
               
               
                   
                   
                   
                 AUC 
                   
                 1684223.1 
                   
                 UUUGGCA 
                   
               
               
                   
               
               
                 AD-887475 
                 A-1684224.1 
                 1079 
                 GCCAAAAUCCUUUUUA 
                 6345-6363 
                 A- 
                 1080 
                 UGAUAAAAAGGA 
                 6345-6363 
               
               
                   
                   
                   
                 UCA 
                   
                 1684225.1 
                   
                 UUUUGGC 
                   
               
               
                   
               
               
                 AD-887476 
                 A-1684226.1 
                 1081 
                 UCGUAAGAGAACUCUG 
                 6463-6481 
                 A- 
                 1082 
                 CUACAGAGUUCU 
                 6463-6481 
               
               
                   
                   
                   
                 UAG 
                   
                 1684227.1 
                   
                 CUUACGA 
                   
               
               
                   
               
               
                 AD-887477 
                 A-1684228.1 
                 1083 
                 UCUGCCUUGUCAUCUU 
                 6563-6581 
                 A- 
                 1084 
                 GAAAAGAUGACA 
                 6563-6581 
               
               
                   
                   
                   
                 UUC 
                   
                 1684229.1 
                   
                 AGGCAGA 
                   
               
               
                   
               
               
                 AD-887478 
                 A-1684230.1 
                 1087 
                 CUGCCUUGUCAUCUUU 
                 6564-6582 
                 A- 
                 1086 
                 UGAAAAGAUGAC 
                 6564-6582 
               
               
                   
                   
                   
                 UCA 
                   
                 1684231.1 
                   
                 AAGGCAG 
                   
               
               
                   
               
               
                 AD-887479 
                 A-1684232.1 
                 1085 
                 UGCCUUGUCAUCUUU 
                 6565-6583 
                 A- 
                 1088 
                 GUGAAAAGAUGA 
                 6565-6583 
               
               
                   
                   
                   
                 UCAC 
                   
                 1684233.1 
                   
                 CAAGGCA 
                   
               
               
                   
               
               
                 AD-887480 
                 A-1684234.1 
                 1089 
                 GCCUUGUCAUCUUUUC 
                 6566-6584 
                 A- 
                 1090 
                 UGUGAAAAGAUG 
                 6566-6584 
               
               
                   
                   
                   
                 ACA 
                   
                 1684235.1 
                   
                 ACAAGGC 
                   
               
               
                   
               
               
                 AD-887481 
                 A-1684236.1 
                 1091 
                 CCUUGUCAUCUUUUCA 
                 6567-6585 
                 A- 
                 1092 
                 CUGUGAAAAGAU 
                 6567-6585 
               
               
                   
                   
                   
                 CAG 
                   
                 1684237.1 
                   
                 GACAAGG 
                   
               
               
                   
               
               
                 AD-887482 
                 A-1684238.1 
                 1093 
                 CAUCUUUUCACAGGAU 
                 6573-6591 
                 A- 
                 1094 
                 ACAAUCCUGUGA 
                 6573-6591 
               
               
                   
                   
                   
                 UGU 
                   
                 1684239.1 
                   
                 AAAGAUG 
                   
               
               
                   
               
               
                 AD-887483 
                 A-1684240.1 
                 1095 
                 CCCAUGUAAAUAAACA 
                 6606-6624 
                 A- 
                 1096 
                 UGUUGUUUAUU 
                 6606-6624 
               
               
                   
                   
                   
                 ACA 
                   
                 1684241.1 
                   
                 UACAUGGG 
                   
               
               
                   
               
               
                 AD-887484 
                 A-1684242.1 
                 1097 
                 CAUUCAUCUUGACUCA 
                 6911-6929 
                 A- 
                 1098 
                 AUGUGAGUCAAG 
                 6911-6929 
               
               
                   
                   
                   
                 CAU 
                   
                 1684243.1 
                   
                 AUGAAUG 
                   
               
               
                   
               
               
                 AD-887485 
                 A-1684244.1 
                 1099 
                 ACAUAUUACACUCCUC 
                 7040-7058 
                 A- 
                 1100 
                 UUUGAGGAGUGU 
                 7040-7058 
               
               
                   
                   
                   
                 AAA 
                   
                 1684245.1 
                   
                 AAUAUGU 
                   
               
               
                   
               
               
                 AD-887486 
                 A-1684246.1 
                 1101 
                 CAUAUUACACUCCUCA 
                 7041-7059 
                 A- 
                 1102 
                 UUUUGAGGAGUG 
                 7041-7059 
               
               
                   
                   
                   
                 AAA 
                   
                 1684247.1 
                   
                 UAAUAUG 
                   
               
               
                   
               
               
                 AD-887487 
                 A-1684248.1 
                 1103 
                 UGCCCAAAAUACUGAU 
                 7140-7158 
                 A- 
                 1104 
                 AUUAUCAGUAUU 
                 7140-7158 
               
               
                   
                   
                   
                 AAU 
                   
                 1684249.1 
                   
                 UUGGGCA 
                   
               
               
                   
               
               
                 AD-887488 
                 A-1684250.1 
                 1105 
                 GCCCAAAAUACUGAUA 
                 7141-7159 
                 A- 
                 1106 
                 UAUUAUCAGUAU 
                 7141-7159 
               
               
                   
                   
                   
                 AUA 
                   
                 1684251.1 
                   
                 UUUGGGC 
                   
               
               
                   
               
               
                 AD-887489 
                 A-1684252.1 
                 1107 
                 CUGAUAAUAGUCUCU 
                 7151-7169 
                 A- 
                 1108 
                 UUUAAGAGACUA 
                 7151-7169 
               
               
                   
                   
                   
                 UAAA 
                   
                 1684253.1 
                   
                 UUAUCAG 
                   
               
               
                   
               
               
                 AD-887490 
                 A-1684254.1 
                 1109 
                 GUCAAAUUUUCCUGCU 
                 7177-7195 
                 A- 
                 1110 
                 GAAAGCAGGAAA 
                 7177-7195 
               
               
                   
                   
                   
                 UUC 
                   
                 1684255.1 
                   
                 AUUUGAC 
                   
               
               
                   
               
               
                 AD-887491 
                 A-1684256.1 
                 1111 
                 UCAAAUUUUCCUGCUU 
                 7178-7196 
                 A- 
                 1112 
                 AGAAAGCAGGAA 
                 7178-7196 
               
               
                   
                   
                   
                 UCU 
                   
                 1684257.1 
                   
                 AAUUUGA 
                   
               
               
                   
               
               
                 AD-887492 
                 A-1684258.1 
                 1113 
                 CAAAUUUUCCUGCUUU 
                 7179-7197 
                 A- 
                 1114 
                 AAGAAAGCAGGA 
                 7179-7197 
               
               
                   
                   
                   
                 CUU 
                   
                 1684259.1 
                   
                 AAAUUUG 
                   
               
               
                   
               
               
                 AD-887493 
                 A-1684260.1 
                 1115 
                 AUUGUUUAGUCAUCC 
                 7205-7223 
                 A- 
                 1116 
                 GAAAGGAUGACU 
                 7205-7223 
               
               
                   
                   
                   
                 UUUC 
                   
                 1684261.1 
                   
                 AAACAAU 
                   
               
               
                   
               
               
                 AD-887494 
                 A-1684262.1 
                 1117 
                 GCAUCACUUGUAUACA 
                 7322-7340 
                 A- 
                 1118 
                 GAUUGUAUACAA 
                 7322-7340 
               
               
                   
                   
                   
                 AUC 
                   
                 1684263.1 
                   
                 GUGAUGC 
                   
               
               
                   
               
               
                 AD-887495 
                 A-1684264.1 
                 1119 
                 CACCAACUUACUUUCC 
                 7453-7471 
                 A- 
                 1120 
                 UUAGGAAAGUAA 
                 7453-7471 
               
               
                   
                   
                   
                 UAA 
                   
                 1684265.1 
                   
                 GUUGGUG 
                   
               
               
                   
               
               
                 AD-887496 
                 A-1684266.1 
                 1121 
                 ACCAACUUACUUUCCU 
                 7454-7472 
                 A- 
                 1122 
                 UUUAGGAAAGUA 
                 7454-7472 
               
               
                   
                   
                   
                 AAA 
                   
                 1684267.1 
                   
                 AGUUGGU 
                   
               
               
                   
               
               
                 AD-887497 
                 A-1684268.1 
                 1123 
                 CCAACUUACUUUCCUA 
                 7455-7473 
                 A- 
                 1124 
                 AUUUAGGAAAGU 
                 7455-7473 
               
               
                   
                   
                   
                 AAU 
                   
                 1684269.1 
                   
                 AAGUUGG 
                   
               
               
                   
               
               
                 AD-887498 
                 A-1684270.1 
                 1125 
                 CAACUUACUUUCCUAA 
                 7456-7474 
                 A- 
                 1126 
                 AAUUUAGGAAAG 
                 7456-7474 
               
               
                   
                   
                   
                 AUU 
                   
                 1684271.1 
                   
                 UAAGUUG 
                   
               
               
                   
               
               
                 AD-887499 
                 A-1684272.1 
                 1127 
                 AGGAAGAUGUCACCUU 
                 7517-7535 
                 A- 
                 5814 
                 GAGAAGGUGACA 
                 7517-7535 
               
               
                   
                   
                   
                 CUC 
                   
                 1684273.1 
                   
                 UCUUCCU 
                   
               
               
                   
               
               
                 AD-887500 
                 A-1684274.1 
                 1128 
                 GAAGAUGUCACCUUCU 
                 7519-7537 
                 A- 
                 1130 
                 AGGAGAAGGUGA 
                 7519-7537 
               
               
                   
                   
                   
                 CCU 
                   
                 1684275.1 
                   
                 CAUCUUC 
                   
               
               
                   
               
               
                 AD-887501 
                 A-1684276.1 
                 1131 
                 AGAUGUCACCUUCUCC 
                 7521-7539 
                 A- 
                 1132 
                 UAAGGAGAAGGU 
                 7521-7539 
               
               
                   
                   
                   
                 UUA 
                   
                 1684277.1 
                   
                 GACAUCU 
                   
               
               
                   
               
               
                 AD-887502 
                 A-1684278.1 
                 1133 
                 GAUGUCACCUUCUCCU 
                 7522-7540 
                 A- 
                 1134 
                 UUAAGGAGAAGG 
                 7522-7540 
               
               
                   
                   
                   
                 UAA 
                   
                 1684279.1 
                   
                 UGACAUC 
                   
               
               
                   
               
               
                 AD-887503 
                 A-1684280.1 
                 1135 
                 AUGUCACCUUCUCCUU 
                 7523-7541 
                 A- 
                 1136 
                 UUUAAGGAGAAG 
                 7523-7541 
               
               
                   
                   
                   
                 AAA 
                   
                 1684281.1 
                   
                 GUGACAU 
                   
               
               
                   
               
               
                 AD-887504 
                 A-1684282.1 
                 1137 
                 UGUCACCUUCUCCUUA 
                 7524-7542 
                 A- 
                 1138 
                 UUUUAAGGAGAA 
                 7524-7542 
               
               
                   
                   
                   
                 AAA 
                   
                 1684283.1 
                   
                 GGUGACA 
                   
               
               
                   
               
               
                 AD-887505 
                 A-1684284.1 
                 1139 
                 GUCACCUUCUCCUUAA 
                 7525-7543 
                 A- 
                 1140 
                 AUUUUAAGGAGA 
                 7525-7543 
               
               
                   
                   
                   
                 AAU 
                   
                 1684285.1 
                   
                 AGGUGAC 
                   
               
               
                   
               
               
                 AD-887506 
                 A-1684286.1 
                 1141 
                 UCACCUUCUCCUUAAA 
                 7526-7544 
                 A- 
                 1142 
                 AAUUUUAAGGAG 
                 7526-7544 
               
               
                   
                   
                   
                 AUU 
                   
                 1684287.1 
                   
                 AAGGUGA 
                   
               
               
                   
               
               
                 AD-887507 
                 A-1684288.1 
                 1143 
                 ACCUUCUCCUUAAAAU 
                 7528-7546 
                 A- 
                 1144 
                 AGAAUUUUAAGG 
                 7528-7546 
               
               
                   
                   
                   
                 UCU 
                   
                 1684289.1 
                   
                 AGAAGGU 
                   
               
               
                   
               
               
                 AD-887508 
                 A-1684290.1 
                 1145 
                 CCUUCUCCUUAAAAUU 
                 7529-7547 
                 A- 
                 1146 
                 UAGAAUUUUAAG 
                 7529-7547 
               
               
                   
                   
                   
                 CUA 
                   
                 1684291.1 
                   
                 GAGAAGG 
                   
               
               
                   
               
               
                 AD-887509 
                 A-1684292.1 
                 1147 
                 CUUCUCCUUAAAAUUC 
                 7530-7548 
                 A- 
                 1148 
                 AUAGAAUUUUAA 
                 7530-7548 
               
               
                   
                   
                   
                 UAU 
                   
                 1684293.1 
                   
                 GGAGAAG 
                   
               
               
                   
               
               
                 AD-887510 
                 A-1684294.1 
                 1149 
                 UGAGAUCUUUCUUCU 
                 7721-7739 
                 A- 
                 1150 
                 UUAUAGAAGAAA 
                 7721-7739 
               
               
                   
                   
                   
                 AUAA 
                   
                 1684295.1 
                   
                 GAUCUCA 
                   
               
               
                   
               
               
                 AD-887511 
                 A-1684296.1 
                 1151 
                 GAUCUUUCUUCUAUA 
                 7724-7742 
                 A- 
                 1152 
                 ACUUUAUAGAAG 
                 7724-7742 
               
               
                   
                   
                   
                 AAGU 
                   
                 1684297.1 
                   
                 AAAGAUC 
                   
               
               
                   
               
               
                 AD-887512 
                 A-1684298.1 
                 1153 
                 UACCAUCUUAGGUUCA 
                 8105-8123 
                 A- 
                 1154 
                 GAAUGAACCUAA 
                 8105-8123 
               
               
                   
                   
                   
                 UUC 
                   
                 1684299.1 
                   
                 GAUGGUA 
                   
               
               
                   
               
               
                 AD-887513 
                 A-1684300.1 
                 1155 
                 ACCAUCUUAGGUUCAU 
                 8106-8124 
                 A- 
                 1156 
                 UGAAUGAACCUA 
                 8106-8124 
               
               
                   
                   
                   
                 UCA 
                   
                 1684301.1 
                   
                 AGAUGGU 
                   
               
               
                   
               
               
                 AD-887514 
                 A-1684302.1 
                 1157 
                 CCAUCUUAGGUUCAUU 
                 8107-8125 
                 A- 
                 1158 
                 AUGAAUGAACCU 
                 8107-8125 
               
               
                   
                   
                   
                 CAU 
                   
                 1684303.1 
                   
                 AAGAUGG 
                   
               
               
                   
               
               
                 AD-887515 
                 A-1684304.1 
                 1159 
                 CAUCUUAGGUUCAUUC 
                 8108-8126 
                 A- 
                 1160 
                 GAUGAAUGAACC 
                 8108-8126 
               
               
                   
                   
                   
                 AUC 
                   
                 1684305.1 
                   
                 UAAGAUG 
                   
               
               
                   
               
               
                 AD-887516 
                 A-1684306.1 
                 1161 
                 UCUUAGGUUCAUUCA 
                 8110-8128 
                 A- 
                 1162 
                 AAGAUGAAUGAA 
                 8110-8128 
               
               
                   
                   
                   
                 UCUU 
                   
                 1684307.1 
                   
                 CCUAAGA 
                   
               
               
                   
               
               
                 AD-887517 
                 A-1684308.1 
                 1163 
                 CUUAGGUUCAUUCAUC 
                 8111-8129 
                 A- 
                 1164 
                 UAAGAUGAAUGA 
                 8111-8129 
               
               
                   
                   
                   
                 UUA 
                   
                 1684309.1 
                   
                 ACCUAAG 
                   
               
               
                   
               
               
                 AD-887518 
                 A-1684310.1 
                 1165 
                 UUAGGUUCAUUCAUC 
                 8112-8130 
                 A- 
                 1166 
                 CUAAGAUGAAUG 
                 8112-8130 
               
               
                   
                   
                   
                 UUAG 
                   
                 1684311.1 
                   
                 AACCUAA 
                   
               
               
                   
               
               
                 AD-887519 
                 A-1684312.1 
                 1167 
                 UAGGUUCAUUCAUCU 
                 8113-8131 
                 A- 
                 1168 
                 CCUAAGAUGAAU 
                 8113-8131 
               
               
                   
                   
                   
                 UAGG 
                   
                 1684313.1 
                   
                 GAACCUA 
                   
               
               
                   
               
               
                 AD-887520 
                 A-1684314.1 
                 1169 
                 CUGCAUUAUGAAUACU 
                 8368-8386 
                 A- 
                 1170 
                 GUAAGUAUUCAU 
                 8368-8386 
               
               
                   
                   
                   
                 UAC 
                   
                 1684315.1 
                   
                 AAUGCAG 
                   
               
               
                   
               
               
                 AD-887521 
                 A-1684316.1 
                 1171 
                 ACACAAUUUCUUCUUA 
                 8500-8518 
                 A- 
                 1172 
                 UGCUAAGAAGAA 
                 8500-8518 
               
               
                   
                   
                   
                 GCA 
                   
                 1684317.1 
                   
                 AUUGUGU 
                   
               
               
                   
               
               
                 AD-887522 
                 A-1684318.1 
                 1173 
                 GUUCUUUUUCCUAUU 
                 8541-8559 
                 A- 
                 1174 
                 AUGAAAUAGGAA 
                 8541-8559 
               
               
                   
                   
                   
                 UCAU 
                   
                 1684319.1 
                   
                 AAAGAAC 
                   
               
               
                   
               
               
                 AD-887523 
                 A-1684320.1 
                 1175 
                 UCCUAUUUCAUGAACU 
                 8549-8567 
                 A- 
                 1176 
                 CAUAGUUCAUGA 
                 8549-8567 
               
               
                   
                   
                   
                 AUG 
                   
                 1684321.1 
                   
                 AAUAGGA 
                   
               
               
                   
               
               
                 AD-887524 
                 A-1684322.1 
                 1177 
                 CCUAUUUCAUGAACUA 
                 8550-8568 
                 A- 
                 1178 
                 ACAUAGUUCAUG 
                 8550-8568 
               
               
                   
                   
                   
                 UGU 
                   
                 1684323.1 
                   
                 AAAUAGG 
                   
               
               
                   
               
               
                 AD-887525 
                 A-1684324.1 
                 1179 
                 AUGUCUACUUGUGAC 
                 8623-8641 
                 A- 
                 1180 
                 AAAAGUCACAAG 
                 8623-8641 
               
               
                   
                   
                   
                 UUUU 
                   
                 1684325.1 
                   
                 UAGACAU 
                   
               
               
                   
               
               
                 AD-887526 
                 A-1684326.1 
                 1181 
                 UGUCUACUUGUGACU 
                 8624-8642 
                 A- 
                 1182 
                 AAAAAGUCACAAG 
                 8624-8642 
               
               
                   
                   
                   
                 UUUU 
                   
                 1684327.1 
                   
                 UAGACA 
                   
               
               
                   
               
               
                 AD-887527 
                 A-1684328.1 
                 1183 
                 UCUACUUGUGACUUU 
                 8626-8644 
                 A- 
                 1184 
                 AUAAAAAGUCAC 
                 8626-8644 
               
               
                   
                   
                   
                 UUAU 
                   
                 1684329.1 
                   
                 AAGUAGA 
                   
               
               
                   
               
               
                 AD-887528 
                 A-1684330.1 
                 1185 
                 CUACUUGUGACUUUU 
                 8627-8645 
                 A- 
                 5815 
                 GAUAAAAAGUCA 
                 8627-8645 
               
               
                   
                   
                   
                 UAUC 
                   
                 1684331.1 
                   
                 CAAGUAG 
                   
               
               
                   
               
               
                 AD-887529 
                 A-1684332.1 
                 1186 
                 GUUCUAAAUAGCUAU 
                 9384-9402 
                 A- 
                 1188 
                 UGAAAUAGCUAU 
                 9384-9402 
               
               
                   
                   
                   
                 UUCA 
                   
                 1684333.1 
                   
                 UUAGAAC 
                   
               
               
                   
               
               
                 AD-887530 
                 A-1684334.1 
                 1189 
                 GCUGUUUACAUAGGA 
                 9600-9618 
                 A- 
                 1190 
                 AGAAUCCUAUGU 
                 9600-9618 
               
               
                   
                   
                   
                 UUCU 
                   
                 1684335.1 
                   
                 AAACAGC 
                   
               
               
                   
               
               
                 AD-887531 
                 A-1684336.1 
                 1191 
                 GCUCAAAAUGUUUGA 
                 9644-9662 
                 A- 
                 1192 
                 AAACUCAAACAUU 
                 9644-9662 
               
               
                   
                   
                   
                 GUUU 
                   
                 1684337.1 
                   
                 UUGAGC 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4A 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A siRNA Modified Single Strands and Duplex Sequences 
               
               
                 Column 1 indicates duplex name and the number following the decimal point in a duplex name merely refers to a batch production number. 
               
               
                 Column 2 indicates the name of the sense sequence. Column 3 indicates the sequence ID for the sequence of column 4. Column 4 provides the 
               
               
                 modified sequence of a sense strand suitable for use in a duplex described herein. Column 5 indicates the antisense sequence name. Column 6 
               
               
                 indicates the sequence ID for the sequence of column 7. Column 7 provides the sequence of a modified antisense strand suitable for use in a 
               
               
                 duplex described herein, e.g., a duplex comprising the sense sequence in the same row of the table. Column 8 indicates the position in the target 
               
               
                 mRNA (NM_001365536.1) that is complementary to the antisense strand of Column 7. Column 9 indicated the sequence ID for the sequence of 
               
               
                 column 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 Seq ID 
                   
                   
                   
               
               
                   
                 Sense 
                 Seq ID 
                   
                 Antisense 
                 NO: 
                   
                 mRNA target  
                   
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 sequence 
                 (anti 
                 Antisense sequence 
                 sequence in 
                 Seq ID NO: 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 name 
                 sense) 
                 (5′-3′) 
                 NM_001365536.1 
                 (mRNA target) 
               
               
                   
               
               
                 AD- 
                 A- 
                 1795 
                 ususugu(Ahd)GfaUf 
                 A- 
                 1796 
                 VPusGfsuaaUfuGf 
                 CUUUUGUAGAUCUUG 
                 3339 
               
               
                 796825.1 
                 1525636.1 
                   
                 CfUfugcaauuacaL96 
                 1257916.1 
                   
                 CfaagaUfcUfacaa 
                 CAAUUACC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1797 
                 ususcug(Uhd)GfuAf 
                 A- 
                 1798 
                 VPusGfsugaAfuUf 
                 GCUUCUGUGUAGGAG 
                 3340 
               
               
                 795366.1 
                 1522818.1 
                   
                 GfGfagaauucacaL96 
                 1522819.1 
                   
                 CfuccuAfcAfcaga 
                 AAUUCACU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1799 
                 asusgug(Ahd)AfaCf 
                 A- 
                 1800 
                 VPusAfscguAfaGf 
                 UUAUGUGAAACAAACC 
                 3341 
               
               
                 797565.2 
                 1527044.1 
                   
                 AfAfaccuuacguaL96 
                 1527045.1 
                   
                 GfuuugUfuUfcac 
                 UUACGUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ausasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1801 
                 usgsuag(Ghd)AfgAf 
                 A- 
                 1802 
                 VPusGfsaaaAfgUf 
                 UGUGUAGGAGAAUUC 
                 3342 
               
               
                 795371.1 
                 1522828.1 
                   
                 AfUfucacuuuucaL96 
                 1522829.1 
                   
                 GfaauuCfuCfcuac 
                 ACUUUUCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ascsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1803 
                 usasugu(Ghd)AfaAf 
                 A- 
                 1804 
                 VPusCfsguaAfgGf 
                 AUUAUGUGAAACAAAC 
                 3343 
               
               
                 797564.2 
                 1527042.1 
                   
                 CfAfaaccuuacgaL96 
                 1527043.1 
                   
                 UfuuguUfuCfaca 
                 CUUACGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uasasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1805 
                 asgscau(Ahd)AfaUf 
                 A- 
                 1806 
                 VPusAfsuuuCfgAf 
                 GAAGCAUAAAUGUUU 
                 3344 
               
               
                 795634.2 
                 1523299.1 
                   
                 GfUfuuucgaaauaL96 
                 1523300.1 
                   
                 AfaacaUfuUfaugc 
                 UCGAAAUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 USUSC 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1807 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 1808 
                 VPusUfscacUfaCf 
                 AUGAUCUUCUUUGUC 
                 3345 
               
               
                 795913.1 
                 1523849.1 
                   
                 UfGfucguagugaaL96 
                 1523850.1 
                   
                 GfacaaAfgAfagau 
                 GUAGUGAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1809 
                 gsgscgu(Uhd)GfuAf 
                 A- 
                 1810 
                 VPusGfsagaUfaGf 
                 AAGGCGUUGUAGUUC 
                 3346 
               
               
                 796618.1 
                 1525247.1 
                   
                 GfUfuccuaucucaL96 
                 1525248.1 
                   
                 GfaacuAfcAfacgc 
                 CUAUCUCC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csusu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1811 
                 asuscuu(Chd)UfuUf 
                 A- 
                 1812 
                 VPusAfsucaCfuAf 
                 UGAUCUUCUUUGUCG 
                 3347 
               
               
                 795914.1 
                 1523851.1 
                   
                 GfUfcguagugauaL96 
                 1523852.1 
                   
                 CfgacaAfaGfaaga 
                 UAGUGAUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uscsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1813 
                 usgsguu(Uhd)CfaGf 
                 A- 
                 1814 
                 VPusCfsugaAfuCf 
                 UGUGGUUUCAGCACA 
                 3348 
               
               
                 795739.1 
                 1523509.1 
                   
                 CfAfcagauucagaL96 
                 1523510.1 
                   
                 UfgugcUfgAfaacc 
                 GAUUCAGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ascsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1815 
                 usgsucg(Ahd)GfuAf 
                 A- 
                 1816 
                 VPusCfsaguAfaAf 
                 AAUGUCGAGUACACUU 
                 3349 
               
               
                 795305.1 
                 1522697.1 
                   
                 CfAfcuuuuacugaL96 
                 1522698.1 
                   
                 AfguguAfcUfcgac 
                 UUACUGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1817 
                 asasgca(Ghd)AfaGf 
                 A- 
                 1818 
                 VPusAfsguaUfuCf 
                 ACAAGCAGAAGAUCUG 
                 3350 
               
               
                 797636.2 
                 1527186.1 
                   
                 AfUfcugaauacuaL96 
                 1527187.1 
                   
                 AfgaucUfuCfugcu 
                 AAUACUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1819 
                 csasagu(Ghd)UfuCf 
                 A- 
                 1820 
                 VPusCfsaugAfcAf 
                 UUCAAGUGUUCCUACU 
                 3351 
               
               
                 802471.2 
                 1536717.1 
                   
                 CfUfacugucaugaL96 
                 1536718.1 
                   
                 GfuaggAfaCfacuu 
                 GUCAUGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1821 
                 asusgcu(Ghd)AfgAf 
                 A- 
                 1822 
                 VPusUfsuucGfaCf 
                 AGAUGCUGAGAAAUU 
                 3352 
               
               
                 796209.1 
                 1524439.1 
                   
                 AfAfuugucgaaaaL96 
                 1524440.1 
                   
                 AfauuuCfuCfagca 
                 GUCGAAAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uscsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1823 
                 asusguu(Uhd)CfuAf 
                 A- 
                 1824 
                 VPusAfsucaAfaUf 
                 GUAUGUUUCUAGCUG 
                 3353 
               
               
                 799223.1 
                 1530270.1 
                   
                 GfCfugauuugauaL96 
                 1530271.1 
                   
                 CfagcuAfgAfaaca 
                 AUUUGAUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usasc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1825 
                 gsasgau(Ghd)GfaUf 
                 A- 
                 1826 
                 VPusGfsaacGfaAf 
                 GGGAGAUGGAUUCUC 
                 3354 
               
               
                 799938.1 
                 1531655.1 
                   
                 UfCfucuucguucaL96 
                 1531656.1 
                   
                 GfagaaUfcCfaucu 
                 UUCGUUCA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 cscsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1827 
                 ususgug(Ahd)CfuUf 
                 A- 
                 1828 
                 VPusCfsacuAfaAf 
                 UAUUGUGACUUUAAG 
                 3355 
               
               
                 797036.1 
                 1526036.1 
                   
                 UfAfaguuuagugaL96 
                 1526037.1 
                   
                 CfuuaaAfgUfcaca 
                 UUUAGUGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1829 
                 asusgau(Chd)UfuCf 
                 A- 
                 1830 
                 VPusAfscuaCfgAf 
                 ACAUGAUCUUCUUUG 
                 3356 
               
               
                 795911.1 
                 1523845.1 
                   
                 UfUfugucguaguaL96 
                 1523846.1 
                   
                 CfaaagAfaGfauca 
                 UCGUAGUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1831 
                 asasggg(Ahd)AfaAf 
                 A- 
                 1832 
                 VPusAfscggAfaGf 
                 CAAAGGGAAAACAAUC 
                 3357 
               
               
                 795132.1 
                 1522351.1 
                   
                 CfAfaucuuccguaL96 
                 1522352.1 
                   
                 AfuuguUfuUfcccu 
                 UUCCGUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1833 
                 csusucu(Ghd)AfaAf 
                 A- 
                 1834 
                 VPusCfsaguUfuGf 
                 UUCUUCUGAAACAUCC 
                 3358 
               
               
                 796138.1 
                 1524297.1 
                   
                 CfAfuccaaacugaL96 
                 1524298.1 
                   
                 GfauguUfuCfagaa 
                 AAACUGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1835 
                 ususgcu(Ahd)UfaGf 
                 A- 
                 1836 
                 VPusGfsaccAfaAf 
                 ACUUGCUAUAGGAAAU 
                 3359 
               
               
                 796919.1 
                 1525802.1 
                   
                 GfAfaauuuggucaL96 
                 1525803.1 
                   
                 UfuuccUfaUfagca 
                 UUGGUCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1837 
                 usasuug(Uhd)GfaCf 
                 A- 
                 1838 
                 VPusCfsuaaAfcUf 
                 CUUAUUGUGACUUUA 
                 3360 
               
               
                 797034.1 
                 1526032.1 
                   
                 UfUfuaaguuuagaL96 
                 1526033.1 
                   
                 UfaaagUfcAfcaau 
                 AGUUUAGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1839 
                 ususggc(Ahd)GfaAf 
                 A- 
                 1840 
                 VPusAfsuaaUfcAf 
                 AAUUGGCAGAAACCCU 
                 3361 
               
               
                 795774.1 
                 1523579.1 
                   
                 AfCfccugauuauaL96 
                 1523580.1 
                   
                 GfgguuUfcUfgcca 
                 GAUUAUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1841 
                 ascsaug(Ahd)UfcUf 
                 A- 
                 1842 
                 VPusUfsacgAfcAf 
                 CUACAUGAUCUUCUUU 
                 3362 
               
               
                 795909.1 
                 1523841.1 
                   
                 UfCfuuugucguaaL96 
                 1523842.1 
                   
                 AfagaaGfaUfcaug 
                 GUCGUAG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1843 
                 asgscuu(Ghd)AfaGf 
                 A- 
                 1844 
                 VPusGfsucuAfaUf 
                 UAAGCUUGAAGUAAAA 
                 3363 
               
               
                 802123.1 
                 1536023.1 
                   
                 UfAfaaauuagacaL96 
                 1536024.1 
                   
                 UfuuacUfuCfaagc 
                 UUAGACC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ususa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1845 
                 uscscaa(Ahd)UfcGf 
                 A- 
                 1846 
                 VPusAfsacaUfuCf 
                 GUUCCAAAUCGUUCCG 
                 3364 
               
               
                 798588.2 
                 1529045.1 
                   
                 UfUfccgaauguuaL96 
                 1529046.1 
                   
                 GfgaacGfaUfuugg 
                 AAUGUUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1847 
                 asuscug(Ahd)GfaCf 
                 A- 
                 1848 
                 VPusCfsggcAfaAf 
                 GGAUCUGAGACUGAA 
                 3365 
               
               
                 796396.1 
                 1524811.1 
                   
                 UfGfaauuugccgaL96 
                 1524812.1 
                   
                 UfucagUfcUfcaga 
                 UUUGCCGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uscsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1849 
                 gscsguu(Ghd)UfaGf 
                 A- 
                 1850 
                 VPusGfsgagAfuAf 
                 AGGCGUUGUAGUUCC 
                 3366 
               
               
                 796619.1 
                 1525249.1 
                   
                 UfUfccuaucuccaL96 
                 1525250.1 
                   
                 GfgaacUfaCfaacg 
                 UAUCUCCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 CSCSU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1851 
                 usasuau(Uhd)UfuAf 
                 A- 
                 1852 
                 VPusAfsacgGfaUf 
                 GAUAUAUUUUACAACA 
                 3367 
               
               
                 801647.1 
                 1535071.1 
                   
                 CfAfacauccguuaL96 
                 1535072.1 
                   
                 GfuuguAfaAfaua 
                 UCCGUUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uasusc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1853 
                 asusguc(Ghd)AfgUf 
                 A- 
                 1854 
                 VPusAfsguaAfaAf 
                 AAAUGUCGAGUACACU 
                 3368 
               
               
                 795304.1 
                 1522695.1 
                   
                 AfCfacuuuuacuaL96 
                 1522696.1 
                   
                 GfuguaCfuCfgaca 
                 UUUACUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ususu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1855 
                 usgsaua(Ghd)UfuAf 
                 A- 
                 1856 
                 VPusUfsgcaAfaCf 
                 UUUGAUAGUUACCUA 
                 3369 
               
               
                 802553.1 
                 1536879.1 
                   
                 CfCfuaguuugcaaL96 
                 1536880.1 
                   
                 UfagguAfaCfuauc 
                 GUUUGCAA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1857 
                 gsascuu(Ahd)CfcUf 
                 A- 
                 1858 
                 VPusCfsaauAfcUf 
                 AAGACUUACCUUUAGA 
                 3370 
               
               
                 800819.1 
                 1533415.1 
                   
                 UfUfagaguauugaL96 
                 1533416.1 
                   
                 CfuaaaGfgUfaagu 
                 GUAUUGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csusu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1859 
                 csusaaa(Uhd)UfaUf 
                 A- 
                 1860 
                 VPusAfsgauUfaCf 
                 UCCUAAAUUAUGGAAG 
                 3371 
               
               
                 801263.1 
                 1534303.1 
                   
                 GfGfaaguaaucuaL96 
                 1534304.1 
                   
                 UfuccaUfaAfuuua 
                 UAAUCUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsgsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1861 
                 asgsuca(Ahd)GfuUf 
                 A- 
                 1862 
                 VPusGfsaacGfaUf 
                 CAAGUCAAGUUCCAAA 
                 3372 
               
               
                 798580.1 
                 1529029.1 
                   
                 CfCfaaaucguucaL96 
                 1529030.1 
                   
                 UfuggaAfcUfugac 
                 UCGUUCC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1863 
                 usgsauc(Uhd)UfcUf 
                 A- 
                 1864 
                 VPusCfsacuAfcGf 
                 CAUGAUCUUCUUUGU 
                 3373 
               
               
                 795912.1 
                 1523847.1 
                   
                 UfUfgucguagugaL96 
                 1523848.1 
                   
                 AfcaaaGfaAfgauc 
                 CGUAGUGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1865 
                 gsusuug(Ahd)AfcAf 
                 A- 
                 1866 
                 VPusCfsgaaAfgAf 
                 AGGUUUGAACACAAAU 
                 3374 
               
               
                 802503.1 
                 1536779.1 
                   
                 CfAfaaucuuucgaL96 
                 1536780.1 
                   
                 UfuuguGfuUfcaa 
                 CUUUCGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 acscsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1867 
                 asasguu(Chd)CfaAf 
                 A- 
                 1868 
                 VPusUfsucgGfaAf 
                 UCAAGUUCCAAAUCGU 
                 3375 
               
               
                 798584.2 
                 1529037.1 
                   
                 AfUfcguuccgaaaL96 
                 1529038.1 
                   
                 CfgauuUfgGfaacu 
                 UCCGAAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1869 
                 usgsuag(Ahd)UfcUf 
                 A- 
                 1870 
                 VPusUfsgguAfaUf 
                 UUUGUAGAUCUUGCA 
                 3376 
               
               
                 796827.1 
                 1525638.1 
                   
                 UfGfcaauuaccaaL96 
                 1257918.1 
                   
                 UfgcaaGfaUfcuac 
                 AUUACCAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1871 
                 csasuga(Uhd)CfuUf 
                 A- 
                 1872 
                 VPusCfsuacGfaCf 
                 UACAUGAUCUUCUUU 
                 3377 
               
               
                 795910.1 
                 1523843.1 
                   
                 CfUfuugucguagaL96 
                 1523844.1 
                   
                 AfaagaAfgAfucau 
                 GUCGUAGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsusa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1873 
                 ususgau(Ahd)GfuUf 
                 A- 
                 1874 
                 VPusGfscaaAfcUf 
                 UUUUGAUAGUUACCU 
                 3378 
               
               
                 802552.1 
                 1536877.1 
                   
                 AfCfcuaguuugcaL96 
                 1536878.1 
                   
                 AfgguaAfcUfauca 
                 AGUUUGCA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1875 
                 csasccu(Uhd)CfuCfC 
                 A- 
                 1876 
                 VPusAfsgaaUfuUf 
                 GUCACCUUCUCCUUAA 
                 3379 
               
               
                 801304.1 
                 1534385.1 
                   
                 fUfuaaaauucuaL96 
                 1534386.1 
                   
                 UfaaggAfgAfaggu 
                 AAUUCUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1877 
                 csusgau(Uhd)UfcCf 
                 A- 
                 1878 
                 VPusCfsaccUfuUf 
                 CUCUGAUUUCCUAAGA 
                 3380 
               
               
                 800334.1 
                 1532445.1 
                   
                 UfAfagaaaggugaL96 
                 1532446.1 
                   
                 CfuuagGfaAfauca 
                 AAGGUGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1879 
                 usgsaga(Chd)UfgAf 
                 A- 
                 1880 
                 VPusAfsuuaCfaAf 
                 CUUGAGACUGACACAU 
                 3381 
               
               
                 802946.1 
                 1537662.1 
                   
                 CfAfcauuguaauaL96 
                 1537663.1 
                   
                 UfguguCfaGfucuc 
                 UGUAAUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1881 
                 csusgaa(Uhd)AfuAf 
                 A- 
                 1882 
                 VPusCfscuaAfuAf 
                 GGCUGAAUAUACAAGU 
                 3382 
               
               
                 796087.1 
                 1524195.1 
                   
                 CfAfaguauuaggaL96 
                 1524196.1 
                   
                 CfuuguAfuAfuuca 
                 AUUAGGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gscsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1883 
                 csasacc(Chd)AfaAfA 
                 A- 
                 1884 
                 VPusAfsugcUfaAf 
                 CACAACCCAAAAUACU 
                 3383 
               
               
                 802625.2 
                 1537023.1 
                   
                 fUfacuuagcauaL96 
                 1537024.1 
                   
                 GfuauuUfuGfggu 
                 UAGCAUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ugsusg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1885 
                 csusgau(Ahd)AfuAf 
                 A- 
                 1886 
                 VPusGfsuuuAfaGf 
                 UACUGAUAAUAGUCUC 
                 3384 
               
               
                 800966.1 
                 1533709.1 
                   
                 GfUfcucuuaaacaL96 
                 1533710.1 
                   
                 AfgacuAfuUfauca 
                 UUAAACU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsusa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1887 
                 ususugu(Chd)GfuAf 
                 A- 
                 1888 
                 VPusAfsggaAfaAf 
                 UCUUUGUCGUAGUGA 
                 3385 
               
               
                 795920.1 
                 1523863.1 
                   
                 GfUfgauuuuccuaL96 
                 1523864.1 
                   
                 UfcacuAfcGfacaa 
                 UUUUCCUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1889 
                 usgsaau(Ahd)UfaCf 
                 A- 
                 1890 
                 VPusUfsccuAfaUf 
                 GCUGAAUAUACAAGUA 
                 3386 
               
               
                 796088.1 
                 1524197.1 
                   
                 AfAfguauuaggaaL96 
                 1524198.1 
                   
                 AfcuugUfaUfauuc 
                 UUAGGAG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1891 
                 asgsaug(Ghd)AfuUf 
                 A- 
                 1892 
                 VPusUfsgaaCfgAf 
                 GGAGAUGGAUUCUCU 
                 3387 
               
               
                 799939.1 
                 1531657.1 
                   
                 CfUfcuucguucaaL96 
                 1531658.1 
                   
                 AfgagaAfuCfcauc 
                 UCGUUCAC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uscsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1893 
                 asasuau(Chd)AfuAf 
                 A- 
                 1894 
                 VPusGfsuaaAfcAf 
                 UGAAUAUCAUAAAGCU 
                 3388 
               
               
                 802853.2 
                 1537477.1 
                   
                 AfAfgcuguuuacaL96 
                 1537478.1 
                   
                 GfcuuuAfuGfaua 
                 GUUUACA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uuscsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1895 
                 uscsuuu(Ahd)UfaCf 
                 A- 
                 1896 
                 VPusAfsaccUfaAf 
                 AUUCUUUAUACCAUCU 
                 3389 
               
               
                 801724.1 
                 1535225.1 
                   
                 CfAfucuuagguuaL96 
                 1535226.1 
                   
                 GfauggUfaUfaaag 
                 UAGGUUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1897 
                 gscsaaa(Ghd)GfuCf 
                 A- 
                 1898 
                 VPusGfsaggAfaAf 
                 GAGCAAAGGUCACAAU 
                 3390 
               
               
                 797699.1 
                 1527312.1 
                   
                 AfCfaauuuccucaL96 
                 1527313.1 
                   
                 UfugugAfcCfuuug 
                 UUCCUCA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csusc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1899 
                 asgsuca(Chd)CfaCf 
                 A- 
                 1900 
                 VPusAfscgaAfuGf 
                 UCAGUCACCACUCAGC 
                 3391 
               
               
                 796304.1 
                 1524627.1 
                   
                 UfCfagcauucguaL96 
                 1524628.1 
                   
                 CfugagUfgGfugac 
                 AUUCGUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1901 
                 usgscua(Uhd)AfgGf 
                 A- 
                 1902 
                 VPusAfsgacCfaAf 
                 CUUGCUAUAGGAAAU 
                 3392 
               
               
                 796920.1 
                 1525804.1 
                   
                 AfAfauuuggucuaL96 
                 1525805.1 
                   
                 AfuuucCfuAfuagc 
                 UUGGUCUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1903 
                 gsascag(Ahd)GfaUf 
                 A- 
                 1904 
                 VPusAfsguaAfaUf 
                 GAGACAGAGAUGAUGA 
                 3393 
               
               
                 800110.1 
                 1531997.1 
                   
                 GfAfugauuuacuaL96 
                 1531998.1 
                   
                 CfaucaUfcUfcugu 
                 UUUACUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csusc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1905 
                 asasguc(Ahd)AfgUf 
                 A- 
                 1906 
                 VPusAfsacgAfuUf 
                 GCAAGUCAAGUUCCAA 
                 3394 
               
               
                 798579.1 
                 1529027.1 
                   
                 UfCfcaaaucguuaL96 
                 1529028.1 
                   
                 UfggaaCfuUfgacu 
                 AUCGUUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1907 
                 usasggc(Uhd)AfaUf 
                 A- 
                 1908 
                 VPusAfsaucUfuGf 
                 UUUAGGCUAAUGACCC 
                 3395 
               
               
                 795841.1 
                 1523713.1 
                   
                 GfAfcccaagauuaL96 
                 1523714.1 
                   
                 GfgucaUfuAfgccu 
                 AAGAUUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1909 
                 asasgag(Chd)UfuAf 
                 A- 
                 1910 
                 VPusCfsuuaUfaCf 
                 GAAAGAGCUUAUUAA 
                 3396 
               
               
                 802105.2 
                 1535987.1 
                   
                 UfUfaaguauaagaL96 
                 1535988.1 
                   
                 UfuaauAfaGfcucu 
                 GUAUAAGC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 USUSC 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1911 
                 usgsgaa(Uhd)AfuUf 
                 A- 
                 1912 
                 VPusUfsaacAfaAf 
                 GUUGGAAUAUUCUAC 
                 3397 
               
               
                 799594.1 
                 1531002.1 
                   
                 CfUfacuuuguuaaL96 
                 1531003.1 
                   
                 GfuagaAfuAfuucc 
                 UUUGUUAG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1913 
                 asusgua(Chd)AfgAf 
                 A- 
                 1914 
                 VPusAfsuagAfaUf 
                 CAAUGUACAGAGGUUA 
                 3398 
               
               
                 800661.1 
                 1533099.1 
                   
                 GfGfuuauucuauaL9 
                 1533100.1 
                   
                 AfaccuCfuGfuaca 
                 UUCUAUA 
                   
               
               
                   
                   
                   
                 6 
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1915 
                 asuscgu(Ahd)AfgAf 
                 A- 
                 1916 
                 VPusCfsuacAfgAf 
                 GAAUCGUAAGAGAACU 
                 3399 
               
               
                 800400.1 
                 1532577.1 
                   
                 GfAfacucuguagaL96 
                 1532578.1 
                   
                 GfuucuCfuUfacga 
                 CUGUAGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 USUSC 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1917 
                 csasucu(Ghd)UfuGf 
                 A- 
                 1918 
                 VPusGfsuagAfaUf 
                 CCCAUCUGUUGGAAUA 
                 3400 
               
               
                 799587.1 
                 1530988.1 
                   
                 GfAfauauucuacaL96 
                 1530989.1 
                   
                 AfuuccAfaCfagau 
                 UUCUACU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsgsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1919 
                 gsuscuu(Uhd)AfcUf 
                 A- 
                 1920 
                 VPusGfscaaAfgAf 
                 UGGUCUUUACUGGAA 
                 3401 
               
               
                 796936.1 
                 1525836.1 
                   
                 GfGfaaucuuugcaL96 
                 1525837.1 
                   
                 UfuccaGfuAfaaga 
                 UCUUUGCA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 cscsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1921 
                 csasaca(Chd)AfaUf 
                 A- 
                 1922 
                 VPusGfscuaAfgAf 
                 AACAACACAAUUUCUU 
                 3402 
               
               
                 802014.1 
                 1535805.1 
                   
                 UfUfcuucuuagcaL96 
                 1535806.1 
                   
                 AfgaaaUfuGfugu 
                 CUUAGCA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ugsusu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1923 
                 usgsgau(Uhd)CfuCf 
                 A- 
                 1924 
                 VPusCfsuguGfaAf 
                 GAUGGAUUCUCUUCG 
                 3403 
               
               
                 799942.1 
                 1531663.1 
                   
                 UfUfcguucacagaL96 
                 1531664.1 
                   
                 CfgaagAfgAfaucc 
                 UUCACAGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1925 
                 gsusaug(Uhd)UfuCf 
                 A- 
                 1926 
                 VPusCfsaaaUfcAf 
                 AGGUAUGUUUCUAGC 
                 3404 
               
               
                 799221.1 
                 1530266.1 
                   
                 UfAfgcugauuugaL96 
                 1530267.1 
                   
                 GfcuagAfaAfcaua 
                 UGAUUUGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 cscsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1927 
                 cscsuuc(Chd)UfgAf 
                 A- 
                 1928 
                 VPusCfsuaaCfuGf 
                 AUCCUUCCUGAUAUGC 
                 3405 
               
               
                 801062.1 
                 1533901.1 
                   
                 UfAfugcaguuagaL96 
                 1533902.1 
                   
                 CfauauCfaGfgaag 
                 AGUUAGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1929 
                 gsgsaga(Uhd)GfgAf 
                 A- 
                 1930 
                 VPusAfsacgAfaGf 
                 GGGGAGAUGGAUUCU 
                 3406 
               
               
                 799937.1 
                 1531653.1 
                   
                 UfUfcucuucguuaL96 
                 1531654.1 
                   
                 AfgaauCfcAfucuc 
                 CUUCGUUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 CSCSC 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1931 
                 gsusaga(Ahd)AfaCf 
                 A- 
                 1932 
                 VPusCfsagaUfgUf 
                 AUGUAGAAAACUUUU 
                 3407 
               
               
                 800461.1 
                 1532699.1 
                   
                 UfUfuuacaucugaL96 
                 1532700.1 
                   
                 AfaaagUfuUfucua 
                 ACAUCUGC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1933 
                 asgscgu(Ghd)CfuUf 
                 A- 
                 1934 
                 VPusGfsuaaCfgUf 
                 UCAGCGUGCUUAUAGA 
                 3408 
               
               
                 800058.1 
                 1531895.1 
                   
                 AfUfagacguuacaL96 
                 1531896.1 
                   
                 CfuauaAfgCfacgc 
                 CGUUACC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1935 
                 gsusuuc(Uhd)AfgCf 
                 A- 
                 1936 
                 VPusCfsaauCfaAf 
                 AUGUUUCUAGCUGAU 
                 3409 
               
               
                 799225.1 
                 1530274.1 
                   
                 UfGfauuugauugaL9 
                 1530275.1 
                   
                 AfucagCfuAfgaaa 
                 UUGAUUGA 
                   
               
               
                   
                   
                   
                 6 
                   
                   
                 csasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1937 
                 gscscca(Ahd)AfaUfA 
                 A- 
                 1938 
                 VPusCfsuauUfaUf 
                 CUGCCCAAAAUACUGA 
                 3410 
               
               
                 800956.1 
                 1533689.1 
                   
                 fCfugauaauagaL96 
                 1533690.1 
                   
                 CfaguaUfuUfuggg 
                 UAAUAGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csasg 
                   
                   
               
               
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1939 
                 ususugu(Chd)CfuAf 
                 A- 
                 1940 
                 VPusUfsauaCfgUf 
                 CAUUUGUCCUAAUCUA 
                 3411 
               
               
                 801681.2 
                 1535139.1 
                   
                 AfUfcuacguauaaL96 
                 1535140.1 
                   
                 AfgauuAfgGfacaa 
                 CGUAUAA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1941 
                 usasauc(Ghd)CfuGf 
                 A- 
                 1942 
                 VPusUfsguaAfuAf 
                 UAUAAUCGCUGAACUU 
                 3412 
               
               
                 802206.2 
                 1536189.1 
                   
                 AfAfcuuauuacaaL96 
                 1536190.1 
                   
                 AfguucAfgCfgauu 
                 AUUACAC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1943 
                 ususuga(Ahd)UfuCf 
                 A- 
                 1944 
                 VPusAfsacgGfuAf 
                 AAUUUGAAUUCAAUC 
                 3413 
               
               
                 801883.2 
                 1535543.1 
                   
                 AfAfucuaccguuaL96 
                 1535544.1 
                   
                 GfauugAfaUfucaa 
                 UACCGUUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1945 
                 csuscuu(Uhd)UfgAf 
                 A- 
                 1946 
                 VPusCfsauaGfaCf 
                 AACUCUUUUGAGGAA 
                 3414 
               
               
                 800273.2 
                 1532323.1 
                   
                 GfGfaagucuaugaL96 
                 1532324.1 
                   
                 UfuccuCfaAfaaga 
                 GUCUAUGC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsusu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1947 
                 asgscug(Ahd)UfuUf 
                 A- 
                 1948 
                 VPusAfscguUfuCf 
                 CUAGCUGAUUUGAUU 
                 3415 
               
               
                 799231.2 
                 1530286.1 
                   
                 GfAfuugaaacguaL96 
                 1530287.1 
                   
                 AfaucaAfaUfcagc 
                 GAAACGUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1949 
                 csusuua(Uhd)AfcCf 
                 A- 
                 1950 
                 VPusGfsaacCfuAf 
                 UUCUUUAUACCAUCUU 
                 3416 
               
               
                 801725.1 
                 1535227.1 
                   
                 AfUfcuuagguucaL96 
                 1535228.1 
                   
                 AfgaugGfuAfuaaa 
                 AGGUUCA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1951 
                 ususgca(Ahd)GfcCf 
                 A- 
                 1952 
                 VPusCfsucaCfaUf 
                 GGUUGCAAGCCUCUUA 
                 3417 
               
               
                 794914.1 
                 1521918.1 
                   
                 UfCfuuaugugagaL96 
                 1521919.1 
                   
                 AfagagGfcUfugca 
                 UGUGAGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ascsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1953 
                 ususauu(Ghd)CfaUf 
                 A- 
                 1954 
                 VPusGfsuauAfcAf 
                 AUUUAUUGCAUCACU 
                 3418 
               
               
                 801132.1 
                 1534041.1 
                   
                 CfAfcuuguauacaL96 
                 1534042.1 
                   
                 AfgugaUfgCfaaua 
                 UGUAUACA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1955 
                 ususuca(Chd)AfgGf 
                 A- 
                 1956 
                 VPusCfsuaaUfuAf 
                 CUUUUCACAGGAUUG 
                 3419 
               
               
                 800492.2 
                 1532761.1 
                   
                 AfUfuguaauuagaL96 
                 1532762.1 
                   
                 CfaaucCfuGfugaa 
                 UAAUUAGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1957 
                 csusuuu(Chd)AfcAf 
                 A- 
                 1958 
                 VPusAfsauuAfcAf 
                 AUCUUUUCACAGGAU 
                 3420 
               
               
                 800490.1 
                 1532757.1 
                   
                 GfGfauuguaauuaL96 
                 1532758.1 
                   
                 AfuccuGfuGfaaaa 
                 UGUAAUUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1959 
                 csusgua(Ghd)GfaAf 
                 A- 
                 1960 
                 VPusAfsuaaUfcAf 
                 CUCUGUAGGAAUUAU 
                 3421 
               
               
                 800414.2 
                 1532605.1 
                   
                 UfUfauugauuauaL96 
                 1532606.1 
                   
                 AfuaauUfcCfuaca 
                 UGAUUAUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1961 
                 ususccu(Ghd)AfuAf 
                 A- 
                 1962 
                 VPusAfsacuAfaCf 
                 CCUUCCUGAUAUGCAG 
                 3422 
               
               
                 801064.1 
                 1533905.1 
                   
                 UfGfcaguuaguuaL96 
                 1533906.1 
                   
                 UfgcauAfuCfagga 
                 UUAGUUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1963 
                 gscsaag(Uhd)CfaAf 
                 A- 
                 1964 
                 VPusCfsgauUfuGf 
                 CUGCAAGUCAAGUUCC 
                 3423 
               
               
                 798577.1 
                 1529023.1 
                   
                 GfUfuccaaaucgaL96 
                 1529024.1 
                   
                 GfaacuUfgAfcuug 
                 AAAUCGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1965 
                 gsgsaag(Ahd)AfaGf 
                 A- 
                 1966 
                 VPusCfsagaCfaUf 
                 AUGGAAGAAAGGUUC 
                 3424 
               
               
                 799959.1 
                 1531697.1 
                   
                 GfUfucaugucugaL96 
                 1531698.1 
                   
                 GfaaccUfuUfcuuc 
                 AUGUCUGC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1967 
                 asuscua(Ghd)GfgCf 
                 A- 
                 1968 
                 VPusAfsagaAfuCf 
                 CAAUCUAGGGCUAAAG 
                 3425 
               
               
                 801708.2 
                 1535193.1 
                   
                 UfAfaagauucuuaL96 
                 1535194.1 
                   
                 UfuuagCfcCfuaga 
                 AUUCUUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1969 
                 usasgcu(Ghd)AfuUf 
                 A- 
                 1970 
                 VPusCfsguuUfcAf 
                 UCUAGCUGAUUUGAU 
                 3426 
               
               
                 799230.2 
                 1530284.1 
                   
                 UfGfauugaaacgaL96 
                 1530285.1 
                   
                 AfucaaAfuCfagcu 
                 UGAAACGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1971 
                 csusucc(Uhd)GfaUf 
                 A- 
                 1972 
                 VPusAfscuaAfcUf 
                 UCCUUCCUGAUAUGCA 
                 3427 
               
               
                 801063.1 
                 1533903.1 
                   
                 AfUfgcaguuaguaL96 
                 1533904.1 
                   
                 GfcauaUfcAfggaa 
                 GUUAGUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsgsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1973 
                 ascsuga(Uhd)GfaUf 
                 A- 
                 1974 
                 VPusAfsuucUfuAf 
                 GCACUGAUGAUUCUU 
                 3428 
               
               
                 800382.2 
                 1532541.1 
                   
                 UfCfuuuaagaauaL96 
                 1532542.1 
                   
                 AfagaaUfcAfucag 
                 UAAGAAUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1975 
                 asgsacg(Uhd)UfaCf 
                 A- 
                 1976 
                 VPusUfsgccUfuAf 
                 AUAGACGUUACCGCUU 
                 3429 
               
               
                 800069.1 
                 1531917.1 
                   
                 CfGfcuuaaggcaaL96 
                 1531918.1 
                   
                 AfgcggUfaAfcguc 
                 AAGGCAA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1977 
                 uscsgug(Ghd)CfuCf 
                 A- 
                 1978 
                 VPusCfsagaAfaAf 
                 AUUCGUGGCUCCUUG 
                 3430 
               
               
                 796318.1 
                 1524655.1 
                   
                 CfUfuguuuucugaL96 
                 1524656.1 
                   
                 CfaaggAfgCfcacg 
                 UUUUCUGC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1979 
                 cscsuuu(Chd)UfuCf 
                 A- 
                 1980 
                 VPusGfsggaUfaUf 
                 AGCCUUUCUUCUUUCA 
                 3431 
               
               
                 800849.2 
                 1533475.1 
                   
                 UfUfucauaucccaL96 
                 1533476.1 
                   
                 GfaaagAfaGfaaag 
                 UAUCCCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gscsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1981 
                 csasucu(Uhd)UfuCf 
                 A- 
                 1982 
                 VPusUfsacaAfuCf 
                 GUCAUCUUUUCACAGG 
                 3432 
               
               
                 800487.1 
                 1532751.1 
                   
                 AfCfaggauuguaaL96 
                 1532752.1 
                   
                 CfugugAfaAfagau 
                 AUUGUAA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1983 
                 csusguu(Ghd)GfaAf 
                 A- 
                 1984 
                 VPusUfscaaAfaCf 
                 GCCUGUUGGAAAUAG 
                 3433 
               
               
                 801835.1 
                 1535447.1 
                   
                 AfUfagguuuugaaL96 
                 1535448.1 
                   
                 CfuauuUfcCfaaca 
                 GUUUUGAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsgsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1985 
                 gsgsgag(Ahd)UfgGf 
                 A- 
                 1986 
                 VPusAfscgaAfgAf 
                 UGGGGAGAUGGAUUC 
                 3434 
               
               
                 799936.1 
                 1531651.1 
                   
                 AfUfucucuucguaL96 
                 1531652.1 
                   
                 GfaaucCfaUfcucc 
                 UCUUCGUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 cscsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1987 
                 ususgaa(Uhd)UfcAf 
                 A- 
                 1988 
                 VPusUfsaacGfgUf 
                 AUUUGAAUUCAAUCU 
                 3435 
               
               
                 801884.2 
                 1535545.1 
                   
                 AfUfcuaccguuaaL96 
                 1535546.1 
                   
                 AfgauuGfaAfuuca 
                 ACCGUUAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1989 
                 uscsauc(Uhd)UfaGf 
                 A- 
                 1990 
                 VPusGfsuucAfaAf 
                 AUUCAUCUUAGGCUA 
                 3436 
               
               
                 801747.2 
                 1535271.1 
                   
                 GfCfuauuugaacaL96 
                 1535272.1 
                   
                 UfagccUfaAfgaug 
                 UUUGAACC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1991 
                 usgsauu(Chd)UfuUf 
                 A- 
                 1992 
                 VPusUfsuacGfaUf 
                 GAUGAUUCUUUAAGA 
                 3437 
               
               
                 800387.2 
                 1532551.1 
                   
                 AfAfgaaucguaaaL96 
                 1532552.1 
                   
                 UfcuuaAfaGfaauc 
                 AUCGUAAG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1993 
                 gsusaau(Ghd)GfaCf 
                 A- 
                 1994 
                 VPusUfscauAfaCf 
                 AAGUAAUGGACAUUA 
                 3438 
               
               
                 800606.2 
                 1532989.1 
                   
                 AfUfuaguuaugaaL96 
                 1532990.1 
                   
                 UfaaugUfcCfauua 
                 GUUAUGAA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csusu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1995 
                 ususgag(Ahd)CfuGf 
                 A- 
                 1996 
                 VPusUfsuacAfaUf 
                 ACUUGAGACUGACACA 
                 3439 
               
               
                 802945.2 
                 1537660.1 
                   
                 AfCfacauuguaaaL96 
                 1537661.1 
                   
                 GfugucAfgUfcuca 
                 UUGUAAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1997 
                 gsasauu(Chd)AfaUf 
                 A- 
                 1998 
                 VPusAfsauaAfcGf 
                 UUGAAUUCAAUCUACC 
                 3440 
               
               
                 801886.2 
                 1535549.1 
                   
                 CfUfaccguuauuaL96 
                 1535550.1 
                   
                 GfuagaUfuGfaau 
                 GUUAUUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ucsasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 1999 
                 asusgau(Uhd)CfuUf 
                 A- 
                 2000 
                 VPusUfsacgAfuUf 
                 UGAUGAUUCUUUAAG 
                 3441 
               
               
                 800386.2 
                 1532549.1 
                   
                 UfAfagaaucguaaL96 
                 1532550.1 
                   
                 CfuuaaAfgAfauca 
                 AAUCGUAA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uscsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2001 
                 asgsccu(Ghd)UfuGf 
                 A- 
                 2002 
                 VPusAfsaacCfuAf 
                 CAAGCCUGUUGGAAAU 
                 3442 
               
               
                 801832.1 
                 1535441.1 
                   
                 GfAfaauagguuuaL96 
                 1535442.1 
                   
                 UfuuccAfaCfaggc 
                 AGGUUUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2003 
                 csgsugc(Uhd)UfaUf 
                 A- 
                 2004 
                 VPusCfsgguAfaCf 
                 AGCGUGCUUAUAGACG 
                 3443 
               
               
                 800060.1 
                 1531899.1 
                   
                 AfGfacguuaccgaL96 
                 1531900.1 
                   
                 GfucuaUfaAfgcac 
                 UUACCGC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gscsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2005 
                 ususuag(Uhd)GfgCf 
                 A- 
                 2006 
                 VPusCfsaagAfgUf 
                 ACUUUAGUGGCAAACA 
                 3444 
               
               
                 798332.1 
                 1528540.1 
                   
                 AfAfacacucuugaL96 
                 1528541.1 
                   
                 GfuuugCfcAfcuaa 
                 CUCUUGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2007 
                 ascscuc(Uhd)CfuUf 
                 A- 
                 2008 
                 VPusAfsucuAfcAf 
                 AGACCUCUCUUUCCAU 
                 3445 
               
               
                 802141.2 
                 1536059.1 
                   
                 UfCfcauguagauaL96 
                 1536060.1 
                   
                 UfggaaAfgAfgagg 
                 GUAGAUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 USCSU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2009 
                 csasacu(Uhd)AfcUf 
                 A- 
                 2010 
                 VPusUfsaauUfuAf 
                 ACCAACUUACUUUCCU 
                 3446 
               
               
                 801251.1 
                 1534279.1 
                   
                 UfUfccuaaauuaaL96 
                 1534280.1 
                   
                 GfgaaaGfuAfaguu 
                 AAAUUAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsgsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2011 
                 gscsuga(Ahd)CfcUf 
                 A- 
                 2012 
                 VPusUfscggAfaUf 
                 AGGCUGAACCUAUGAA 
                 3447 
               
               
                 797963.1 
                 1527829.1 
                   
                 AfUfgaauuccgaaL96 
                 1527830.1 
                   
                 UfcauaGfgUfucag 
                 UUCCGAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 CSCSU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2013 
                 usasuca(Ahd)AfaUf 
                 A- 
                 2014 
                 VPusCfscuuCfgAf 
                 UUUAUCAAAAUAUUC 
                 3448 
               
               
                 800297.2 
                 1532371.1 
                   
                 AfUfucucgaaggaL96 
                 1532372.1 
                   
                 GfaauaUfuUfuga 
                 UCGAAGGC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uasasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2015 
                 ascsauc(Chd)GfuUf 
                 A- 
                 2016 
                 VPusCfsucaAfaGf 
                 CAACAUCCGUUAUUAC 
                 3449 
               
               
                 801658.2 
                 1535093.1 
                   
                 AfUfuacuuugagaL96 
                 1535094.1 
                   
                 UfaauaAfcGfgaug 
                 UUUGAGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2017 
                 asgsaca(Uhd)UfuGf 
                 A- 
                 2018 
                 VPusGfsuagAfuUf 
                 UGAGACAUUUGUCCUA 
                 3450 
               
               
                 801676.2 
                 1535129.1 
                   
                 UfCfcuaaucuacaL96 
                 1535130.1 
                   
                 AfggacAfaAfuguc 
                 AUCUACG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uscsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2019 
                 usgscca(Chd)UfgAf 
                 A- 
                 2020 
                 VPusCfsaguAfcUf 
                 GUUGCCACUGAAGAAA 
                 3451 
               
               
                 799683.1 
                 1531160.1 
                   
                 AfGfaaaguacugaL96 
                 1531161.1 
                   
                 UfucuuCfaGfuggc 
                 GUACUGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2021 
                 uscsauc(Uhd)UfuUf 
                 A- 
                 2022 
                 VPusAfscaaUfcCf 
                 UGUCAUCUUUUCACAG 
                 3452 
               
               
                 800486.1 
                 1532749.1 
                   
                 CfAfcaggauuguaL96 
                 1532750.1 
                   
                 UfgugaAfaAfgaug 
                 GAUUGUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ascsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2023 
                 csgsgac(Uhd)UfgGf 
                 A- 
                 2024 
                 VPusGfsagaUfaGf 
                 GUCGGACUUGGUUACC 
                 3453 
               
               
                 798672.1 
                 1529207.1 
                   
                 UfUfaccuaucucaL96 
                 1529208.1 
                   
                 GfuaacCfaAfgucc 
                 UAUCUCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2025 
                 csuscuu(Uhd)CfcAf 
                 A- 
                 2026 
                 VPusAfsguaAfuCf 
                 CUCUCUUUCCAUGUAG 
                 3454 
               
               
                 802145.2 
                 1536067.1 
                   
                 UfGfuagauuacuaL9 
                 1536068.1 
                   
                 UfacauGfgAfaaga 
                 AUUACUG 
                   
               
               
                   
                   
                   
                 6 
                   
                   
                 gsasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2027 
                 ascsaac(Uhd)UfuCf 
                 A- 
                 2028 
                 VPusAfsgcaAfaUf 
                 AAACAACUUUCACUAA 
                 3455 
               
               
                 801540.2 
                 1534857.1 
                   
                 AfCfuaauuugcuaL96 
                 1534858.1 
                   
                 UfagugAfaAfguug 
                 UUUGCUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 USUSU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2029 
                 usascaa(Chd)AfuCf 
                 A- 
                 2030 
                 VPusAfsaguAfaUf 
                 UUUACAACAUCCGUUA 
                 3456 
               
               
                 801654.2 
                 1535085.1 
                   
                 CfGfuuauuacuuaL96 
                 1535086.1 
                   
                 AfacggAfuGfuugu 
                 UUACUUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2031 
                 asasugu(Chd)GfgAf 
                 A- 
                 2032 
                 VPusAfsgguAfaCf 
                 AUAAUGUCGGACUUG 
                 3457 
               
               
                 798667.1 
                 1529197.1 
                   
                 CfUfugguuaccuaL96 
                 1529198.1 
                   
                 CfaaguCfcGfacau 
                 GUUACCUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2033 
                 ascsaac(Ahd)UfcCf 
                 A- 
                 2034 
                 VPusAfsaagUfaAf 
                 UUACAACAUCCGUUAU 
                 3458 
               
               
                 801655.2 
                 1535087.1 
                   
                 GfUfuauuacuuuaL9 
                 1535088.1 
                   
                 UfaacgGfaUfguug 
                 UACUUUG 
                   
               
               
                   
                   
                   
                 6 
                   
                   
                 usasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2035 
                 csusucu(Uhd)AfgCf 
                 A- 
                 2036 
                 VPusGfsccuAfaAf 
                 GCCUUCUUAGCCUUGU 
                 3459 
               
               
                 795826.1 
                 1523683.1 
                   
                 CfUfuguuuaggcaL96 
                 1523684.1 
                   
                 CfaaggCfuAfagaa 
                 UUAGGCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsgsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2037 
                 ascsaca(Ghd)GfuAf 
                 A- 
                 2038 
                 VPusAfsaacUfaCf 
                 CUACACAGGUAGAAUG 
                 3460 
               
               
                 801490.2 
                 1534757.1 
                   
                 GfAfauguaguuuaL9 
                 1534758.1 
                   
                 AfuucuAfcCfugug 
                 UAGUUUU 
                   
               
               
                   
                   
                   
                 6 
                   
                   
                 usasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2039 
                 csusgaa(Chd)CfuAf 
                 A- 
                 2040 
                 VPusAfsucgGfaAf 
                 GGCUGAACCUAUGAAU 
                 3461 
               
               
                 797964.1 
                 1527831.1 
                   
                 UfGfaauuccgauaL96 
                 1527832.1 
                   
                 UfucauAfgGfuuca 
                 UCCGAUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gscsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2041 
                 asusucu(Uhd)UfaAf 
                 A- 
                 2042 
                 VPusUfscuuAfcGf 
                 UGAUUCUUUAAGAAU 
                 3462 
               
               
                 800389.2 
                 1532555.1 
                   
                 GfAfaucguaagaaL96 
                 1532556.1 
                   
                 AfuucuUfaAfagaa 
                 CGUAAGAG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uscsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2043 
                 gsasuuc(Uhd)UfuAf 
                 A- 
                 2044 
                 VPusCfsuuaCfgAf 
                 AUGAUUCUUUAAGAA 
                 3463 
               
               
                 800388.2 
                 1532553.1 
                   
                 AfGfaaucguaagaL96 
                 1532554.1 
                   
                 UfucuuAfaAfgaau 
                 UCGUAAGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2045 
                 gsusuuc(Ahd)GfgAf 
                 A- 
                 2046 
                 VPusCfsaagUfaGf 
                 UUGUUUCAGGAAUGU 
                 3464 
               
               
                 802070.2 
                 1535917.1 
                   
                 AfUfgucuacuugaL96 
                 1535918.1 
                   
                 AfcauuCfcUfgaaa 
                 CUACUUGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2047 
                 usasuag(Ahd)AfaCf 
                 A- 
                 2048 
                 VPusCfsauaAfaUf 
                 CCUAUAGAAACAAAGA 
                 3465 
               
               
                 801601.2 
                 1534979.1 
                   
                 AfAfagauuuaugaL96 
                 1534980.1 
                   
                 CfuuugUfuUfcua 
                 UUUAUGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uasgsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2049 
                 ususaca(Ahd)CfaUf 
                 A- 
                 2050 
                 VPusAfsguaAfuAf 
                 UUUUACAACAUCCGUU 
                 3466 
               
               
                 801653.1 
                 1535083.1 
                   
                 CfCfguuauuacuaL96 
                 1535084.1 
                   
                 AfcggaUfgUfugua 
                 AUUACUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2051 
                 ususuca(Ghd)GfaAf 
                 A- 
                 2052 
                 VPusAfscaaGfuAf 
                 UGUUUCAGGAAUGUC 
                 3467 
               
               
                 802071.2 
                 1535919.1 
                   
                 UfGfucuacuuguaL96 
                 1535920.1 
                   
                 GfacauUfcCfugaa 
                 UACUUGUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ascsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2053 
                 gsasuaa(Uhd)AfgUf 
                 A- 
                 2054 
                 VPusGfsaguUfuAf 
                 CUGAUAAUAGUCUCU 
                 3468 
               
               
                 800968.2 
                 1533713.1 
                   
                 CfUfcuuaaacucaL96 
                 1533714.1 
                   
                 AfgagaCfuAfuuau 
                 UAAACUCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2055 
                 asgsagg(Uhd)UfaUf 
                 A- 
                 2056 
                 VPusCfsaaaAfuAf 
                 ACAGAGGUUAUUCUA 
                 3469 
               
               
                 800667.2 
                 1533111.1 
                   
                 UfCfuauauuuugaL96 
                 1533112.1 
                   
                 UfagaaUfaAfccuc 
                 UAUUUUGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2057 
                 uscsaca(Ahd)CfcAfC 
                 A- 
                 2058 
                 VPusCfscguUfuUf 
                 CAUCACAACCACACUAA 
                 3470 
               
               
                 800008.2 
                 1531795.1 
                   
                 fAfcuaaaacggaL96 
                 1531796.1 
                   
                 AfguguGfgUfugu 
                 AACGGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gasusg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2059 
                 ascsaca(Ahd)UfuUf 
                 A- 
                 2060 
                 VPusAfsugcUfaAf 
                 CAACACAAUUUCUUCU 
                 3471 
               
               
                 802016.2 
                 1535809.1 
                   
                 CfUfucuuagcauaL96 
                 1535810.1 
                   
                 GfaagaAfaUfugug 
                 UAGCAUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2061 
                 uscsauc(Chd)UfgGf 
                 A- 
                 2062 
                 VPusCfsaacUfgAf 
                 GUUCAUCCUGGAAGU 
                 3472 
               
               
                 799549.1 
                 1530912.1 
                   
                 AfAfguucaguugaL96 
                 1530913.1 
                   
                 AfcuucCfaGfgaug 
                 UCAGUUGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2063 
                 ususgca(Uhd)CfaGf 
                 A- 
                 2064 
                 VPusAfsuaaAfuUf 
                 CAUUGCAUCAGAACCA 
                 3473 
               
               
                 800706.2 
                 1533189.1 
                   
                 AfAfccaauuuauaL96 
                 1533190.1 
                   
                 GfguucUfgAfugca 
                 AUUUAUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2065 
                 ususcau(Chd)UfuAf 
                 A- 
                 2066 
                 VPusUfsucaAfaUf 
                 CAUUCAUCUUAGGCUA 
                 3474 
               
               
                 801746.2 
                 1535269.1 
                   
                 GfGfcuauuugaaaL96 
                 1535270.1 
                   
                 AfgccuAfaGfauga 
                 UUUGAAC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2067 
                 gsasuuc(Uhd)UfuAf 
                 A- 
                 2068 
                 VPusCfsuaaGfaUf 
                 AAGAUUCUUUAUACCA 
                 3475 
               
               
                 801721.2 
                 1535219.1 
                   
                 UfAfccaucuuagaL96 
                 1535220.1 
                   
                 GfguauAfaAfgaau 
                 UCUUAGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csusu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2069 
                 asusaau(Chd)GfcUf 
                 A- 
                 2070 
                 VPusGfsuaaUfaAf 
                 UUAUAAUCGCUGAACU 
                 3476 
               
               
                 802205.2 
                 1536187.1 
                   
                 GfAfacuuauuacaL96 
                 1536188.1 
                   
                 GfuucaGfcGfauua 
                 UAUUACA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2071 
                 asusuug(Uhd)CfcUf 
                 A- 
                 2072 
                 VPusAfsuacGfuAf 
                 ACAUUUGUCCUAAUCU 
                 3477 
               
               
                 801680.2 
                 1535137.1 
                   
                 AfAfucuacguauaL96 
                 1535138.1 
                   
                 GfauuaGfgAfcaaa 
                 ACGUAUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2073 
                 ususuua(Chd)AfuCf 
                 A- 
                 2074 
                 VPusAfsugaCfaAf 
                 ACUUUUACAUCUGCCU 
                 3478 
               
               
                 800470.1 
                 1532717.1 
                   
                 UfGfccuugucauaL96 
                 1532718.1 
                   
                 GfgcagAfuGfuaaa 
                 UGUCAUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2075 
                 ascsauu(Uhd)GfuCf 
                 A- 
                 2076 
                 VPusAfscguAfgAf 
                 AGACAUUUGUCCUAAU 
                 3479 
               
               
                 801678.2 
                 1535133.1 
                   
                 CfUfaaucuacguaL96 
                 1535134.1 
                   
                 UfuaggAfcAfaaug 
                 CUACGUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uscsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2077 
                 usgsuuu(Ahd)GfuCf 
                 A- 
                 2078 
                 VPusAfsgcgAfaAf 
                 AUUGUUUAGUCAUCC 
                 3480 
               
               
                 801022.2 
                 1533821.1 
                   
                 AfUfccuuucgcuaL96 
                 1533822.1 
                   
                 GfgaugAfcUfaaac 
                 UUUCGCUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2079 
                 uscsucc(Uhd)UfaAf 
                 A- 
                 2080 
                 VPusAfsucaUfaGf 
                 CUUCUCCUUAAAAUUC 
                 3481 
               
               
                 801309.2 
                 1534395.1 
                   
                 AfAfuucuaugauaL96 
                 1534396.1 
                   
                 AfauuuUfaAfggag 
                 UAUGAUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2081 
                 ascsagg(Ahd)UfuGf 
                 A- 
                 2082 
                 VPusAfsagaCfuAf 
                 UCACAGGAUUGUAAU 
                 3482 
               
               
                 800496.2 
                 1532769.1 
                   
                 UfAfauuagucuuaL96 
                 1532770.1 
                   
                 AfuuacAfaUfccug 
                 UAGUCUUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2083 
                 usasggu(Uhd)CfaUf 
                 A- 
                 2084 
                 VPusGfsccuAfaGf 
                 CUUAGGUUCAUUCAUC 
                 3483 
               
               
                 801738.2 
                 1535253.1 
                   
                 UfCfaucuuaggcaL96 
                 1535254.1 
                   
                 AfugaaUfgAfaccu 
                 UUAGGCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2085 
                 asascaa(Chd)UfuUf 
                 A- 
                 2086 
                 VPusGfscaaAfuUf 
                 AAAACAACUUUCACUA 
                 3484 
               
               
                 801539.2 
                 1534855.1 
                   
                 CfAfcuaauuugcaL96 
                 1534856.1 
                   
                 AfgugaAfaGfuugu 
                 AUUUGCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ususu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2087 
                 asasgcc(Uhd)UfuGf 
                 A- 
                 2088 
                 VPusGfsauaCfuAf 
                 UCAAGCCUUUGAUAU 
                 3485 
               
               
                 799010.2 
                 1529846.1 
                   
                 AfUfauuaguaucaL96 
                 1529847.1 
                   
                 AfuaucAfaAfggcu 
                 UAGUAUCA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2089 
                 csusuuc(Uhd)UfcUf 
                 A- 
                 2090 
                 VPusAfsgggAfuAf 
                 GCCUUUCUUCUUUCAU 
                 3486 
               
               
                 800850.2 
                 1533477.1 
                   
                 UfUfcauaucccuaL96 
                 1533478.1 
                   
                 UfgaaaGfaAfgaaa 
                 AUCCCUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsgsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2091 
                 uscsaca(Ghd)GfaUf 
                 A- 
                 2092 
                 VPusGfsacuAfaUf 
                 UUUCACAGGAUUGUA 
                 3487 
               
               
                 800494.2 
                 1532765.1 
                   
                 UfGfuaauuagucaL96 
                 1532766.1 
                   
                 UfacaaUfcCfugug 
                 AUUAGUCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2093 
                 ususgcc(Chd)UfuAf 
                 A- 
                 2094 
                 VPusAfscuaAfcAf 
                 UUUUGCCCUUAUGAA 
                 3488 
               
               
                 798614.1 
                 1529091.1 
                   
                 UfGfaauguuaguaL96 
                 1529092.1 
                   
                 UfucauAfaGfggca 
                 UGUUAGUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2095 
                 csasuca(Ghd)AfaCfC 
                 A- 
                 2096 
                 VPusCfsauaUfaAf 
                 UGCAUCAGAACCAAUU 
                 3489 
               
               
                 800709.2 
                 1533195.1 
                   
                 fAfauuuauaugaL96 
                 1533196.1 
                   
                 AfuuggUfuCfugau 
                 UAUAUGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gscsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2097 
                 asusuca(Ahd)UfcUf 
                 A- 
                 2098 
                 VPusGfsaaaUfaAf 
                 GAAUUCAAUCUACCGU 
                 3490 
               
               
                 801888.2 
                 1535553.1 
                   
                 AfCfcguuauuucaL96 
                 1535554.1 
                   
                 CfgguaGfaUfugaa 
                 UAUUUCA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 USUSC 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2099 
                 ususucg(Chd)UfgUf 
                 A- 
                 2100 
                 VPusCfsaacUfuUf 
                 CCUUUCGCUGUAAGCA 
                 3491 
               
               
                 801035.2 
                 1533847.1 
                   
                 AfAfgcaaaguugaL96 
                 1533848.1 
                   
                 GfcuuaCfaGfcgaa 
                 AAGUUGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2101 
                 asusugu(Uhd)UfaGf 
                 A- 
                 2102 
                 VPusCfsgaaAfgGf 
                 GUAUUGUUUAGUCAU 
                 3492 
               
               
                 801020.2 
                 1533817.1 
                   
                 UfCfauccuuucgaL96 
                 1533818.1 
                   
                 AfugacUfaAfacaa 
                 CCUUUCGC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usasc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2103 
                 gsasgac(Ahd)UfuUf 
                 A- 
                 2104 
                 VPusUfsagaUfuAf 
                 UUGAGACAUUUGUCC 
                 3493 
               
               
                 801675.2 
                 1535127.1 
                   
                 GfUfccuaaucuaaL96 
                 1535128.1 
                   
                 GfgacaAfaUfgucu 
                 UAAUCUAC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2105 
                 ususgcc(Ahd)AfcUf 
                 A- 
                 2106 
                 VPusGfscaaGfaGf 
                 UCUUGCCAACUUGCUC 
                 3494 
               
               
                 801228.2 
                 1534233.1 
                   
                 UfGfcucucuugcaL96 
                 1534234.1 
                   
                 AfgcaaGfuUfggca 
                 UCUUGCC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2107 
                 asusgua(Uhd)AfuUf 
                 A- 
                 2108 
                 VPusUfscacUfaGf 
                 GGAUGUAUAUUUGAC 
                 3495 
               
               
                 798984.1 
                 1529794.1 
                   
                 UfGfaccuagugaaL96 
                 1529795.1 
                   
                 GfucaaAfuAfuaca 
                 CUAGUGAC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 uscsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2109 
                 csascag(Ghd)AfuUf 
                 A- 
                 2110 
                 VPusAfsgacUfaAf 
                 UUCACAGGAUUGUAA 
                 3496 
               
               
                 800495.2 
                 1532767.1 
                   
                 GfUfaauuagucuaL96 
                 1532768.1 
                   
                 UfuacaAfuCfcugu 
                 UUAGUCUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2111 
                 gsasugu(Uhd)UfgAf 
                 A- 
                 2112 
                 VPusAfscacGfaAf 
                 AAGAUGUUUGACAGG 
                 3497 
               
               
                 801957.2 
                 1535691.1 
                   
                 CfAfgguucguguaL96 
                 1535692.1 
                   
                 CfcuguCfaAfacau 
                 UUCGUGUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csusu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2113 
                 usasgcu(Ghd)UfaGf 
                 A- 
                 2114 
                 VPusAfsaacUfaGf 
                 AUUAGCUGUAGACAUC 
                 3498 
               
               
                 801399.2 
                 1534575.1 
                   
                 AfCfaucuaguuuaL96 
                 1534576.1 
                   
                 AfugucUfaCfagcu 
                 UAGUUUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2115 
                 usascac(Ahd)GfgUf 
                 A- 
                 2116 
                 VPusAfsacuAfcAf 
                 GCUACACAGGUAGAAU 
                 3499 
               
               
                 801489.2 
                 1534755.1 
                   
                 AfGfaauguaguuaL96 
                 1534756.1 
                   
                 UfucuaCfcUfgugu 
                 GUAGUUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2117 
                 asgsucu(Chd)UfuAf 
                 A- 
                 2118 
                 VPusAfscaaAfaGf 
                 AUAGUCUCUUAAACUC 
                 3500 
               
               
                 800974.2 
                 1533725.1 
                   
                 AfAfcucuuuuguaL96 
                 1533726.1 
                   
                 AfguuuAfaGfagac 
                 UUUUGUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usasu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2119 
                 asuscac(Ahd)AfcCfA 
                 A- 
                 2120 
                 VPusCfsguuUfuAf 
                 CCAUCACAACCACACUA 
                 3501 
               
               
                 800007.2 
                 1531793.1 
                   
                 fCfacuaaaacgaL96 
                 1531794.1 
                   
                 GfugugGfuUfgug 
                 AAACGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ausgsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2121 
                 csasuuu(Ghd)UfcCf 
                 A- 
                 2122 
                 VPusUfsacgUfaGf 
                 GACAUUUGUCCUAAUC 
                 3502 
               
               
                 801679.2 
                 1535135.1 
                   
                 UfAfaucuacguaaL96 
                 1535136.1 
                   
                 AfuuagGfaCfaaau 
                 UACGUAU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsusc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2123 
                 csusgcc(Ahd)AfgUf 
                 A- 
                 2124 
                 VPusAfscucUfaUf 
                 UGCUGCCAAGUUAACA 
                 3503 
               
               
                 798031.1 
                 1527964.1 
                   
                 UfAfacauagaguaL96 
                 1527965.1 
                   
                 GfuuaaCfuUfggca 
                 UAGAGUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gscsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2125 
                 asusuag(Chd)UfgUf 
                 A- 
                 2126 
                 VPusAfscuaGfaUf 
                 GCAUUAGCUGUAGACA 
                 3504 
               
               
                 801397.2 
                 1534571.1 
                   
                 AfGfacaucuaguaL96 
                 1534572.1 
                   
                 GfucuaCfaGfcuaa 
                 UCUAGUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2127 
                 gsuscuc(Uhd)UfaAf 
                 A- 
                 2128 
                 VPusGfsacaAfaAf 
                 UAGUCUCUUAAACUCU 
                 3505 
               
               
                 800975.2 
                 1533727.1 
                   
                 AfCfucuuuugucaL96 
                 1533728.1 
                   
                 GfaguuUfaAfgaga 
                 UUUGUCA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csusa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2129 
                 gsascau(Uhd)UfgUf 
                 A- 
                 2130 
                 VPusCfsguaGfaUf 
                 GAGACAUUUGUCCUAA 
                 3506 
               
               
                 801677.2 
                 1535131.1 
                   
                 CfCfuaaucuacgaL96 
                 1535132.1 
                   
                 UfaggaCfaAfaugu 
                 UCUACGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 csusc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2131 
                 ususcuu(Uhd)AfuAf 
                 A- 
                 2132 
                 VPusAfsccuAfaGf 
                 GAUUCUUUAUACCAUC 
                 3507 
               
               
                 801723.2 
                 1535223.1 
                   
                 CfCfaucuuagguaL96 
                 1535224.1 
                   
                 AfugguAfuAfaaga 
                 UUAGGUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2133 
                 csascag(Ghd)UfaGf 
                 A- 
                 2134 
                 VPusAfsaaaCfuAf 
                 UACACAGGUAGAAUGU 
                 3508 
               
               
                 801491.2 
                 1534759.1 
                   
                 AfAfuguaguuuuaL96 
                 1534760.1 
                   
                 CfauucUfaCfcugu 
                 AGUUUUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsusa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2135 
                 asusgua(Ghd)AfuUf 
                 A- 
                 2136 
                 VPusGfsuacAfaAf 
                 CCAUGUAGAUUACUGU 
                 3509 
               
               
                 802153.2 
                 1536083.1 
                   
                 AfCfuguuuguacaL96 
                 1536084.1 
                   
                 CfaguaAfuCfuaca 
                 UUGUACU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2137 
                 uscsacu(Uhd)GfuAf 
                 A- 
                 2138 
                 VPusAfscggGfaUf 
                 CAUCACUUGUAUACAA 
                 3510 
               
               
                 801140.2 
                 1534057.1 
                   
                 UfAfcaaucccguaL96 
                 1534058.1 
                   
                 UfguauAfcAfagug 
                 UCCCGUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asusg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2139 
                 asusuca(Uhd)CfuUf 
                 A- 
                 2140 
                 VPusUfscaaAfuAf 
                 UCAUUCAUCUUAGGCU 
                 3511 
               
               
                 801745.2 
                 1535267.1 
                   
                 AfGfgcuauuugaaL96 
                 1535268.1 
                   
                 GfccuaAfgAfugaa 
                 AUUUGAA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 usgsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2141 
                 csasuuc(Ahd)UfcUf 
                 A- 
                 2142 
                 VPusCfsaaaUfaGf 
                 UUCAUUCAUCUUAGGC 
                 3512 
               
               
                 801744.2 
                 1535265.1 
                   
                 UfAfggcuauuugaL96 
                 1535266.1 
                   
                 CfcuaaGfaUfgaau 
                 UAUUUGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2143 
                 asgsagc(Uhd)UfaUf 
                 A- 
                 2144 
                 VPusGfscuuAfuAf 
                 AAAGAGCUUAUUAAG 
                 3513 
               
               
                 802106.2 
                 1535989.1 
                   
                 UfAfaguauaagcaL96 
                 1535990.1 
                   
                 CfuuaaUfaAfgcuc 
                 UAUAAGCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 ususu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2145 
                 usgsaug(Ahd)UfuCf 
                 A- 
                 2146 
                 VPusCfsgauUfcUf 
                 ACUGAUGAUUCUUUA 
                 3514 
               
               
                 800384.2 
                 1532545.1 
                   
                 UfUfuaagaaucgaL96 
                 1532546.1 
                   
                 UfaaagAfaUfcauc 
                 AGAAUCGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 asgsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2147 
                 csasaca(Ghd)AfuGf 
                 A- 
                 2148 
                 VPusAfsgacGfgUf 
                 UUCAACAGAUGUUAGA 
                 3515 
               
               
                 796041.1 
                 1524103.1 
                   
                 UfUfagaccgucuaL96 
                 1524104.1 
                   
                 CfuaacAfuCfuguu 
                 CCGUCUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsasa 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4B 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A Unmodified Single Strands and Duplex Sequences. 
               
               
                 Column 1 indicates duplex name and the number following the decimal 
               
               
                 point in a duplex name merely refers to a batch production number. 
               
               
                 Column 2 indicates the sense sequence name. Column 3 indicates the 
               
               
                 sequence ID for the sequence of column 4. Column 4 provides the 
               
               
                 unmodified sequence of a sense strand suitable for use in a duplex 
               
               
                 described herein. Column 5 provides the position in the target mRNA 
               
               
                 (NM_001365536.1) of the sense strand of Column 4. Column 6 indicates 
               
               
                 the antisense sequence name. Column 7 indicates the sequence ID for 
               
               
                 the sequence of column 8. Column 8 provides the sequence of an 
               
               
                 antisense strand suitable for use in a duplex described herein, 
               
               
                 without specifying chemical modifications. Column 9 indicates 
               
               
                 the position in the target mRNA (NM_001365536.1) that is 
               
               
                 complementary to the antisense strand of Column 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                 mRNA target 
                 Anti 
                 Seq ID 
                   
                 mRNA target 
               
               
                   
                 Sense 
                 Seq ID 
                   
                 range in 
                 sense 
                 NO: 
                 antisense 
                 range in 
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 NM_00136 
                 sequence 
                 (anti 
                 sequence 
                 NM_0013 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 5536.1 
                 name 
                 sense) 
                 (5′-3′) 
                 65536.1 
               
               
                   
               
               
                 AD- 
                 A- 
                 2149 
                 UUUGUAGAUCUUGCAAUU 
                 2531-2551 
                 A- 
                 2150 
                 UGUAAUUGCAAGAUC 
                 2529-2551 
               
               
                 796825.1 
                 1525636.1 
                   
                 ACA 
                   
                 1257916.1 
                   
                 UACAAAAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2151 
                 UUCUGUGUAGGAGAAUUC 
                 824-844 
                 A- 
                 2152 
                 UGUGAAUUCUCCUACA 
                 822-844 
               
               
                 795366.1 
                 1522818.1 
                   
                 ACA 
                   
                 1522819.1 
                   
                 CAGAAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2153 
                 AUGUGAAACAAACCUUAC 
                 3300-3320 
                 A- 
                 2154 
                 UACGUAAGGUUUGUU 
                 3298-3320 
               
               
                 797565.2 
                 1527044.1 
                   
                 GUA 
                   
                 1527045.1 
                   
                 UCACAUAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2155 
                 UGUAGGAGAAUUCACUUU 
                 829-849 
                 A- 
                 2156 
                 UGAAAAGUGAAUUCUC 
                 827-849 
               
               
                 795371.1 
                 1522828.1 
                   
                 UCA 
                   
                 1522829.1 
                   
                 CUACACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2157 
                 UAUGUGAAACAAACCUUA 
                 3299-3319 
                 A- 
                 2158 
                 UCGUAAGGUUUGUUU 
                 3297-3319 
               
               
                 797564.2 
                 1527042.1 
                   
                 CGA 
                   
                 1527043.1 
                   
                 CACAUAAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2159 
                 AGCAUAAAUGUUUUCGAA 
                 1113-1133 
                 A- 
                 2160 
                 UAUUUCGAAAACAUU 
                 1111-1133 
               
               
                 795634.2 
                 1523299.1 
                   
                 AUA 
                   
                 1523300.1 
                   
                 UAUGCUUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2161 
                 GAUCUUCUUUGUCGUAGU 
                 1435-1455 
                 A- 
                 2162 
                 UUCACUACGACAAAGA 
                 1433-1455 
               
               
                 795913.1 
                 1523849.1 
                   
                 GAA 
                   
                 1523850.1 
                   
                 AGAUCAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2163 
                 GGCGUUGUAGUUCCUAUC 
                 2301-2321 
                 A- 
                 2164 
                 UGAGAUAGGAACUACA 
                 2299-2321 
               
               
                 796618.1 
                 1525247.1 
                   
                 UCA 
                   
                 1525248.1 
                   
                 ACGCCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2165 
                 AUCUUCUUUGUCGUAGUG 
                 1436-1456 
                 A- 
                 2166 
                 UAUCACUACGACAAAG 
                 1434-1456 
               
               
                 795914.1 
                 1523851.1 
                   
                 AUA 
                   
                 1523852.1 
                   
                 AAGAUCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2167 
                 UGGUUUCAGCACAGAUUC 
                 1243-1263 
                 A- 
                 2168 
                 UCUGAAUCUGUGCUG 
                 1241-1263 
               
               
                 795739.1 
                 1523509.1 
                   
                 AGA 
                   
                 1523510.1 
                   
                 AAACCACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2169 
                 UGUCGAGUACACUUUUAC 
                 760-780 
                 A- 
                 2170 
                 UCAGUAAAAGUGUACU 
                 758-780 
               
               
                 795305.1 
                 1522697.1 
                   
                 UGA 
                   
                 1522698.1 
                   
                 CGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2171 
                 AAGCAGAAGAUCUGAAUA 
                 3375-3395 
                 A- 
                 2172 
                 UAGUAUUCAGAUCUU 
                 3373-3395 
               
               
                 797636.2 
                 1527186.1 
                   
                 CUA 
                   
                 1527187.1 
                   
                 CUGCUUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2173 
                 CAAGUGUUCCUACUGUCA 
                 9104-9124 
                 A- 
                 2174 
                 UCAUGACAGUAGGAAC 
                 9102-9124 
               
               
                 802471.2 
                 1536717.1 
                   
                 UGA 
                   
                 1536718.1 
                   
                 ACUUGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2175 
                 AUGCUGAGAAAUUGUCGA 
                 1785-1805 
                 A- 
                 2176 
                 UUUUCGACAAUUUCUC 
                 1783-1805 
               
               
                 796209.1 
                 1524439.1 
                   
                 AAA 
                   
                 1524440.1 
                   
                 AGCAUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2177 
                 AUGUUUCUAGCUGAUUU 
                 5075-5095 
                 A- 
                 2178 
                 UAUCAAAUCAGCUAGA 
                 5073-5095 
               
               
                 799223.1 
                 1530270.1 
                   
                 GAUA 
                   
                 1530271.1 
                   
                 AACAUAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2179 
                 GAGAUGGAUUCUCUUCGU 
                 5861-5881 
                 A- 
                 2180 
                 UGAACGAAGAGAAUCC 
                 5859-5881 
               
               
                 799938.1 
                 1531655.1 
                   
                 UCA 
                   
                 1531656.1 
                   
                 AUCUCCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2181 
                 UUGUGACUUUAAGUUUA 
                 2742-2762 
                 A- 
                 2182 
                 UCACUAAACUUAAAGU 
                 2740-2762 
               
               
                 797036.1 
                 1526036.1 
                   
                 GUGA 
                   
                 1526037.1 
                   
                 CACAAUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2183 
                 AUGAUCUUCUUUGUCGUA 
                 1433-1453 
                 A- 
                 2184 
                 UACUACGACAAAGAAG 
                 1431-1453 
               
               
                 795911.1 
                 1523845.1 
                   
                 GUA 
                   
                 1523846.1 
                   
                 AUCAUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2185 
                 AAGGGAAAACAAUCUUCC 
                 576-596 
                 A- 
                 2186 
                 UACGGAAGAUUGUUU 
                 574-596 
               
               
                 795132.1 
                 1522351.1 
                   
                 GUA 
                   
                 1522352.1 
                   
                 UCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2187 
                 CUUCUGAAACAUCCAAACU 
                 1683-1703 
                 A- 
                 2188 
                 UCAGUUUGGAUGUUU 
                 1681-1703 
               
               
                 796138.1 
                 1524297.1 
                   
                 GA 
                   
                 1524298.1 
                   
                 CAGAAGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2189 
                 UUGCUAUAGGAAAUUUGG 
                 2625-2645 
                 A- 
                 2190 
                 UGACCAAAUUUCCUAU 
                 2623-2645 
               
               
                 796919.1 
                 1525802.1 
                   
                 UCA 
                   
                 1525803.1 
                   
                 AGCAAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2191 
                 UAUUGUGACUUUAAGUU 
                 2740-2760 
                 A- 
                 2192 
                 UCUAAACUUAAAGUCA 
                 2738-2760 
               
               
                 797034.1 
                 1526032.1 
                   
                 UAGA 
                   
                 1526033.1 
                   
                 CAAUAAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2193 
                 UUGGCAGAAACCCUGAUU 
                 1296-1316 
                 A- 
                 2194 
                 UAUAAUCAGGGUUUC 
                 1294-1316 
               
               
                 795774.1 
                 1523579.1 
                   
                 AUA 
                   
                 1523580.1 
                   
                 UGCCAAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2195 
                 ACAUGAUCUUCUUUGUCG 
                 1431-1451 
                 A- 
                 2196 
                 UUACGACAAAGAAGAU 
                 1429-1451 
               
               
                 795909.1 
                 1523841.1 
                   
                 UAA 
                   
                 1523842.1 
                   
                 CAUGUAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2197 
                 AGCUUGAAGUAAAAUUAG 
                 8687-8707 
                 A- 
                 2198 
                 UGUCUAAUUUUACUU 
                 8685-8707 
               
               
                 802123.1 
                 1536023.1 
                   
                 ACA 
                   
                 1536024.1 
                   
                 CAAGCUUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2199 
                 UCCAAAUCGUUCCGAAUG 
                 4390-4410 
                 A- 
                 2200 
                 UAACAUUCGGAACGAU 
                 4388-4410 
               
               
                 798588.2 
                 1529045.1 
                   
                 UUA 
                   
                 1529046.1 
                   
                 UUGGAAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2201 
                 AUCUGAGACUGAAUUUGC 
                 1993-2013 
                 A- 
                 2202 
                 UCGGCAAAUUCAGUCU 
                 1991-2013 
               
               
                 796396.1 
                 1524811.1 
                   
                 CGA 
                   
                 1524812.1 
                   
                 CAGAUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2203 
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                 7769-7789 
                 A- 
                 2470 
                 UAACUACAUUCUACCU 
                 7767-7789 
               
               
                 801489.2 
                 1534755.1 
                   
                 UUA 
                   
                 1534756.1 
                   
                 GUGUAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2471 
                 AGUCUCUUAAACUCUUUU 
                 7159-7179 
                 A- 
                 2472 
                 UACAAAAGAGUUUAAG 
                 7157-7179 
               
               
                 800974.2 
                 1533725.1 
                   
                 GUA 
                   
                 1533726.1 
                   
                 AGACUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2473 
                 AUCACAACCACACUAAAAC 
                 5936-5956 
                 A- 
                 2474 
                 UCGUUUUAGUGUGGU 
                 5934-5956 
               
               
                 800007.2 
                 1531793.1 
                   
                 GA 
                   
                 1531794.1 
                   
                 UGUGAUGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2475 
                 CAUUUGUCCUAAUCUACG 
                 8054-8074 
                 A- 
                 2476 
                 UUACGUAGAUUAGGA 
                 8052-8074 
               
               
                 801679.2 
                 1535135.1 
                   
                 UAA 
                   
                 1535136.1 
                   
                 CAAAUGUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2477 
                 CUGCCAAGUUAACAUAGA 
                 3793-3813 
                 A- 
                 2478 
                 UACUCUAUGUUAACU 
                 3791-3813 
               
               
                 798031.1 
                 1527964.1 
                   
                 GUA 
                   
                 1527965.1 
                   
                 UGGCAGCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2479 
                 AUUAGCUGUAGACAUCUA 
                 7623-7643 
                 A- 
                 2480 
                 UACUAGAUGUCUACAG 
                 7621-7643 
               
               
                 801397.2 
                 1534571.1 
                   
                 GUA 
                   
                 1534572.1 
                   
                 CUAAUGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2481 
                 GUCUCUUAAACUCUUUUG 
                 7160-7180 
                 A- 
                 2482 
                 UGACAAAAGAGUUUAA 
                 7158-7180 
               
               
                 800975.2 
                 1533727.1 
                   
                 UCA 
                   
                 1533728.1 
                   
                 GAGACUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2483 
                 GACAUUUGUCCUAAUCUA 
                 8052-8072 
                 A- 
                 2484 
                 UCGUAGAUUAGGACAA 
                 8050-8072 
               
               
                 801677.2 
                 1535131.1 
                   
                 CGA 
                   
                 1535132.1 
                   
                 AUGUCUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2485 
                 UUCUUUAUACCAUCUUAG 
                 8098-8118 
                 A- 
                 2486 
                 UACCUAAGAUGGUAUA 
                 8096-8118 
               
               
                 801723.2 
                 1535223.1 
                   
                 GUA 
                   
                 1535224.1 
                   
                 AAGAAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2487 
                 CACAGGUAGAAUGUAGUU 
                 7771-7791 
                 A- 
                 2488 
                 UAAAACUACAUUCUAC 
                 7769-7791 
               
               
                 801491.2 
                 1534759.1 
                   
                 UUA 
                   
                 1534760.1 
                   
                 CUGUGUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2489 
                 AUGUAGAUUACUGUUUG 
                 8717-8737 
                 A- 
                 2490 
                 UGUACAAACAGUAAUC 
                 8715-8737 
               
               
                 802153.2 
                 1536083.1 
                   
                 UACA 
                   
                 1536084.1 
                   
                 UACAUGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2491 
                 UCACUUGUAUACAAUCCC 
                 7325-7345 
                 A- 
                 2492 
                 UACGGGAUUGUAUAC 
                 7323-7345 
               
               
                 801140.2 
                 1534057.1 
                   
                 GUA 
                   
                 1534058.1 
                   
                 AAGUGAUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2493 
                 AUUCAUCUUAGGCUAUUU 
                 8120-8140 
                 A- 
                 2494 
                 UUCAAAUAGCCUAAGA 
                 8118-8140 
               
               
                 801745.2 
                 1535267.1 
                   
                 GAA 
                   
                 1535268.1 
                   
                 UGAAUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2495 
                 CAUUCAUCUUAGGCUAUU 
                 8119-8139 
                 A- 
                 2496 
                 UCAAAUAGCCUAAGAU 
                 8117-8139 
               
               
                 801744.2 
                 1535265.1 
                   
                 UGA 
                   
                 1535266.1 
                   
                 GAAUGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2497 
                 AGAGCUUAUUAAGUAUAA 
                 8670-8690 
                 A- 
                 2498 
                 UGCUUAUACUUAAUA 
                 8668-8690 
               
               
                 802106.2 
                 1535989.1 
                   
                 GCA 
                   
                 1535990.1 
                   
                 AGCUCUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2499 
                 UGAUGAUUCUUUAAGAAU 
                 6446-6466 
                 A- 
                 2500 
                 UCGAUUCUUAAAGAAU 
                 6444-6466 
               
               
                 800384.2 
                 1532545.1 
                   
                 CGA 
                   
                 1532546.1 
                   
                 CAUCAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2501 
                 CAACAGAUGUUAGACCGU 
                 1568-1588 
                 A- 
                 2502 
                 UAGACGGUCUAACAUC 
                 1566-1588 
               
               
                 796041.1 
                 1524103.1 
                   
                 CUA 
                   
                 1524104.1 
                   
                 UGUUGAA 
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5A 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A siRNA Modified Single Strands and Duplex Sequences 
               
               
                 Column 1 indicates duplex name and the number following the decimal point in a duplex name merely refers to a batch production number. Column  
               
               
                 2 indicates the name of the sense sequence. Column 3 indicates the sequence ID for the sequence of column 4. Column 4 provides the modified 
               
               
                 sequence of a sense strand suitable for use in a duplex described herein. Column 5 indicates the antisense sequence name. Column 6 indicates 
               
               
                 the sequence ID for the sequence of column 7. Column 7 provides the sequence of a modified antisense strand suitable for use in a duplex 
               
               
                 described herein, e.g., a duplex comprising the sense sequence in the same row of the table. Column 8 indicates the position in the target 
               
               
                 mRNA (NM_002977.3) that is complementary to the antisense strand of Column 7. Column 9 indicated the sequence ID for the sequence of column 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                   
                   
                 SEQ ID 
               
               
                   
                   
                   
                   
                   
                 Seq ID 
                   
                   
                 NO: 
               
               
                   
                 Sense 
                 Seq ID 
                   
                 Antisense 
                 NO: 
                   
                 mRNA target 
                 (mRNA 
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 sequence 
                 (anti 
                 Antisense sequence 
                 sequence 
                 target) 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 name 
                 sense) 
                 (5′-3′) 
                 in NM_002977.3 
               
               
                   
               
               
                 AD- 
                 A- 
                 2503 
                 ususgug(Ahd)cudTu 
                 A- 
                 2593 
                 VPusdCsacdTadAacuu 
                 UAUUGUGACUUUAAG 
                 3516 
               
               
                 961208.1 
                 1812652.1 
                   
                 dAaguuuagugaL96 
                 1812653.1 
                   
                 dAadAgdTcacaasusa 
                 UUUAGUGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2504 
                 usasuug(Uhd)gadCu 
                 A- 
                 2594 
                 VPusdCsuadAadCuua 
                 CUUAUUGUGACUUUA 
                 3517 
               
               
                 961207.1 
                 1812650.1 
                   
                 dTuaaguuuagaL96 
                 1812651.1 
                   
                 adAgdTcdAcaauasasg 
                 AGUUUAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2505 
                 ususcug(Uhd)gudAg 
                 A- 
                 2595 
                 VPusdGsugdAadTucu 
                 GCUUCUGUGUAGGAG 
                 3518 
               
               
                 1010662.1 
                 1851786.1 
                   
                 dGagaauucacaL96 
                 1875200.1 
                   
                 cdCudAcdAcagaasgsc 
                 AAUUCACU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2506 
                 csasuga(Uhd)cudTc 
                 A- 
                 2596 
                 VPusdCsuadCgdAcaa 
                 UACAUGAUCUUCUUU 
                 3519 
               
               
                 961188.1 
                 1812612.1 
                   
                 dTuugucguagaL96 
                 1812613.1 
                   
                 adGadAgdAucaugsus 
                 GUCGUAGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2507 
                 usgsuag(Ghd)agdAa 
                 A- 
                 2597 
                 VPusdGsaadAadGuga 
                 UGUGUAGGAGAAUUC 
                 3520 
               
               
                 1010663.1 
                 1851796.1 
                   
                 dTucacuuuucaL96 
                 1875201.1 
                   
                 adTudCudCcuacascsa 
                 ACUUUUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2508 
                 usgsucg(Ahd)gudAc 
                 A- 
                 2598 
                 VPusdCsagdTadAaag 
                 AAUGUCGAGUACACUU 
                 3521 
               
               
                 1010661.1 
                 1851664.1 
                   
                 dAcuuuuacugaL96 
                 1875199.1 
                   
                 udGudAcdTcgacasus 
                 UUACUGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2509 
                 asusgau(Chd)uudCu 
                 A- 
                 2599 
                 VPusdAscudAcdGaca 
                 ACAUGAUCUUCUUUG 
                 3522 
               
               
                 961189.1 
                 1812614.1 
                   
                 dTugucguaguaL96 
                 1812615.1 
                   
                 adAgdAadGaucausgs 
                 UCGUAGUG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2510 
                 asuscug(Ahd)gadCu 
                 A- 
                 2600 
                 VPusdCsggdCadAauu 
                 GGAUCUGAGACUGAA 
                 3523 
               
               
                 1010671.1 
                 1853827.1 
                   
                 dGaauuugccgaL96 
                 1875209.1 
                   
                 cdAgdTcdTcagauscsc 
                 UUUGCCGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2511 
                 usgsauc(Uhd)ucdTu 
                 A- 
                 2601 
                 VPusdCsacdTadCgaca 
                 CAUGAUCUUCUUUGU 
                 3524 
               
               
                 961190.1 
                 1812616.1 
                   
                 dTgucguagugaL96 
                 1812617.1 
                   
                 dAadGadAgaucasusg 
                 CGUAGUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2512 
                 asasggg(Ahd)aadAc 
                 A- 
                 2602 
                 VPusdAscgdGadAgau 
                 CAAAGGGAAAACAAUC 
                 3525 
               
               
                 961179.1 
                 1812594.1 
                   
                 dAaucuuccguaL96 
                 1812595.1 
                   
                 udGudTudTcccuusus 
                 UUCCGUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2513 
                 asgscuu(Ghd)aadGu 
                 A- 
                 2603 
                 VPusdGsucdTadAuuu 
                 UAAGCUUGAAGUAAAA 
                 3526 
               
               
                 961342.1 
                 1812920.1 
                   
                 dAaaauuagacaL96 
                 1812921.1 
                   
                 udAcdTudCaagcususa 
                 UUAGACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2514 
                 usgscua(Uhd)agdGa 
                 A- 
                 2604 
                 VPusdAsgadCcdAaau 
                 CUUGCUAUAGGAAAU 
                 3527 
               
               
                 1010673.1 
                 1854804.1 
                   
                 dAauuuggucuaL96 
                 1875211.1 
                   
                 udTcdCudAuagcasasg 
                 UUGGUCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2515 
                 asuscuu(Chd)uudTg 
                 A- 
                 2605 
                 VPusdAsucdAcdTacga 
                 UGAUCUUCUUUGUCG 
                 3528 
               
               
                 961192.1 
                 1812620.1 
                   
                 dTcguagugauaL96 
                 1812621.1 
                   
                 dCadAadGaagauscsa 
                 UAGUGAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2516 
                 gsasucu(Uhd)cudTu 
                 A- 
                 2606 
                 VPusdTscadCudAcgac 
                 AUGAUCUUCUUUGUC 
                 3529 
               
               
                 961191.1 
                 1812618.1 
                   
                 dGucguagugaaL96 
                 1812619.1 
                   
                 dAadAgdAagaucsasu 
                 GUAGUGAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2517 
                 ususauu(Ghd)cadTc 
                 A- 
                 2607 
                 VPusdGsuadTadCaag 
                 AUUUAUUGCAUCACU 
                 3530 
               
               
                 1010693.1 
                 1863139.1 
                   
                 dAcuuguauacaL96 
                 1875231.1 
                   
                 udGadTgdCaauaasas 
                 UGUAUACA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2518 
                 csasaca(Chd)aadTu 
                 A- 
                 2608 
                 VPusdGscudAadGaag 
                 AACAACACAAUUUCUU 
                 3531 
               
               
                 961334.1 
                 1812904.1 
                   
                 dTcuucuuagcaL96 
                 1812905.1 
                   
                 adAadTudGuguugsus 
                 CUUAGCA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2519 
                 csusguu(Ghd)gadAa 
                 A- 
                 2609 
                 VPusdTscadAadAccua 
                 GCCUGUUGGAAAUAG 
                 3532 
               
               
                 1010697.1 
                 1864516.1 
                   
                 dTagguuuugaaL96 
                 1875235.1 
                   
                 dTudTcdCaacagsgsc 
                 GUUUUGAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2520 
                 ususugu(Ahd)gadTc 
                 A- 
                 2610 
                 VPusdGsuadAudTgca 
                 CUUUUGUAGAUCUUG 
                 3533 
               
               
                 961203.1 
                 1812642.1 
                   
                 dTugcaauuacaL96 
                 1812643.1 
                   
                 adGadTcdTacaaasasg 
                 CAAUUACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2521 
                 usgsguu(Uhd)cadGc 
                 A- 
                 2611 
                 VPusdCsugdAadTcug 
                 UGUGGUUUCAGCACA 
                 3534 
               
               
                 1010664.1 
                 1852529.1 
                   
                 dAcagauucagaL96 
                 1875202.1 
                   
                 udGcdTgdAaaccascsa 
                 GAUUCAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2522 
                 ususgau(Ahd)gudTa 
                 A- 
                 2612 
                 VPusdGscadAadCuag 
                 UUUUGAUAGUUACCU 
                 3535 
               
               
                 1010698.1 
                 1865925.1 
                   
                 dCcuaguuugcaL96 
                 1875236.1 
                   
                 gdTadAcdTaucaasasa 
                 AGUUUGCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2523 
                 ascsaug(Ahd)ucdTu 
                 A- 
                 2613 
                 VPusdTsacdGadCaaag 
                 CUACAUGAUCUUCUUU 
                 3536 
               
               
                 961187.1 
                 1812610.1 
                   
                 dCuuugucguaaL96 
                 1812611.1 
                   
                 dAadGadTeaugusasg 
                 GUCGUAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2524 
                 gsusuug(Ahd)acdAc 
                 A- 
                 2614 
                 VPusdCsgadAadGauu 
                 AGGUUUGAACACAAAU 
                 3537 
               
               
                 961350.1 
                 1812936.1 
                   
                 dAaaucuuucgaL96 
                 1812937.1 
                   
                 udGudGudTcaaacscs 
                 CUUUCGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2525 
                 usgsaga(Chd)ugdAc 
                 A- 
                 2615 
                 VPusdAsuudAcdAaug 
                 CUUGAGACUGACACAU 
                 3538 
               
               
                 1010700.1 
                 1866708.1 
                   
                 dAcauuguaauaL96 
                 1875238.1 
                   
                 udGudCadGucucasas 
                 UGUAAUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2526 
                 asusguc(Ghd)agdTa 
                 A- 
                 2616 
                 VPusdAsgudAadAagu 
                 AAAUGUCGAGUACACU 
                 3539 
               
               
                 961182.1 
                 1812600.1 
                   
                 dCacuuuuacuaL96 
                 1812601.1 
                   
                 gdTadCudCgacaususu 
                 UUUACUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2527 
                 usgsaua(Ghd)uudAc 
                 A- 
                 2617 
                 VPusdTsgcdAadAcuag 
                 UUUGAUAGUUACCUA 
                 3540 
               
               
                 1010699.1 
                 1865927.1 
                   
                 dCuaguuugcaaL96 
                 1875237.1 
                   
                 dGudAadCuaucasasa 
                 GUUUGCAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2528 
                 usasuau(Uhd)uudA 
                 A- 
                 2618 
                 VPusdAsacdGgdAugu 
                 GAUAUAUUUUACAACA 
                 3541 
               
               
                 1010696.1 
                 1864159.1 
                   
                 cdAacauccguuaL96 
                 1875234.1 
                   
                 udGudAadAauauasus 
                 UCCGUUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2529 
                 csusuua(Uhd)acdCa 
                 A- 
                 2619 
                 VPusdGsaadCcdTaaga 
                 UUCUUUAUACCAUCUU 
                 3542 
               
               
                 961321.1 
                 1812878.1 
                   
                 dTcuuagguucaL96 
                 1812879.1 
                   
                 dTgdGudAuaaagsasa 
                 AGGUUCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2530 
                 asusgua(Chd)agdAg 
                 A- 
                 2620 
                 VPusdAsuadGadAuaa 
                 CAAUGUACAGAGGUUA 
                 3543 
               
               
                 961279.1 
                 1812794.1 
                   
                 dGuuauucuauaL96 
                 1812795.1 
                   
                 cdCudCudGuacausus 
                 UUCUAUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2531 
                 gscsguu(Ghd)uadG 
                 A- 
                 2621 
                 VPusdGsgadGadTagg 
                 AGGCGUUGUAGUUCC 
                 3544 
               
               
                 1010672.1 
                 1854206.1 
                   
                 udTccuaucuccaL96 
                 1875210.1 
                   
                 adAcdTadCaacgcscsu 
                 UAUCUCCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2532 
                 asasguc(Ahd)agdTu 
                 A- 
                 2622 
                 VPusdAsacdGadTuug 
                 GCAAGUCAAGUUCCAA 
                 3545 
               
               
                 961226.1 
                 1812688.1 
                   
                 dCcaaaucguuaL96 
                 1812689.1 
                   
                 gdAadCudTgacuusgsc 
                 AUCGUUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2533 
                 gscsaag(Uhd)cadAg 
                 A- 
                 2623 
                 VPusdCsgadTudTggaa 
                 CUGCAAGUCAAGUUCC 
                 3546 
               
               
                 961225.1 
                 1812686.1 
                   
                 dTuccaaaucgaL96 
                 1812687.1 
                   
                 dCudTgdAcuugcsasg 
                 AAAUCGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2534 
                 ususggc(Ahd)gadAa 
                 A- 
                 2624 
                 VPusdAsuadAudCagg 
                 AAUUGGCAGAAACCCU 
                 3547 
               
               
                 1010665.1 
                 1852599.1 
                   
                 dCccugauuauaL96 
                 1875203.1 
                   
                 gdTudTcdTgccaasusu 
                 GAUUAUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2535 
                 csusgau(Uhd)ucdCu 
                 A- 
                 2625 
                 VPusdCsacdCudTucu 
                 CUCUGAUUUCCUAAGA 
                 3548 
               
               
                 961259.1 
                 1812754.1 
                   
                 dAagaaaggugaL96 
                 1812755.1 
                   
                 udAgdGadAaucagsas 
                 AAGGUGG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2536 
                 uscsgug(Ghd)cudCc 
                 A- 
                 2626 
                 VPusdCsagdAadAaca 
                 AUUCGUGGCUCCUUG 
                 3549 
               
               
                 961201.1 
                 1812638.1 
                   
                 dTuguuuucugaL96 
                 1812639.1 
                   
                 adGgdAgdCcacgasasu 
                 UUUUCUGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2537 
                 gsuscuu(Uhd)acdTg 
                 A- 
                 2627 
                 VPusdGscadAadGauu 
                 UGGUCUUUACUGGAA 
                 3550 
               
               
                 1010674.1 
                 1854836.1 
                   
                 dGaaucuuugcaL96 
                 1875212.1 
                   
                 cdCadGudAaagacscsa 
                 UCUUUGCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2538 
                 csusucu(Ghd)aadAc 
                 A- 
                 2628 
                 VPusdCsagdTudTggau 
                 UUCUUCUGAAACAUCC 
                 3551 
               
               
                 1010670.1 
                 1853318.1 
                   
                 dAuccaaacugaL96 
                 1875208.1 
                   
                 dGudTudCagaagsasa 
                 AAACUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2539 
                 ususgcu(Ahd)uadGg 
                 A- 
                 2629 
                 VPusdGsacdCadAauu 
                 ACUUGCUAUAGGAAAU 
                 3552 
               
               
                 961206.1 
                 1812648.1 
                   
                 dAaauuuggucaL96 
                 1812649.1 
                   
                 udCcdTadTagcaasgsu 
                 UUGGUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2540 
                 asgsccu(Ghd)uudGg 
                 A- 
                 2630 
                 VPusdAsaadCcdTauu 
                 CAAGCCUGUUGGAAAU 
                 3553 
               
               
                 961326.1 
                 1812888.1 
                   
                 dAaauagguuuaL96 
                 1812889.1 
                   
                 udCcdAadCaggcususg 
                 AGGUUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2541 
                 asusguu(Uhd)cudAg 
                 A- 
                 2631 
                 VPusdAsucdAadAuca 
                 GUAUGUUUCUAGCUG 
                 3554 
               
               
                 961239.1 
                 1812714.1 
                   
                 dCugauuugauaL96 
                 1812715.1 
                   
                 gdCudAgdAaacausasc 
                 AUUUGAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2542 
                 ususgca(Ahd)gcdCu 
                 A- 
                 2632 
                 VPusdCsucdAcdAuaa 
                 GGUUGCAAGCCUCUUA 
                 3555 
               
               
                 1010660.1 
                 1850886.1 
                   
                 dCuuaugugagaL96 
                 1875198.1 
                   
                 gdAgdGcdTugcaascsc 
                 UGUGAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2543 
                 ususuag(Uhd)ggdCa 
                 A- 
                 2633 
                 VPusdCsaadGadGugu 
                 ACUUUAGUGGCAAACA 
                 3556 
               
               
                 1010677.1 
                 1857611.1 
                   
                 dAacacucuugaL96 
                 1875215.1 
                   
                 udTgdCcdAcuaaasgsu 
                 CUCUUGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2544 
                 gsascuu(Ahd)ccdTu 
                 A- 
                 2634 
                 VPusdCsaadTadCucua 
                 AAGACUUACCUUUAGA 
                 3557 
               
               
                 1010690.1 
                 1862528.1 
                   
                 dTagaguauugaL96 
                 1875228.1 
                   
                 dAadGgdTaagucsusu 
                 GUAUUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2545 
                 gsgscgu(Uhd)gudAg 
                 A- 
                 2635 
                 VPusdGsagdAudAgga 
                 AAGGCGUUGUAGUUC 
                 3558 
               
               
                 961202.1 
                 1812640.1 
                   
                 dTuccuaucucaL96 
                 1812641.1 
                   
                 adCudAcdAacgccsusu 
                 CUAUCUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2546 
                 ususugu(Chd)gudAg 
                 A- 
                 2636 
                 VPusdAsggdAadAauc 
                 UCUUUGUCGUAGUGA 
                 3559 
               
               
                 1010668.1 
                 1852884.1 
                   
                 dTgauuuuccuaL96 
                 1875206.1 
                   
                 adCudAcdGacaaasgsa 
                 UUUUCCUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2547 
                 csasacu(Uhd)acdTu 
                 A- 
                 2637 
                 VPusdTsaadTudTagga 
                 ACCAACUUACUUUCCU 
                 3560 
               
               
                 1010694.1 
                 1863376.1 
                   
                 dTccuaaauuaaL96 
                 1875232.1 
                   
                 dAadGudAaguugsgsu 
                 AAAUUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2548 
                 gsusaug(Uhd)uudC 
                 A- 
                 2638 
                 VPusdCsaadAudCagc 
                 AGGUAUGUUUCUAGC 
                 3561 
               
               
                 1010679.1 
                 1859377.1 
                   
                 udAgcugauuugaL96 
                 1875217.1 
                   
                 udAgdAadAcauacscs 
                 UGAUUUGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 U 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2549 
                 gsascag(Ahd)gadTg 
                 A- 
                 2639 
                 VPusdAsgudAadAuca 
                 GAGACAGAGAUGAUG 
                 3562 
               
               
                 961257.1 
                 1812750.1 
                   
                 dAugauuuacuaL96 
                 1812751.1 
                   
                 udCadTcdTcugucsusc 
                 AUUUACUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2550 
                 gsasgau(Ghd)gadTu 
                 A- 
                 2640 
                 VPusdGsaadCgdAaga 
                 GGGAGAUGGAUUCUC 
                 3563 
               
               
                 961245.1 
                 1812726.1 
                   
                 dCucuucguucaL96 
                 1812727.1 
                   
                 gdAadTcdCaucucscsc 
                 UUCGUUCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2551 
                 ususccu(Ghd)audAu 
                 A- 
                 2641 
                 VPusdAsacdTadAcugc 
                 CCUUCCUGAUAUGCAG 
                 3564 
               
               
                 1010692.1 
                 1863006.1 
                   
                 dGcaguuaguuaL96 
                 1875230.1 
                   
                 dAudAudCaggaasgsg 
                 UUAGUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2552 
                 csasccu(Uhd)cudCc 
                 A- 
                 2642 
                 VPusdAsgadAudTuua 
                 GUCACCUUCUCCUUAA 
                 3565 
               
               
                 1010695.1 
                 1863481.1 
                   
                 dTuaaaauucuaL96 
                 1875233.1 
                   
                 adGgdAgdAaggugsas 
                 AAUUCUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2553 
                 csusgau(Ahd)audAg 
                 A- 
                 2643 
                 VPusdGsuudTadAgag 
                 UACUGAUAAUAGUCUC 
                 3566 
               
               
                 961285.1 
                 1812806.1 
                   
                 dTcucuuaaacaL96 
                 1812807.1 
                   
                 adCudAudTaucagsus 
                 UUAAACU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2554 
                 csusaaa(Uhd)uadTg 
                 A- 
                 2644 
                 VPusdAsgadTudAcuu 
                 UCCUAAAUUAUGGAAG 
                 3567 
               
               
                 961300.1 
                 1812836.1 
                   
                 dGaaguaaucuaL96 
                 1812837.1 
                   
                 cdCadTadAuuuagsgsa 
                 UAAUCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2555 
                 uscsuuu(Ahd)uadCc 
                 A- 
                 2645 
                 VPusdAsacdCudAaga 
                 AUUCUUUAUACCAUCU 
                 3568 
               
               
                 961320.1 
                 1812876.1 
                   
                 dAucuuagguuaL96 
                 1812877.1 
                   
                 udGgdTadTaaagasasu 
                 UAGGUUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2556 
                 gsgsaga(Uhd)ggdAu 
                 A- 
                 2646 
                 VPusdAsacdGadAgag 
                 GGGGAGAUGGAUUCU 
                 3569 
               
               
                 1010684.1 
                 1860794.1 
                   
                 dTcucuucguuaL96 
                 1875222.1 
                   
                 adAudCcdAucuccscsc 
                 CUUCGUUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2557 
                 usgsaau(Ahd)uadCa 
                 A- 
                 2647 
                 VPusdTsccdTadAuacu 
                 GCUGAAUAUACAAGUA 
                 3570 
               
               
                 1010669.1 
                 1853216.1 
                   
                 dAguauuaggaaL96 
                 1875207.1 
                   
                 dTgdTadTauucasgsc 
                 UUAGGAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2558 
                 gsusuuc(Uhd)agdCu 
                 A- 
                 2648 
                 VPusdCsaadTcdAaauc 
                 AUGUUUCUAGCUGAU 
                 3571 
               
               
                 1010680.1 
                 1859383.1 
                   
                 dGauuugauugaL96 
                 1875218.1 
                   
                 dAgdCudAgaaacsasu 
                 UUGAUUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2559 
                 asgsuca(Ahd)gudTc 
                 A- 
                 2649 
                 VPusdGsaadCgdAuuu 
                 CAAGUCAAGUUCCAAA 
                 3572 
               
               
                 961227.1 
                 1812690.1 
                   
                 dCaaaucguucaL96 
                 1812691.1 
                   
                 gdGadAcdTugacusus 
                 UCGUUCC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2560 
                 csasucu(Ghd)uudGg 
                 A- 
                 2650 
                 VPusdGsuadGadAuau 
                 CCCAUCUGUUGGAAUA 
                 3573 
               
               
                 961243.1 
                 1812722.1 
                   
                 dAauauucuacaL96 
                 1812723.1 
                   
                 udCcdAadCagaugsgsg 
                 UUCUACU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2561 
                 csusgaa(Chd)cudAu 
                 A- 
                 2651 
                 VPusdAsucdGgdAauu 
                 GGCUGAACCUAUGAAU 
                 3574 
               
               
                 961221.1 
                 1812678.1 
                   
                 dGaauuccgauaL96 
                 1812679.1 
                   
                 cdAudAgdGuucagscsc 
                 UCCGAUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2562 
                 csusuuu(Chd)acdAg 
                 A- 
                 2652 
                 VPusdAsaudTadCaau 
                 AUCUUUUCACAGGAU 
                 3575 
               
               
                 961271.1 
                 1812778.1 
                   
                 dGauuguaauuaL96 
                 1812779.1 
                   
                 cdCudGudGaaaagsas 
                 UGUAAUUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 U 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2563 
                 asgscgu(Ghd)cudTa 
                 A- 
                 2653 
                 VPusdGsuadAcdGucu 
                 UCAGCGUGCUUAUAGA 
                 3576 
               
               
                 961251.1 
                 1812738.1 
                   
                 dTagacguuacaL96 
                 1812739.1 
                   
                 adTadAgdCacgcusgsa 
                 CGUUACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2564 
                 csusucc(Uhd)gadTa 
                 A- 
                 2654 
                 VPusdAscudAadCugc 
                 UCCUUCCUGAUAUGCA 
                 3577 
               
               
                 961296.1 
                 1812828.1 
                   
                 dTgcaguuaguaL96 
                 1812829.1 
                   
                 adTadTcdAggaagsgsa 
                 GUUAGUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2565 
                 gsgsaag(Ahd)aadGg 
                 A- 
                 2655 
                 VPusdCsagdAcdAuga 
                 AUGGAAGAAAGGUUC 
                 3578 
               
               
                 961246.1 
                 1812728.1 
                   
                 dTucaugucugaL96 
                 1812729.1 
                   
                 adCcdTudTcuuccsasu 
                 AUGUCUGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2566 
                 gsusaga(Ahd)aadCu 
                 A- 
                 2656 
                 VPusdCsagdAudGuaa 
                 AUGUAGAAAACUUUU 
                 3579 
               
               
                 1010688.1 
                 1861826.1 
                   
                 dTuuacaucugaL96 
                 1875226.1 
                   
                 adAgdTudTucuacsasu 
                 ACAUCUGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2567 
                 uscsauc(Uhd)uudTc 
                 A- 
                 2657 
                 VPusdAscadAudCcug 
                 UGUCAUCUUUUCACAG 
                 3580 
               
               
                 961269.1 
                 1812774.1 
                   
                 dAcaggauuguaL96 
                 1812775.1 
                   
                 udGadAadAgaugascs 
                 GAUUGUA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2568 
                 gscscca(Ahd)aadTa 
                 A- 
                 2658 
                 VPusdCsuadTudAuca 
                 CUGCCCAAAAUACUGA 
                 3581 
               
               
                 1010691.1 
                 1862804.1 
                   
                 dCugauaauagaL96 
                 1875229.1 
                   
                 gdTadTudTugggcsasg 
                 UAAUAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2569 
                 ususuua(Chd)audCu 
                 A- 
                 2659 
                 VPusdAsugdAcdAagg 
                 ACUUUUACAUCUGCCU 
                 3582 
               
               
                 1010689.1 
                 1861844.1 
                   
                 dGccuugucauaL96 
                 1875227.1 
                   
                 cdAgdAudGuaaaasgs 
                 UGUCAUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2570 
                 usasggc(Uhd)aadTg 
                 A- 
                 2660 
                 VPusdAsaudCudTggg 
                 UUUAGGCUAAUGACCC 
                 3583 
               
               
                 1010667.1 
                 1852732.1 
                   
                 dAcccaagauuaL96 
                 1875205.1 
                   
                 udCadTudAgccuasasa 
                 AAGAUUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2571 
                 csgsugc(Uhd)uadTa 
                 A- 
                 2661 
                 VPusdCsggdTadAcguc 
                 AGCGUGCUUAUAGACG 
                 3584 
               
               
                 961252.1 
                 1812740.1 
                   
                 dGacguuaccgaL96 
                 1812741.1 
                   
                 dTadTadAgcacgscsu 
                 UUACCGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2572 
                 csusucu(Uhd)agdCc 
                 A- 
                 2662 
                 VPusdGsccdTadAacaa 
                 GCCUUCUUAGCCUUGU 
                 3585 
               
               
                 1010666.1 
                 1852704.1 
                   
                 dTuguuuaggcaL96 
                 1875204.1 
                   
                 dGgdCudAagaagsgsc 
                 UUAGGCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2573 
                 usgsgaa(Uhd)audTc 
                 A- 
                 2663 
                 VPusdTsaadCadAagu 
                 GUUGGAAUAUUCUAC 
                 3586 
               
               
                 1010682.1 
                 1860117.1 
                   
                 dTacuuuguuaaL96 
                 1875220.1 
                   
                 adGadAudAuuccasas 
                 UUUGUUAG 
                   
               
               
                   
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2574 
                 csusgaa(Uhd)audAc 
                 A- 
                 2664 
                 VPusdCscudAadTacu 
                 GGCUGAAUAUACAAGU 
                 3587 
               
               
                 961196.1 
                 1812628.1 
                   
                 dAaguauuaggaL96 
                 1812629.1 
                   
                 udGudAudAuucagscs 
                 AUUAGGA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2575 
                 csusgcc(Ahd)agdTu 
                 A- 
                 2665 
                 VPusdAscudCudAugu 
                 UGCUGCCAAGUUAACA 
                 3588 
               
               
                 1010676.1 
                 1857011.1 
                   
                 dAacauagaguaL96 
                 1875214.1 
                   
                 udAadCudTggcagscsa 
                 UAGAGUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2576 
                 usgsgau(Uhd)cudCu 
                 A- 
                 2666 
                 VPusdCsugdTgdAacga 
                 GAUGGAUUCUCUUCG 
                 3589 
               
               
                 1010686.1 
                 1860802.1 
                   
                 dTcguucacagaL96 
                 1875224.1 
                   
                 dAgdAgdAauccasusc 
                 UUCACAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2577 
                 gscsaaa(Ghd)gudCa 
                 A- 
                 2667 
                 VPusdGsagdGadAauu 
                 GAGCAAAGGUCACAAU 
                 3590 
               
               
                 1010675.1 
                 1856353.1 
                   
                 dCaauuuccucaL96 
                 1875213.1 
                   
                 gdTgdAcdCuuugcsusc 
                 UUCCUCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2578 
                 usgscca(Chd)ugdAa 
                 A- 
                 2668 
                 VPusdCsagdTadCuuu 
                 GUUGCCACUGAAGAAA 
                 3591 
               
               
                 961244.1 
                 1812724.1 
                   
                 dGaaaguacugaL96 
                 1812725.1 
                   
                 cdTudCadGuggcasasc 
                 GUACUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2579 
                 cscsuuc(Chd)ugdAu 
                 A- 
                 2669 
                 VPusdCsuadAcdTgcau 
                 AUCCUUCCUGAUAUGC 
                 3592 
               
               
                 961295.1 
                 1812826.1 
                   
                 dAugcaguuagaL96 
                 1812827.1 
                   
                 dAudCadGgaaggsasu 
                 AGUUAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2580 
                 csasucu(Uhd)uudCa 
                 A- 
                 2670 
                 VPusdTsacdAadTccug 
                 GUCAUCUUUUCACAGG 
                 3593 
               
               
                 961270.1 
                 1812776.1 
                   
                 dCaggauuguaaL96 
                 1812777.1 
                   
                 dTgdAadAagaugsasc 
                 AUUGUAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2581 
                 gsgsgag(Ahd)ugdGa 
                 A- 
                 2671 
                 VPusdAscgdAadGaga 
                 UGGGGAGAUGGAUUC 
                 3594 
               
               
                 1010683.1 
                 1860792.1 
                   
                 dTucucuucguaL96 
                 1875221.1 
                   
                 adTcdCadTcucccscsa 
                 UCUUCGUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2582 
                 asasugu(Chd)ggdAc 
                 A- 
                 2672 
                 VPusdAsggdTadAccaa 
                 AUAAUGUCGGACUUG 
                 3595 
               
               
                 1010678.1 
                 1858274.1 
                   
                 dTugguuaccuaL96 
                 1875216.1 
                   
                 dGudCcdGacauusasu 
                 GUUACCUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2583 
                 uscsauc(Chd)ugdGa 
                 A- 
                 2673 
                 VPusdCsaadCudGaac 
                 GUUCAUCCUGGAAGU 
                 3596 
               
               
                 1010681.1 
                 1860028.1 
                   
                 dAguucaguugaL96 
                 1875219.1 
                   
                 udTcdCadGgaugasasc 
                 UCAGUUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2584 
                 asusgua(Uhd)audTu 
                 A- 
                 2674 
                 VPusdTscadCudAgguc 
                 GGAUGUAUAUUUGAC 
                 3597 
               
               
                 961233.1 
                 1812702.1 
                   
                 dGaccuagugaaL96 
                 1812703.1 
                   
                 dAadAudAuacauscsc 
                 CUAGUGAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2585 
                 asgsuca(Chd)cadCu 
                 A- 
                 2675 
                 VPusdAscgdAadTgcug 
                 UCAGUCACCACUCAGC 
                 3598 
               
               
                 961200.1 
                 1812636.1 
                   
                 dCagcauucguaL96 
                 1812637.1 
                   
                 dAgdTgdGugacusgsa 
                 AUUCGUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2586 
                 asuscgu(Ahd)agdAg 
                 A- 
                 2676 
                 VPusdCsuadCadGagu 
                 GAAUCGUAAGAGAACU 
                 3599 
               
               
                 961267.1 
                 1812770.1 
                   
                 dAacucuguagaL96 
                 1812771.1 
                   
                 udCudCudTacgaususc 
                 CUGUAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2587 
                 gscsuga(Ahd)ccdTa 
                 A- 
                 2677 
                 VPusdTscgdGadAuuc 
                 AGGCUGAACCUAUGAA 
                 3600 
               
               
                 961220.1 
                 1812676.1 
                   
                 dTgaauuccgaaL96 
                 1812677.1 
                   
                 adTadGgdTucagcscsu 
                 UUCCGAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2588 
                 csgsgac(Uhd)ugdGu 
                 A- 
                 2678 
                 VPusdGsagdAudAggu 
                 GUCGGACUUGGUUAC 
                 3601 
               
               
                 961232.1 
                 1812700.1 
                   
                 dTaccuaucucaL96 
                 1812701.1 
                   
                 adAcdCadAguccgsasc 
                 CUAUCUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2589 
                 asgsaug(Ghd)audTc 
                 A- 
                 2679 
                 VPusdTsgadAcdGaag 
                 GGAGAUGGAUUCUCU 
                 3602 
               
               
                 1010685.1 
                 1860796.1 
                   
                 dTcuucguucaaL96 
                 1875223.1 
                   
                 adGadAudCcaucuscsc 
                 UCGUUCAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2590 
                 asgsacg(Uhd)uadCc 
                 A- 
                 2680 
                 VPusdTsgcdCudTaagc 
                 AUAGACGUUACCGCUU 
                 3603 
               
               
                 1010687.1 
                 1861054.1 
                   
                 dGcuuaaggcaaL96 
                 1875225.1 
                   
                 dGgdTadAcgucusasu 
                 AAGGCAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2591 
                 usgsuag(Ahd)ucdTu 
                 A- 
                 2681 
                 VPusdTsggdTadAuugc 
                 UUUGUAGAUCUUGCA 
                 3604 
               
               
                 961204.1 
                 1812644.1 
                   
                 dGcaauuaccaaL96 
                 1812645.1 
                   
                 dAadGadTcuacasasa 
                 AUUACCAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2592 
                 ususgcc(Chd)uudAu 
                 A- 
                 2682 
                 VPusdAscudAadCauu 
                 UUUUGCCCUUAUGAA 
                 3605 
               
               
                 961231.1 
                 1812698.1 
                   
                 dGaauguuaguaL96 
                 1812699.1 
                   
                 cdAudAadGggcaasas 
                 UGUUAGUC 
                   
               
               
                   
                   
                   
                   
                   
                   
                 a 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5B 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A Unmodified Single Strands and Duplex Sequences. 
               
               
                 Column 1 indicates duplex name and the number following the decimal 
               
               
                 point in a duplex name merely refers to a batch production number. 
               
               
                 Column 2 indicates the sense sequence name. Column 3 indicates the 
               
               
                 sequence ID for the sequence of column 4. Column 4 provides the 
               
               
                 unmodified sequence of a sense strand suitable for use in a duplex 
               
               
                 described herein. Column 5 provides the position in the target mRNA 
               
               
                 (NM_002977.3) of the sense strand of Column 4. Column 6 indicates 
               
               
                 the antisense sequence name. Column 7 indicates the sequence ID 
               
               
                 for the sequence of column 8. Column 8 provides the sequence of 
               
               
                 an antisense strand suitable for use in a duplex described herein, 
               
               
                 without specifying chemical modifications. Column 9 indicates the 
               
               
                 position in the target mRNA (NM_002977.3) that is complementary 
               
               
                 to the antisense strand of Column 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                 mRNA  
                   
                   
                   
                 mRNA 
               
               
                   
                   
                   
                   
                 target 
                 Anti 
                 Seq ID 
                   
                 target 
               
               
                   
                 Sense 
                 Seq ID 
                   
                 range in 
                 sense 
                 NO: 
                   
                 range in 
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 NM_ 
                 sequence 
                 (anti 
                 antisense sequence 
                 NM_00297 
               
               
                 Name 
                 name 
                 (sense) 
                  (5′-3′) 
                 002977.3 
                 name 
                 sense) 
                  (5′-3′) 
                 7.3 
               
               
                   
               
               
                 AD- 
                 A- 
                 2683 
                 UUGUGACUTUAAGUUUA 
                 2752-2772 
                 A- 
                 2773 
                 UCACTAAACUUAAAGTCAC 
                 2750-2772 
               
               
                 961208.1 
                 1812652.1 
                   
                 GUGA 
                   
                 1812653.1 
                   
                 AAUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2684 
                 UAUUGUGACUTUAAGUU 
                 2750-2770 
                 A- 
                 2774 
                 UCUAAACUUAAAGTCACAA 
                 2748-2770 
               
               
                 961207.1 
                 1812650.1 
                   
                 UAGA 
                   
                 1812651.1 
                   
                 UAAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2685 
                 UUCUGUGUAGGAGAAUU 
                 867-887 
                 A- 
                 2775 
                 UGUGAATUCUCCUACACAG 
                 865-887 
               
               
                 1010662.1 
                 1851786.1 
                   
                 CACA 
                   
                 1875200.1 
                   
                 AAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2686 
                 CAUGAUCUTCTUUGUCGU 
                 1475-1495 
                 A- 
                 2776 
                 UCUACGACAAAGAAGAUCA 
                 1473-1495 
               
               
                 961188.1 
                 1812612.1 
                   
                 AGA 
                   
                 1812613.1 
                   
                 UGUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2687 
                 UGUAGGAGAATUCACUUU 
                 872-892 
                 A- 
                 2777 
                 UGAAAAGUGAATUCUCCUA 
                 870-892 
               
               
                 1010663.1 
                 1851796.1 
                   
                 UCA 
                   
                 1875201.1 
                   
                 CACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2688 
                 UGUCGAGUACACUUUUA 
                 803-823 
                 A- 
                 2778 
                 UCAGTAAAAGUGUACTCGA 
                 801-823 
               
               
                 1010661.1 
                 1851664.1 
                   
                 CUGA 
                   
                 1875199.1 
                   
                 CAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2689 
                 AUGAUCUUCUTUGUCGU 
                 1476-1496 
                 A- 
                 2779 
                 UACUACGACAAAGAAGAUC 
                 1474-1496 
               
               
                 961189.1 
                 1812614.1 
                   
                 AGUA 
                   
                 1812615.1 
                   
                 AUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2690 
                 AUCUGAGACUGAAUUUG 
                 2036-2056 
                 A- 
                 2780 
                 UCGGCAAAUUCAGTCTCAG 
                 2034-2056 
               
               
                 1010671.1 
                 1853827.1 
                   
                 CCGA 
                   
                 1875209.1 
                   
                 AUCC 
                   
               
               
                 AD- 
                 A- 
                 2691 
                 UGAUCUUCTUTGUCGUAG 
                 1477-1497 
                 A- 
                 2781 
                 UCACTACGACAAAGAAGAU 
                 1475-1497 
               
               
                 961190.1 
                 1812616.1 
                   
                 UGA 
                   
                 1812617.1 
                   
                 CAUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2692 
                 AAGGGAAAACAAUCUUCC 
                 619-639 
                 A- 
                 2782 
                 UACGGAAGAUUGUTUTCCC 
                 617-639 
               
               
                 961179.1 
                 1812594.1 
                   
                 GUA 
                   
                 1812595.1 
                   
                 UUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2693 
                 AGCUUGAAGUAAAAUUA 
                 8697-8717 
                 A- 
                 2783 
                 UGUCTAAUUUUACTUCAAG 
                 8695-8717 
               
               
                 961342.1 
                 1812920.1 
                   
                 GACA 
                   
                 1812921.1 
                   
                 CUUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2694 
                 UGCUAUAGGAAAUUUGG 
                 2636-2656 
                 A- 
                 2784 
                 UAGACCAAAUUTCCUAUAG 
                 2634-2656 
               
               
                 1010673.1 
                 1854804.1 
                   
                 UCUA 
                   
                 1875211.1 
                   
                 CAAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2695 
                 AUCUUCUUTGTCGUAGUG 
                 1479-1499 
                 A- 
                 2785 
                 UAUCACTACGACAAAGAAG 
                 1477-1499 
               
               
                 961192.1 
                 1812620.1 
                   
                 AUA 
                   
                 1812621.1 
                   
                 AUCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2696 
                 GAUCUUCUTUGUCGUAG 
                 1478-1498 
                 A- 
                 2786 
                 UTCACUACGACAAAGAAGA 
                 1476-1498 
               
               
                 961191.1 
                 1812618.1 
                   
                 UGAA 
                   
                 1812619.1 
                   
                 UCAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2697 
                 UUAUUGCATCACUUGUAU 
                 7327-7347 
                 A- 
                 2787 
                 UGUATACAAGUGATGCAAU 
                 7325-7347 
               
               
                 1010693.1 
                 1863139.1 
                   
                 ACA 
                   
                 1875231.1 
                   
                 AAAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2698 
                 CAACACAATUTCUUCUUA 
                 8508-8528 
                 A- 
                 2788 
                 UGCUAAGAAGAAATUGUG 
                 8506-8528 
               
               
                 961334.1 
                 1812904.1 
                   
                 GCA 
                   
                 1812905.1 
                   
                 UUGUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2699 
                 CUGUUGGAAATAGGUUU 
                 8232-8252 
                 A- 
                 2789 
                 UTCAAAACCUATUTCCAACA 
                 8230-8252 
               
               
                 1010697.1 
                 1864516.1 
                   
                 UGAA 
                   
                 1875235.1 
                   
                 GGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2700 
                 UUUGUAGATCTUGCAAUU 
                 2541-2561 
                 A- 
                 2790 
                 UGUAAUTGCAAGATCTACA 
                 2539-2561 
               
               
                 961203.1 
                 1812642.1 
                   
                 ACA 
                   
                 1812643.1 
                   
                 AAAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2701 
                 UGGUUUCAGCACAGAUUC 
                 1286-1306 
                 A- 
                 2791 
                 UCUGAATCUGUGCTGAAAC 
                 1284-1306 
               
               
                 1010664.1 
                 1852529.1 
                   
                 AGA 
                   
                 1875202.1 
                   
                 CACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2702 
                 UUGAUAGUTACCUAGUU 
                 9235-9255 
                 A- 
                 2792 
                 UGCAAACUAGGTAACTAUC 
                 9233-9255 
               
               
                 1010698.1 
                 1865925.1 
                   
                 UGCA 
                   
                 1875236.1 
                   
                 AAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2703 
                 ACAUGAUCTUCUUUGUCG 
                 1474-1494 
                 A- 
                 2793 
                 UTACGACAAAGAAGATCAU 
                 1472-1494 
               
               
                 961187.1 
                 1812610.1 
                   
                 UAA 
                   
                 1812611.1 
                   
                 GUAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2704 
                 GUUUGAACACAAAUCUU 
                 9184-9204 
                 A- 
                 2794 
                 UCGAAAGAUUUGUGUTCA 
                 9182-9204 
               
               
                 961350.1 
                 1812936.1 
                   
                 UCGA 
                   
                 1812937.1 
                   
                 AACCU 
                   
               
               
                 AD- 
                 A- 
                 2705 
                 UGAGACUGACACAUUGUA 
                 9710-9730 
                 A- 
                 2795 
                 UAUUACAAUGUGUCAGUC 
                 9708-9730 
               
               
                 1010700.1 
                 1866708.1 
                   
                 AUA 
                   
                 1875238.1 
                   
                 UCAAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2706 
                 AUGUCGAGTACACUUUUA 
                 802-822 
                 A- 
                 2796 
                 UAGUAAAAGUGTACUCGAC 
                 800-822 
               
               
                 961182.1 
                 1812600.1 
                   
                 CUA 
                   
                 1812601.1 
                   
                 AUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2707 
                 UGAUAGUUACCUAGUUU 
                 9236-9256 
                 A- 
                 2797 
                 UTGCAAACUAGGUAACUAU 
                 9234-9256 
               
               
                 1010699.1 
                 1865927.1 
                   
                 GCAA 
                   
                 1875237.1 
                   
                 CAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2708 
                 UAUAUUUUACAACAUCCG 
                 8032-8052 
                 A- 
                 2798 
                 UAACGGAUGUUGUAAAAU 
                 8030-8052 
               
               
                 1010696.1 
                 1864159.1 
                   
                 UUA 
                   
                 1875234.1 
                   
                 AUAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2709 
                 CUUUAUACCATCUUAGGU 
                 8110-8130 
                 A- 
                 2799 
                 UGAACCTAAGATGGUAUAA 
                 8108-8130 
               
               
                 961321.1 
                 1812878.1 
                   
                 UCA 
                   
                 1812879.1 
                   
                 AGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2710 
                 AUGUACAGAGGUUAUUC 
                 6788-6808 
                 A- 
                 2800 
                 UAUAGAAUAACCUCUGUA 
                 6786-6808 
               
               
                 961279.1 
                 1812794.1 
                   
                 UAUA 
                   
                 1812795.1 
                   
                 CAUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2711 
                 GCGUUGUAGUTCCUAUCU 
                 2312-2332 
                 A- 
                 2801 
                 UGGAGATAGGAACTACAAC 
                 2310-2332 
               
               
                 1010672.1 
                 1854206.1 
                   
                 CCA 
                   
                 1875210.1 
                   
                 GCCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2712 
                 AAGUCAAGTUCCAAAUCG 
                 4391-4411 
                 A- 
                 2802 
                 UAACGATUUGGAACUTGAC 
                 4389-4411 
               
               
                 961226.1 
                 1812688.1 
                   
                 UUA 
                   
                 1812689.1 
                   
                 UUGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2713 
                 GCAAGUCAAGTUCCAAAU 
                 4389-4409 
                 A- 
                 2803 
                 UCGATUTGGAACUTGACUU 
                 4387-4409 
               
               
                 961225.1 
                 1812686.1 
                   
                 CGA 
                   
                 1812687.1 
                   
                 GCAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2714 
                 UUGGCAGAAACCCUGAUU 
                 1339-1359 
                 A- 
                 2804 
                 UAUAAUCAGGGTUTCTGCC 
                 1337-1359 
               
               
                 1010665.1 
                 1852599.1 
                   
                 AUA 
                   
                 1875203.1 
                   
                 AAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2715 
                 CUGAUUUCCUAAGAAAGG 
                 6406-6426 
                 A- 
                 2805 
                 UCACCUTUCUUAGGAAAUC 
                 6404-6426 
               
               
                 961259.1 
                 1812754.1 
                   
                 UGA 
                   
                 1812755.1 
                   
                 AGAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2716 
                 UCGUGGCUCCTUGUUUUC 
                 1958-1978 
                 A- 
                 2806 
                 UCAGAAAACAAGGAGCCAC 
                 1956-1978 
               
               
                 961201.1 
                 1812638.1 
                   
                 UGA 
                   
                 1812639.1 
                   
                 GAAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2717 
                 GUCUUUACTGGAAUCUU 
                 2652-2672 
                 A- 
                 2807 
                 UGCAAAGAUUCCAGUAAA 
                 2650-2672 
               
               
                 1010674.1 
                 1854836.1 
                   
                 UGCA 
                   
                 1875212.1 
                   
                 GACCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2718 
                 CUUCUGAAACAUCCAAAC 
                 1726-1746 
                 A- 
                 2808 
                 UCAGTUTGGAUGUTUCAGA 
                 1724-1746 
               
               
                 1010670.1 
                 1853318.1 
                   
                 UGA 
                   
                 1875208.1 
                   
                 AGAA 
                   
               
               
                 AD- 
                 A- 
                 2719 
                 UUGCUAUAGGAAAUUUG 
                 2635-2655 
                 A- 
                 2809 
                 UGACCAAAUUUCCTATAGC 
                 2633-2655 
               
               
                 961206.1 
                 1812648.1 
                   
                 GUCA 
                   
                 1812649.1 
                   
                 AAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2720 
                 AGCCUGUUGGAAAUAGG 
                 8229-8249 
                 A- 
                 2810 
                 UAAACCTAUUUCCAACAGG 
                 8227-8249 
               
               
                 961326.1 
                 1812888.1 
                   
                 UUUA 
                   
                 1812889.1 
                   
                 CUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2721 
                 AUGUUUCUAGCUGAUUU 
                 5085-5105 
                 A- 
                 2811 
                 UAUCAAAUCAGCUAGAAAC 
                 5083-5105 
               
               
                 961239.1 
                 1812714.1 
                   
                 GAUA 
                   
                 1812715.1 
                   
                 AUAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2722 
                 UUGCAAGCCUCUUAUGU 
                 286-306 
                 A- 
                 2812 
                 UCUCACAUAAGAGGCTUGC 
                 284-306 
               
               
                 1010660.1 
                 1850886.1 
                   
                 GAGA 
                   
                 1875198.1 
                   
                 AACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2723 
                 UUUAGUGGCAAACACUCU 
                 4124-4144 
                 A- 
                 2813 
                 UCAAGAGUGUUTGCCACUA 
                 4122-4144 
               
               
                 1010677.1 
                 1857611.1 
                   
                 UGA 
                   
                 1875215.1 
                   
                 AAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2724 
                 GACUUACCTUTAGAGUAU 
                 6954-6974 
                 A- 
                 2814 
                 UCAATACUCUAAAGGTAAG 
                 6952-6974 
               
               
                 1010690.1 
                 1862528.1 
                   
                 UGA 
                   
                 1875228.1 
                   
                 UCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2725 
                 GGCGUUGUAGTUCCUAUC 
                 2311-2331 
                 A- 
                 2815 
                 UGAGAUAGGAACUACAAC 
                 2309-2331 
               
               
                 961202.1 
                 1812640.1 
                   
                 UCA 
                   
                 1812641.1 
                   
                 GCCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2726 
                 UUUGUCGUAGTGAUUUU 
                 1485-1505 
                 A- 
                 2816 
                 UAGGAAAAUCACUACGACA 
                 1483-1505 
               
               
                 1010668.1 
                 1852884.1 
                   
                 CCUA 
                   
                 1875206.1 
                   
                 AAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2727 
                 CAACUUACTUTCCUAAAU 
                 7466-7486 
                 A- 
                 2817 
                 UTAATUTAGGAAAGUAAGU 
                 7464-7486 
               
               
                 1010694.1 
                 1863376.1 
                   
                 UAA 
                   
                 1875232.1 
                   
                 UGGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2728 
                 GUAUGUUUCUAGCUGAU 
                 5083-5103 
                 A- 
                 2818 
                 UCAAAUCAGCUAGAAACAU 
                 5081-5103 
               
               
                 1010679.1 
                 1859377.1 
                   
                 UUGA 
                   
                 1875217.1 
                   
                 ACCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2729 
                 GACAGAGATGAUGAUUUA 
                 6069-6089 
                 A- 
                 2819 
                 UAGUAAAUCAUCATCTCUG 
                 6067-6089 
               
               
                 961257.1 
                 1812750.1 
                   
                 CUA 
                   
                 1812751.1 
                   
                 UCUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2730 
                 GAGAUGGATUCUCUUCG 
                 5871-5891 
                 A- 
                 2820 
                 UGAACGAAGAGAATCCAUC 
                 5869-5891 
               
               
                 961245.1 
                 1812726.1 
                   
                 UUCA 
                   
                 1812727.1 
                   
                 UCCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2731 
                 UUCCUGAUAUGCAGUUA 
                 7259-7279 
                 A- 
                 2821 
                 UAACTAACUGCAUAUCAGG 
                 7257-7279 
               
               
                 1010692.1 
                 1863006.1 
                   
                 GUUA 
                   
                 1875230.1 
                   
                 AAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2732 
                 CACCUUCUCCTUAAAAUU 
                 7537-7557 
                 A- 
                 2822 
                 UAGAAUTUUAAGGAGAAG 
                 7535-7557 
               
               
                 1010695.1 
                 1863481.1 
                   
                 CUA 
                   
                 1875233.1 
                   
                 GUGAC 
                   
               
               
                 AD- 
                 A- 
                 2733 
                 CUGAUAAUAGTCUCUUAA 
                 7161-7181 
                 A- 
                 2823 
                 UGUUTAAGAGACUAUTAUC 
                 7159-7181 
               
               
                 961285.1 
                 1812806.1 
                   
                 ACA 
                   
                 1812807.1 
                   
                 AGUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2734 
                 CUAAAUUATGGAAGUAAU 
                 7478-7498 
                 A- 
                 2824 
                 UAGATUACUUCCATAAUUU 
                 7476-7498 
               
               
                 961300.1 
                 1812836.1 
                   
                 CUA 
                   
                 1812837.1 
                   
                 AGGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2735 
                 UCUUUAUACCAUCUUAG 
                 8109-8129 
                 A- 
                 2825 
                 UAACCUAAGAUGGTATAAA 
                 8107-8129 
               
               
                 961320.1 
                 1812876.1 
                   
                 GUUA 
                   
                 1812877.1 
                   
                 GAAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2736 
                 GGAGAUGGAUTCUCUUCG 
                 5870-5890 
                 A- 
                 2826 
                 UAACGAAGAGAAUCCAUCU 
                 5868-5890 
               
               
                 1010684.1 
                 1860794.1 
                   
                 UUA 
                   
                 1875222.1 
                   
                 CCCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2737 
                 UGAAUAUACAAGUAUUA 
                 1676-1696 
                 A- 
                 2827 
                 UTCCTAAUACUTGTATAUU 
                 1674-1696 
               
               
                 1010669.1 
                 1853216.1 
                   
                 GGAA 
                   
                 1875207.1 
                   
                 CAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2738 
                 GUUUCUAGCUGAUUUGA 
                 5087-5107 
                 A- 
                 2828 
                 UCAATCAAAUCAGCUAGAA 
                 5085-5107 
               
               
                 1010680.1 
                 1859383.1 
                   
                 UUGA 
                   
                 1875218.1 
                   
                 ACAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2739 
                 AGUCAAGUTCCAAAUCGU 
                 4392-4412 
                 A- 
                 2829 
                 UGAACGAUUUGGAACTUG 
                 4390-4412 
               
               
                 961227.1 
                 1812690.1 
                   
                 UCA 
                   
                 1812691.1 
                   
                 ACUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2740 
                 CAUCUGUUGGAAUAUUC 
                 5506-5526 
                 A- 
                 2830 
                 UGUAGAAUAUUCCAACAG 
                 5504-5526 
               
               
                 961243.1 
                 1812722.1 
                   
                 UACA 
                   
                 1812723.1 
                   
                 AUGGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2741 
                 CUGAACCUAUGAAUUCCG 
                 3736-3756 
                 A- 
                 2831 
                 UAUCGGAAUUCAUAGGUU 
                 3734-3756 
               
               
                 961221.1 
                 1812678.1 
                   
                 AUA 
                   
                 1812679.1 
                   
                 CAGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2742 
                 CUUUUCACAGGAUUGUA 
                 6586-6606 
                 A- 
                 2832 
                 UAAUTACAAUCCUGUGAAA 
                 6584-6606 
               
               
                 961271.1 
                 1812778.1 
                   
                 AUUA 
                   
                 1812779.1 
                   
                 AGAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2743 
                 AGCGUGCUTATAGACGUU 
                 5998-6018 
                 A- 
                 2833 
                 UGUAACGUCUATAAGCACG 
                 5996-6018 
               
               
                 961251.1 
                 1812738.1 
                   
                 ACA 
                   
                 1812739.1 
                   
                 CUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2744 
                 CUUCCUGATATGCAGUUA 
                 7258-7278 
                 A- 
                 2834 
                 UACUAACUGCATATCAGGA 
                 7256-7278 
               
               
                 961296.1 
                 1812828.1 
                   
                 GUA 
                   
                 1812829.1 
                   
                 AGGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2745 
                 GGAAGAAAGGTUCAUGUC 
                 5897-5917 
                 A- 
                 2835 
                 UCAGACAUGAACCTUTCUU 
                 5895-5917 
               
               
                 961246.1 
                 1812728.1 
                   
                 UGA 
                   
                 1812729.1 
                   
                 CCAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2746 
                 GUAGAAAACUTUUACAUC 
                 6557-6577 
                 A- 
                 2836 
                 UCAGAUGUAAAAGTUTUCU 
                 6555-6577 
               
               
                 1010688.1 
                 1861826.1 
                   
                 UGA 
                   
                 1875226.1 
                   
                 ACAU 
                   
               
               
                 AD- 
                 A- 
                 2747 
                 UCAUCUUUTCACAGGAUU 
                 6582-6602 
                 A- 
                 2837 
                 UACAAUCCUGUGAAAAGA 
                 6580-6602 
               
               
                 961269.1 
                 1812774.1 
                   
                 GUA 
                   
                 1812775.1 
                   
                 UGACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2748 
                 GCCCAAAATACUGAUAAU 
                 7151-7171 
                 A- 
                 2838 
                 UCUATUAUCAGTATUTUGG 
                 7149-7171 
               
               
                 1010691.1 
                 1862804.1 
                   
                 AGA 
                   
                 1875229.1 
                   
                 GCAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2749 
                 UUUUACAUCUGCCUUGU 
                 6566-6586 
                 A- 
                 2839 
                 UAUGACAAGGCAGAUGUA 
                 6564-6586 
               
               
                 1010689.1 
                 1861844.1 
                   
                 CAUA 
                   
                 1875227.1 
                   
                 AAAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2750 
                 UAGGCUAATGACCCAAGA 
                 1406-1426 
                 A- 
                 2840 
                 UAAUCUTGGGUCATUAGCC 
                 1404-1426 
               
               
                 1010667.1 
                 1852732.1 
                   
                 UUA 
                   
                 1875205.1 
                   
                 UAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2751 
                 CGUGCUUATAGACGUUAC 
                 6000-6020 
                 A- 
                 2841 
                 UCGGTAACGUCTATAAGCA 
                 5998-6020 
               
               
                 961252.1 
                 1812740.1 
                   
                 CGA 
                   
                 1812741.1 
                   
                 CGCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2752 
                 CUUCUUAGCCTUGUUUAG 
                 1391-1411 
                 A- 
                 2842 
                 UGCCTAAACAAGGCUAAGA 
                 1389-1411 
               
               
                 1010666.1 
                 1852704.1 
                   
                 GCA 
                   
                 1875204.1 
                   
                 AGGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2753 
                 UGGAAUAUTCTACUUUGU 
                 5513-5533 
                 A- 
                 2843 
                 UTAACAAAGUAGAAUAUUC 
                 5511-5533 
               
               
                 1010682.1 
                 1860117.1 
                   
                 UAA 
                   
                 1875220.1 
                   
                 CAAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2754 
                 CUGAAUAUACAAGUAUUA 
                 1675-1695 
                 A- 
                 2844 
                 UCCUAATACUUGUAUAUUC 
                 1673-1695 
               
               
                 961196.1 
                 1812628.1 
                   
                 GGA 
                   
                 1812629.1 
                   
                 AGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2755 
                 CUGCCAAGTUAACAUAGA 
                 3803-3823 
                 A- 
                 2845 
                 UACUCUAUGUUAACUTGG 
                 3801-3823 
               
               
                 1010676.1 
                 1857011.1 
                   
                 GUA 
                   
                 1875214.1 
                   
                 CAGCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2756 
                 UGGAUUCUCUTCGUUCAC 
                 5875-5895 
                 A- 
                 2846 
                 UCUGTGAACGAAGAGAAUC 
                 5873-5895 
               
               
                 1010686.1 
                 1860802.1 
                   
                 AGA 
                   
                 1875224.1 
                   
                 CAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2757 
                 GCAAAGGUCACAAUUUCC 
                 3448-3468 
                 A- 
                 2847 
                 UGAGGAAAUUGTGACCUU 
                 3446-3468 
               
               
                 1010675.1 
                 1856353.1 
                   
                 UCA 
                   
                 1875213.1 
                   
                 UGCUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2758 
                 UGCCACUGAAGAAAGUAC 
                 5603-5623 
                 A- 
                 2848 
                 UCAGTACUUUCTUCAGUGG 
                 5601-5623 
               
               
                 961244.1 
                 1812724.1 
                   
                 UGA 
                   
                 1812725.1 
                   
                 CAAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2759 
                 CCUUCCUGAUAUGCAGUU 
                 7257-7277 
                 A- 
                 2849 
                 UCUAACTGCAUAUCAGGAA 
                 7255-7277 
               
               
                 961295.1 
                 1812826.1 
                   
                 AGA 
                   
                 1812827.1 
                   
                 GGAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2760 
                 CAUCUUUUCACAGGAUU 
                 6583-6603 
                 A- 
                 2850 
                 UTACAATCCUGTGAAAAGA 
                 6581-6603 
               
               
                 961270.1 
                 1812776.1 
                   
                 GUAA 
                   
                 1812777.1 
                   
                 UGAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2761 
                 GGGAGAUGGATUCUCUUC 
                 5869-5889 
                 A- 
                 2851 
                 UACGAAGAGAATCCATCUC 
                 5867-5889 
               
               
                 1010683.1 
                 1860792.1 
                   
                 GUA 
                   
                 1875221.1 
                   
                 CCCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2762 
                 AAUGUCGGACTUGGUUAC 
                 4479-4499 
                 A- 
                 2852 
                 UAGGTAACCAAGUCCGACA 
                 4477-4499 
               
               
                 1010678.1 
                 1858274.1 
                   
                 CUA 
                   
                 1875216.1 
                   
                 UUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2763 
                 UCAUCCUGGAAGUUCAGU 
                 5468-5488 
                 A- 
                 2853 
                 UCAACUGAACUTCCAGGAU 
                 5466-5488 
               
               
                 1010681.1 
                 1860028.1 
                   
                 UGA 
                   
                 1875219.1 
                   
                 GAAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2764 
                 AUGUAUAUTUGACCUAG 
                 4826-4846 
                 A- 
                 2854 
                 UTCACUAGGUCAAAUAUAC 
                 4824-4846 
               
               
                 961233.1 
                 1812702.1 
                   
                 UGAA 
                   
                 1812703.1 
                   
                 AUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2765 
                 AGUCACCACUCAGCAUUC 
                 1942-1962 
                 A- 
                 2855 
                 UACGAATGCUGAGTGGUGA 
                 1940-1962 
               
               
                 961200.1 
                 1812636.1 
                   
                 GUA 
                   
                 1812637.1 
                   
                 CUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2766 
                 AUCGUAAGAGAACUCUGU 
                 6472-6492 
                 A- 
                 2856 
                 UCUACAGAGUUCUCUTACG 
                 6470-6492 
               
               
                 961267.1 
                 1812770.1 
                   
                 AGA 
                   
                 1812771.1 
                   
                 AUUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2767 
                 GCUGAACCTATGAAUUCC 
                 3735-3755 
                 A- 
                 2857 
                 UTCGGAAUUCATAGGTUCA 
                 3733-3755 
               
               
                 961220.1 
                 1812676.1 
                   
                 GAA 
                   
                 1812677.1 
                   
                 GCCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2768 
                 CGGACUUGGUTACCUAUC 
                 4484-4504 
                 A- 
                 2858 
                 UGAGAUAGGUAACCAAGU 
                 4482-4504 
               
               
                 961232.1 
                 1812700.1 
                   
                 UCA 
                   
                 1812701.1 
                   
                 CCGAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2769 
                 AGAUGGAUTCTCUUCGUU 
                 5872-5892 
                 A- 
                 2859 
                 UTGAACGAAGAGAAUCCAU 
                 5870-5892 
               
               
                 1010685.1 
                 1860796.1 
                   
                 CAA 
                   
                 1875223.1 
                   
                 CUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2770 
                 AGACGUUACCGCUUAAGG 
                 6009-6029 
                 A- 
                 2860 
                 UTGCCUTAAGCGGTAACGU 
                 6007-6029 
               
               
                 1010687.1 
                 1861054.1 
                   
                 CAA 
                   
                 1875225.1 
                   
                 CUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2771 
                 UGUAGAUCTUGCAAUUAC 
                 2543-2563 
                 A- 
                 2861 
                 UTGGTAAUUGCAAGATCUA 
                 2541-2563 
               
               
                 961204.1 
                 1812644.1 
                   
                 CAA 
                   
                 1812645.1 
                   
                 CAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2772 
                 UUGCCCUUAUGAAUGUU 
                 4420-4440 
                 A- 
                 2862 
                 UACUAACAUUCAUAAGGGC 
                 4418-4440 
               
               
                 961231.1 
                 1812698.1 
                   
                 AGUA 
                   
                 1812699.1 
                   
                 AAAA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6A 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A siRNA Modified Single Strands and Duplex Sequences 
               
               
                 Column 1 indicates duplex name and the number following the decimal 
               
               
                 pointin a duplex name merely refers to a batch production number. 
               
               
                 Column 2 indicates the name of the sense sequence. Column 3 indicates 
               
               
                 the sequence ID for the sequence of column 4. Column 4 provides the 
               
               
                 modified sequence of a sense strand suitable for use in a duplex 
               
               
                 described herein. Column 5 indicates the antisense sequence name. 
               
               
                 Column 6 indicates the sequence ID for the sequence of column 7. 
               
               
                 Column 7 provides the sequence of a modified antisense strand 
               
               
                 suitable for use in a duplex described herein, e.g., a duplex 
               
               
                 comprising the sense sequence in the same row of the table. 
               
               
                 Column 8 indicates the position in the target mRNA (NM_001365536.1) 
               
               
                 that is complementary to the antisense strand of Column 7. 
               
               
                 Column 9 indicated the sequence ID for the sequence of column 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 Seq ID 
                   
                 mRNA target 
                 SEQ ID 
               
               
                   
                 Sense 
                 Seq ID 
                   
                 Antisense 
                 NO: 
                   
                 sequence in 
                 NO: 
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 sequence 
                 (anti 
                 Antisense sequence 
                 NM_0013 
                 (mRNA 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 name 
                 sense) 
                 (5′-3′) 
                 65536.1 
                 target) 
               
               
                   
               
               
                 AD- 
                 A- 
                 5816 
                 gsgscgu(Uhd)GfuAf 
                 A- 
                 5905 
                 VPusGfsagau(Agn)gg 
                 AAGGCGUUGUAGU 
                 3606 
               
               
                 996318. 
                 1525247.1 
                   
                 GfUfuccuaucucaL96 
                 1240821.1 
                   
                 aacuAfcAfacgccsusu 
                 UCCUAUCUCC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5817 
                 ususcug(Uhd)GfuAf 
                 A- 
                 5906 
                 VPusGfsugaa(Tgn)uc 
                 GCUUCUGUGUAGG 
                 3607 
               
               
                 995116. 
                 1522818.1 
                   
                 GfGfagaauucacaL96 
                 1238317.1 
                   
                 uccuAfcAfcagaasgsc 
                 AGAAUUCACU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5818 
                 usgsguu(Uhd)CfaGf 
                 A- 
                 5907 
                 VPusCfsugaa(Tgn)cu 
                 UGUGGUUUCAGCA 
                 3608 
               
               
                 995486. 
                 1523509.1 
                   
                 CfAfcagauucagaL96 
                 1239063.1 
                   
                 gugcUfgAfaaccascsa 
                 CAGAUUCAGG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5819 
                 usgsuag(Ghd)AfgAf 
                 A- 
                 5908 
                 VPusGfsaaaa(Ggn)ug 
                 UGUGUAGGAGAA 
                 3609 
               
               
                 995121. 
                 1522828.1 
                   
                 AfUfucacuuuucaL96 
                 1238327.1 
                   
                 aauuCfuCfcuacascsa 
                 UUCACUUUUCU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5820 
                 ususugu(Ahd)GfaUf 
                 A- 
                 5909 
                 VPusGfsuaau(Tgn)gc 
                 CUUUUGUAGAUCU 
                 3610 
               
               
                 961022. 
                 1525636.1 
                   
                 CfUfugcaauuacaL96 
                 1241249.1 
                   
                 aagaUfcUfacaaasasg 
                 UGCAAUUACC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5821 
                 gsusuug(Ahd)AfcAf 
                 A- 
                 5910 
                 VPusCfsgaaa(Ggn)au 
                 AGGUUUGAACACA 
                 3611 
               
               
                 1002051 
                 1536779.1 
                   
                 CfAfaaucuuucgaL96 
                 1252583.1 
                   
                 uuguGfuUfcaaacscs 
                 AAUCUUUCGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5822 
                 csusucu(Ghd)AfaAf 
                 A- 
                 5911 
                 VPusCfsaguu(Tgn)gg 
                 UUCUUCUGAAACA 
                 3612 
               
               
                 995873. 
                 1524297.1 
                   
                 CfAfuccaaacugaL96 
                 1239861.1 
                   
                 auguUfuCfagaagsasa 
                 UCCAAACUGA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5823 
                 asgsuca(Ahd)GfuUf 
                 A- 
                 5912 
                 VPusGfsaacg(Agn)uu 
                 CAAGUCAAGUUCC 
                 3613 
               
               
                 961040. 
                 1529029.1 
                   
                 CfCfaaaucguucaL96 
                 1244745.1 
                   
                 uggaAfcUfugacususg 
                 AAAUCGUUCC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5824 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 5913 
                 VPusUfscacu(Agn)cg 
                 AUGAUCUUCUUUG 
                 3614 
               
               
                 961013. 
                 1523849.1 
                   
                 UfGfucguagugaaL96 
                 1239411.1 
                   
                 acaaAfgAfagaucsasu 
                 UCGUAGUGAU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5825 
                 usgsucg(Ahd)GfuAf 
                 A- 
                 5914 
                 VPusCfsagua(Agn)aa 
                 AAUGUCGAGUACA 
                 3615 
               
               
                 995055. 
                 1522697.1 
                   
                 CfAfcuuuuacugaL96 
                 1238195.1 
                   
                 guguAfcUfcgacasusu 
                 CUUUUACUGG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5826 
                 csasuga(Uhd)CfuUf 
                 A- 
                 5915 
                 VPusCfsuacg(Agn)ca 
                 UACAUGAUCUUCU 
                 3616 
               
               
                 961010. 
                 1523843.1 
                   
                 CfUfuugucguagaL96 
                 1239405.1 
                   
                 aagaAfgAfucaugsusa 
                 UUGUCGUAGU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5827 
                 asasggg(Ahd)AfaAf 
                 A- 
                 5916 
                 VPusAfscgga(Agn)ga 
                 CAAAGGGAAAACA 
                 3617 
               
               
                 961000. 
                 1522351.1 
                   
                 CfAfaucuuccguaL96 
                 1237849.1 
                   
                 uuguUfuUfcccuusus 
                 AUCUUCCGUU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5828 
                 asgsaug(Ghd)AfuUf 
                 A- 
                 5917 
                 VPusUfsgaac(Ggn)aa 
                 GGAGAUGGAUUCU 
                 3618 
               
               
                 999598. 
                 1531657.1 
                   
                 CfUfcuucguucaaL96 
                 1247453.1 
                   
                 gagaAfuCfcaucuscsc 
                 CUUCGUUCAC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5829 
                 usgsaua(Ghd)UfuAf 
                 A- 
                 5918 
                 VPusUfsgcaa(Agn)cu 
                 UUUGAUAGUUACC 
                 3619 
               
               
                 1002101 
                 1536879.1 
                   
                 CfCfuaguuugcaaL96 
                 1252683.1 
                   
                 agguAfaCfuaucasasa 
                 UAGUUUGCAA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5830 
                 usasuau(Uhd)UfuAf 
                 A- 
                 5919 
                 VPusAfsacgg(Agn)ug 
                 GAUAUAUUUUACA 
                 3620 
               
               
                 1001246 
                 1535071.1 
                   
                 CfAfacauccguuaL96 
                 1250879.1 
                   
                 uuguAfaAfauauasus 
                 ACAUCCGUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5831 
                 ususgcu(Ahd)UfaGf 
                 A- 
                 5920 
                 VPusGfsacca(Agn)au 
                 ACUUGCUAUAGGA 
                 3621 
               
               
                 996618. 
                 1525802.1 
                   
                 GfAfaauuuggucaL96 
                 1241423.1 
                   
                 uuccUfaUfagcaasgsu 
                 AAUUUGGUCU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5832 
                 asuscuu(Chd)UfuUf 
                 A- 
                 5921 
                 VPusAfsucac(Tgn)ac 
                 UGAUCUUCUUUG 
                 3622 
               
               
                 961014. 
                 1523851.1 
                   
                 GfUfcguagugauaL96 
                 1239413.1 
                   
                 gacaAfaGfaagauscsa 
                 UCGUAGUGAUU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5833 
                 asuscgu(Ahd)AfgAf 
                 A- 
                 5922 
                 VPusCfsuaca(Ggn)ag 
                 GAAUCGUAAGAGA 
                 3623 
               
               
                 1000046 
                 1532577.1 
                   
                 GfAfacucuguagaL96 
                 1248385.1 
                   
                 uucuCfuUfacgaususc 
                 ACUCUGUAGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5834 
                 gscsguu(Ghd)UfaGf 
                 A- 
                 5923 
                 VPusGfsgaga(Tgn)ag 
                 AGGCGUUGUAGU 
                 3624 
               
               
                 996319. 
                 1525249.1 
                   
                 UfUfccuaucuccaL96 
                 1240823.1 
                   
                 gaacUfaCfaacgcscsu 
                 UCCUAUCUCCU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5835 
                 asusgau(Chd)UfuCf 
                 A- 
                 5924 
                 VPusAfscuac(Ggn)ac 
                 ACAUGAUCUUCUU 
                 3625 
               
               
                 961011. 
                 1523845.1 
                   
                 UfUfugucguaguaL96 
                 1239407.1 
                   
                 aaagAfaGfaucausgsu 
                 UGUCGUAGUG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5836 
                 gscsugu(Uhd)UfaCf 
                 A- 
                 5925 
                 VPusAfsagaa(Tgn)cc 
                 AAGCUGUUUACAU 
                 3626 
               
               
                 1002409 
                 1537499.1 
                   
                 AfUfaggauucuuaL96 
                 1253305.1 
                   
                 uaugUfaAfacagcsusu 
                 AGGAUUCUUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5837 
                 csasccu(Uhd)CfuCfC 
                 A- 
                 5926 
                 VPusAfsgaau(Tgn)uu 
                 GUCACCUUCUCCU 
                 3627 
               
               
                 1000916 
                 1534385.1 
                   
                 fUfuaaaauucuaL96 
                 1250193.1 
                   
                 aaggAfgAfaggugsasc 
                 UAAAAUUCUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5838 
                 ususgug(Ahd)CfuUf 
                 A- 
                 5927 
                 VPusCfsacua(Agn)ac 
                 UAUUGUGACUUU 
                 3628 
               
               
                 996733. 
                 1526036.1 
                   
                 UfAfaguuuagugaL96 
                 1241657.1 
                   
                 uuaaAfgUfcacaasusa 
                 AAGUUUAGUGG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5839 
                 uscsuuu(Ahd)UfaCf 
                 A- 
                 5928 
                 VPusAfsaccu(Agn)ag 
                 AUUCUUUAUACCA 
                 3629 
               
               
                 961137. 
                 1535225.1 
                   
                 CfAfucuuagguuaL96 
                 1251033.1 
                   
                 auggUfaUfaaagasas 
                 UCUUAGGUUC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5840 
                 gsasgau(Ghd)GfaUf 
                 A- 
                 5929 
                 VPusGfsaacg(Agn)ag 
                 GGGAGAUGGAUUC 
                 3630 
               
               
                 961057. 
                 1531655.1 
                   
                 UfCfucuucguucaL96 
                 1247451.1 
                   
                 agaaUfcCfaucucscsc 
                 UCUUCGUUCA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5841 
                 ususgau(Ahd)GfuUf 
                 A- 
                 5930 
                 VPusGfscaaa(Cgn)ua 
                 UUUUGAUAGUUA 
                 3631 
               
               
                 1002100 
                 1536877.1 
                   
                 AfCfcuaguuugcaL96 
                 1252681.1 
                   
                 gguaAfcUfaucaasasa 
                 CCUAGUUUGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5842 
                 gsascag(Ahd)GfaUf 
                 A- 
                 5931 
                 VPusAfsguaa(Agn)uc 
                 GAGACAGAGAUGA 
                 3632 
               
               
                 999762. 
                 1531997.1 
                   
                 GfAfugauuuacuaL96 
                 1247805.1 
                   
                 aucaUfcUfcugucsusc 
                 UGAUUUACUC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5843 
                 asusgua(Chd)AfgAf 
                 A- 
                 5932 
                 VPusAfsuaga(Agn)ua 
                 CAAUGUACAGAGG 
                 3633 
               
               
                 961085. 
                 1533099.1 
                   
                 GfGfuuauucuauaL9 
                 1248907.1 
                   
                 accuCfuGfuacaususg 
                 UUAUUCUAUA 
                   
               
               
                 1 
                   
                   
                 6 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5844 
                 asusguu(Uhd)CfuAf 
                 A- 
                 5933 
                 VPusAfsucaa(Agn)uc 
                 GUAUGUUUCUAGC 
                 3634 
               
               
                 961049. 
                 1530270.1 
                   
                 GfCfugauuugauaL96 
                 1246031.1 
                   
                 agcuAfgAfaacausasc 
                 UGAUUUGAUU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5845 
                 csasaca(Chd)AfaUf 
                 A- 
                 5934 
                 VPusGfscuaa(Ggn)aa 
                 AACAACACAAUUU 
                 3635 
               
               
                 961155. 
                 1535805.1 
                   
                 UfUfcuucuuagcaL96 
                 1251613.1 
                   
                 gaaaUfuGfuguugsus 
                 CUUCUUAGCA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5846 
                 gscsaag(Uhd)CfaAf 
                 A- 
                 5935 
                 VPusCfsgauu(Tgn)gg 
                 CUGCAAGUCAAGU 
                 3636 
               
               
                 961039. 
                 1529023.1 
                   
                 GfUfuccaaaucgaL96 
                 1244739.1 
                   
                 aacuUfgAfcuugcsasg 
                 UCCAAAUCGU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5847 
                 asasugu(Chd)GfgAf 
                 A- 
                 5936 
                 VPusAfsggua(Agn)cc 
                 AUAAUGUCGGACU 
                 3637 
               
               
                 998346. 
                 1529197.1 
                   
                 CfUfugguuaccuaL96 
                 1244919.1 
                   
                 aaguCfcGfacauusasu 
                 UGGUUACCUA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5848 
                 csasucu(Ghd)UfuGf 
                 A- 
                 5937 
                 VPusGfsuaga(Agn)ua 
                 CCCAUCUGUUGGA 
                 3638 
               
               
                 961056. 
                 1530988.1 
                   
                 GfAfauauucuacaL96 
                 1246759.1 
                   
                 uuccAfaCfagaugsgsg 
                 AUAUUCUACU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5849 
                 usgsgaa(Uhd)AfuUf 
                 A- 
                 5938 
                 VPusUfsaaca(Agn)ag 
                 GUUGGAAUAUUCU 
                 3639 
               
               
                 999259. 
                 1531002.1 
                   
                 CfUfacuuuguuaaL96 
                 1246773.1 
                   
                 uagaAfuAfuuccasasc 
                 ACUUUGUUAG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5850 
                 csusgau(Ahd)AfuAf 
                 A- 
                 5939 
                 VPusGfsuuua(Agn)ga 
                 UACUGAUAAUAGU 
                 3640 
               
               
                 961093. 
                 1533709.1 
                   
                 GfUfcucuuaaacaL96 
                 1249517.1 
                   
                 gacuAfuUfaucagsusa 
                 CUCUUAAACU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5851 
                 ususggc(Ahd)GfaAf 
                 A- 
                 5940 
                 VPusAfsuaau(Cgn)ag 
                 AAUUGGCAGAAAC 
                 3641 
               
               
                 995521. 
                 1523579.1 
                   
                 AfCfccugauuauaL96 
                 1239133.1 
                   
                 gguuUfcUfgccaasusu 
                 CCUGAUUAUG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5852 
                 gscsaaa(Ghd)GfuCf 
                 A- 
                 5941 
                 VPusGfsagga(Agn)au 
                 GAGCAAAGGUCAC 
                 3642 
               
               
                 997386. 
                 1527312.1 
                   
                 AfCfaauuuccucaL96 
                 1242983.1 
                   
                 ugugAfcCfuuugcsusc 
                 AAUUUCCUCA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5853 
                 csusgaa(Chd)CfuAf 
                 A- 
                 5942 
                 VPusAfsucgg(Agn)au 
                 GGCUGAACCUAUG 
                 3643 
               
               
                 961037. 
                 1527831.1 
                   
                 UfGfaauuccgauaL96 
                 1243513.1 
                   
                 ucauAfgGfuucagscsc 
                 AAUUCCGAUG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5854 
                 gsgsaag(Ahd)AfaGf 
                 A- 
                 5943 
                 VPusCfsagac(Agn)ug 
                 AUGGAAGAAAGGU 
                 3644 
               
               
                 961058. 
                 1531697.1 
                   
                 GfUfucaugucugaL96 
                 1247503.1 
                   
                 aaccUfuUfcuuccsasu 
                 UCAUGUCUGC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5855 
                 asgsccu(Ghd)UfuGf 
                 A- 
                 5944 
                 VPusAfsaacc(Tgn)au 
                 CAAGCCUGUUGGA 
                 3645 
               
               
                 961146. 
                 1535441.1 
                   
                 GfAfaauagguuuaL96 
                 1251249.1 
                   
                 uuccAfaCfaggcususg 
                 AAUAGGUUUU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5856 
                 ususauu(Ghd)CfaUf 
                 A- 
                 5945 
                 VPusGfsuaua(Cgn)aa 
                 AUUUAUUGCAUCA 
                 3646 
               
               
                 1000747 
                 1534041.1 
                   
                 CfAfcuuguauacaL96 
                 1249849.1 
                   
                 gugaUfgCfaauaasasu 
                 CUUGUAUACA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5857 
                 csusguu(Ghd)GfaAf 
                 A- 
                 5946 
                 VPusUfscaaa(Agn)cc 
                 GCCUGUUGGAAAU 
                 3647 
               
               
                 1001409 
                 1535447.1 
                   
                 AfUfagguuuugaaL96 
                 1251255.1 
                   
                 uauuUfcCfaacagsgsc 
                 AGGUUUUGAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5858 
                 asuscug(Ahd)GfaCf 
                 A- 
                 5947 
                 VPusCfsggca(Agn)au 
                 GGAUCUGAGACUG 
                 3648 
               
               
                 996130. 
                 1524811.1 
                   
                 UfGfaauuugccgaL96 
                 1240377.1 
                   
                 ucagUfcUfcagauscsc 
                 AAUUUGCCGA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5859 
                 asgscgu(Ghd)CfuUf 
                 A- 
                 5948 
                 VPusGfsuaac(Ggn)uc 
                 UCAGCGUGCUUAU 
                 3649 
               
               
                 999715. 
                 1531895.1 
                   
                 AfUfagacguuacaL96 
                 1247701.1 
                   
                 uauaAfgCfacgcusgsa 
                 AGACGUUACC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5860 
                 cscsuuc(Chd)UfgAf 
                 A- 
                 5949 
                 VPusCfsuaac(Tgn)gc 
                 AUCCUUCCUGAUA 
                 3650 
               
               
                 1000678 
                 1533901.1 
                   
                 UfAfugcaguuagaL96 
                 1249709.1 
                   
                 auauCfaGfgaaggsasu 
                 UGCAGUUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5861 
                 gsusaga(Ahd)AfaCf 
                 A- 
                 5950 
                 VPusCfsagau(Ggn)ua 
                 AUGUAGAAAACUU 
                 3651 
               
               
                 1000106 
                 1532699.1 
                   
                 UfUfuuacaucugaL96 
                 1248507.1 
                   
                 aaagUfuUfucuacsas 
                 UUACAUCUGC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5862 
                 gscscca(Ahd)AfaUfA 
                 A- 
                 5951 
                 VPusCfsuauu(Agn)uc 
                 CUGCCCAAAAUAC 
                 3652 
               
               
                 1000585 
                 1533689.1 
                   
                 fCfugauaauagaL96 
                 1249497.1 
                   
                 aguaUfuUfugggcsas 
                 UGAUAAUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5863 
                 gsuscuu(Uhd)AfcUf 
                 A- 
                 5952 
                 VPusGfscaaa(Ggn)au 
                 UGGUCUUUACUG 
                 3653 
               
               
                 996635. 
                 1525836.1 
                   
                 GfGfaaucuuugcaL96 
                 1241457.1 
                   
                 uccaGfuAfaagacscsa 
                 GAAUCUUUGCA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5864 
                 asgscuu(Ghd)AfaGf 
                 A- 
                 5953 
                 VPusGfsucua(Agn)uu 
                 UAAGCUUGAAGUA 
                 3654 
               
               
                 961163. 
                 1536023.1 
                   
                 UfAfaaauuagacaL96 
                 1251831.1 
                   
                 uuacUfuCfaagcususa 
                 AAAUUAGACC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5865 
                 usgsgau(Uhd)CfuCf 
                 A- 
                 5954 
                 VPusCfsugug(Agn)ac 
                 GAUGGAUUCUCUU 
                 3655 
               
               
                 999601. 
                 1531663.1 
                   
                 UfUfcguucacagaL96 
                 1247459.1 
                   
                 gaagAfgAfauccasusc 
                 CGUUCACAGA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5866 
                 ususuag(Uhd)GfgCf 
                 A- 
                 5955 
                 VPusCfsaaga(Ggn)ug 
                 ACUUUAGUGGCAA 
                 3656 
               
               
                 998015. 
                 1528540.1 
                   
                 AfAfacacucuugaL96 
                 1244249.1 
                   
                 uuugCfcAfcuaaasgsu 
                 ACACUCUUGG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5867 
                 ascsaug(Ahd)UfcUf 
                 A- 
                 5956 
                 VPusUfsacga(Cgn)aa 
                 CUACAUGAUCUUC 
                 3657 
               
               
                 961009. 
                 1523841.1 
                   
                 UfCfuuugucguaaL96 
                 1239403.1 
                   
                 agaaGfaUfcaugusasg 
                 UUUGUCGUAG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5868 
                 csasucu(Uhd)UfuCf 
                 A- 
                 5957 
                 VPusUfsacaa(Tgn)cc 
                 GUCAUCUUUUCAC 
                 3658 
               
               
                 961078. 
                 1532751.1 
                   
                 AfCfaggauuguaaL96 
                 1248559.1 
                   
                 ugugAfaAfagaugsasc 
                 AGGAUUGUAA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5869 
                 csusgau(Uhd)UfcCf 
                 A- 
                 5958 
                 VPusCfsaccu(Tgn)uc 
                 CUCUGAUUUCCUA 
                 3659 
               
               
                 999986. 
                 1532445.1 
                   
                 UfAfagaaaggugaL96 
                 1248253.1 
                   
                 uuagGfaAfaucagsasg 
                 AGAAAGGUGG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5870 
                 csusuua(Uhd)AfcCf 
                 A- 
                 5959 
                 VPusGfsaacc(Tgn)aa 
                 UUCUUUAUACCAU 
                 3660 
               
               
                 961138. 
                 1535227.1 
                   
                 AfUfcuuagguucaL96 
                 1251035.1 
                   
                 gaugGfuAfuaaagsas 
                 CUUAGGUUCA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5871 
                 csgsugc(Uhd)UfaUf 
                 A- 
                 5960 
                 VPusCfsggua(Agn)cg 
                 AGCGUGCUUAUAG 
                 3661 
               
               
                 961066. 
                 1531899.1 
                   
                 AfGfacguuaccgaL96 
                 1247705.1 
                   
                 ucuaUfaAfgcacgscsu 
                 ACGUUACCGC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5872 
                 asasguc(Ahd)AfgUf 
                 A- 
                 5961 
                 VPusAfsacga(Tgn)uu 
                 GCAAGUCAAGUUC 
                 3662 
               
               
                 998261. 
                 1529027.1 
                   
                 UfCfcaaaucguuaL96 
                 1244743.1 
                   
                 ggaaCfuUfgacuusgsc 
                 CAAAUCGUUC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5873 
                 csusgaa(Uhd)AfuAf 
                 A- 
                 5962 
                 VPusCfscuaa(Tgn)ac 
                 GGCUGAAUAUACA 
                 3663 
               
               
                 995823. 
                 1524195.1 
                   
                 CfAfaguauuaggaL96 
                 1239759.1 
                   
                 uuguAfuAfuucagscsc 
                 AGUAUUAGGA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5874 
                 uscsgug(Ghd)CfuCf 
                 A- 
                 5963 
                 VPusCfsagaa(Agn)ac 
                 AUUCGUGGCUCCU 
                 3664 
               
               
                 996052. 
                 1524655.1 
                   
                 CfUfuguuuucugaL96 
                 1240221.1 
                   
                 aaggAfgCfcacgasasu 
                 UGUUUUCUGC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5875 
                 asgsacg(Uhd)UfaCf 
                 A- 
                 5964 
                 VPusUfsgccu(Tgn)aa 
                 AUAGACGUUACCG 
                 3665 
               
               
                 999721. 
                 1531917.1 
                   
                 CfGfcuuaaggcaaL96 
                 1247723.1 
                   
                 gcggUfaAfcgucusasu 
                 CUUAAGGCAA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5876 
                 uscsauc(Uhd)UfuUf 
                 A- 
                 5965 
                 VPusAfscaau(Cgn)cu 
                 UGUCAUCUUUUCA 
                 3666 
               
               
                 1000130 
                 1532749.1 
                   
                 CfAfcaggauuguaL96 
                 1248557.1 
                   
                 gugaAfaAfgaugascsa 
                 CAGGAUUGUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5877 
                 ususuua(Chd)AfuCf 
                 A- 
                 5966 
                 VPusAfsugac(Agn)ag 
                 ACUUUUACAUCUG 
                 3667 
               
               
                 1000115 
                 1532717.1 
                   
                 UfGfccuugucauaL96 
                 1248525.1 
                   
                 gcagAfuGfuaaaasgsu 
                 CCUUGUCAUC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5878 
                 csusucc(Uhd)GfaUf 
                 A- 
                 5967 
                 VPusAfscuaa(Cgn)ug 
                 UCCUUCCUGAUAU 
                 3668 
               
               
                 961106. 
                 1533903.1 
                   
                 AfUfgcaguuaguaL96 
                 1249711.1 
                   
                 cauaUfcAfggaagsgsa 
                 GCAGUUAGUU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5879 
                 usgsaau(Ahd)UfaCf 
                 A- 
                 5968 
                 VPusUfsccua(Agn)ua 
                 GCUGAAUAUACAA 
                 3669 
               
               
                 995824. 
                 1524197.1 
                   
                 AfAfguauuaggaaL96 
                 1239761.1 
                   
                 cuugUfaUfauucasgsc 
                 GUAUUAGGAG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5880 
                 gsusuuc(Uhd)AfgCf 
                 A- 
                 5969 
                 VPusCfsaauc(Agn)aa 
                 AUGUUUCUAGCUG 
                 3670 
               
               
                 998897. 
                 1530274.1 
                   
                 UfGfauuugauugaL9 
                 1246035.1 
                   
                 ucagCfuAfgaaacsasu 
                 AUUUGAUUGA 
                   
               
               
                 1 
                   
                   
                 6 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5881 
                 usgscca(Chd)UfgAf 
                 A- 
                 5970 
                 VPusCfsagua(Cgn)uu 
                 GUUGCCACUGAAG 
                 3671 
               
               
                 999348. 
                 1531160.1 
                   
                 AfGfaaaguacugaL96 
                 1246951.1 
                   
                 ucuuCfaGfuggcasasc 
                 AAAGUACUGA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 AD- 
                 A- 
                 5882 
                 usgsauc(Uhd)UfcUf 
                 A- 
                 5971 
                 VPusCfsacua(Cgn)ga 
                 CAUGAUCUUCUUU 
                 3672 
               
               
                 961012. 
                 1523847.1 
                   
                 UfUfgucguagugaL96 
                 1239409.1 
                   
                 caaaGfaAfgaucasusg 
                 GUCGUAGUGA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5883 
                 uscsauc(Chd)UfgGf 
                 A- 
                 5972 
                 VPusCfsaacu(Ggn)aa 
                 GUUCAUCCUGGAA 
                 3673 
               
               
                 999215. 
                 1530912.1 
                   
                 AfAfguucaguugaL96 
                 1246683.1 
                   
                 cuucCfaGfgaugasasc 
                 GUUCAGUUGA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5884 
                 asusgua(Uhd)AfuUf 
                 A- 
                 5973 
                 VPusUfscacu(Agn)gg 
                 GGAUGUAUAUUU 
                 3674 
               
               
                 961044. 
                 1529794.1 
                   
                 UfGfaccuagugaaL96 
                 1245553.1 
                   
                 ucaaAfuAfuacauscsc 
                 GACCUAGUGAC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5885 
                 asusguc(Ghd)AfgUf 
                 A- 
                 5974 
                 VPusAfsguaa(Agn)ag 
                 AAAUGUCGAGUAC 
                 3675 
               
               
                 961004. 
                 1522695.1 
                   
                 AfCfacuuuuacuaL96 
                 1238193.1 
                   
                 uguaCfuCfgacaususu 
                 ACUUUUACUG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5886 
                 usasuug(Uhd)GfaCf 
                 A- 
                 5975 
                 VPusCfsuaaa(Cgn)uu 
                 CUUAUUGUGACUU 
                 3676 
               
               
                 961024. 
                 1526032.1 
                   
                 UfUfuaaguuuagaL9 
                 1241653.1 
                   
                 aaagUfcAfcaauasasg 
                 UAAGUUUAGU 
                   
               
               
                 1 
                   
                   
                 6 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5887 
                 gsusaug(Uhd)UfuCf 
                 A- 
                 5976 
                 VPusCfsaaau(Cgn)ag 
                 AGGUAUGUUUCUA 
                 3677 
               
               
                 998894. 
                 1530266.1 
                   
                 UfAfgcugauuugaL96 
                 1246027.1 
                   
                 cuagAfaAfcauacscsu 
                 GCUGAUUUGA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5888 
                 gsgsgag(Ahd)UfgGf 
                 A- 
                 5977 
                 VPusAfscgaa(Ggn)ag 
                 UGGGGAGAUGGA 
                 3678 
               
               
                 999596. 
                 1531651.1 
                   
                 AfUfucucuucguaL96 
                 1247447.1 
                   
                 aaucCfaUfcucccscsa 
                 UUCUCUUCGUU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5889 
                 ususccu(Ghd)AfuAf 
                 A- 
                 5978 
                 VPusAfsacua(Agn)cu 
                 CCUUCCUGAUAUG 
                 3679 
               
               
                 1000679 
                 1533905.1 
                   
                 UfGfcaguuaguuaL96 
                 1249713.1 
                   
                 gcauAfuCfaggaasgsg 
                 CAGUUAGUUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5890 
                 csasacu(Uhd)AfcUf 
                 A- 
                 5979 
                 VPusUfsaauu(Tgn)ag 
                 ACCAACUUACUUU 
                 3680 
               
               
                 1000864 
                 1534279.1 
                   
                 UfUfccuaaauuaaL96 
                 1250087.1 
                   
                 gaaaGfuAfaguugsgs 
                 CCUAAAUUAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5891 
                 usgscua(Uhd)AfgGf 
                 A- 
                 5980 
                 VPusAfsgacc(Agn)aa 
                 CUUGCUAUAGGAA 
                 3681 
               
               
                 996619. 
                 1525804.1 
                   
                 AfAfauuuggucuaL96 
                 1241425.1 
                   
                 uuucCfuAfuagcasasg 
                 AUUUGGUCUU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 AD- 
                 A- 
                 5892 
                 csusaaa(Uhd)UfaUf 
                 A- 
                 5981 
                 VPusAfsgauu(Agn)cu 
                 UCCUAAAUUAUGG 
                 3682 
               
               
                 961109. 
                 1534303.1 
                   
                 GfGfaaguaaucuaL96 
                 1250111.1 
                   
                 uccaUfaAfuuuagsgsa 
                 AAGUAAUCUU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5893 
                 gsascuu(Ahd)CfcUf 
                 A- 
                 5982 
                 VPusCfsaaua(Cgn)uc 
                 AAGACUUACCUUU 
                 3683 
               
               
                 1000451 
                 1533415.1 
                   
                 UfUfagaguauugaL9 
                 1249223.1 
                   
                 uaaaGfgUfaagucsus 
                 AGAGUAUUGU 
                   
               
               
                 .1 
                   
                   
                 6 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5894 
                 csgsgac(Uhd)UfgGf 
                 A- 
                 5983 
                 VPusGfsagau(Agn)gg 
                 GUCGGACUUGGUU 
                 3684 
               
               
                 961043. 
                 1529207.1 
                   
                 UfUfaccuaucucaL96 
                 1244929.1 
                   
                 uaacCfaAfguccgsasc 
                 ACCUAUCUCU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5895 
                 asgsuca(Chd)CfaCf 
                 A- 
                 5984 
                 VPusAfscgaa(Tgn)gc 
                 UCAGUCACCACUC 
                 3685 
               
               
                 996036. 
                 1524627.1 
                   
                 UfCfagcauucguaL96 
                 1240189.1 
                   
                 ugagUfgGfugacusgs 
                 AGCAUUCGUG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5896 
                 ususgcc(Chd)UfuAf 
                 A- 
                 5985 
                 VPusAfscuaa(Cgn)au 
                 UUUUGCCCUUAUG 
                 3686 
               
               
                 961042. 
                 1529091.1 
                   
                 UfGfaauguuaguaL9 
                 1244801.1 
                   
                 ucauAfaGfggcaasasa 
                 AAUGUUAGUC 
                   
               
               
                 1 
                   
                   
                 6 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5897 
                 csusuuu(Chd)AfcAf 
                 A- 
                 5986 
                 VPusAfsauua(Cgn)aa 
                 AUCUUUUCACAGG 
                 3687 
               
               
                 1000133 
                 1532757.1 
                   
                 GfGfauuguaauuaL9 
                 1248565.1 
                   
                 uccuGfuGfaaaagsas 
                 AUUGUAAUUA 
                   
               
               
                 .1 
                   
                   
                 6 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5898 
                 gscsuga(Ahd)CfcUf 
                 A- 
                 5987 
                 VPusUfscgga(Agn)uu 
                 AGGCUGAACCUAU 
                 3688 
               
               
                 961036. 
                 1527829.1 
                   
                 AfUfgaauuccgaaL96 
                 1243511.1 
                   
                 cauaGfgUfucagcscsu 
                 GAAUUCCGAU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5899 
                 csusucu(Uhd)AfgCf 
                 A- 
                 5988 
                 VPusGfsccua(Agn)ac 
                 GCCUUCUUAGCCU 
                 3689 
               
               
                 995573. 
                 1523683.1 
                   
                 CfUfuguuuaggcaL96 
                 1239237.1 
                   
                 aaggCfuAfagaagsgsc 
                 UGUUUAGGCU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5900 
                 csusgcc(Ahd)AfgUf 
                 A- 
                 5989 
                 VPusAfscucu(Agn)ug 
                 UGCUGCCAAGUUA 
                 3690 
               
               
                 997715. 
                 1527964.1 
                   
                 UfAfacauagaguaL96 
                 1243647.1 
                   
                 uuaaCfuUfggcagscsa 
                 ACAUAGAGUC 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5901 
                 usgsuag(Ahd)UfcUf 
                 A- 
                 5990 
                 VPusUfsggua(Agn)uu 
                 UUUGUAGAUCUU 
                 3691 
               
               
                 996533. 
                 1525638.1 
                   
                 UfGfcaauuaccaaL96 
                 1241253.1 
                   
                 gcaaGfaUfcuacasasa 
                 GCAAUUACCAU 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5902 
                 usasggc(Uhd)AfaUf 
                 A- 
                 5991 
                 VPusAfsaucu(Tgn)gg 
                 UUUAGGCUAAUGA 
                 3692 
               
               
                 995587. 
                 1523713.1 
                   
                 GfAfcccaagauuaL96 
                 1239267.1 
                   
                 gucaUfuAfgccuasasa 
                 CCCAAGAUUA 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5903 
                 ususugu(Chd)GfuAf 
                 A- 
                 5992 
                 VPusAfsggaa(Agn)au 
                 UCUUUGUCGUAG 
                 3693 
               
               
                 995660. 
                 1523863.1 
                   
                 GfUfgauuuuccuaL96 
                 1239425.1 
                   
                 cacuAfcGfacaaasgsa 
                 UGAUUUUCCUG 
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5904 
                 ususgca(Ahd)GfcCf 
                 A- 
                 5993 
                 VPusCfsucac(Agn)ua 
                 GGUUGCAAGCCUC 
                 3694 
               
               
                 994670. 
                 1521918.1 
                   
                 UfCfuuaugugagaL96 
                 1237413.1 
                   
                 agagGfcUfugcaascsc 
                 UUAUGUGAGG 
                   
               
               
                 1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6B 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A Unmodified Single Strands and Duplex Sequences. 
               
               
                 Column 1 indicates duplex name and the number following the decimal point in 
               
               
                 a duplex name merely refers to a batch production number. Column 2 indicates 
               
               
                 the sense sequence name. Column 3 indicates the sequence ID for the sequence 
               
               
                 of column 4. Column 4 provides the unmodified sequence of a sense strand 
               
               
                 suitable for use in a duplex described herein. Column 5 provides the position 
               
               
                 in the target mRNA (NM_001365536.1) of the sense strand of Column 4. Column 6 
               
               
                 indicates the antisense sequence name. Column 7 indicates the sequence ID for 
               
               
                 the sequence of column 8. Column 8 provides the sequence of an antisense strand 
               
               
                 suitable for use in a duplex described herein, without specifying chemical 
               
               
                 modifications. Column 9 indicates the position in the target mRNA 
               
               
                 (NM_001365536.1) that is complementary to the antisense strand of Column 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Seq ID 
                   
                 mRNA target 
                 Anti 
                 Seq ID 
                   
                 mRNA target 
               
               
                   
                 Sense 
                 NO: 
                   
                 range in 
                 sense 
                 NO: 
                   
                 range in 
               
               
                 Duplex 
                 sequence 
                 (sense) 
                 Sense 
                 NM_00136 
                 sequence 
                 (anti 
                 antisense sequence 
                 NM_0013655 
               
               
                 Name 
                 name 
                   
                 sequence (5′-3′) 
                 5536.1 
                 name 
                 sense) 
                 (5′-3′) 
                 36.1 
               
               
                   
               
               
                 AD- 
                 A- 
                 5994 
                 GGCGUUGUAGUUCCUAUC 
                 2301-2321 
                 A- 
                 2950 
                 UGAGAUAGGAACUACAAC 
                 2299-2321 
               
               
                 996318.1 
                 1525247.1 
                   
                 UCA 
                   
                 1240821.1 
                   
                 GCCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5995 
                 UUCUGUGUAGGAGAAUU 
                 824-844 
                 A- 
                 2951 
                 UGUGAATUCUCCUACACA 
                 822-844 
               
               
                 995116.1 
                 1522818.1 
                   
                 CACA 
                   
                 1238317.1 
                   
                 GAAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2863 
                 UGGUUUCAGCACAGAUUC 
                 1243-1263 
                 A- 
                 2952 
                 UCUGAATCUGUGCUGAAA 
                 1241-1263 
               
               
                 995486.1 
                 1523509.1 
                   
                 AGA 
                   
                 1239063.1 
                   
                 CCACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2864 
                 UGUAGGAGAAUUCACUU 
                 829-849 
                 A- 
                 2953 
                 UGAAAAGUGAAUUCUCCU 
                 827-849 
               
               
                 995121.1 
                 1522828.1 
                   
                 UUCA 
                   
                 1238327.1 
                   
                 ACACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2865 
                 UUUGUAGAUCUUGCAAU 
                 2531-2551 
                 A- 
                 2954 
                 UGUAAUTGCAAGAUCUAC 
                 2529-2551 
               
               
                 961022.1 
                 1525636.1 
                   
                 UACA 
                   
                 1241249.1 
                   
                 AAAAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2866 
                 GUUUGAACACAAAUCUUU 
                 9174-9194 
                 A- 
                 2955 
                 UCGAAAGAUUUGUGUUC 
                 9172-9194 
               
               
                 1002051.1 
                 1536779.1 
                   
                 CGA 
                   
                 1252583.1 
                   
                 AAACCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2867 
                 CUUCUGAAACAUCCAAAC 
                 1683-1703 
                 A- 
                 2956 
                 UCAGUUTGGAUGUUUCA 
                 1681-1703 
               
               
                 995873.1 
                 1524297.1 
                   
                 UGA 
                   
                 1239861.1 
                   
                 GAAGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2868 
                 AGUCAAGUUCCAAAUCGU 
                 4382-4402 
                 A- 
                 2957 
                 UGAACGAUUUGGAACUU 
                 4380-4402 
               
               
                 961040.1 
                 1529029.1 
                   
                 UCA 
                   
                 1244745.1 
                   
                 GACUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2869 
                 GAUCUUCUUUGUCGUAG 
                 1435-1455 
                 A- 
                 2958 
                 UUCACUACGACAAAGAAG 
                 1433-1455 
               
               
                 961013.1 
                 1523849.1 
                   
                 UGAA 
                   
                 1239411.1 
                   
                 AUCAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2870 
                 UGUCGAGUACACUUUUAC 
                 760-780 
                 A- 
                 2959 
                 UCAGUAAAAGUGUACUCG 
                 758-780 
               
               
                 995055.1 
                 1522697.1 
                   
                 UGA 
                   
                 1238195.1 
                   
                 ACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2871 
                 CAUGAUCUUCUUUGUCG 
                 1432-1452 
                 A- 
                 2960 
                 UCUACGACAAAGAAGAUC 
                 1430-1452 
               
               
                 961010.1 
                 1523843.1 
                   
                 UAGA 
                   
                 1239405.1 
                   
                 AUGUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2872 
                 AAGGGAAAACAAUCUUCC 
                 576-596 
                 A- 
                 2961 
                 UACGGAAGAUUGUUUUC 
                 574-596 
               
               
                 961000.1 
                 1522351.1 
                   
                 GUA 
                   
                 1237849.1 
                   
                 CCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2873 
                 AGAUGGAUUCUCUUCGU 
                 5862-5882 
                 A- 
                 2962 
                 UUGAACGAAGAGAAUCCA 
                 5860-5882 
               
               
                 999598.1 
                 1531657.1 
                   
                 UCAA 
                   
                 1247453.1 
                   
                 UCUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2874 
                 UGAUAGUUACCUAGUUU 
                 9226-9246 
                 A- 
                 2963 
                 UUGCAAACUAGGUAACUA 
                 9224-9246 
               
               
                 1002101.1 
                 1536879.1 
                   
                 GCAA 
                   
                 1252683.1 
                   
                 UCAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2875 
                 UAUAUUUUACAACAUCCG 
                 8022-8042 
                 A- 
                 2964 
                 UAACGGAUGUUGUAAAA 
                 8020-8042 
               
               
                 1001246.1 
                 1535071.1 
                   
                 UUA 
                   
                 1250879.1 
                   
                 UAUAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2876 
                 UUGCUAUAGGAAAUUUG 
                 2625-2645 
                 A- 
                 2965 
                 UGACCAAAUUUCCUAUAG 
                 2623-2645 
               
               
                 996618.1 
                 1525802.1 
                   
                 GUCA 
                   
                 1241423.1 
                   
                 CAAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2877 
                 AUCUUCUUUGUCGUAGU 
                 1436-1456 
                 A- 
                 2966 
                 UAUCACTACGACAAAGAA 
                 1434-1456 
               
               
                 961014.1 
                 1523851.1 
                   
                 GAUA 
                   
                 1239413.1 
                   
                 GAUCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2878 
                 AUCGUAAGAGAACUCUGU 
                 6462-6482 
                 A- 
                 2967 
                 UCUACAGAGUUCUCUUAC 
                 6460-6482 
               
               
                 1000046.1 
                 1532577.1 
                   
                 AGA 
                   
                 1248385.1 
                   
                 GAUUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2879 
                 GCGUUGUAGUUCCUAUCU 
                 2302-2322 
                 A- 
                 2968 
                 UGGAGATAGGAACUACAA 
                 2300-2322 
               
               
                 996319.1 
                 1525249.1 
                   
                 CCA 
                   
                 1240823.1 
                   
                 CGCCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2880 
                 AUGAUCUUCUUUGUCGU 
                 1433-1453 
                 A- 
                 2969 
                 UACUACGACAAAGAAGAU 
                 1431-1453 
               
               
                 961011.1 
                 1523845.1 
                   
                 AGUA 
                   
                 1239407.1 
                   
                 CAUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2881 
                 GCUGUUUACAUAGGAUUC 
                 9600-9620 
                 A- 
                 2970 
                 UAAGAATCCUAUGUAAAC 
                 9598-9620 
               
               
                 1002409.1 
                 1537499.1 
                   
                 UUA 
                   
                 1253305.1 
                   
                 AGCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2882 
                 CACCUUCUCCUUAAAAUU 
                 7527-7547 
                 A- 
                 2971 
                 UAGAAUTUUAAGGAGAAG 
                 7525-7547 
               
               
                 1000916.1 
                 1534385.1 
                   
                 CUA 
                   
                 1250193.1 
                   
                 GUGAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2883 
                 UUGUGACUUUAAGUUUA 
                 2742-2762 
                 A- 
                 2972 
                 UCACUAAACUUAAAGUCA 
                 2740-2762 
               
               
                 996733.1 
                 1526036.1 
                   
                 GUGA 
                   
                 1241657.1 
                   
                 CAAUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2884 
                 UCUUUAUACCAUCUUAGG 
                 8099-8119 
                 A- 
                 2973 
                 UAACCUAAGAUGGUAUAA 
                 8097-8119 
               
               
                 961137.1 
                 1535225.1 
                   
                 UUA 
                   
                 1251033.1 
                   
                 AGAAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2885 
                 GAGAUGGAUUCUCUUCG 
                 5861-5881 
                 A- 
                 2974 
                 UGAACGAAGAGAAUCCAU 
                 5859-5881 
               
               
                 961057.1 
                 1531655.1 
                   
                 UUCA 
                   
                 1247451.1 
                   
                 CUCCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2886 
                 UUGAUAGUUACCUAGUU 
                 9225-9245 
                 A- 
                 2975 
                 UGCAAACUAGGUAACUAU 
                 9223-9245 
               
               
                 1002100.1 
                 1536877.1 
                   
                 UGCA 
                   
                 1252681.1 
                   
                 CAAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2887 
                 GACAGAGAUGAUGAUUUA 
                 6059-6079 
                 A- 
                 2976 
                 UAGUAAAUCAUCAUCUCU 
                 6057-6079 
               
               
                 999762.1 
                 1531997.1 
                   
                 CUA 
                   
                 1247805.1 
                   
                 GUCUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2888 
                 AUGUACAGAGGUUAUUC 
                 6778-6798 
                 A- 
                 2977 
                 UAUAGAAUAACCUCUGUA 
                 6776-6798 
               
               
                 961085.1 
                 1533099.1 
                   
                 UAUA 
                   
                 1248907.1 
                   
                 CAUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2889 
                 AUGUUUCUAGCUGAUUU 
                 5075-5095 
                 A- 
                 2978 
                 UAUCAAAUCAGCUAGAAA 
                 5073-5095 
               
               
                 961049.1 
                 1530270.1 
                   
                 GAUA 
                   
                 1246031.1 
                   
                 CAUAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2890 
                 CAACACAAUUUCUUCUUA 
                 8498-8518 
                 A- 
                 2979 
                 UGCUAAGAAGAAAUUGU 
                 8496-8518 
               
               
                 961155.1 
                 1535805.1 
                   
                 GCA 
                   
                 1251613.1 
                   
                 GUUGUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2891 
                 GCAAGUCAAGUUCCAAAU 
                 4379-4399 
                 A- 
                 2980 
                 UCGAUUTGGAACUUGACU 
                 4377-4399 
               
               
                 961039.1 
                 1529023.1 
                   
                 CGA 
                   
                 1244739.1 
                   
                 UGCAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2892 
                 AAUGUCGGACUUGGUUAC 
                 4469-4489 
                 A- 
                 2981 
                 UAGGUAACCAAGUCCGAC 
                 4467-4489 
               
               
                 998346.1 
                 1529197.1 
                   
                 CUA 
                   
                 1244919.1 
                   
                 AUUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2893 
                 CAUCUGUUGGAAUAUUCU 
                 5496-5516 
                 A- 
                 2982 
                 UGUAGAAUAUUCCAACAG 
                 5494-5516 
               
               
                 961056.1 
                 1530988.1 
                   
                 ACA 
                   
                 1246759.1 
                   
                 AUGGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2894 
                 UGGAAUAUUCUACUUUG 
                 5503-5523 
                 A- 
                 2983 
                 UUAACAAAGUAGAAUAUU 
                 5501-5523 
               
               
                 999259.1 
                 1531002.1 
                   
                 UUAA 
                   
                 1246773.1 
                   
                 CCAAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2895 
                 CUGAUAAUAGUCUCUUAA 
                 7151-7171 
                 A- 
                 2984 
                 UGUUUAAGAGACUAUUA 
                 7149-7171 
               
               
                 961093.1 
                 1533709.1 
                   
                 ACA 
                   
                 1249517.1 
                   
                 UCAGUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2896 
                 UUGGCAGAAACCCUGAUU 
                 1296-1316 
                 A- 
                 2985 
                 UAUAAUCAGGGUUUCUG 
                 1294-1316 
               
               
                 995521.1 
                 1523579.1 
                   
                 AUA 
                   
                 1239133.1 
                   
                 CCAAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2897 
                 GCAAAGGUCACAAUUUCC 
                 3438-3458 
                 A- 
                 2986 
                 UGAGGAAAUUGUGACCU 
                 3436-3458 
               
               
                 997386.1 
                 1527312.1 
                   
                 UCA 
                   
                 1242983.1 
                   
                 UUGCUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2898 
                 CUGAACCUAUGAAUUCCG 
                 3726-3746 
                 A- 
                 2987 
                 UAUCGGAAUUCAUAGGU 
                 3724-3746 
               
               
                 961037.1 
                 1527831.1 
                   
                 AUA 
                   
                 1243513.1 
                   
                 UCAGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2899 
                 GGAAGAAAGGUUCAUGUC 
                 5887-5907 
                 A- 
                 2988 
                 UCAGACAUGAACCUUUCU 
                 5885-5907 
               
               
                 961058.1 
                 1531697.1 
                   
                 UGA 
                   
                 1247503.1 
                   
                 UCCAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2900 
                 AGCCUGUUGGAAAUAGG 
                 8219-8239 
                 A- 
                 2989 
                 UAAACCTAUUUCCAACAG 
                 8217-8239 
               
               
                 961146.1 
                 1535441.1 
                   
                 UUUA 
                   
                 1251249.1 
                   
                 GCUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2901 
                 UUAUUGCAUCACUUGUA 
                 7317-7337 
                 A- 
                 2990 
                 UGUAUACAAGUGAUGCAA 
                 7315-7337 
               
               
                 1000747.1 
                 1534041.1 
                   
                 UACA 
                   
                 1249849.1 
                   
                 UAAAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2902 
                 CUGUUGGAAAUAGGUUU 
                 8222-8242 
                 A- 
                 2991 
                 UUCAAAACCUAUUUCCAA 
                 8220-8242 
               
               
                 1001409.1 
                 1535447.1 
                   
                 UGAA 
                   
                 1251255.1 
                   
                 CAGGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2903 
                 AUCUGAGACUGAAUUUGC 
                 1993-2013 
                 A- 
                 2992 
                 UCGGCAAAUUCAGUCUCA 
                 1991-2013 
               
               
                 996130.1 
                 1524811.1 
                   
                 CGA 
                   
                 1240377.1 
                   
                 GAUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2904 
                 AGCGUGCUUAUAGACGUU 
                 5988-6008 
                 A- 
                 2993 
                 UGUAACGUCUAUAAGCAC 
                 5986-6008 
               
               
                 999715.1 
                 1531895.1 
                   
                 ACA 
                   
                 1247701.1 
                   
                 GCUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2905 
                 CCUUCCUGAUAUGCAGUU 
                 7247-7267 
                 A- 
                 2994 
                 UCUAACTGCAUAUCAGGA 
                 7245-7267 
               
               
                 1000678.1 
                 1533901.1 
                   
                 AGA 
                   
                 1249709.1 
                   
                 AGGAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2906 
                 GUAGAAAACUUUUACAUC 
                 6547-6567 
                 A- 
                 2995 
                 UCAGAUGUAAAAGUUUU 
                 6545-6567 
               
               
                 1000106.1 
                 1532699.1 
                   
                 UGA 
                   
                 1248507.1 
                   
                 CUACAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2907 
                 GCCCAAAAUACUGAUAAU 
                 7141-7161 
                 A- 
                 2996 
                 UCUAUUAUCAGUAUUUU 
                 7139-7161 
               
               
                 1000585.1 
                 1533689.1 
                   
                 AGA 
                   
                 1249497.1 
                   
                 GGGCAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2908 
                 GUCUUUACUGGAAUCUU 
                 2642-2662 
                 A- 
                 2997 
                 UGCAAAGAUUCCAGUAAA 
                 2640-2662 
               
               
                 996635.1 
                 1525836.1 
                   
                 UGCA 
                   
                 1241457.1 
                   
                 GACCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2909 
                 AGCUUGAAGUAAAAUUAG 
                 8687-8707 
                 A- 
                 2998 
                 UGUCUAAUUUUACUUCA 
                 8685-8707 
               
               
                 961163.1 
                 1536023.1 
                   
                 ACA 
                   
                 1251831.1 
                   
                 AGCUUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2910 
                 UGGAUUCUCUUCGUUCAC 
                 5865-5885 
                 A- 
                 2999 
                 UCUGUGAACGAAGAGAAU 
                 5863-5885 
               
               
                 999601.1 
                 1531663.1 
                   
                 AGA 
                   
                 1247459.1 
                   
                 CCAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2911 
                 UUUAGUGGCAAACACUCU 
                 4114-4134 
                 A- 
                 3000 
                 UCAAGAGUGUUUGCCACU 
                 4112-4134 
               
               
                 998015.1 
                 1528540.1 
                   
                 UGA 
                   
                 1244249.1 
                   
                 AAAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2912 
                 ACAUGAUCUUCUUUGUCG 
                 1431-1451 
                 A- 
                 3001 
                 UUACGACAAAGAAGAUCA 
                 1429-1451 
               
               
                 961009.1 
                 1523841.1 
                   
                 UAA 
                   
                 1239403.1 
                   
                 UGUAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2913 
                 CAUCUUUUCACAGGAUUG 
                 6573-6593 
                 A- 
                 3002 
                 UUACAATCCUGUGAAAAG 
                 6571-6593 
               
               
                 961078.1 
                 1532751.1 
                   
                 UAA 
                   
                 1248559.1 
                   
                 AUGAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2914 
                 CUGAUUUCCUAAGAAAGG 
                 6396-6416 
                 A- 
                 3003 
                 UCACCUTUCUUAGGAAAU 
                 6394-6416 
               
               
                 999986.1 
                 1532445.1 
                   
                 UGA 
                   
                 1248253.1 
                   
                 CAGAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2915 
                 CUUUAUACCAUCUUAGGU 
                 8100-8120 
                 A- 
                 3004 
                 UGAACCTAAGAUGGUAUA 
                 8098-8120 
               
               
                 961138.1 
                 1535227.1 
                   
                 UCA 
                   
                 1251035.1 
                   
                 AAGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2916 
                 CGUGCUUAUAGACGUUAC 
                 5990-6010 
                 A- 
                 3005 
                 UCGGUAACGUCUAUAAGC 
                 5988-6010 
               
               
                 961066.1 
                 1531899.1 
                   
                 CGA 
                   
                 1247705.1 
                   
                 ACGCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2917 
                 AAGUCAAGUUCCAAAUCG 
                 4381-4401 
                 A- 
                 3006 
                 UAACGATUUGGAACUUGA 
                 4379-4401 
               
               
                 998261.1 
                 1529027.1 
                   
                 UUA 
                   
                 1244743.1 
                   
                 CUUGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2918 
                 CUGAAUAUACAAGUAUUA 
                 1632-1652 
                 A- 
                 3007 
                 UCCUAATACUUGUAUAUU 
                 1630-1652 
               
               
                 995823.1 
                 1524195.1 
                   
                 GGA 
                   
                 1239759.1 
                   
                 CAGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2919 
                 UCGUGGCUCCUUGUUUU 
                 1915-1935 
                 A- 
                 3008 
                 UCAGAAAACAAGGAGCCA 
                 1913-1935 
               
               
                 996052.1 
                 1524655.1 
                   
                 CUGA 
                   
                 1240221.1 
                   
                 CGAAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2920 
                 AGACGUUACCGCUUAAGG 
                 5999-6019 
                 A- 
                 3009 
                 UUGCCUTAAGCGGUAACG 
                 5997-6019 
               
               
                 999721.1 
                 1531917.1 
                   
                 CAA 
                   
                 1247723.1 
                   
                 UCUAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2921 
                 UCAUCUUUUCACAGGAUU 
                 6572-6592 
                 A- 
                 3010 
                 UACAAUCCUGUGAAAAGA 
                 6570-6592 
               
               
                 1000130.1 
                 1532749.1 
                   
                 GUA 
                   
                 1248557.1 
                   
                 UGACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2922 
                 UUUUACAUCUGCCUUGUC 
                 6556-6576 
                 A- 
                 3011 
                 UAUGACAAGGCAGAUGUA 
                 6554-6576 
               
               
                 1000115.1 
                 1532717.1 
                   
                 AUA 
                   
                 1248525.1 
                   
                 AAAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2923 
                 CUUCCUGAUAUGCAGUUA 
                 7248-7268 
                 A- 
                 3012 
                 UACUAACUGCAUAUCAGG 
                 7246-7268 
               
               
                 961106.1 
                 1533903.1 
                   
                 GUA 
                   
                 1249711.1 
                   
                 AAGGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2924 
                 UGAAUAUACAAGUAUUAG 
                 1633-1653 
                 A- 
                 3013 
                 UUCCUAAUACUUGUAUA 
                 1631-1653 
               
               
                 995824.1 
                 1524197.1 
                   
                 GAA 
                   
                 1239761.1 
                   
                 UUCAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2925 
                 GUUUCUAGCUGAUUUGA 
                 5077-5097 
                 A- 
                 3014 
                 UCAAUCAAAUCAGCUAGA 
                 5075-5097 
               
               
                 998897.1 
                 1530274.1 
                   
                 UUGA 
                   
                 1246035.1 
                   
                 AACAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2926 
                 UGCCACUGAAGAAAGUAC 
                 5593-5613 
                 A- 
                 3015 
                 UCAGUACUUUCUUCAGU 
                 5591-5613 
               
               
                 999348.1 
                 1531160.1 
                   
                 UGA 
                   
                 1246951.1 
                   
                 GGCAAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2927 
                 UGAUCUUCUUUGUCGUA 
                 1434-1454 
                 A- 
                 3016 
                 UCACUACGACAAAGAAGA 
                 1432-1454 
               
               
                 961012.1 
                 1523847.1 
                   
                 GUGA 
                   
                 1239409.1 
                   
                 UCAUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2928 
                 UCAUCCUGGAAGUUCAGU 
                 5458-5478 
                 A- 
                 3017 
                 UCAACUGAACUUCCAGGA 
                 5456-5478 
               
               
                 999215.1 
                 1530912.1 
                   
                 UGA 
                   
                 1246683.1 
                   
                 UGAAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2929 
                 AUGUAUAUUUGACCUAG 
                 4816-4836 
                 A- 
                 3018 
                 UUCACUAGGUCAAAUAUA 
                 4814-4836 
               
               
                 961044.1 
                 1529794.1 
                   
                 UGAA 
                   
                 1245553.1 
                   
                 CAUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2930 
                 AUGUCGAGUACACUUUUA 
                 759-779 
                 A- 
                 3019 
                 UAGUAAAAGUGUACUCGA 
                 757-779 
               
               
                 961004.1 
                 1522695.1 
                   
                 CUA 
                   
                 1238193.1 
                   
                 CAUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2931 
                 UAUUGUGACUUUAAGUU 
                 2740-2760 
                 A- 
                 3020 
                 UCUAAACUUAAAGUCACA 
                 2738-2760 
               
               
                 961024.1 
                 1526032.1 
                   
                 UAGA 
                   
                 1241653.1 
                   
                 AUAAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2932 
                 GUAUGUUUCUAGCUGAU 
                 5073-5093 
                 A- 
                 3021 
                 UCAAAUCAGCUAGAAACA 
                 5071-5093 
               
               
                 998894.1 
                 1530266.1 
                   
                 UUGA 
                   
                 1246027.1 
                   
                 UACCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2933 
                 GGGAGAUGGAUUCUCUU 
                 5859-5879 
                 A- 
                 3022 
                 UACGAAGAGAAUCCAUCU 
                 5857-5879 
               
               
                 999596.1 
                 1531651.1 
                   
                 CGUA 
                   
                 1247447.1 
                   
                 CCCCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2934 
                 UUCCUGAUAUGCAGUUAG 
                 7249-7269 
                 A- 
                 3023 
                 UAACUAACUGCAUAUCAG 
                 7247-7269 
               
               
                 1000679.1 
                 1533905.1 
                   
                 UUA 
                   
                 1249713.1 
                   
                 GAAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2935 
                 CAACUUACUUUCCUAAAU 
                 7456-7476 
                 A- 
                 3024 
                 UUAAUUTAGGAAAGUAAG 
                 7454-7476 
               
               
                 1000864.1 
                 1534279.1 
                   
                 UAA 
                   
                 1250087.1 
                   
                 UUGGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2936 
                 UGCUAUAGGAAAUUUGG 
                 2626-2646 
                 A- 
                 3025 
                 UAGACCAAAUUUCCUAUA 
                 2624-2646 
               
               
                 996619.1 
                 1525804.1 
                   
                 UCUA 
                   
                 1241425.1 
                   
                 GCAAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2937 
                 CUAAAUUAUGGAAGUAAU 
                 7468-7488 
                 A- 
                 3026 
                 UAGAUUACUUCCAUAAUU 
                 7466-7488 
               
               
                 961109.1 
                 1534303.1 
                   
                 CUA 
                   
                 1250111.1 
                   
                 UAGGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2938 
                 GACUUACCUUUAGAGUAU 
                 6944-6964 
                 A- 
                 3027 
                 UCAAUACUCUAAAGGUAA 
                 6942-6964 
               
               
                 1000451.1 
                 1533415.1 
                   
                 UGA 
                   
                 1249223.1 
                   
                 GUCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2939 
                 CGGACUUGGUUACCUAUC 
                 4474-4494 
                 A- 
                 3028 
                 UGAGAUAGGUAACCAAGU 
                 4472-4494 
               
               
                 961043.1 
                 1529207.1 
                   
                 UCA 
                   
                 1244929.1 
                   
                 CCGAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2940 
                 AGUCACCACUCAGCAUUC 
                 1899-1919 
                 A- 
                 3029 
                 UACGAATGCUGAGUGGUG 
                 1897-1919 
               
               
                 996036.1 
                 1524627.1 
                   
                 GUA 
                   
                 1240189.1 
                   
                 ACUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2941 
                 UUGCCCUUAUGAAUGUUA 
                 4410-4430 
                 A- 
                 3030 
                 UACUAACAUUCAUAAGGG 
                 4408-4430 
               
               
                 961042.1 
                 1529091.1 
                   
                 GUA 
                   
                 1244801.1 
                   
                 CAAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2942 
                 CUUUUCACAGGAUUGUAA 
                 6576-6596 
                 A- 
                 3031 
                 UAAUUACAAUCCUGUGAA 
                 6574-6596 
               
               
                 1000133.1 
                 1532757.1 
                   
                 UUA 
                   
                 1248565.1 
                   
                 AAGAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2943 
                 GCUGAACCUAUGAAUUCC 
                 3725-3745 
                 A- 
                 3032 
                 UUCGGAAUUCAUAGGUU 
                 3723-3745 
               
               
                 961036.1 
                 1527829.1 
                   
                 GAA 
                   
                 1243511.1 
                   
                 CAGCCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2944 
                 CUUCUUAGCCUUGUUUA 
                 1348-1368 
                 A- 
                 3033 
                 UGCCUAAACAAGGCUAAG 
                 1346-1368 
               
               
                 995573.1 
                 1523683.1 
                   
                 GGCA 
                   
                 1239237.1 
                   
                 AAGGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2945 
                 CUGCCAAGUUAACAUAGA 
                 3793-3813 
                 A- 
                 3034 
                 UACUCUAUGUUAACUUG 
                 3791-3813 
               
               
                 997715.1 
                 1527964.1 
                   
                 GUA 
                   
                 1243647.1 
                   
                 GCAGCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2946 
                 UGUAGAUCUUGCAAUUAC 
                 2533-2553 
                 A- 
                 3035 
                 UUGGUAAUUGCAAGAUC 
                 2531-2553 
               
               
                 996533.1 
                 1525638.1 
                   
                 CAA 
                   
                 1241253.1 
                   
                 UACAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2947 
                 UAGGCUAAUGACCCAAGA 
                 1363-1383 
                 A- 
                 3036 
                 UAAUCUTGGGUCAUUAGC 
                 1361-1383 
               
               
                 995587.1 
                 1523713.1 
                   
                 UUA 
                   
                 1239267.1 
                   
                 CUAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2948 
                 UUUGUCGUAGUGAUUUU 
                 1442-1462 
                 A- 
                 3037 
                 UAGGAAAAUCACUACGAC 
                 1440-1462 
               
               
                 995660.1 
                 1523863.1 
                   
                 CCUA 
                   
                 1239425.1 
                   
                 AAAGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 2949 
                 UUGCAAGCCUCUUAUGUG 
                 243-263 
                 A- 
                 3038 
                 UCUCACAUAAGAGGCUUG 
                 241-263 
               
               
                 994670.1 
                 1521918.1 
                   
                 AGA 
                   
                 1237413.1 
                   
                 CAACC 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13A 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A siRNA Modified Single Strands and Duplex Sequences 
               
               
                 Column 1 indicates duplex name and the number following the decimal point in a duplex 
               
               
                 name merely refers to a batch production number. Column 2 indicates the name of the 
               
               
                 sense sequence. Column 3 indicates the sequence ID for the sequence of column 4. 
               
               
                 Column 4 provides the modified sequence of a sense strand suitable for use in a 
               
               
                 duplex described herein. Column 5 indicates the antisense sequence name. Column 6 
               
               
                 indicates the sequence ID for the sequence of column 7. Column 7 provides the 
               
               
                 sequence of a modified antisense strand suitable for use in a duplex described 
               
               
                 herein, e.g., a duplex comprising the sense sequence in the same row of the table. 
               
               
                 Column 8 indicates the position in the target mRNA (NM_001365536.1) that is 
               
               
                 complementary to the antisense strand of Column 7. Column 9 indicated the sequence 
               
               
                 ID for the sequence of column 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 Seq ID 
                   
                 mRNA target 
                 SEQ ID 
               
               
                   
                 Sense 
                 Seq ID 
                   
                 Antisense 
                 NO: 
                 Antisense 
                 sequence in 
                 NO: 
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 sequence 
                 (anti 
                 sequence 
                 NM_00136 
                 (mRNA 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 name 
                 sense) 
                 (5′-3′) 
                 5536.1 
                 target) 
               
               
                   
               
               
                 AD- 
                 A- 
                 4000 
                 ascsacaaagdGgdAa 
                 A- 
                 4266 
                 VPusAfsgadTu(G2p) 
                   
                   
               
               
                 1251302 
                 2337487.1 
                   
                 aa(Chd)aaucuaL96 
                 2337488.1 
                   
                 uuuudCcCfuUfugugu 
                   
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 susc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5802 
                 csascaaagggAfAfaac 
                 A- 
                 4267 
                 VPusAfsagdAudTguu 
                   
                   
               
               
                 1251303 
                 2337489.1 
                   
                 aa(Uhd)cuuaL96 
                 2337490.1 
                   
                 uucCfcUfuugugsusu 
                   
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5803 
                 ascsaaagggAfAfAfac 
                 A- 
                 4268 
                 VPudGaadGadTuguu 
                 GAACAAAGGGAAA 
                 4534 
               
               
                 1251304 
                 2337491.1 
                   
                 aa(Uhd)cuucaL96 
                 2337492.1 
                   
                 uuCfcCfuuugusgsu 
                 ACAAUCUUCC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4003 
                 csasaagggaAfAfAfca 
                 A- 
                 4269 
                 VPudGgadAgdAuugu 
                 AACAAAGGGAAAA 
                 4535 
               
               
                 1251305 
                 2337493.1 
                   
                 au(Chd)uuccaL96 
                 2337494.1 
                   
                 uuUfcCfcuuugsusg 
                 CAAUCUUCCG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4004 
                 asasagggAfaAfAfCfa 
                 A- 
                 4270 
                 VPusCfsggdAadGauu 
                 ACAAAGGGAAAAC 
                 4536 
               
               
                 1251306 
                 2337495.1 
                   
                 auc(Uhd)uccgaL96 
                 2337496.1 
                   
                 guuUfuCfccuuusgsu 
                 AAUCUUCCGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4005 
                 asasagggaadAaCfaa 
                 A- 
                 4271 
                 VPuCfggdAadGauug 
                 ACAAAGGGAAAAC 
                 4537 
               
               
                 1251307 
                 2337497.1 
                   
                 uc(Uhd)uccgaL96 
                 2337498.1 
                   
                 dTuUfuCfccuuusgsu 
                 AAUCUUCCGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4006 
                 asasgggaaaAfCfAfa 
                 A- 
                 4272 
                 VPusdAscgdGa(A2p) 
                 CAAAGGGAAAACA 
                 4538 
               
               
                 1251315 
                 2337506.1 
                   
                 ucu(Uhd)ccguaL96 
                 2337501.1 
                   
                 gauudGuUfudTcccu 
                 AUCUUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4007 
                 asasgggaaadAcdAa 
                 A- 
                 4273 
                 VPusdAscgdGa(A2p) 
                 CAAAGGGAAAACA 
                 4539 
               
               
                 1251310 
                 2337499.1 
                   
                 ucu(Uhd)ccguaL96 
                 2337501.1 
                   
                 gauudGuUfudTcccu 
                 AUCUUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4008 
                 asasggg(Ahd)aadAc 
                 A- 
                 4274 
                 VPusdAscgdGadAga 
                 CAAAGGGAAAACA 
                 4540 
               
               
                 961179. 
                 1812594.1 
                   
                 dAaucuuccguaL96 
                 1812595.1 
                   
                 uudGudTudTcccuus 
                 AUCUUCCGUU 
                   
               
               
                 3 
                   
                   
                   
                   
                   
                 usg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4009 
                 asasgggaaadAcdAa 
                 A- 
                 4275 
                 VPusdAscgdGadAga 
                 CAAAGGGAAAACA 
                 4541 
               
               
                 1251308 
                 2337499.1 
                   
                 ucu(Uhd)ccguaL96 
                 1812595.1 
                   
                 uudGudTudTcccuus 
                 AUCUUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 usg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4010 
                 asasgggaaaAfCfAfa 
                 A- 
                 4276 
                 VPusdAscgdGa(Agn) 
                 CAAAGGGAAAACA 
                 4542 
               
               
                 1251314 
                 2337506.1 
                   
                 ucu(Uhd)ccguaL96 
                 2337500.1 
                   
                 gauudGuUfudTcccu 
                 AUCUUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4011 
                 asasgggaaadAcdAa 
                 A- 
                 4277 
                 VPusdAscgdGa(Agn) 
                 CAAAGGGAAAACA 
                 4543 
               
               
                 1251309 
                 2337499.1 
                   
                 ucu(Uhd)ccguaL96 
                 2337500.1 
                   
                 gauudGuUfudTcccu 
                 AUCUUCCGUU 
                   
               
               
                 .2 
                   
                   
                   
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4012 
                 asasgggaaaAfCfAfa 
                 A- 
                 4278 
                 VPudAcgdGa(Agn)ga 
                 CAAAGGGAAAACA 
                 4544 
               
               
                 1251316 
                 2337506.1 
                   
                 ucu(Uhd)ccguaL96 
                 2337507.1 
                   
                 uudGuUfudTcccuus 
                 AUCUUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 usg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4013 
                 asasgggaaaAfCfAfa 
                 A- 
                 4279 
                 VPudAcgdGa(A2p)ga 
                 CAAAGGGAAAACA 
                 4545 
               
               
                 1251317 
                 2337506.1 
                   
                 ucu(Uhd)ccguaL96 
                 2337508.1 
                   
                 uudGuUfudTcccuus 
                 AUCUUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 usg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4014 
                 asasgggaaadAcdAa 
                 A- 
                 4280 
                 VPusdAscgdGa(A2p) 
                 CAAAGGGAAAACA 
                 4546 
               
               
                 1251311 
                 2337499.1 
                   
                 ucu(Uhd)ccguaL96 
                 2337502.1 
                   
                 gauudGuUfudTcccu 
                 AUCUUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 uscsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4015 
                 asasgggaaadAcdAa 
                 A- 
                 4281 
                 VPusdAscgdGa(Agn) 
                 CAAAGGGAAAACA 
                 4547 
               
               
                 1251309 
                 2337499.1 
                   
                 ucu(Uhd)ccguaL96 
                 2337500.1 
                   
                 gauudGuUfudTcccu 
                 AUCUUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 ususg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4016 
                 asgsggaaAfaCfAfAfu 
                 A- 
                 4282 
                 VPusAfsacdGgdAaga 
                 AAAGGGAAAACAA 
                 4548 
               
               
                 1251318 
                 2337509.1 
                   
                 cuu(Chd)cguuaL96 
                 2337510.1 
                   
                 uugUfuUfucccususu 
                 UCUUCCGUUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4017 
                 asgsggaaaaCfadAuc 
                 A- 
                 4283 
                 VPudAacdGgdAagau 
                 AAAGGGAAAACAA 
                 4549 
               
               
                 1251319 
                 2337511.1 
                   
                 uu(Chd)cguuaL96 
                 2337512.1 
                   
                 dTgUfuUfucccususu 
                 UCUUCCGUUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4018 
                 gsgsgaaadAcdAauc 
                 A- 
                 4284 
                 VPusdAscgdGa(A2p) 
                 AAGGGAAAACAAU 
                 4550 
               
               
                 1251313 
                 2337503.1 
                   
                 u(Uhd)ccguaL96 
                 2337505.1 
                   
                 gauudGuUfudTcccsu 
                 CUUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 SU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4019 
                 gsgsgaaadAcdAauc 
                 A- 
                 4285 
                 VPusdAscgdGa(Agn) 
                 AAGGGAAAACAAU 
                 4551 
               
               
                 1251312 
                 2337503.1 
                   
                 u(Uhd)ccguaL96 
                 2337504.1 
                   
                 gauudGuUfudTcccsu 
                 CUUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4020 
                 gsgsgaaaAfcAfaUfc 
                 A- 
                 4286 
                 VPusAfsaadCgdGaag 
                 AAGGGAAAACAAU 
                 4552 
               
               
                 1251320 
                 2337513.1 
                   
                 uuc(Chd)guuuaL96 
                 2337514.1 
                   
                 adTudGuUfuucccsus 
                 CUUCCGUUUC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4021 
                 gsgsaaaa(Chd)aaUf 
                 A- 
                 4287 
                 VPudGaadAcdGgaag 
                 AGGGAAAACAAUC 
                 4553 
               
               
                 1251321 
                 2337515.1 
                   
                 CfuuccguuucaL96 
                 2337516.1 
                   
                 auUfgUfuuuccscsu 
                 UUCCGUUUCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4022 
                 gsasaaa(Chd)aaUfCf 
                 A- 
                 4288 
                 VPuUfgadAa(C2p)gg 
                 GGGAAAACAAUCU 
                 4554 
               
               
                 1251323 
                 2337519.1 
                   
                 UfuccguuucaaL96 
                 2337520.1 
                   
                 aagaUfudGuuuucscs 
                 UCCGUUUCAA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4023 
                 gsasaaa(Chd)aaUfCf 
                 A- 
                 4289 
                 VPuUfgadAadTggaag 
                 GGGAAAACAAUCU 
                 4555 
               
               
                 1251322 
                 2337517.1 
                   
                 UfuccauuucaaL96 
                 2337518.1 
                   
                 aUfudGuuuucscsc 
                 UCCGUUUCAA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4024 
                 asasaacaauCfUfUfc 
                 A- 
                 4290 
                 VPuUfugdAadAcgga 
                 GGAAAACAAUCUU 
                 4556 
               
               
                 1251325 
                 2337523.1 
                   
                 cgu(Uhd)ucaaaL96 
                 2337524.1 
                   
                 dAgdAuUfguuuuscsc 
                 CCGUUUCAAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4025 
                 asasaacaAfuCfUfUf 
                 A- 
                 4291 
                 VPusUfsugdAadAcgg 
                 GGAAAACAAUCUU 
                 4557 
               
               
                 1251324 
                 2337521.1 
                   
                 ccgu(Uhd)ucaaaL96 
                 2337522.1 
                   
                 aagAfuUfguuuuscsc 
                 CCGUUUCAAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4026 
                 usgsucgaguAfCfAfc 
                 A- 
                 4292 
                 VPusCfsagdTadAaag 
                 AAUGUCGAGUACA 
                 4558 
               
               
                 1251249 
                 2337423.1 
                   
                 uuu(Uhd)acugaL96 
                 2337424.1 
                   
                 uguAfcUfcgacasusu 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4027 
                 usgsucgaguAfCfAfc 
                 A- 
                 4293 
                 VPuCfagdTadAaagug 
                 AAUGUCGAGUACA 
                 4559 
               
               
                 1251254 
                 2337423.1 
                   
                 uuu(Uhd)acugaL96 
                 2337431.1 
                   
                 uAfcUfcgacascsc 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4028 
                 usgsucgaguAfCfAfc 
                 A- 
                 4294 
                 VPusCfsaguAfaAfAfg 
                 AAUGUCGAGUACA 
                 4560 
               
               
                 1251248 
                 2337423.1 
                   
                 uuu(Uhd)acugaL96 
                 1522698.1 
                   
                 uguAfcUfcgacasusu 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4029 
                 usgsucgaguAfCfAfc 
                 A- 
                 4295 
                 VPusCfsagdTadAaag 
                 AAUGUCGAGUACA 
                 4561 
               
               
                 1251284 
                 2337423.1 
                   
                 uuu(Uhd)acugaL96 
                 2337467.1 
                   
                 udGuAfcdTcgacasus 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4030 
                 usgsucgagudAcdAc 
                 A- 
                 4296 
                 VPusCfsagdTadAaag 
                 AAUGUCGAGUACA 
                 4562 
               
               
                 1251253 
                 2337428.1 
                   
                 uuu(Uhd)acugaL96 
                 2337430.1 
                   
                 udGudAcUfcgacascs 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4031 
                 usgsucgaguAfCfAfc 
                 A- 
                 4297 
                 VPusCfsagdTadAaag 
                 AAUGUCGAGUACA 
                 4563 
               
               
                 1251286 
                 2337423.1 
                   
                 uuu(Uhd)acugaL96 
                 2337469.1 
                   
                 udGuAfcdTcgacascsc 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4032 
                 usgsucgaguAfCfAfc 
                 A- 
                 4298 
                 VPusdCsagdTadAaag 
                 AAUGUCGAGUACA 
                 4564 
               
               
                 1251282 
                 2337423.1 
                   
                 uuu(Uhd)acugaL96 
                 1875199.1 
                   
                 udGudAcdTcgacasus 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4033 
                 usgsucg(Ahd)gudAc 
                 A- 
                 4299 
                 VPusdCsagdTadAaag 
                 AAUGUCGAGUACA 
                 4565 
               
               
                 1010661 
                 1851664.1 
                   
                 dAcuuuuacugaL96 
                 1875199.1 
                   
                 udGudAcdTcgacasus 
                 CUUUUACUGG 
                   
               
               
                 .3 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4034 
                 usgsucg(Ahd)GfuAf 
                 A- 
                 4300 
                 VPusCfsaguAfaAfAfg 
                 AAUGUCGAGUACA 
                 4566 
               
               
                 795305. 
                 1522697.1 
                   
                 CfAfcuuuuacugaL96 
                 1522698.1 
                   
                 uguAfcUfcgacasusu 
                 CUUUUACUGG 
                   
               
               
                 3 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4035 
                 usgsucgaguAfCfAfc 
                 A- 
                 4301 
                 VPusCfsagdTadAaag 
                 AAUGUCGAGUACA 
                 4567 
               
               
                 1251250 
                 2337423.1 
                   
                 uuu(Uhd)acugaL96 
                 2337425.1 
                   
                 uguAfcUfcgacascsc 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4036 
                 usgsucgaguAfCfAfc 
                 A- 
                 4302 
                 VPusCfsagdTadAaag 
                 AAUGUCGAGUACA 
                 4568 
               
               
                 1251283 
                 2337423.1 
                   
                 uuu(Uhd)acugaL96 
                 2337466.1 
                   
                 udGudAcdTcgacasus 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4037 
                 usgsucgagudAcdAc 
                 A- 
                 4303 
                 VPusCfsagdTadAaag 
                 AAUGUCGAGUACA 
                 4569 
               
               
                 1251281 
                 2337428.1 
                   
                 uuu(Uhd)acugaL96 
                 2337466.1 
                   
                 udGudAcdTcgacasus 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4038 
                 usgsucgagudAcdAc 
                 A- 
                 4304 
                 VPuCfagdTadAaagud 
                 AAUGUCGAGUACA 
                 4570 
               
               
                 1251255 
                 2337428.1 
                   
                 uuu(Uhd)acugaL96 
                 2337432.1 
                   
                 GudAcUfcgacascsc 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4039 
                 usgsucgagudAcdAc 
                 A- 
                 4305 
                 VPuCfagdTadAaagud 
                 AAUGUCGAGUACA 
                 4571 
               
               
                 1251289 
                 2337428.1 
                   
                 uuu(Uhd)acugaL96 
                 2337473.1 
                   
                 GudAcdTcgacasusu 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4040 
                 usgsucgagudAcdAc 
                 A- 
                 4306 
                 VPusCfsagdTadAaag 
                 AAUGUCGAGUACA 
                 4572 
               
               
                 1251252 
                 2337428.1 
                   
                 uuu(Uhd)acugaL96 
                 2337429.1 
                   
                 udGudAcUfcgacasus 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4041 
                 usgsucgagudAcdAc 
                 A- 
                 4307 
                 VPusCfsagdTadAaag 
                 AAUGUCGAGUACA 
                 4573 
               
               
                 1251285 
                 2337428.1 
                   
                 uuu(Uhd)acugaL96 
                 2337468.1 
                   
                 udGudAcdTcgacascs 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4042 
                 usgsucgagudAcdAc 
                 A- 
                 4308 
                 VPuCfagdTadAaagud 
                 AAUGUCGAGUACA 
                 4574 
               
               
                 1251291 
                 2337428.1 
                   
                 uuu(Uhd)acugaL96 
                 2337475.1 
                   
                 GudAcdTcgacascsc 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4043 
                 usgsucgaguAfCfAfc 
                 A- 
                 4309 
                 VPuCfagdTadAaagud 
                 AAUGUCGAGUACA 
                 4575 
               
               
                 1251290 
                 2337423.1 
                   
                 uuu(Uhd)acugaL96 
                 2337474.1 
                   
                 GuAfcdTcgacasusu 
                 CUUUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4044 
                 uscsgaguAfCfAfcuu 
                 A- 
                 4310 
                 VPusCfsagdTadAaag 
                 UGUCGAGUACACU 
                 4576 
               
               
                 1251251 
                 2337426.1 
                   
                 u(Uhd)acugaL96 
                 2337427.1 
                   
                 uguAfcUfcgascsg 
                 UUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4045 
                 uscsgagudAcdAcuu 
                 A- 
                 4311 
                 VPusCfsagdTadAaag 
                 UGUCGAGUACACU 
                 4577 
               
               
                 1251287 
                 2337470.1 
                   
                 u(Uhd)acugaL96 
                 2337471.1 
                   
                 udGudAcdTcgascsg 
                 UUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4046 
                 uscsgaguAfCfAfcuu 
                 A- 
                 4312 
                 VPusCfsagdTadAaag 
                 UGUCGAGUACACU 
                 4578 
               
               
                 1251288 
                 2337426.1 
                   
                 u(Uhd)acugaL96 
                 2337472.1 
                   
                 udGuAfcdTcgascsg 
                 UUUACUGG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4047 
                 gsasggc(Uhd)UfcUf 
                 A- 
                 4313 
                 VPuUfucdTc(C2p)ua 
                 AAGAGGCUUCUGU 
                 4579 
               
               
                 1251326 
                 2337525.1 
                   
                 gUfguaggagaaaL96 
                 2337526.1 
                   
                 cadCadGaAfgccucsu 
                 GUAGGAGAAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 SU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4048 
                 asgsgcu(Uhd)cudGu 
                 A- 
                 4314 
                 VPudAuudCu(C2p)cu 
                 AGAGGCUUCUGUG 
                 4580 
               
               
                 1251327 
                 1851778.1 
                   
                 dGuaggagaauaL96 
                 2337527.1 
                   
                 acdAcdAgdAagccusc 
                 UAGGAGAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 SU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4049 
                 gsgscuu(Chd)UfgUf 
                 A- 
                 4315 
                 VPudAaudTc(Tgn)cc 
                 GAGGCUUCUGUGU 
                 4581 
               
               
                 1251328 
                 2337528.1 
                   
                 gUfaggagaauuaL96 
                 2337529.1 
                   
                 uadCaCfadGaagccsu 
                 AGGAGAAUUC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4050 
                 gscsuuc(Uhd)gugUf 
                 A- 
                 4316 
                 VPudGaadTu(C2p)uc 
                 AGGCUUCUGUGUA 
                 4582 
               
               
                 1251329 
                 2337530.1 
                   
                 AfggagaauucaL96 
                 2337531.1 
                   
                 cuacAfcAfgaagcscsu 
                 GGAGAAUUCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4051 
                 csusucug(Uhd)gdTa 
                 A- 
                 4317 
                 VPuUfgadAu(Tgn)cu 
                 GGCUUCUGUGUAG 
                 4583 
               
               
                 1251330 
                 2337532.1 
                   
                 dGgagaauucaaL96 
                 2337533.1 
                   
                 ccdTaCfaCfagaagscs 
                 GAGAAUUCAC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4052 
                 ususcug(Uhd)GfuAf 
                 A- 
                 4318 
                 VPusGfsugaAfuUfCf 
                 GCUUCUGUGUAGG 
                 4584 
               
               
                 795366. 
                 1522818.1 
                   
                 GfGfagaauucacaL96 
                 1522819.1 
                   
                 uccuAfcAfcagaasgsc 
                 AGAAUUCACU 
                   
               
               
                 3 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4053 
                 ususcug(Uhd)GfuAf 
                 A- 
                 4319 
                 VPusGfsugdAa(Tgn) 
                 GCUUCUGUGUAGG 
                 4585 
               
               
                 1251331 
                 1522818.1 
                   
                 GfGfagaauucacaL96 
                 2337534.1 
                   
                 ucuccuAfcAfcagaasg 
                 AGAAUUCACU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4054 
                 ususcug(Uhd)guAfg 
                 A- 
                 4320 
                 VPusdGsugdAa(U2p) 
                 GCUUCUGUGUAGG 
                 4586 
               
               
                 1251334 
                 2337536.1 
                   
                 dGagaauucacaL96 
                 2337538.1 
                   
                 ucucdCuAfcAfcagaas 
                 AGAAUUCACU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 gsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4055 
                 ususcug(Uhd)guAfg 
                 A- 
                 4321 
                 VPusdGsugdAa(Tgn) 
                 GCUUCUGUGUAGG 
                 4587 
               
               
                 1251333 
                 2337536.1 
                   
                 dGagaauucacaL96 
                 2337537.1 
                   
                 ucucdCuAfcAfcagaas 
                 AGAAUUCACU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 gsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4056 
                 ususcug(Uhd)gudAg 
                 A- 
                 4322 
                 VPudGugdAa(U2p)u 
                 GCUUCUGUGUAGG 
                 4588 
               
               
                 1251338 
                 1851786.1 
                   
                 dGagaauucacaL96 
                 2337542.1 
                   
                 cucdCudAcdAcagaas 
                 AGAAUUCACU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 gsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4057 
                 ususcug(Uhd)gudAg 
                 A- 
                 4323 
                 VPudGugdAa(Tgn)uc 
                 GCUUCUGUGUAGG 
                 4589 
               
               
                 1251337 
                 1851786.1 
                   
                 dGagaauucacaL96 
                 2337541.1 
                   
                 ucdCudAcdAcagaasg 
                 AGAAUUCACU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4058 
                 ususcug(Uhd)guAfg 
                 A- 
                 4324 
                 VPusdGsugdAa(U2p) 
                 GCUUCUGUGUAGG 
                 4590 
               
               
                 1251336 
                 2337536.1 
                   
                 dGagaauucacaL96 
                 2337540.1 
                   
                 ucucdCuAfcAfcagaas 
                 AGAAUUCACU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 use 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4059 
                 ususcug(Uhd)guAfg 
                 A- 
                 4325 
                 VPusdGsugdAa(Tgn) 
                 GCUUCUGUGUAGG 
                 4591 
               
               
                 1251335 
                 2337536.1 
                   
                 dGagaauucacaL96 
                 2337539.1 
                   
                 ucucdCuAfcAfcagaas 
                 AGAAUUCACU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 use 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4060 
                 uscsuguguadGgdAg 
                 A- 
                 4326 
                 VPudAgudGa(Agn)u 
                 CUUCUGUGUAGGA 
                 4592 
               
               
                 1251339 
                 2337543.1 
                   
                 aau(Uhd)cacuaL96 
                 2337544.1 
                   
                 ucudCcUfaCfacagasg 
                 GAAUUCACUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4061 
                 csusgug(Uhd)agdGa 
                 A- 
                 4327 
                 VPudAagdTgdAauuc 
                 UUCUGUGUAGGA 
                 4593 
               
               
                 1251340 
                 1851790.1 
                   
                 dGaauucacuuaL96 
                 2337545.1 
                   
                 dTcCfudAcacagsgsg 
                 GAAUUCACUUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4062 
                 usgsug(Uhd)aggAfg 
                 A- 
                 4328 
                 VPudAaadGu(G2p)a 
                 UCUGUGUAGGAGA 
                 4594 
               
               
                 1251341 
                 2337546.1 
                   
                 AfauucacuuuaL96 
                 2337547.1 
                   
                 auudCuCfcUfacacas 
                 AUUCACUUUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 gsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4063 
                 gsusguaggadGadAu 
                 A- 
                 4329 
                 VPudAaadAgdTgaau 
                 CUGUGUAGGAGAA 
                 4595 
               
               
                 1251342 
                 2337548.1 
                   
                 uca(Chd)uuuuaL96 
                 2337549.1 
                   
                 dTcUfcCfuacacsgsg 
                 UUCACUUUUC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4064 
                 usgsuaggagdAaUfu 
                 A- 
                 4330 
                 VPusdGsaadAa(G2p) 
                 UGUGUAGGAGAA 
                 4596 
               
               
                 1251347 
                 2337481.1 
                   
                 cac(Uhd)uuucaL96 
                 2337555.1 
                   
                 ugaadTuCfuCfcuacas 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 esg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4065 
                 usgsuag(Ghd)AfgAf 
                 A- 
                 4331 
                 VPusGfsaaaAfgUfGfa 
                 UGUGUAGGAGAA 
                 4597 
               
               
                 795371. 
                 1522828.1 
                   
                 AfUfucacuuuucaL96 
                 1522829.1 
                   
                 auuCfuCfcuacascsa 
                 UUCACUUUUCU 
                   
               
               
                 3 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4066 
                 usgsuag(Ghd)agdAa 
                 A- 
                 4332 
                 VPusdGsaadAadGug 
                 UGUGUAGGAGAA 
                 4598 
               
               
                 1010663 
                 1851796.1 
                   
                 dTucacuuuucaL96 
                 1875201.1 
                   
                 aadTudCudCcuacasc 
                 UUCACUUUUCU 
                   
               
               
                 .3 
                   
                   
                   
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4067 
                 usgsuaggagdAaUfU 
                 A- 
                 4333 
                 VPudGaadAa(G2p)u 
                 UGUGUAGGAGAA 
                 4599 
               
               
                 1251301 
                 2337482.1 
                   
                 fcac(Uhd)uuucaL96 
                 2337486.1 
                   
                 gaadTudCudCcuacas 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 csg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4068 
                 usgsuaggagdAaUfu 
                 A- 
                 4334 
                 VPusdGsaadAadAug 
                 UGUGUAGGAGAA 
                 4600 
               
               
                 1251348 
                 2337556.1 
                   
                 cau(Uhd)uuucaL96 
                 2337557.1 
                   
                 aadTuCfuCfcuacascs 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4069 
                 usgsuaggAfgAfAfUf 
                 A- 
                 4335 
                 VPusGfsaaaAfgUfGfa 
                 UGUGUAGGAGAA 
                 4601 
               
               
                 1251343 
                 2337550.1 
                   
                 ucac(Uhd)uuucaL96 
                 1522829.1 
                   
                 auuCfuCfcuacascsa 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4070 
                 usgsuaggAfgAfAfUf 
                 A- 
                 4336 
                 VPusdGsaadAa(G2p) 
                 UGUAGGAGAAUUC 
                 4602 
               
               
                 1251346 
                 2337550.1 
                   
                 ucac(Uhd)uuucaL96 
                 2337554.1 
                   
                 ugaauuCfuCfcuascsg 
                 ACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4071 
                 usgsuaggagdAadTu 
                 A- 
                 4337 
                 VPudGaadAa(G2p)u 
                 UGUGUAGGAGAA 
                 4603 
               
               
                 1251299 
                 2337476.1 
                   
                 cac(Uhd)uuucaL96 
                 2337486.1 
                   
                 gaadTudCudCcuacas 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 csg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4072 
                 usgsuaggAfgAfAfUf 
                 A- 
                 4338 
                 VPusdGsaadAadAug 
                 UGUGUAGGAGAA 
                 4604 
               
               
                 1251345 
                 2337552.1 
                   
                 ucau(Uhd)uuucaL96 
                 2337553.1 
                   
                 aauuCfuCfcuacascsg 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4073 
                 usgsuaggagdAaUfu 
                 A- 
                 4339 
                 VPudGaadAa(G2p)u 
                 UGUGUAGGAGAA 
                 4605 
               
               
                 1251349 
                 2337481.1 
                   
                 cac(Uhd)uuucaL96 
                 2337558.1 
                   
                 gaadTuCfuCfcuacasc 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4074 
                 usgsuaggagdAadTu 
                 A- 
                 4340 
                 VPusdGsaadAadGug 
                 UGUGUAGGAGAA 
                 4606 
               
               
                 1251292 
                 2337476.1 
                   
                 cac(Uhd)uuucaL96 
                 2337477.1 
                   
                 aadTudCudCcuacasc 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4075 
                 usgsuaggagdAadTu 
                 A- 
                 4341 
                 VPusdGsaadAa(G2p) 
                 UGUGUAGGAGAA 
                 4607 
               
               
                 1251293 
                 2337476.1 
                   
                 cac(Uhd)uuucaL96 
                 2337478.1 
                   
                 ugaadTudCudCcuac 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 ascsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4076 
                 usgsuaggagdAadTu 
                 A- 
                 4342 
                 VPusdGsaadAadAug 
                 UGUGUAGGAGAA 
                 4608 
               
               
                 1251294 
                 2337479.1 
                   
                 cau(Uhd)uuucaL96 
                 2337480.1 
                   
                 aadTudCudCcuacasc 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4077 
                 usgsuaggAfgAfAfUf 
                 A- 
                 4343 
                 VPusdGsaadAa(G2p) 
                 UGUGUAGGAGAA 
                 4609 
               
               
                 1251344 
                 2337550.1 
                   
                 ucac(Uhd)uuucaL96 
                 2337551.1 
                   
                 ugaauuCfuCfcuacasc 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4078 
                 usgsuaggagdAaUfu 
                 A- 
                 4344 
                 VPudGaadAa(G2p)u 
                 UGUGUAGGAGAA 
                 4610 
               
               
                 1251300 
                 2337481.1 
                   
                 cac(Uhd)uuucaL96 
                 2337486.1 
                   
                 gaadTudCudCcuacas 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 csg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4079 
                 usgsuaggagdAaUfu 
                 A- 
                 4345 
                 VPusdGsaadAa(G2p) 
                 UGUGUAGGAGAA 
                 4611 
               
               
                 1251295 
                 2337481.1 
                   
                 cac(Uhd)uuucaL96 
                 2337478.1 
                   
                 ugaadTudCudCcuac 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 ascsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4080 
                 usgsuaggagdAaUfu 
                 A- 
                 4346 
                 VPusdGsaadAa(G2p) 
                 UGUGUAGGAGAA 
                 4612 
               
               
                 1251296 
                 2337482.1 
                   
                 fcac(Uhd)uuucaL96 
                 2337478.1 
                   
                 ugaadTudCudCcuac 
                 UUCACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 ascsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4081 
                 gsusaggagaAfUfUfc 
                 A- 
                 4347 
                 VPusAfsgadAadAgug 
                 GUGUAGGAGAAU 
                 4613 
               
               
                 1251350 
                 2337559.1 
                   
                 acu(Uhd)uucuaL96 
                 2337560.1 
                   
                 aauUfcUfccuacsgsc 
                 UCACUUUUCUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4082 
                 gsusaggagaaUfUfca 
                 A- 
                 4348 
                 VPudAgadAadAguga 
                 GUGUAGGAGAAU 
                 4614 
               
               
                 1251351 
                 2337561.1 
                   
                 cu(Uhd)uucuaL96 
                 2337562.1 
                   
                 auUfcUfccuacsgsc 
                 UCACUUUUCUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4083 
                 usasggagaaUfUfCfa 
                 A- 
                 4349 
                 VPusdAsagdAadAag 
                 UGUAGGAGAAUUC 
                 4615 
               
               
                 1251353 
                 2337565.1 
                   
                 cuu(Uhd)ucuuaL96 
                 2337566.1 
                   
                 ugaaUfuCfuccuascsg 
                 ACUUUUCUUC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4084 
                 usasggagAfaUfUfCf 
                 A- 
                 4350 
                 VPusAfsagdAadAagu 
                 UGUAGGAGAAUUC 
                 4616 
               
               
                 1251352 
                 2337563.1 
                   
                 acuu(Uhd)ucuuaL96 
                 2337564.1 
                   
                 gaaUfuCfuccuascsg 
                 ACUUUUCUUC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4085 
                 usasggagdAaUfUfca 
                 A- 
                 4351 
                 VPusdGsaadAa(G2p) 
                 UGUAGGAGAAUUC 
                 4617 
               
               
                 1251298 
                 2337485.1 
                   
                 c(Uhd)uuucaL96 
                 2337484.1 
                   
                 ugaadTudCudCcuasc 
                 ACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4086 
                 usasggagdAaUfucac 
                 A- 
                 4352 
                 VPusdGsaadAa(G2p) 
                 UGUAGGAGAAUUC 
                 4618 
               
               
                 1251297 
                 2337483.1 
                   
                 (Uhd)uuucaL96 
                 2337484.1 
                   
                 ugaadTudCudCcuasc 
                 ACUUUUCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4087 
                 asgsgagaauUfcdAcu 
                 A- 
                 4353 
                 VPudGaadGadAaagu 
                 GUAGGAGAAUUCA 
                 4619 
               
               
                 1251354 
                 2337567.1 
                   
                 uu(Uhd)cuucaL96 
                 2337568.1 
                   
                 dGaAfuUfcuccusgsc 
                 CUUUUCUUCG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4088 
                 gsgsagaaUfuCfAfCf 
                 A- 
                 4354 
                 VPusCfsgadAgdAaaa 
                 UAGGAGAAUUCAC 
                 4620 
               
               
                 1251355 
                 2337569.1 
                   
                 uuuu(Chd)uucgaL96 
                 2337570.1 
                   
                 gugAfaUfucuccsusg 
                 UUUUCUUCGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4089 
                 gsgsagaaUfuCfaCfu 
                 A- 
                 4355 
                 VPuCfgadAgdAaaagd 
                 UAGGAGAAUUCAC 
                 4621 
               
               
                 1251356 
                 2337571.1 
                   
                 uuu(Chd)uucgaL96 
                 2337572.1 
                   
                 TgdAaUfucuccsusg 
                 UUUUCUUCGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4090 
                 gsasgaa(Uhd)UfcaC 
                 A- 
                 4356 
                 VPudAcgdAadGaaaa 
                 AGGAGAAUUCACU 
                 4622 
               
               
                 1251357 
                 2337573.1 
                   
                 fUfuuucuucguaL96 
                 2337574.1 
                   
                 dGudGadAuucucscs 
                 UUUCUUCGUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4091 
                 cscsugaagcAfUfAfa 
                 A- 
                 4357 
                 VPusdGsaadAadCau 
                 AACCUGAAGCAUA 
                 4623 
               
               
                 1251358 
                 2337575.1 
                   
                 aug(Uhd)uuucaL96 
                 2337576.1 
                   
                 uudAudGcUfucaggs 
                 AAUGUUUUCG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 USU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4092 
                 csusgaagCfaUfAfAf 
                 A- 
                 4358 
                 VPusCfsgadAadAcau 
                 ACCUGAAGCAUAA 
                 4624 
               
               
                 1251359 
                 2337577.1 
                   
                 augu(Uhd)uucgaL96 
                 2337578.1 
                   
                 uuaUfgCfuucagsgsu 
                 AUGUUUUCGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4093 
                 csusgaagcadTadAau 
                 A- 
                 4359 
                 VPuCfgadAadAcauu 
                 ACCUGAAGCAUAA 
                 4625 
               
               
                 1251360 
                 2337579.1 
                   
                 gu(Uhd)uucgaL96 
                 2337580.1 
                   
                 uaUfgCfuucagsgsu 
                 AUGUUUUCGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4094 
                 usgsaag(Chd)audAa 
                 A- 
                 4360 
                 VPuUfcgdAadAacau 
                 CCUGAAGCAUAAA 
                 4626 
               
               
                 1251361 
                 1852317.1 
                   
                 dAuguuuucgaaL96 
                 2337581.1 
                   
                 dTuAfudGcuucasgsg 
                 UGUUUUCGAA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4095 
                 gsasagcauadAaUfgu 
                 A- 
                 4361 
                 VPuUfucdGadAaaca 
                 CUGAAGCAUAAAU 
                 4627 
               
               
                 1251363 
                 2337584.1 
                   
                 uu(Uhd)cgaaaL96 
                 2337585.1 
                   
                 dTuUfaUfgcuucsasg 
                 GUUUUCGAAA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4096 
                 gsasagcaUfaAfAfUf 
                 A- 
                 4362 
                 VPusUfsucdGadAaac 
                 CUGAAGCAUAAAU 
                 4628 
               
               
                 1251362 
                 2337582.1 
                   
                 guuu(Uhd)cgaaaL96 
                 2337583.1 
                   
                 auuUfaUfgcuucsasg 
                 GUUUUCGAAA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4097 
                 asasgca(Uhd)aadAu 
                 A- 
                 4363 
                 VPuUfuudCgdAaaac 
                 UGAAGCAUAAAUG 
                 4629 
               
               
                 1251364 
                 1812604.1 
                   
                 dGuuuucgaaaaL96 
                 2337586.1 
                   
                 dAuUfudAugcuuscsg 
                 UUUUCGAAAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4098 
                 asgscauaaaUfgUfuu 
                 A- 
                 4364 
                 VPudAuudTc(G2p)aa 
                 GAAGCAUAAAUGU 
                 4630 
               
               
                 1251372 
                 2337591.1 
                   
                 u(Chd)gaaauaL96 
                 2337598.1 
                   
                 aadCaUfuUfaugcusu 
                 UUUCGAAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4099 
                 asgscauaAfaUfGfUf 
                 A- 
                 4365 
                 VPusAfsuuuCfgAfAfa 
                 GAAGCAUAAAUGU 
                 4631 
               
               
                 1251366 
                 2337589.1 
                   
                 uuu(Chd)gaaauaL96 
                 1523300.1 
                   
                 acaUfuUfaugcususc 
                 UUUCGAAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4100 
                 asgscauaAfaUfGfUf 
                 A- 
                 4366 
                 VPusAfsuudTc(G2p)a 
                 GAAGCAUAAAUGU 
                 4632 
               
               
                 1251367 
                 2337589.1 
                   
                 uuu(Chd)gaaauaL96 
                 2337590.1 
                   
                 aaacaUfuUfaugcusu 
                 UUUCGAAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4101 
                 asgscau(Ahd)AfaUf 
                 A- 
                 4367 
                 VPusAfsuuuCfgAfAfa 
                 GAAGCAUAAAUGU 
                 4633 
               
               
                 795634. 
                 1523299.1 
                   
                 GfUfuuucgaaauaL9 
                 1523300.1 
                   
                 acaUfuUfaugcususc 
                 UUUCGAAAUU 
                   
               
               
                 4 
                   
                   
                 6 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4102 
                 asgscauaaaUfgUfuu 
                 A- 
                 4368 
                 VPusAfsuudTcdAaaa 
                 GAAGCAUAAAUGU 
                 4634 
               
               
                 1251369 
                 2337593.1 
                   
                 u(Uhd)gaaauaL96 
                 2337594.1 
                   
                 adCaUfuUfaugcusus 
                 UUUCGAAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4103 
                 asgscauaaaUfgUfuu 
                 A- 
                 4369 
                 VPusAfsuudTc(G2p)a 
                 GAAGCAUAAAUGU 
                 4635 
               
               
                 1251368 
                 2337591.1 
                   
                 u(Chd)gaaauaL96 
                 2337592.1 
                   
                 aaadCaUfuUfaugcus 
                 UUUCGAAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 use 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4104 
                 asgscauaaaUfgUfuu 
                 A- 
                 4370 
                 VPudAuudTc(G2p)aa 
                 GAAGCAUAAAUGU 
                 4636 
               
               
                 1251373 
                 2337591.1 
                   
                 u(Chd)gaaauaL96 
                 2337599.1 
                   
                 aadCaUfuUfaugcusc 
                 UUUCGAAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4105 
                 asgsca(Uhd)aaaUfg 
                 A- 
                 4371 
                 VPudAuudTcdGaaaa 
                 GAAGCAUAAAUGU 
                 4637 
               
               
                 1251365 
                 2337587.1 
                   
                 UfuuucgaaauaL96 
                 2337588.1 
                   
                 dCaUfuUfaugcususc 
                 UUUCGAAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4106 
                 asgscauaaaUfgUfuu 
                 A- 
                 4372 
                 VPusdAsuudTc(G2p) 
                 GAAGCAUAAAUGU 
                 4638 
               
               
                 1251370 
                 2337591.1 
                   
                 u(Chd)gaaauaL96 
                 2337595.1 
                   
                 aaaadCaUfuUfaugcu 
                 UUUCGAAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 scsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4107 
                 gscsa(Uhd)aaaugUf 
                 A- 
                 4373 
                 VPusdAsaudTu(C2p) 
                 AAGCAUAAAUGUU 
                 4639 
               
               
                 1251374 
                 2337600.1 
                   
                 UfuucgaaauuaL96 
                 2337601.1 
                   
                 gaaaacAfuUfuaugcs 
                 UUCGAAAUUC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 usu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4108 
                 csasuaaa(Uhd)gUfU 
                 A- 
                 4374 
                 VPusdGsaadTu(Tgn) 
                 AGCAUAAAUGUUU 
                 4640 
               
               
                 1251375 
                 2337602.1 
                   
                 fUfucgaaauucaL96 
                 2337603.1 
                   
                 cgaaaaCfaUfuuaugsc 
                 UCGAAAUUCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4109 
                 csasuaaaUfgUfuuu( 
                 A- 
                 4375 
                 VPusdAsuudTc(G2p) 
                 AGCAUAAAUGUUU 
                 4641 
               
               
                 1251371 
                 2337596.1 
                   
                 Chd)gaaauaL96 
                 2337597.1 
                   
                 aaaadCaUfuUfaugsc 
                 UCGAAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4110 
                 asusaaa(Uhd)guUfU 
                 A- 
                 4376 
                 VPusUfsgadAudTucg 
                 GCAUAAAUGUUUU 
                 4642 
               
               
                 1251376 
                 2337604.1 
                   
                 fUfcgaaauucaaL96 
                 2337605.1 
                   
                 aaaAfcAfuuuausgsc 
                 CGAAAUUCAC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4111 
                 asusaaa(Uhd)guUfU 
                 A- 
                 4377 
                 VPusUfsgadAudTucg 
                 GCAUAAAUGUUUU 
                 4643 
               
               
                 1251377 
                 2337604.1 
                   
                 fUfcgaaauucaaL96 
                 2337606.1 
                   
                 aaaAfcAfuuuausgsu 
                 CGAAAUUCAC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4112 
                 usasaaugUfuUfuCfg 
                 A- 
                 4378 
                 VPudGugdAadTuucg 
                 CAUAAAUGUUUUC 
                 4644 
               
               
                 1251378 
                 2337607.1 
                   
                 aaa(Uhd)ucacaL96 
                 2337608.1 
                   
                 dAadAaCfauuuasusg 
                 GAAAUUCACU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4113 
                 asasaug(Uhd)uuUfc 
                 A- 
                 4379 
                 VPudAgudGa(A2p)u 
                 AUAAAUGUUUUCG 
                 4645 
               
               
                 1251379 
                 2337609.1 
                   
                 dGaaauucacuaL96 
                 2337610.1 
                   
                 uucdGaAfaAfcauuus 
                 AAAUUCACUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 gsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4114 
                 usasca(Uhd)gAfuCf 
                 A- 
                 4380 
                 VPusAfscgdAcdAaag 
                 CCUACAUGAUCUU 
                 4646 
               
               
                 1251380 
                 2337611.1 
                   
                 UfUfcuuugucguaL96 
                 2337612.1 
                   
                 aagAfuCfauguasgsg 
                 CUUUGUCGUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4115 
                 usasca(Uhd)gauCfU 
                 A- 
                 4381 
                 VPudAscgdAcdAaag 
                 CCUACAUGAUCUU 
                 4647 
               
               
                 1251381 
                 2337613.1 
                   
                 fUfcuuugucguaL96 
                 2337614.1 
                   
                 aagAfuCfauguascsc 
                 CUUUGUCGUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4116 
                 ascsaugaUfcUfUfCf 
                 A- 
                 4382 
                 VPuUfacdGa(C2p)aa 
                 CUACAUGAUCUUC 
                 4648 
               
               
                 1251382 
                 2337615.1 
                   
                 uuug(Uhd)cguaaL96 
                 2337616.1 
                   
                 agdAadGaUfcaugusg 
                 UUUGUCGUAG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4117 
                 csasuga(Uhd)CfuUf 
                 A- 
                 4383 
                 VPuCfuadCgdAcaaad 
                 UACAUGAUCUUCU 
                 4649 
               
               
                 1251384 
                 1523843.1 
                   
                 CfUfuugucguagaL96 
                 2337457.1 
                   
                 GadAgdAucaugsusg 
                 UUGUCGUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4118 
                 csasuga(Uhd)cuUfC 
                 A- 
                 4384 
                 VPuCfuadCgdAcaaad 
                 UACAUGAUCUUCU 
                 4650 
               
               
                 1251274 
                 2337449.1 
                   
                 fUfuugucguagaL96 
                 2337457.1 
                   
                 GadAgdAucaugsusg 
                 UUGUCGUAGU 
                   
               
               
                 .2 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4119 
                 csasuga(Uhd)cudTc 
                 A- 
                 4385 
                 VPusdCsuadCgdAcaa 
                 UACAUGAUCUUCU 
                 4651 
               
               
                 961188. 
                 1812612.1 
                   
                 dTuugucguagaL96 
                 1812613.1 
                   
                 adGadAgdAucaugsu 
                 UUGUCGUAGU 
                   
               
               
                 3 
                   
                   
                   
                   
                   
                 sa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4120 
                 csasuga(Uhd)CfuUf 
                 A- 
                 4386 
                 VPusCfsuadCgdAcaa 
                 UACAUGAUCUUCU 
                 4652 
               
               
                 1251383 
                 1523843.1 
                   
                 CfUfuugucguagaL96 
                 2337617.1 
                   
                 agaAfgAfucaugsusg 
                 UUGUCGUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4121 
                 csasuga(Uhd)cuUfC 
                 A- 
                 4387 
                 VPusCfsuadCgdAcaa 
                 UACAUGAUCUUCU 
                 4653 
               
               
                 1251269 
                 2337449.1 
                   
                 fUfuugucguagaL96 
                 2337451.1 
                   
                 adGadAgdAucaugsu 
                 UUGUCGUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4122 
                 csasuga(Uhd)cuUfC 
                 A- 
                 4388 
                 VPusdCsuadCgdAcaa 
                 UACAUGAUCUUCU 
                 4654 
               
               
                 1251270 
                 2337449.1 
                   
                 fUfuugucguagaL96 
                 2337452.1 
                   
                 adGadAgdAucaugscs 
                 UUGUCGUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4123 
                 csasuga(Uhd)cuUfC 
                 A- 
                 4389 
                 VPusdCsuadCgdAcaa 
                 UACAUGAUCUUCU 
                 4655 
               
               
                 1251268 
                 2337449.1 
                   
                 fUfuugucguagaL96 
                 2337450.1 
                   
                 adGadAgdAucaugsu 
                 UUGUCGUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4124 
                 csasuga(Uhd)cuUfC 
                 A- 
                 4390 
                 VPuCfuadCgdAcaaad 
                 UACAUGAUCUUCU 
                 4656 
               
               
                 1251274 
                 2337449.1 
                   
                 fUfuugucguagaL96 
                 2337457.1 
                   
                 GadAgdAucaugsusg 
                 UUGUCGUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4125 
                 csasuga(Uhd)cuUfC 
                 A- 
                 4391 
                 VPusCfsuadCgdAcaa 
                 UACAUGAUCUUCU 
                 4657 
               
               
                 1251271 
                 2337449.1 
                   
                 fUfuugucguagaL96 
                 2337453.1 
                   
                 adGadAgdAucaugscs 
                 UUGUCGUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 c 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4126 
                 csasuga(Uhd)cuUfC 
                 A- 
                 4392 
                 VPudCuadCgdAcaaa 
                 UACAUGAUCUUCU 
                 4658 
               
               
                 1251275 
                 2337449.1 
                   
                 fUfuugucguagaL96 
                 2337458.1 
                   
                 dGadAgdAucaugsus 
                 UUGUCGUAGU 
                   
               
               
                 .2 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4127 
                 csasuga(Uhd)cuUfC 
                 A- 
                 4393 
                 VPudCuadCgdAcaaa 
                 UACAUGAUCUUCU 
                 4659 
               
               
                 1251275 
                 2337449.1 
                   
                 fUfuugucguagaL96 
                 2337458.1 
                   
                 dGadAgdAucaugsus 
                 UUGUCGUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4128 
                 asusgau(Chd)UfuCf 
                 A- 
                 4394 
                 VPudAcudAcdGacaa 
                 ACAUGAUCUUCUU 
                 4660 
               
               
                 1251385 
                 1523845.1 
                   
                 UfUfugucguaguaL96 
                 2337618.1 
                   
                 dAgdAadGaucausgs 
                 UGUCGUAGUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4129 
                 usgsaucuUfCfUfuug 
                 A- 
                 4395 
                 VPusdCsuadCgdAcaa 
                 CAUGAUCUUCUUU 
                 4661 
               
               
                 1251272 
                 2337454.1 
                   
                 u(Chd)guagaL96 
                 2337455.1 
                   
                 adGadAgdAucasusg 
                 GUCGUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4130 
                 usgsauc(Uhd)UfcUf 
                 A- 
                 4396 
                 VPudCacdTadCgacad 
                 CAUGAUCUUCUUU 
                 4662 
               
               
                 1251386 
                 1523847.1 
                   
                 UfUfgucguagugaL96 
                 2337619.1 
                   
                 AadGadAgaucasusg 
                 GUCGUAGUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4131 
                 usgsaucuUfCfUfuug 
                 A- 
                 4397 
                 VPusCfsuadCgdAcaa 
                 CAUGAUCUUCUUU 
                 4663 
               
               
                 1251273 
                 2337454.1 
                   
                 u(Chd)guagaL96 
                 2337456.1 
                   
                 adGadAgdAucasusg 
                 GUCGUAGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4132 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4398 
                 VPusUfscadCu(A2p)c 
                 AUGAUCUUCUUUG 
                 4664 
               
               
                 1251390 
                 2337622.1 
                   
                 udGucguagugaaL96 
                 2337624.1 
                   
                 gacdAaAfgAfagaucsg 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4133 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4399 
                 VPuUfcadCu(A2p)cg 
                 AUGAUCUUCUUUG 
                 4665 
               
               
                 1251398 
                 2337622.1 
                   
                 udGucguagugaaL96 
                 2337630.1 
                   
                 acdAaAfgAfagaucsgs 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4134 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4400 
                 VPusUfscadCu(A2p)c 
                 AUGAUCUUCUUUG 
                 4666 
               
               
                 1251396 
                 2337629.1 
                   
                 UfgUfCfguagugaaL9 
                 2337621.1 
                   
                 gacaaAfgAfagaucsgs 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                 6 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4135 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4401 
                 VPuUfcadCu(A2p)cg 
                 AUGAUCUUCUUUG 
                 4667 
               
               
                 1251399 
                 2337628.1 
                   
                 udGUfcguagugaaL9 
                 2337630.1 
                   
                 acdAaAfgAfagaucsgs 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                 6 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4136 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4402 
                 VPusUfscacUfaCfGfa 
                 AUGAUCUUCUUUG 
                 4668 
               
               
                 795913. 
                 1523849.1 
                   
                 UfGfucguagugaaL96 
                 1523850.1 
                   
                 caaAfgAfagaucsasu 
                 UCGUAGUGAU 
                   
               
               
                 3 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4137 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4403 
                 VPuUfcadCu(A2p)cg 
                 AUGAUCUUCUUUG 
                 4669 
               
               
                 1251400 
                 2337629.1 
                   
                 UfgUfCfguagugaaL9 
                 2337631.1 
                   
                 acaaAfgAfagaucsgsu 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                 6 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4138 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4404 
                 VPusUfscadCu(A2p)c 
                 AUGAUCUUCUUUG 
                 4670 
               
               
                 1251388 
                 1523849.1 
                   
                 UfGfucguagugaaL96 
                 2337621.1 
                   
                 gacaaAfgAfagaucsgs 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4139 
                 gsasucu(Uhd)cudTu 
                 A- 
                 4405 
                 VPusUfscadCu(A2p)c 
                 AUGAUCUUCUUUG 
                 4671 
               
               
                 1251397 
                 1812618.1 
                   
                 dGucguagugaaL96 
                 2337624.1 
                   
                 gacdAaAfgAfagaucsg 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 SU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4140 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4406 
                 VPusUfscadCu(A2p)c 
                 AUGAUCUUCUUUG 
                 4672 
               
               
                 1251395 
                 2337628.1 
                   
                 udGUfcguagugaaL9 
                 2337624.1 
                   
                 gacdAaAfgAfagaucsg 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                 6 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4141 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4407 
                 VPusUfscadCu(Agn)c 
                 AUGAUCUUCUUUG 
                 4673 
               
               
                 1251387 
                 1523849.1 
                   
                 UfGfucguagugaaL96 
                 2337620.1 
                   
                 gacaaAfgAfagaucsgs 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4142 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4408 
                 VPusUfscadCu(Agn)c 
                 AUGAUCUUCUUUG 
                 4674 
               
               
                 1251389 
                 2337622.1 
                   
                 udGucguagugaaL96 
                 2337623.1 
                   
                 gacdAaAfgAfagaucsg 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4143 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4409 
                 VPusUfscadCu(Agn)c 
                 AUGAUCUUCUUUG 
                 4675 
               
               
                 1251393 
                 2337628.1 
                   
                 udGUfcguagugaaL9 
                 2337623.1 
                   
                 gacdAaAfgAfagaucsg 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                 6 
                   
                   
                 su 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4144 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 4410 
                 VPusUfscadCu(Agn)c 
                 AUGAUCUUCUUUG 
                 4676 
               
               
                 1251394 
                 2337629.1 
                   
                 UfgUfCfguagugaaL9 
                 2337620.1 
                   
                 gacaaAfgAfagaucsgs 
                 UCGUAGUGAU 
                   
               
               
                 .1 
                   
                   
                 6 
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4145 
                 asuscuu(Chd)UfuUf 
                 A- 
                 4411 
                 VPudAsucdAc(Tgn)a 
                 UGAUCUUCUUUG 
                 4677 
               
               
                 1251401 
                 2337632.1 
                   
                 gUfcguagugauaL96 
                 2337633.1 
                   
                 cgadCaAfadGaagaus 
                 UCGUAGUGAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 csg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4146 
                 uscsu(Uhd)CfuUfud 
                 A- 
                 4412 
                 VPusUfscadCu(Agn)c 
                 GAUCUUCUUUGUC 
                 4678 
               
               
                 1251391 
                 2337625.1 
                   
                 GucguagugaaL96 
                 2337626.1 
                   
                 gacdAaAfgAfagasusc 
                 GUAGUGAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4147 
                 uscsu(Uhd)CfuUfud 
                 A- 
                 4413 
                 VPusUfscadCu(A2p)c 
                 GAUCUUCUUUGUC 
                 4679 
               
               
                 1251392 
                 2337625.1 
                   
                 GucguagugaaL96 
                 2337627.1 
                   
                 gacdAaAfgAfagasusc 
                 GUAGUGAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4148 
                 uscsuuc(Uhd)UfugU 
                 A- 
                 4414 
                 VPudAaudCa(C2p)ua 
                 GAUCUUCUUUGUC 
                 4680 
               
               
                 1251402 
                 2337634.1 
                   
                 fCfguagugauuaL96 
                 2337635.1 
                   
                 cgacAfaAfgaagasusc 
                 GUAGUGAUUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4149 
                 csusucu(Uhd)ugUfc 
                 A- 
                 4415 
                 VPudAaadTc(A2p)cu 
                 AUCUUCUUUGUCG 
                 4681 
               
               
                 1251403 
                 2337636.1 
                   
                 dGuagugauuuaL96 
                 2337637.1 
                   
                 acdGaCfaAfagaagsgs 
                 UAGUGAUUUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4150 
                 ususcuu(Uhd)guCfg 
                 A- 
                 4416 
                 VPudAaadAu(C2p)ac 
                 UCUUCUUUGUCGU 
                 4682 
               
               
                 1251404 
                 2337638.1 
                   
                 UfagugauuuuaL96 
                 2337639.1 
                   
                 uadCgAfcAfaagaasgs 
                 AGUGAUUUUC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4151 
                 uscsuuugUfcgUfAfg 
                 A- 
                 4417 
                 VPudGaadAadTcacu 
                 CUUCUUUGUCGUA 
                 4683 
               
               
                 1251405 
                 2337640.1 
                   
                 uga(Uhd)uuucaL96 
                 2337641.1 
                   
                 dAcdGaCfaaagasgsg 
                 GUGAUUUUCC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4152 
                 asusccu(Uhd)UfugU 
                 A- 
                 4418 
                 VPusUfsgcdAa(G2p) 
                 GGAUCCUUUUGUA 
                 4684 
               
               
                 1251406 
                 2337642.1 
                   
                 fAfgaucuugcaaL96 
                 2337643.1 
                   
                 aucuacAfaAfaggausc 
                 GAUCUUGCAA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4153 
                 uscscuu(Uhd)UfgUf 
                 A- 
                 4419 
                 VPusUfsugdCa(Agn) 
                 GAUCCUUUUGUAG 
                 4685 
               
               
                 1251407 
                 2337644.1 
                   
                 adGaucuugcaaaL96 
                 2337645.1 
                   
                 gaucdTaCfaAfaaggas 
                 AUCUUGCAAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 use 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4154 
                 cscsuuu(Uhd)gudAg 
                 A- 
                 4420 
                 VPudAuudGc(A2p)ag 
                 AUCCUUUUGUAGA 
                 4686 
               
               
                 1251408 
                 1854629.1 
                   
                 dAucuugcaauaL96 
                 2337646.1 
                   
                 audCuAfcAfaaaggsgs 
                 UCUUGCAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4155 
                 csusuuugUfagAfUfc 
                 A- 
                 4421 
                 VPusAfsaudTg(C2p)a 
                 UCCUUUUGUAGAU 
                 4687 
               
               
                 1251409 
                 2337647.1 
                   
                 uug(Chd)aauuaL96 
                 2337648.1 
                   
                 agaucUfaCfaaaagsgs 
                 CUUGCAAUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4156 
                 ususuug(Uhd)agAfU 
                 A- 
                 4422 
                 VPusUfsaadTu(G2p) 
                   
                   
               
               
                 1251411 
                 2337650.1 
                   
                 fCfuugcaauuaaL96 
                 2337651.1 
                   
                 caagauCfuAfcaaagsc 
                   
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4157 
                 ususuug(Uhd)AfgAf 
                 A- 
                 4423 
                 VPusUfsaadTu(G2p) 
                 CCUUUUGUAGAUC 
                 4689 
               
               
                 1251410 
                 1525635.1 
                   
                 UfCfuugcaauuaaL96 
                 2337649.1 
                   
                 caagauCfuAfcaaaasg 
                 UUGCAAUUAC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4158 
                 ususug(Uhd)agaUfC 
                 A- 
                 4424 
                 VPusGfsuaaUfuGfCf 
                 CUUUUGUAGAUCU 
                 4690 
               
               
                 1251412 
                 2337652.1 
                   
                 fUfugcaauuacaL96 
                 2337653.1 
                   
                 aagaUfcUfacaaasgsg 
                 UGCAAUUACC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4159 
                 ususugu(Ahd)GfaUf 
                 A- 
                 4425 
                 VPusGfsuaaUfuGfCf 
                 CUUUUGUAGAUCU 
                 4691 
               
               
                 796825. 
                 1525636.1 
                   
                 CfUfugcaauuacaL96 
                 1257916.1 
                   
                 aagaUfcUfacaaasasg 
                 UGCAAUUACC 
                   
               
               
                 3 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4160 
                 ususug(Uhd)agaUfC 
                 A- 
                 4426 
                 VPusdGsuadAu(Tgn) 
                 CUUUUGUAGAUCU 
                 4692 
               
               
                 1251413 
                 2337652.1 
                   
                 fUfugcaauuacaL96 
                 2337654.1 
                   
                 gcaagaUfcUfacaaasg 
                 UGCAAUUACC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4161 
                 ususug(Uhd)agaUfC 
                 A- 
                 4427 
                 VPusdGsuadAu(U2p) 
                 CUUUUGUAGAUCU 
                 4693 
               
               
                 1251414 
                 2337652.1 
                   
                 fUfugcaauuacaL96 
                 2337655.1 
                   
                 gcaagaUfcUfacaaasg 
                 UGCAAUUACC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4162 
                 ususug(Uhd)agaUfC 
                 A- 
                 4428 
                 VPudGuadAu(Tgn)gc 
                 CUUUUGUAGAUCU 
                 4694 
               
               
                 1251415 
                 2337652.1 
                   
                 fUfugcaauuacaL96 
                 2337656.1 
                   
                 aagaUfcUfacaaasgsg 
                 UGCAAUUACC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4163 
                 ususug(Uhd)agaUfC 
                 A- 
                 4429 
                 VPudGuadAu(U2p)g 
                 CUUUUGUAGAUCU 
                 4695 
               
               
                 1251416 
                 2337652.1 
                   
                 fUfugcaauuacaL96 
                 2337657.1 
                   
                 caagaUfcUfacaaasgs 
                 UGCAAUUACC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4164 
                 ususguagauCfUfUfg 
                 A- 
                 4430 
                 VPusdGsgudAa(U2p) 
                 UUUUGUAGAUCU 
                 4696 
               
               
                 1251417 
                 2337658.1 
                   
                 caa(Uhd)uaccaL96 
                 2337659.1 
                   
                 ugcaagAfuCfuacaasg 
                 UGCAAUUACCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4165 
                 usgsuagaUfcUfudG 
                 A- 
                 4431 
                 VPuUfggdTadAuugc 
                 UUUGUAGAUCUU 
                 4697 
               
               
                 1251418 
                 2337660.1 
                   
                 caau(Uhd)accaaL96 
                 2337661.1 
                   
                 dAadGaUfcuacasgsg 
                 GCAAUUACCAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4166 
                 gsusaga(Uhd)CfuUf 
                 A- 
                 4432 
                 VPudAugdGudAauug 
                 UUGUAGAUCUUGC 
                 4698 
               
               
                 1251419 
                 2337662.1 
                   
                 gCfaauuaccauaL96 
                 2337663.1 
                   
                 dCaAfgAfucuacsgsg 
                 AAUUACCAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4167 
                 usasgau(Chd)UfugC 
                 A- 
                 4433 
                 VPusAfsaudGg(Tgn)a 
                 UGUAGAUCUUGCA 
                 4699 
               
               
                 1251420 
                 2337664.1 
                   
                 fAfauuaccauuaL96 
                 2337665.1 
                   
                 auugcAfadGaucuasc 
                 AUUACCAUUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4168 
                 asgsauc(Uhd)UfgCf 
                 A- 
                 4434 
                 VPusAfsaadTg(G2p)u 
                 GUAGAUCUUGCAA 
                 4700 
               
               
                 1251421 
                 1525641.1 
                   
                 AfAfuuaccauuuaL96 
                 2337666.1 
                   
                 aauugCfaAfgaucusgs 
                 UUACCAUUUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 C 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4169 
                 asgsauc(Uhd)ugCfa 
                 A- 
                 4435 
                 VPudAaadTg(G2p)ua 
                 GUAGAUCUUGCAA 
                 4701 
               
               
                 1251422 
                 2337667.1 
                   
                 dAuuaccauuuaL96 
                 2337668.1 
                   
                 audTgCfadAgaucusg 
                 UUACCAUUUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4170 
                 usasaau(Uhd)audG 
                 A- 
                 4436 
                 VPudGgudTu(G2p)u 
                 AAUAAAUUAUGUG 
                 4702 
               
               
                 1251423 
                 1856083.1 
                   
                 udGaaacaaaccaL96 
                 2337669.1 
                   
                 uucdAcAfuAfauuuas 
                 AAACAAACCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 usu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4171 
                 asasuua(Uhd)gudG 
                 A- 
                 4437 
                 VPudAagdGu(U2p)u 
                 UAAAUUAUGUGAA 
                 4703 
               
               
                 1251425 
                 1856087.1 
                   
                 adAacaaaccuuaL96 
                 2337672.1 
                   
                 guudTcAfcAfuaauus 
                 ACAAACCUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 usg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4172 
                 asusuaugugdAadAc 
                 A- 
                 4438 
                 VPuUfaadGg(Tgn)uu 
                 AAAUUAUGUGAAA 
                 4704 
               
               
                 1251427 
                 2337675.1 
                   
                 aaa(Chd)cuuaaL96 
                 2337676.1 
                   
                 gudTuCfaCfauaausu 
                 CAAACCUUAC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 SU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4173 
                 asusuaugUfgAfAfAf 
                 A- 
                 4439 
                 VPusUfsaadGg(Tgn) 
                 AAAUUAUGUGAAA 
                 4705 
               
               
                 1251426 
                 2337673.1 
                   
                 caaa(Chd)cuuaaL96 
                 2337674.1 
                   
                 uuguuuCfaCfauaaus 
                 CAAACCUUAC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 usu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4174 
                 ususaug(Uhd)gaAfA 
                 A- 
                 4440 
                 VPudGuadAg(G2p)u 
                 AAUUAUGUGAAAC 
                 4706 
               
               
                 1251428 
                 2337677.1 
                   
                 fCfaaaccuuacaL96 
                 2337678.1 
                   
                 uuguuUfcAfcauaasu 
                 AAACCUUACG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 SU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4175 
                 usasugu(Ghd)AfaAf 
                 A- 
                 4441 
                 VPusCfsguaAfgGfUfu 
                 AUUAUGUGAAACA 
                 4707 
               
               
                 797564. 
                 1527042.1 
                   
                 CfAfaaccuuacgaL96 
                 1527043.1 
                   
                 uguUfuCfacauasasu 
                 AACCUUACGU 
                   
               
               
                 4 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4176 
                 usasugugAfaAfCfAf 
                 A- 
                 4442 
                 VPuCfgudAa(G2p)gu 
                 AUUAUGUGAAACA 
                 4708 
               
               
                 1251434 
                 2337679.1 
                   
                 aacc(Uhd)uacgaL96 
                 2337687.1 
                   
                 uuguUfuCfacauasgs 
                 AACCUUACGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4177 
                 usasugugAfaAfCfAf 
                 A- 
                 4443 
                 VPusCfsgudAadAguu 
                 AUUAUGUGAAACA 
                 4709 
               
               
                 1251431 
                 2337681.1 
                   
                 aacu(Uhd)uacgaL96 
                 2337682.1 
                   
                 uguUfuCfacauasgsu 
                 AACCUUACGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4178 
                 usasugugaadAcdAa 
                 A- 
                 4444 
                 VPusCfsgudAa(G2p) 
                 AUUAUGUGAAACA 
                 4710 
               
               
                 1251433 
                 2337685.1 
                   
                 acc(Uhd)uacgaL96 
                 2337686.1 
                   
                 guuudGuUfuCfacaua 
                 AACCUUACGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sgsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4179 
                 usasugugAfaAfCfAf 
                 A- 
                 4445 
                 VPusCfsgudAa(G2p) 
                 AUUAUGUGAAACA 
                 4711 
               
               
                 1251430 
                 2337679.1 
                   
                 aacc(Uhd)uacgaL96 
                 2337680.1 
                   
                 guuuguUfuCfacauas 
                 AACCUUACGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 gsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4180 
                 usasugugAfaAfCfAf 
                 A- 
                 4446 
                 VPusCfsguaAfgGfUfu 
                 AUUAUGUGAAACA 
                 4712 
               
               
                 1251429 
                 2337679.1 
                   
                 aacc(Uhd)uacgaL96 
                 1527043.1 
                   
                 uguUfuCfacauasasu 
                 AACCUUACGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4181 
                 usasugugaadAcdAa 
                 A- 
                 4447 
                 VPuCfgudAa(G2p)gu 
                 AUUAUGUGAAACA 
                 4713 
               
               
                 1251435 
                 2337685.1 
                   
                 acc(Uhd)uacgaL96 
                 2337688.1 
                   
                 uudGuUfuCfacauasg 
                 AACCUUACGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 SU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4182 
                 asusgugaAfaCfAfAf 
                 A- 
                 4448 
                 VPusAfscgdTa(A2p)g 
                 UUAUGUGAAACAA 
                 4714 
               
               
                 1251438 
                 2337689.1 
                   
                 accu(Uhd)acguaL96 
                 2337691.1 
                   
                 guuugUfuUfcacausg 
                 ACCUUACGUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4183 
                 asusgugaAfaCfAfAf 
                 A- 
                 4449 
                 VPusAfscguAfaGfGfu 
                 UUAUGUGAAACAA 
                 4715 
               
               
                 1251436 
                 2337689.1 
                   
                 accu(Uhd)acguaL96 
                 1527045.1 
                   
                 uugUfuUfcacausasa 
                 ACCUUACGUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4184 
                 asusgugaAfaCfAfAf 
                 A- 
                 4450 
                 VPusAfscgdTa(Agn)g 
                 UUAUGUGAAACAA 
                 4716 
               
               
                 1251437 
                 2337689.1 
                   
                 accu(Uhd)acguaL96 
                 2337690.1 
                   
                 guuugUfuUfcacausg 
                 ACCUUACGUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4185 
                 asusgug(Ahd)AfaCf 
                 A- 
                 4451 
                 VPusAfscguAfaGfGfu 
                 UUAUGUGAAACAA 
                 4717 
               
               
                 797565. 
                 1527044.1 
                   
                 AfAfaccuuacguaL96 
                 1527045.1 
                   
                 uugUfuUfcacausasa 
                 ACCUUACGUG 
                   
               
               
                 4 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4186 
                 asusgugaAfaCfAfAf 
                 A- 
                 4452 
                 VPuAfcgdTa(Agn)gg 
                 UUAUGUGAAACAA 
                 4718 
               
               
                 1251443 
                 2337689.1 
                   
                 accu(Uhd)acguaL96 
                 2337698.1 
                   
                 uuugUfuUfcacausgs 
                 ACCUUACGUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4187 
                 asusgugaaaCfadAac 
                 A- 
                 4453 
                 VPudAcgdTa(A2p)gg 
                 UUAUGUGAAACAA 
                 4719 
               
               
                 1251444 
                 2337695.1 
                   
                 cu(Uhd)acguaL96 
                 2337699.1 
                   
                 uudTgUfuUfcacausg 
                 ACCUUACGUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4188 
                 asusgugaaaCfadAac 
                 A- 
                 4454 
                 VPusdAscgdTa(A2p) 
                 UUAUGUGAAACAA 
                 4720 
               
               
                 1251442 
                 2337695.1 
                   
                 cu(Uhd)acguaL96 
                 2337697.1 
                   
                 gguudTgUfuUfcacau 
                 ACCUUACGUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sgsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4189 
                 asusgugaaaCfadAac 
                 A- 
                 4455 
                 VPusdAscgdTa(Agn) 
                 UUAUGUGAAACAA 
                 4721 
               
               
                 1251441 
                 2337695.1 
                   
                 cu(Uhd)acguaL96 
                 2337696.1 
                   
                 gguudTgUfuUfcacau 
                 ACCUUACGUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sgsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4190 
                 usgsugaaacdAadAc 
                 A- 
                 4456 
                 VPusdCsacdGudAag 
                 UAUGUGAAACAAA 
                 4722 
               
               
                 1251445 
                 2337700.1 
                   
                 cu(Uhd)acgugaL96 
                 2337701.1 
                   
                 gudTudGuUfucacasu 
                 CCUUACGUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4191 
                 gsusgaAfaCfAfAfacc 
                 A- 
                 4457 
                 VPusAfscgdTa(Agn)g 
                 AUGUGAAACAAAC 
                 4723 
               
               
                 1251439 
                 2337692.1 
                   
                 u(Uhd)acguaL96 
                 2337693.1 
                   
                 guuugUfuUfcacsgsu 
                 CUUACGUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4192 
                 gsusgaaaCfadAaCfc 
                 A- 
                 4458 
                 VPuUfcadCgdTaaggd 
                 AUGUGAAACAAAC 
                 4724 
               
               
                 1251447 
                 2337704.1 
                   
                 uua(Chd)gugaaL96 
                 2337705.1 
                   
                 TuUfgUfuucacsgsu 
                 CUUACGUGAA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4193 
                 gsusgaaaCfaAfAfCfc 
                 A- 
                 4459 
                 VPusUfscadCgdTaag 
                 AUGUGAAACAAAC 
                 4725 
               
               
                 1251446 
                 2337702.1 
                   
                 uua(Chd)gugaaL96 
                 2337703.1 
                   
                 guuUfgUfuucacsgsu 
                 CUUACGUGAA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4194 
                 usgsaaa(Chd)aaaCf 
                 A- 
                 4460 
                 VPusUfsucdAc(G2p) 
                 UGUGAAACAAACC 
                 4726 
               
               
                 1251448 
                 2337706.1 
                   
                 CfuuacgugaaaL96 
                 2337707.1 
                   
                 uaagguUfudGuuuca 
                 UUACGUGAAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 scsa 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4195 
                 gsasaacaaaCfCfUfu 
                 A- 
                 4461 
                 VPusdAsuudCa(C2p) 
                 GUGAAACAAACCU 
                 4727 
               
               
                 1251450 
                 2337710.1 
                   
                 acg(Uhd)gaauaL96 
                 2337711.1 
                   
                 guaaggUfuUfguuucs 
                 UACGUGAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 asc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4196 
                 gsasaacaAfaCfCfUfu 
                 A- 
                 4462 
                 VPusAfsuudCa(C2p)g 
                 GUGAAACAAACCU 
                 4728 
               
               
                 1251449 
                 2337708.1 
                   
                 acg(Uhd)gaauaL96 
                 2337709.1 
                   
                 uaaggUfuUfguuucsa 
                 UACGUGAAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4197 
                 asasacaaacCfUfUfac 
                 A- 
                 4463 
                 VPusdAsaudTc(A2p) 
                   
                   
               
               
                 1251451 
                 2337712.1 
                   
                 g(Uhd)gaauuaL96 
                 2337713.1 
                   
                 cugadAgdGuUfuguu 
                   
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 uscsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4198 
                 usgsuga(Uhd)auaUf 
                 A- 
                 4464 
                 VPudAugdTu(G2p)u 
                 AUUGUGAUAUAU 
                 4730 
               
               
                 1251453 
                 2337716.1 
                   
                 UfuuacaacauaL96 
                 2337717.1 
                   
                 aaaauAfuAfucacasgs 
                 UUUACAACAUC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4199 
                 usgsuga(Uhd)AfuAf 
                 A- 
                 4465 
                 VPusAfsugdTu(G2p) 
                 AUUGUGAUAUAU 
                 4731 
               
               
                 1251452 
                 2337714.1 
                   
                 UfUfuuacaacauaL96 
                 2337715.1 
                   
                 uaaaauAfuAfucacas 
                 UUUACAACAUC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 gsu 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4200 
                 gsusga(Uhd)aUfaUf 
                 A- 
                 4466 
                 VPudGaudGu(U2p)g 
                 UUGUGAUAUAUU 
                 4732 
               
               
                 1251454 
                 2337718.1 
                   
                 UfUfuacaacaucaL96 
                 2337719.1 
                   
                 uaaaaUfaUfaucacsgs 
                 UUACAACAUCC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4201 
                 usgsaua(Uhd)auUf 
                 A- 
                 4467 
                 VPudGgadTg(U2p)ug 
                 UGUGAUAUAUUU 
                 4733 
               
               
                 1251455 
                 2337720.1 
                   
                 UfUfacaacauccaL96 
                 2337721.1 
                   
                 uaaaAfuAfuaucascsg 
                 UACAACAUCCG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4202 
                 gsasua(Uhd)aUfuUf 
                 A- 
                 4468 
                 VPusCfsggdAudGuug 
                 GUGAUAUAUUUU 
                 4734 
               
               
                 1251456 
                 2337722.1 
                   
                 UfAfcaacauccgaL96 
                 2337723.1 
                   
                 uaaAfaUfauaucsgsc 
                 ACAACAUCCGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4203 
                 gsasua(Uhd)aUfuUf 
                 A- 
                 4469 
                 VPuCfggdAudGuugu 
                 GUGAUAUAUUUU 
                 4735 
               
               
                 1251457 
                 2337724.1 
                   
                 udAcaacauccgaL96 
                 2337725.1 
                   
                 dAadAaUfauaucsgsc 
                 ACAACAUCCGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4204 
                 asusaua(Uhd)UfuUf 
                 A- 
                 4470 
                 VPudAcgdGadTguug 
                 UGAUAUAUUUUAC 
                 4736 
               
               
                 1251459 
                 2337727.1 
                   
                 aCfaacauccguaL96 
                 2337728.1 
                   
                 dTadAadAuauauscsg 
                 AACAUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4205 
                 asusaua(Uhd)UfuUf 
                 A- 
                 4471 
                 VPusAfscgdGadTguu 
                 UGAUAUAUUUUAC 
                 4737 
               
               
                 1251458 
                 1535069.1 
                   
                 AfCfaacauccguaL96 
                 2337726.1 
                   
                 guaAfaAfuauauscsg 
                 AACAUCCGUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4206 
                 usasuau(Uhd)UfuAf 
                 A- 
                 4472 
                 VPusAfsacdGg(Agn)u 
                 GAUAUAUUUUACA 
                 4738 
               
               
                 1251462 
                 1535071.1 
                   
                 CfAfacauccguuaL96 
                 2337731.1 
                   
                 guuguAfaAfauauasc 
                 ACAUCCGUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4207 
                 usasuau(Uhd)UfuAf 
                 A- 
                 4473 
                 VPusAfsacdGg(A2p) 
                 GAUAUAUUUUACA 
                 4739 
               
               
                 1251461 
                 1535071.1 
                   
                 CfAfacauccguuaL96 
                 2337730.1 
                   
                 uguuguAfaAfauauas 
                 ACAUCCGUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 use 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4208 
                 usasuau(Uhd)UfuAf 
                 A- 
                 4474 
                 VPuAfacdGg(Agn)ug 
                 GAUAUAUUUUACA 
                 4740 
               
               
                 1251468 
                 1535071.1 
                   
                 CfAfacauccguuaL96 
                 2337738.1 
                   
                 uuguAfaAfauauascsc 
                 ACAUCCGUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4209 
                 usasuau(Uhd)UfuAf 
                 A- 
                 4475 
                 VPusAfsacdGg(A2p) 
                 GAUAUAUUUUACA 
                 4741 
               
               
                 1251463 
                 1535071.1 
                   
                 CfAfacauccguuaL96 
                 2337732.1 
                   
                 uguuguAfaAfauauas 
                 ACAUCCGUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 CSC 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4210 
                 usasuau(Uhd)UfuAf 
                 A- 
                 4476 
                 VPusAfsacdGg(Agn)u 
                 GAUAUAUUUUACA 
                 4742 
               
               
                 1251460 
                 1535071.1 
                   
                 CfAfacauccguuaL96 
                 2337729.1 
                   
                 guuguAfaAfauauasu 
                 ACAUCCGUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4211 
                 usasuau(Uhd)uudA 
                 A- 
                 4477 
                 VPudAacdGg(A2p)ug 
                 GAUAUAUUUUACA 
                 4743 
               
               
                 1251469 
                 1864159.1 
                   
                 cdAacauccguuaL96 
                 2337739.1 
                   
                 uudGudAadAauauas 
                 ACAUCCGUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 use 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4212 
                 usasuau(Uhd)UfuAf 
                 A- 
                 4478 
                 VPusAfsacgGfaUfGfu 
                 GAUAUAUUUUACA 
                 4744 
               
               
                 801647. 
                 1535071.1 
                   
                 CfAfacauccguuaL96 
                 1535072.1 
                   
                 uguAfaAfauauasusc 
                 ACAUCCGUUA 
                   
               
               
                 3 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4213 
                 usasuau(Uhd)uudA 
                 A- 
                 4479 
                 VPusdAsacdGg(A2p) 
                 GAUAUAUUUUACA 
                 4745 
               
               
                 1251467 
                 1864159.1 
                   
                 cdAacauccguuaL96 
                 2337737.1 
                   
                 uguudGudAadAauau 
                 ACAUCCGUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 asusc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4214 
                 usasuau(Uhd)Ufud 
                 A- 
                 4480 
                 VPusdAsacdGg(A2p) 
                 GAUAUAUUUUACA 
                 4746 
               
               
                 1251466 
                 2337736.1 
                   
                 AcdAacauccguuaL9 
                 2337737.1 
                   
                 uguudGudAadAauau 
                 ACAUCCGUUA 
                   
               
               
                 .1 
                   
                   
                 6 
                   
                   
                 asusc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4215 
                 asusauu(Uhd)UfaCf 
                 A- 
                 4481 
                 VPusUfsaadCgdGaug 
                 AUAUAUUUUACAA 
                 4747 
               
               
                 1251470 
                 1535073.1 
                   
                 AfAfcauccguuaaL96 
                 2337740.1 
                   
                 uugUfaAfaauausgsu 
                 CAUCCGUUAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4216 
                 asusauu(Uhd)UfaCf 
                 A- 
                 4482 
                 VPuUfaadCgdGaugu 
                 AUAUAUUUUACAA 
                 4748 
               
               
                 1251471 
                 2337741.1 
                   
                 adAcauccguuaaL96 
                 2337742.1 
                   
                 dTgUfadAaauausgsu 
                 CAUCCGUUAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4217 
                 usasu(Uhd)UfuAfCf 
                 A- 
                 4483 
                 VPusAfsacdGg(A2p) 
                 UAUAUUUUACAAC 
                 4749 
               
               
                 1251465 
                 2337733.1 
                   
                 AfacauccguuaL96 
                 2337735.1 
                   
                 uguuguAfaAfauasus 
                 AUCCGUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4218 
                 usasuuu(Uhd)acdA 
                 A- 
                 4484 
                 VPudAuadAcdGgaug 
                 UAUAUUUUACAAC 
                 4750 
               
               
                 1251472 
                 2337743.1 
                   
                 aCfauccguuauaL96 
                 2337744.1 
                   
                 dTudGudAaaauasus 
                 AUCCGUUAUU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4219 
                 usasu(Uhd)UfuAfCf 
                 A- 
                 4485 
                 VPusAfsacdGg(Agn)u 
                 UAUAUUUUACAAC 
                 4751 
               
               
                 1251464 
                 2337733.1 
                   
                 AfacauccguuaL96 
                 2337734.1 
                   
                 guuguAfaAfauasusg 
                 AUCCGUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4220 
                 asusuuuaCfaAfCfAf 
                 A- 
                 4486 
                 VPusAfsaudAadCgga 
                 AUAUUUUACAACA 
                 4752 
               
               
                 1251473 
                 2337745.1 
                   
                 uccg(Uhd)uauuaL96 
                 2337746.1 
                   
                 uguUfgUfaaaausgsu 
                 UCCGUUAUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4221 
                 asusuuuacadAcdAu 
                 A- 
                 4487 
                 VPudAaudAadCggau 
                 AUAUUUUACAACA 
                 4753 
               
               
                 1251474 
                 2337747.1 
                   
                 ccg(Uhd)uauuaL96 
                 2337748.1 
                   
                 dGuUfgUfaaaausgsu 
                 UCCGUUAUUA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4222 
                 ususuua(Chd)aaCfa 
                 A- 
                 4488 
                 VPuUfaadTadAcggad 
                 UAUUUUACAACAU 
                 4754 
               
               
                 1251475 
                 2337749.1 
                   
                 UfccguuauuaaL96 
                 2337750.1 
                   
                 TgUfudGuaaaasusg 
                 CCGUUAUUAC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4223 
                 ususua(Chd)aacaUf 
                 A- 
                 4489 
                 VPudGuadAudAacgg 
                 AUUUUACAACAUC 
                 4755 
               
               
                 1251476 
                 2337751.1 
                   
                 CfcguuauuacaL96 
                 2337752.1 
                   
                 dAudGuUfguaaasgs 
                 CGUUAUUACU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4224 
                 csasaca(Chd)aaUfUf 
                 A- 
                 4490 
                 VPudGcudAadGaaga 
                 AACAACACAAUUU 
                 4756 
               
               
                 1251279 
                 2337459.1 
                   
                 UfcuucuuagcaL96 
                 2337464.1 
                   
                 dAaUfudGuguugsus 
                 CUUCUUAGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4225 
                 csasaca(Chd)aaUfUf 
                 A- 
                 4491 
                 VPusdGscudAadGaa 
                 AACAACACAAUUU 
                 4757 
               
               
                 1251276 
                 2337459.1 
                   
                 UfcuucuuagcaL96 
                 2337460.1 
                   
                 gadAaUfudGuguugs 
                 CUUCUUAGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 USU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4226 
                 csasaca(Chd)aaUfUf 
                 A- 
                 4492 
                 VPudGcudAadGaaga 
                 AACAACACAAUUU 
                 4758 
               
               
                 1251280 
                 2337459.1 
                   
                 UfcuucuuagcaL96 
                 2337465.1 
                   
                 dAaUfudGuguugscsc 
                 CUUCUUAGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4227 
                 csasaca(Chd)aaUfUf 
                 A- 
                 4493 
                 VPusdGscudAadGaa 
                 AACAACACAAUUU 
                 4759 
               
               
                 1251277 
                 2337459.1 
                   
                 UfcuucuuagcaL96 
                 2337461.1 
                   
                 gadAaUfudGuguugs 
                 CUUCUUAGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 CSC 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4228 
                 csasaca(Chd)aadTu 
                 A- 
                 4494 
                 VPusdGscudAadGaa 
                 AACAACACAAUUU 
                 4760 
               
               
                 961334. 
                 1812904.1 
                   
                 dTcuucuuagcaL96 
                 1812905.1 
                   
                 gadAadTudGuguugs 
                 CUUCUUAGCA 
                   
               
               
                 3 
                   
                   
                   
                   
                   
                 USU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4229 
                 ascsacaaUfUfUfcuu 
                 A- 
                 4495 
                 VPusdGscudAadGaa 
                 CAACACAAUUUCU 
                 4761 
               
               
                 1251278 
                 2337462.1 
                   
                 c(Uhd)uagcaL96 
                 2337463.1 
                   
                 gadAaUfudGugusus 
                 UCUUAGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4230 
                 gsgscuu(Chd)aadGu 
                 A- 
                 4496 
                 VPuCfagdTadGgaacd 
                 CUGGCUUCAAGUG 
                 4762 
               
               
                 1251477 
                 1865763.1 
                   
                 dGuuccuacugaL96 
                 2337753.1 
                   
                 AcUfudGaagccsgsg 
                 UUCCUACUGU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4231 
                 gscsuu(Chd)aagUfg 
                 A- 
                 4497 
                 VPudAcadGu(Agn)gg 
                 UGGCUUCAAGUGU 
                 4763 
               
               
                 1251478 
                 2337754.1 
                   
                 UfuccuacuguaL96 
                 2337755.1 
                   
                 aadCaCfuUfgaagcscs 
                 UCCUACUGUC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4232 
                 csusucaagugUfUfcc 
                 A- 
                 4498 
                 VPusdGsacdAg(Tgn) 
                 GGCUUCAAGUGUU 
                 4764 
               
               
                 1251479 
                 2337756.1 
                   
                 ua(Chd)ugucaL96 
                 2337757.1 
                   
                 aggaacAfcUfugaagsc 
                 CCUACUGUCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4233 
                 ususcaagUfgUfUfCf 
                 A- 
                 4499 
                 VPuUfgadCa(G2p)ua 
                 GCUUCAAGUGUUC 
                 4765 
               
               
                 1251481 
                 2337758.1 
                   
                 cuac(Uhd)gucaaL96 
                 2337760.1 
                   
                 ggaaCfaCfuugaasgsc 
                 CUACUGUCAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4234 
                 ususcaagUfgUfUfCf 
                 A- 
                 4500 
                 VPusUfsgadCa(G2p) 
                 GCUUCAAGUGUUC 
                 4766 
               
               
                 1251480 
                 2337758.1 
                   
                 cuac(Uhd)gucaaL96 
                 2337759.1 
                   
                 uaggaaCfaCfuugaasg 
                 CUACUGUCAU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4235 
                 uscsaag(Uhd)guUfC 
                 A- 
                 4501 
                 VPusAfsugdAc(Agn)g 
                 CUUCAAGUGUUCC 
                 4767 
               
               
                 1251482 
                 2337761.1 
                   
                 fCfuacugucauaL96 
                 2337762.1 
                   
                 uaggaAfcAfcuugasgs 
                 UACUGUCAUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4236 
                 uscsaag(Uhd)guUfC 
                 A- 
                 4502 
                 VPusdAsugdAc(A2p) 
                 CUUCAAGUGUUCC 
                 4768 
               
               
                 1251483 
                 2337761.1 
                   
                 fCfuacugucauaL96 
                 2337763.1 
                   
                 guagdGadAcdAcuug 
                 UACUGUCAUG 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 asgsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4237 
                 csasagugUfuCfCfUf 
                 A- 
                 4503 
                 VPuCfaudGa(C2p)ag 
                 UUCAAGUGUUCCU 
                 4769 
               
               
                 1251492 
                 2337764.1 
                   
                 acug(Uhd)caugaL96 
                 2337773.1 
                   
                 uaggAfaCfacuugscsc 
                 ACUGUCAUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4238 
                 csasagugUfuCfCfUf 
                 A- 
                 4504 
                 VPusCfsaudGadCagu 
                 UUCAAGUGUUCCU 
                 4770 
               
               
                 1251485 
                 2337764.1 
                   
                 acug(Uhd)caugaL96 
                 2337766.1 
                   
                 adGgdAaCfacuugsgs 
                 ACUGUCAUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4239 
                 csasagu(Ghd)UfuCf 
                 A- 
                 4505 
                 VPusCfsaugAfcAfGfu 
                 UUCAAGUGUUCCU 
                 4771 
               
               
                 802471. 
                 1536717.1 
                   
                 CfUfacugucaugaL96 
                 1536718.1 
                   
                 aggAfaCfacuugsasa 
                 ACUGUCAUGA 
                   
               
               
                 4 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4240 
                 csasagugUfuCfCfUf 
                 A- 
                 4506 
                 VPusCfsaugAfcAfGfu 
                 UUCAAGUGUUCCU 
                 4772 
               
               
                 1251486 
                 2337764.1 
                   
                 acug(Uhd)caugaL96 
                 1536718.1 
                   
                 aggAfaCfacuugsasa 
                 ACUGUCAUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4241 
                 csasagugUfuCfCfUf 
                 A- 
                 4507 
                 VPusCfsaudGadCagu 
                 UUCAAGUGUUCCU 
                 4773 
               
               
                 1251484 
                 2337764.1 
                   
                 acug(Uhd)caugaL96 
                 2337765.1 
                   
                 aggAfaCfacuugsgsg 
                 ACUGUCAUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4242 
                 csasagugUfuCfCfUf 
                 A- 
                 4508 
                 VPuCfaudGa(C2p)ag 
                 UUCAAGUGUUCCU 
                 4774 
               
               
                 1251491 
                 2337764.1 
                   
                 acug(Uhd)caugaL96 
                 2337772.1 
                   
                 uaggAfaCfacuugsgsg 
                 ACUGUCAUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4243 
                 csasagugUfuCfCfUf 
                 A- 
                 4509 
                 VPusCfsaudGa(C2p) 
                 UUCAAGUGUUCCU 
                 4775 
               
               
                 1251487 
                 2337764.1 
                   
                 acug(Uhd)caugaL96 
                 2337767.1 
                   
                 aguaggAfaCfacuugsg 
                 ACUGUCAUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4244 
                 csasagugUfuCfCfUf 
                 A- 
                 4510 
                 VPusCfsaudGa(C2p) 
                 UUCAAGUGUUCCU 
                 4776 
               
               
                 1251488 
                 2337764.1 
                   
                 acug(Uhd)caugaL96 
                 2337768.1 
                   
                 aguaggAfaCfacuugsc 
                 ACUGUCAUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4245 
                 csasagugUfuCfCfUf 
                 A- 
                 4511 
                 VPusCfsaudGa(C2p) 
                 UUCAAGUGUUCCU 
                 4777 
               
               
                 1251490 
                 2337764.1 
                   
                 acug(Uhd)caugaL96 
                 2337771.1 
                   
                 aguadGgdAaCfacuug 
                 ACUGUCAUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sgsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4246 
                 asasgug(Uhd)UfcCf 
                 A- 
                 4512 
                 VPuUfcadTg(A2p)ca 
                 UCAAGUGUUCCUA 
                 4778 
               
               
                 1251494 
                 2337775.1 
                   
                 udAcugucaugaaL96 
                 2337776.1 
                   
                 gudAgdGadAcacuus 
                 CUGUCAUGAC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 gsg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4247 
                 asgsugUfuCfCfUfac 
                 A- 
                 4513 
                 VPuCfaudGa(C2p)ag 
                 CAAGUGUUCCUAC 
                 4779 
               
               
                 1251493 
                 2337769.1 
                   
                 ug(Uhd)caugaL96 
                 2337774.1 
                   
                 uaggAfaCfacususg 
                 UGUCAUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4248 
                 asgsugUfuCfCfUfac 
                 A- 
                 4514 
                 VPusCfsaudGa(C2p) 
                 CAAGUGUUCCUAC 
                 4780 
               
               
                 1251489 
                 2337769.1 
                   
                 ug(Uhd)caugaL96 
                 2337770.1 
                   
                 aguaggAfaCfacususg 
                 UGUCAUGA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4249 
                 asgsugu(Uhd)CfcUf 
                 A- 
                 4515 
                 VPudGucdAu(G2p)ac 
                 CAAGUGUUCCUAC 
                 4781 
               
               
                 1251495 
                 2337777.1 
                   
                 aCfugucaugacaL96 
                 2337778.1 
                   
                 agdTadGgdAacacusu 
                 UGUCAUGACC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4250 
                 gsusguu(Chd)CfuaC 
                 A- 
                 4516 
                 VPudGgudCa(Tgn)ga 
                 AAGUGUUCCUACU 
                 4782 
               
               
                 1251496 
                 2337779.1 
                   
                 fUfgucaugaccaL96 
                 2337780.1 
                   
                 caguAfgdGaacacsus 
                 GUCAUGACCU 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 u 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4251 
                 usgsuuc(Chd)UfaCf 
                 A- 
                 4517 
                 VPudAggdTc(Agn)ug 
                 AGUGUUCCUACUG 
                 4783 
               
               
                 1251497 
                 2337781.1 
                   
                 udGUfcaugaccuaL9 
                 2337782.1 
                   
                 acdAgUfadGgaacasc 
                 UCAUGACCUG 
                   
               
               
                 .1 
                   
                   
                 6 
                   
                   
                 SU 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4252 
                 gsusucc(Uhd)acUfg 
                 A- 
                 4518 
                 VPuCfagdGu(C2p)au 
                 GUGUUCCUACUGU 
                 4784 
               
               
                 1251498 
                 2337783.1 
                   
                 UfcaugaccugaL96 
                 2337784.1 
                   
                 gadCadGudAggaacs 
                 CAUGACCUGC 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 gsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4253 
                 ususgau(Ahd)GfuUf 
                 A- 
                 4519 
                 VPusGfscaaAfcUfAfg 
                 UUUUGAUAGUUA 
                 4785 
               
               
                 802552. 
                 1536877.1 
                   
                 AfCfcuaguuugcaL96 
                 1536878.1 
                   
                 guaAfcUfaucaasasa 
                 CCUAGUUUGCA 
                   
               
               
                 3 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4254 
                 ususgauagudTadCc 
                 A- 
                 4520 
                 VPudGcadAadCuagg 
                 UUUUGAUAGUUA 
                 4786 
               
               
                 1251267 
                 2337439.1 
                   
                 uag(Uhd)uugcaL96 
                 2337448.1 
                   
                 dTadAcUfaucaasgsg 
                 CCUAGUUUGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4255 
                 ususgauagudTadCc 
                 A- 
                 4521 
                 VPusdGscadAadCua 
                 UUUUGAUAGUUA 
                 4787 
               
               
                 1251260 
                 2337439.1 
                   
                 uag(Uhd)uugcaL96 
                 2337438.1 
                   
                 ggdTadAcUfaucaasg 
                 CCUAGUUUGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4256 
                 ususgauaGfuUfAfCf 
                 A- 
                 4522 
                 VPusGfscaaAfcUfAfg 
                 UUUUGAUAGUUA 
                 4788 
               
               
                 1251256 
                 2337433.1 
                   
                 cuag(Uhd)uugcaL96 
                 1536878.1 
                   
                 guaAfcUfaucaasasa 
                 CCUAGUUUGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4257 
                 ususgauaguUfAfCfc 
                 A- 
                 4523 
                 VPudGcadAadCuagg 
                 UUUUGAUAGUUA 
                 4789 
               
               
                 1251265 
                 2337436.1 
                   
                 uag(Uhd)uugcaL96 
                 2337447.1 
                   
                 uaAfcUfaucaasgsg 
                 CCUAGUUUGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4258 
                 ususgau(Ahd)guUfA 
                 A- 
                 4524 
                 VPusdGscadAadCua 
                 UUUUGAUAGUUA 
                 4790 
               
               
                 1251257 
                 2337434.1 
                   
                 fCfcuaguuugcaL96 
                 2337435.1 
                   
                 gguaAfcUfaucaasgsg 
                 CCUAGUUUGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4259 
                 ususgauaguUfaCfcu 
                 A- 
                 4525 
                 VPudGcadAadCuagg 
                 UUUUGAUAGUUA 
                 4791 
               
               
                 1251266 
                 2337437.1 
                   
                 ag(Uhd)uugcaL96 
                 2337448.1 
                   
                 dTadAcUfaucaasgsg 
                 CCUAGUUUGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4260 
                 ususgauaguUfAfCfc 
                 A- 
                 4526 
                 VPusdGscadAadTua 
                   
                   
               
               
                 1251264 
                 2337445.1 
                   
                 uaa(Uhd)uugcaL96 
                 2337446.1 
                   
                 gguaAfcUfaucaasgsg 
                   
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4261 
                 ususgauaguUfaCfcu 
                 A- 
                 4527 
                 VPusdGscadAadCua 
                 UUUUGAUAGUUA 
                 4793 
               
               
                 1251259 
                 2337437.1 
                   
                 ag(Uhd)uugcaL96 
                 2337438.1 
                   
                 ggdTadAcUfaucaasg 
                 CCUAGUUUGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                 sg 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4262 
                 ususgauaguUfAfCfc 
                 A- 
                 4528 
                 VPusdGscadAadCua 
                 UUUUGAUAGUUA 
                 4794 
               
               
                 1251258 
                 2337436.1 
                   
                 uag(Uhd)uugcaL96 
                 2337435.1 
                   
                 gguaAfcUfaucaasgsg 
                 CCUAGUUUGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4263 
                 gsasuagudTadCcua 
                 A- 
                 4529 
                 VPusdGscadAadCua 
                 UUGAUAGUUACCU 
                 4795 
               
               
                 1251263 
                 2337444.1 
                   
                 g(Uhd)uugcaL96 
                 2337443.1 
                   
                 ggdTadAcUfaucsgsg 
                 AGUUUGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4264 
                 gsasuaguUfaCfcuag 
                 A- 
                 4530 
                 VPusdGscadAadCua 
                 UUGAUAGUUACCU 
                 4796 
               
               
                 1251262 
                 2337442.1 
                   
                 (Uhd)uugcaL96 
                 2337443.1 
                   
                 ggdTadAcUfaucsgsg 
                 AGUUUGCA 
                   
               
               
                 .1 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4265 
                 gsasuaguUfAfCfcua 
                 A- 
                 4531 
                 VPusdGscadAadCua 
                 UUGAUAGUUACCU 
                 4797 
               
               
                 1251261 
                 2337440.1 
                   
                 g(Uhd)uugcaL96 
                 2337441.1 
                   
                 gguaAfcUfaucsgsg 
                 AGUUUGCA 
                   
               
               
                 .1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13B 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A Unmodified Single Strands and Duplex Sequences. 
               
               
                 Column 1 indicates duplex name; the number following the decimal point in a duplex name merely refers to a batch production number. Column 
               
               
                 2 indicates the sense sequence name. Column 3 indicates the sequence ID for the sequence of column 4. Column 4 provides the unmodified 
               
               
                 sequence of a sense strand suitable for use in a duplex described herein. Column 5 provides the position in the target mRNA (NM_001365536.1) 
               
               
                 of the sense strand of Column 4. Column 6 indicates the antisense sequence name. Column 7 indicates the sequence ID for the sequence of 
               
               
                 column 8. Column 8 provides the sequence of an antisense strand suitable for use in a duplex described herein, without specifying chemical 
               
               
                 modifications. Column 9 indicates the position in the target mRNA (NM_001365536.1) that is complementary to the antisense strand of Column 
               
               
                 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 Sense 
                 Seq ID 
                   
                 mRNA target 
                 Antisense 
                   
                   
                 mRNA target 
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 range in 
                 sequence 
                 Seq ID NO: 
                 antisense sequence 
                 range in 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 NM_001365536.1 
                 name 
                 (antisense) 
                 (5′-3′) 
                 NM_001365536.1 
               
               
                   
               
               
                 AD- 
                 A- 
                 4798 
                 ACACAAAGGGAAAAC 
                  571-591 
                 A- 
                 5064 
                 UAGATUGUUUUCCC 
                   
               
               
                 1251302.1 
                 2337487.1 
                   
                 AAUCUA 
                   
                 2337488.1 
                   
                 UUUGUGUUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4799 
                 CACAAAGGGAAAACA 
                  572-592 
                 A- 
                 5065 
                 UAAGAUTGUUUUCC 
                   
               
               
                 1251303.1 
                 2337489.1 
                   
                 AUCUUA 
                   
                 2337490.1 
                   
                 CUUUGUGUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4800 
                 ACAAAGGGAAAACAA 
                  573-593 
                 A- 
                 5066 
                 UGAAGATUGUUUU 
                  571-593 
               
               
                 1251304.1 
                 2337491.1 
                   
                 UCUUCA 
                   
                 2337492.1 
                   
                 CCCUUUGUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4801 
                 CAAAGGGAAAACAAU 
                  574-594 
                 A- 
                 5067 
                 UGGAAGAUUGUUU 
                  572-594 
               
               
                 1251305.1 
                 2337493.1 
                   
                 CUUCCA 
                   
                 2337494.1 
                   
                 UCCCUUUGUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4802 
                 AAAGGGAAAACAAUC 
                  575-595 
                 A- 
                 5068 
                 UCGGAAGAUUGUU 
                  573-595 
               
               
                 1251306.1 
                 2337495.1 
                   
                 UUCCGA 
                   
                 2337496.1 
                   
                 UUCCCUUUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4803 
                 AAAGGGAAAACAAUC 
                  575-595 
                 A- 
                 5069 
                 UCGGAAGAUUGTU 
                  573-595 
               
               
                 1251307.1 
                 2337497.1 
                   
                 UUCCGA 
                   
                 2337498.1 
                   
                 UUCCCUUUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4804 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5070 
                 UACGGAAGAUUGU 
                  574-596 
               
               
                 1251315.1 
                 2337506.1 
                   
                 UCCGUA 
                   
                 2337501.1 
                   
                 UUTCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4805 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5071 
                 UACGGAAGAUUGU 
                  574-596 
               
               
                 1251310.1 
                 2337499.1 
                   
                 UCCGUA 
                   
                 2337501.1 
                   
                 UUTCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4806 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5072 
                 UACGGAAGAUUGUT 
                  574-596 
               
               
                 961179.3 
                 1812594.1 
                   
                 UCCGUA 
                   
                 1812595.1 
                   
                 UTCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4807 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5073 
                 UACGGAAGAUUGUT 
                  574-596 
               
               
                 1251308.1 
                 2337499.1 
                   
                 UCCGUA 
                   
                 1812595.1 
                   
                 UTCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4808 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5074 
                 UACGGAAGAUUGU 
                  574-596 
               
               
                 1251314.1 
                 2337506.1 
                   
                 UCCGUA 
                   
                 2337500.1 
                   
                 UUTCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4809 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5075 
                 UACGGAAGAUUGU 
                  574-596 
               
               
                 1251309.2 
                 2337499.1 
                   
                 UCCGUA 
                   
                 2337500.1 
                   
                 UUTCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4810 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5076 
                 UACGGAAGAUUGU 
                  574-596 
               
               
                 1251316.1 
                 2337506.1 
                   
                 UCCGUA 
                   
                 2337507.1 
                   
                 UUTCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4811 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5077 
                 UACGGAAGAUUGU 
                  574-596 
               
               
                 1251317.1 
                 2337506.1 
                   
                 UCCGUA 
                   
                 2337508.1 
                   
                 UUTCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4812 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5078 
                 UACGGAAGAUUGU 
                  574-596 
               
               
                 1251311.1 
                 2337499.1 
                   
                 UCCGUA 
                   
                 2337502.1 
                   
                 UUTCCCUUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4813 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5079 
                 UACGGAAGAUUGU 
                  574-596 
               
               
                 1251309.1 
                 2337499.1 
                   
                 UCCGUA 
                   
                 2337500.1 
                   
                 UUTCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4814 
                 AGGGAAAACAAUCU 
                  577-597 
                 A- 
                 5080 
                 UAACGGAAGAUUG 
                  575-597 
               
               
                 1251318.1 
                 2337509.1 
                   
                 UCCGUUA 
                   
                 2337510.1 
                   
                 UUUUCCCUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4815 
                 AGGGAAAACAAUCU 
                  577-597 
                 A- 
                 5081 
                 UAACGGAAGAUTGU 
                  575-597 
               
               
                 1251319.1 
                 2337511.1 
                   
                 UCCGUUA 
                   
                 2337512.1 
                   
                 UUUCCCUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4816 
                 GGGAAAACAAUCUU 
                  578-596 
                 A- 
                 5082 
                 UACGGAAGAUUGU 
                  576-596 
               
               
                 1251313.1 
                 2337503.1 
                   
                 CCGUA 
                   
                 2337505.1 
                   
                 UUTCCCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4817 
                 GGGAAAACAAUCUU 
                  578-596 
                 A- 
                 5083 
                 UACGGAAGAUUGU 
                  576-596 
               
               
                 1251312.1 
                 2337503.1 
                   
                 CCGUA 
                   
                 2337504.1 
                   
                 UUTCCCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4818 
                 GGGAAAACAAUCUU 
                  578-598 
                 A- 
                 5084 
                 UAAACGGAAGATUG 
                  576-598 
               
               
                 1251320.1 
                 2337513.1 
                   
                 CCGUUUA 
                   
                 2337514.1 
                   
                 UUUUCCCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4819 
                 GGAAAACAAUCUUCC 
                  579-599 
                 A- 
                 5085 
                 UGAAACGGAAGAU 
                  577-599 
               
               
                 1251321.1 
                 2337515.1 
                   
                 GUUUCA 
                   
                 2337516.1 
                   
                 UGUUUUCCCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4820 
                 GAAAACAAUCUUCCG 
                  580-600 
                 A- 
                 5086 
                 UUGAAACGGAAGA 
                  578-600 
               
               
                 1251323.1 
                 2337519.1 
                   
                 UUUCAA 
                   
                 2337520.1 
                   
                 UUGUUUUCCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4821 
                 GAAAACAAUCUUCCA 
                  580-600 
                 A- 
                 5087 
                 UUGAAATGGAAGAU 
                  578-600 
               
               
                 1251322.1 
                 2337517.1 
                   
                 UUUCAA 
                   
                 2337518.1 
                   
                 UGUUUUCCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4822 
                 AAAACAAUCUUCCGU 
                  581-601 
                 A- 
                 5088 
                 UUUGAAACGGAAG 
                  579-601 
               
               
                 1251325.1 
                 2337523.1 
                   
                 UUCAAA 
                   
                 2337524.1 
                   
                 AUUGUUUUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4823 
                 AAAACAAUCUUCCGU 
                  581-601 
                 A- 
                 5089 
                 UUUGAAACGGAAG 
                  579-601 
               
               
                 1251324.1 
                 2337521.1 
                   
                 UUCAAA 
                   
                 2337522.1 
                   
                 AUUGUUUUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4824 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5090 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251249.1 
                 2337423.1 
                   
                 UUACUGA 
                   
                 2337424.1 
                   
                 CUCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4825 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5091 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251254.1 
                 2337423.1 
                   
                 UUACUGA 
                   
                 2337431.1 
                   
                 CUCGACACC 
                   
               
               
                 AD- 
                 A- 
                 4826 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5092 
                 UCAGUAAAAGUGU 
                  758-780 
               
               
                   
               
               
                 1251248.1 
                 2337423.1 
                   
                 UUACUGA 
                   
                 1522698.1 
                   
                 ACUCGACAUU 
                   
               
               
                 AD- 
                 A- 
                 4827 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5093 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251284.1 
                 2337423.1 
                   
                 UUACUGA 
                   
                 2337467.1 
                   
                 CTCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4828 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5094 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251253.1 
                 2337428.1 
                   
                 UUACUGA 
                   
                 2337430.1 
                   
                 CUCGACACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4829 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5095 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251286.1 
                 2337423.1 
                   
                 UUACUGA 
                   
                 2337469.1 
                   
                 CTCGACACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4830 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5096 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251282.1 
                 2337423.1 
                   
                 UUACUGA 
                   
                 1875199.1 
                   
                 CTCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4831 
                 UGUCGAGUACACUU 
                  803-823 
                 A- 
                 5097 
                 UCAGTAAAAGUGUA 
                  801-823 
               
               
                 1010661.3 
                 1851664.1 
                   
                 UUACUGA 
                   
                 1875199.1 
                   
                 CTCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4832 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5098 
                 UCAGUAAAAGUGU 
                  758-780 
               
               
                 795305.3 
                 1522697.1 
                   
                 UUACUGA 
                   
                 1522698.1 
                   
                 ACUCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4833 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5099 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251250.1 
                 2337423.1 
                   
                 UUACUGA 
                   
                 2337425.1 
                   
                 CUCGACACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4834 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5100 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251283.1 
                 2337423.1 
                   
                 UUACUGA 
                   
                 2337466.1 
                   
                 CTCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4835 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5101 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251281.1 
                 2337428.1 
                   
                 UUACUGA 
                   
                 2337466.1 
                   
                 CTCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4836 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5102 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251255.1 
                 2337428.1 
                   
                 UUACUGA 
                   
                 2337432.1 
                   
                 CUCGACACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4837 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5103 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251289.1 
                 2337428.1 
                   
                 UUACUGA 
                   
                 2337473.1 
                   
                 CTCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4838 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5104 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251252.1 
                 2337428.1 
                   
                 UUACUGA 
                   
                 2337429.1 
                   
                 CUCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4839 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5105 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251285.1 
                 2337428.1 
                   
                 UUACUGA 
                   
                 2337468.1 
                   
                 CTCGACACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4840 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5106 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251291.1 
                 2337428.1 
                   
                 UUACUGA 
                   
                 2337475.1 
                   
                 CTCGACACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4841 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5107 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251290.1 
                 2337423.1 
                   
                 UUACUGA 
                   
                 2337474.1 
                   
                 CTCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4842 
                 UCGAGUACACUUUU 
                  762-780 
                 A- 
                 5108 
                 UCAGTAAAAGUGUA 
                  760-780 
               
               
                 1251251.1 
                 2337426.1 
                   
                 ACUGA 
                   
                 2337427.1 
                   
                 CUCGACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4843 
                 UCGAGUACACUUUU 
                  762-780 
                 A- 
                 5109 
                 UCAGTAAAAGUGUA 
                  760-780 
               
               
                 1251287.1 
                 2337470.1 
                   
                 ACUGA 
                   
                 2337471.1 
                   
                 CTCGACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4844 
                 UCGAGUACACUUUU 
                  762-780 
                 A- 
                 5110 
                 UCAGTAAAAGUGUA 
                  760-780 
               
               
                 1251288.1 
                 2337426.1 
                   
                 ACUGA 
                   
                 2337472.1 
                   
                 CTCGACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4845 
                 GAGGCUUCUGUGUA 
                  819-839 
                 A- 
                 5111 
                 UUUCTCCUACACAG 
                  817-839 
               
               
                 1251326.1 
                 2337525.1 
                   
                 GGAGAAA 
                   
                 2337526.1 
                   
                 AAGCCUCUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4846 
                 AGGCUUCUGUGUAG 
                  863-883 
                 A- 
                 5112 
                 UAUUCUCCUACACA 
                  861-883 
               
               
                 1251327.1 
                 1851778.1 
                   
                 GAGAAUA 
                   
                 2337527.1 
                   
                 GAAGCCUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4847 
                 GGCUUCUGUGUAGG 
                  821-841 
                 A- 
                 5113 
                 UAAUTCTCCUACAC 
                  819-841 
               
               
                 1251328.1 
                 2337528.1 
                   
                 AGAAUUA 
                   
                 2337529.1 
                   
                 AGAAGCCUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4848 
                 GCUUCUGUGUAGGA 
                  822-842 
                 A- 
                 5114 
                 UGAATUCUCCUACA 
                  820-842 
               
               
                 1251329.1 
                 2337530.1 
                   
                 GAAUUCA 
                   
                 2337531.1 
                   
                 CAGAAGCCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4849 
                 CUUCUGUGTAGGAG 
                  823-843 
                 A- 
                 5115 
                 UUGAAUTCUCCTAC 
                  821-843 
               
               
                 1251330.1 
                 2337532.1 
                   
                 AAUUCAA 
                   
                 2337533.1 
                   
                 ACAGAAGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4850 
                 UUCUGUGUAGGAGA 
                  824-844 
                 A- 
                 5116 
                 UGUGAAUUCUCCU 
                  822-844 
               
               
                 795366.3 
                 1522818.1 
                   
                 AUUCACA 
                   
                 1522819.1 
                   
                 ACACAGAAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4851 
                 UUCUGUGUAGGAGA 
                  824-844 
                 A- 
                 5117 
                 UGUGAATUCUCCUA 
                  822-844 
               
               
                 1251331.1 
                 1522818.1 
                   
                 AUUCACA 
                   
                 2337534.1 
                   
                 CACAGAAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4852 
                 UUCUGUGUAGGAGA 
                  824-844 
                 A- 
                 5118 
                 UGUGAAUUCUCCU 
                  822-844 
               
               
                 1251334.1 
                 2337536.1 
                   
                 AUUCACA 
                   
                 2337538.1 
                   
                 ACACAGAAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4853 
                 UUCUGUGUAGGAGA 
                  824-844 
                 A- 
                 5119 
                 UGUGAATUCUCCUA 
                  822-844 
               
               
                 1251333.1 
                 2337536.1 
                   
                 AUUCACA 
                   
                 2337537.1 
                   
                 CACAGAAGC 
                   
               
               
                 AD- 
                 A- 
                 4854 
                 UUCUGUGUAGGAGA 
                  867-887 
                 A- 
                 5120 
                 UGUGAAUUCUCCU 
                  865-887 
               
               
                 1251338.1 
                 1851786.1 
                   
                 AUUCACA 
                   
                 2337542.1 
                   
                 ACACAGAAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4855 
                 UUCUGUGUAGGAGA 
                  867-887 
                 A- 
                 5121 
                 UGUGAATUCUCCUA 
                  865-887 
               
               
                 1251337.1 
                 1851786.1 
                   
                 AUUCACA 
                   
                 2337541.1 
                   
                 CACAGAAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4856 
                 UUCUGUGUAGGAGA 
                  824-844 
                 A- 
                 5122 
                 UGUGAAUUCUCCU 
                  822-844 
               
               
                 1251336.1 
                 2337536.1 
                   
                 AUUCACA 
                   
                 2337540.1 
                   
                 ACACAGAAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4857 
                 UUCUGUGUAGGAGA 
                  824-844 
                 A- 
                 5123 
                 UGUGAATUCUCCUA 
                  822-844 
               
               
                 1251335.1 
                 2337536.1 
                   
                 AUUCACA 
                   
                 2337539.1 
                   
                 CACAGAAUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4858 
                 UCUGUGUAGGAGAA 
                  825-845 
                 A- 
                 5124 
                 UAGUGAAUUCUCC 
                  823-845 
               
               
                 1251339.1 
                 2337543.1 
                   
                 UUCACUA 
                   
                 2337544.1 
                   
                 UACACAGAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4859 
                 CUGUGUAGGAGAAU 
                  869-889 
                 A- 
                 5125 
                 UAAGTGAAUUCTCC 
                  867-889 
               
               
                 1251340.1 
                 1851790.1 
                   
                 UCACUUA 
                   
                 2337545.1 
                   
                 UACACAGGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4860 
                 UGUGUAGGAGAAUU 
                  827-847 
                 A- 
                 5126 
                 UAAAGUGAAUUCU 
                  825-847 
               
               
                 1251341.1 
                 2337546.1 
                   
                 CACUUUA 
                   
                 2337547.1 
                   
                 CCUACACAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4861 
                 GUGUAGGAGAAUUC 
                  828-848 
                 A- 
                 5127 
                 UAAAAGTGAAUTCU 
                  826-848 
               
               
                 1251342.1 
                 2337548.1 
                   
                 ACUUUUA 
                   
                 2337549.1 
                   
                 CCUACACGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4862 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5128 
                 UGAAAAGUGAATUC 
                  827-849 
               
               
                 1251347.1 
                 2337481.1 
                   
                 CUUUUCA 
                   
                 2337555.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4863 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5129 
                 UGAAAAGUGAAUU 
                  827-849 
               
               
                 795371.3 
                 1522828.1 
                   
                 CUUUUCA 
                   
                 1522829.1 
                   
                 CUCCUACACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4864 
                 UGUAGGAGAATUCA 
                  872-892 
                 A- 
                 5130 
                 UGAAAAGUGAATUC 
                  870-892 
               
               
                 1010663.3 
                 1851796.1 
                   
                 CUUUUCA 
                   
                 1875201.1 
                   
                 UCCUACACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4865 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5131 
                 UGAAAAGUGAATUC 
                  827-849 
               
               
                 1251301.1 
                 2337482.1 
                   
                 CUUUUCA 
                   
                 2337486.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4866 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5132 
                 UGAAAAAUGAATUC 
                  827-849 
               
               
                 1251348.1 
                 2337556.1 
                   
                 UUUUUCA 
                   
                 2337557.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4867 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5133 
                 UGAAAAGUGAAUU 
                  827-849 
               
               
                 1251343.1 
                 2337550.1 
                   
                 CUUUUCA 
                   
                 1522829.1 
                   
                 CUCCUACACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4868 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5134 
                 UGAAAAGUGAAUU 
                  829-849 
               
               
                 1251346.1 
                 2337550.1 
                   
                 CUUUUCA 
                   
                 2337554.1 
                   
                 CUCCUACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4869 
                 UGUAGGAGAATUCA 
                  829-849 
                 A- 
                 5135 
                 UGAAAAGUGAATUC 
                  827-849 
               
               
                 1251299.1 
                 2337476.1 
                   
                 CUUUUCA 
                   
                 2337486.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4870 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5136 
                 UGAAAAAUGAAUUC 
                  827-849 
               
               
                 1251345.1 
                 2337552.1 
                   
                 UUUUUCA 
                   
                 2337553.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4871 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5137 
                 UGAAAAGUGAATUC 
                  827-849 
               
               
                 1251349.1 
                 2337481.1 
                   
                 CUUUUCA 
                   
                 2337558.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4872 
                 UGUAGGAGAATUCA 
                  829-849 
                 A- 
                 5138 
                 UGAAAAGUGAATUC 
                  827-849 
               
               
                 1251292.1 
                 2337476.1 
                   
                 CUUUUCA 
                   
                 2337477.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4873 
                 UGUAGGAGAATUCA 
                  829-849 
                 A- 
                 5139 
                 UGAAAAGUGAATUC 
                  827-849 
               
               
                 1251293.1 
                 2337476.1 
                   
                 CUUUUCA 
                   
                 2337478.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4874 
                 UGUAGGAGAATUCA 
                  829-849 
                 A- 
                 5140 
                 UGAAAAAUGAATUC 
                  827-849 
               
               
                 1251294.1 
                 2337479.1 
                   
                 UUUUUCA 
                   
                 2337480.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4875 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5141 
                 UGAAAAGUGAAUU 
                  827-849 
               
               
                 1251344.1 
                 2337550.1 
                   
                 CUUUUCA 
                   
                 2337551.1 
                   
                 CUCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4876 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5142 
                 UGAAAAGUGAATUC 
                  827-849 
               
               
                 1251300.1 
                 2337481.1 
                   
                 CUUUUCA 
                   
                 2337486.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4877 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5143 
                 UGAAAAGUGAATUC 
                  827-849 
               
               
                 1251295.1 
                 2337481.1 
                   
                 CUUUUCA 
                   
                 2337478.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4878 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5144 
                 UGAAAAGUGAATUC 
                  827-849 
               
               
                 1251296.1 
                 2337482.1 
                   
                 CUUUUCA 
                   
                 2337478.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4879 
                 GUAGGAGAAUUCAC 
                  830-850 
                 A- 
                 5145 
                 UAGAAAAGUGAAU 
                  828-850 
               
               
                 1251350.1 
                 2337559.1 
                   
                 UUUUCUA 
                   
                 2337560.1 
                   
                 UCUCCUACGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4880 
                 GUAGGAGAAUUCAC 
                  830-850 
                 A- 
                 5146 
                 UAGAAAAGUGAAU 
                  828-850 
               
               
                 1251351.1 
                 2337561.1 
                   
                 UUUUCUA 
                   
                 2337562.1 
                   
                 UCUCCUACGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4881 
                 UAGGAGAAUUCACU 
                  831-851 
                 A- 
                 5147 
                 UAAGAAAAGUGAA 
                  829-851 
               
               
                 1251353.1 
                 2337565.1 
                   
                 UUUCUUA 
                   
                 2337566.1 
                   
                 UUCUCCUACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4882 
                 UAGGAGAAUUCACU 
                  831-851 
                 A- 
                 5148 
                 UAAGAAAAGUGAA 
                  829-851 
               
               
                 1251352.1 
                 2337563.1 
                   
                 UUUCUUA 
                   
                 2337564.1 
                   
                 UUCUCCUACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4883 
                 UAGGAGAAUUCACU 
                  831-849 
                 A- 
                 5149 
                 UGAAAAGUGAATUC 
                  829-849 
               
               
                 1251298.1 
                 2337485.1 
                   
                 UUUCA 
                   
                 2337484.1 
                   
                 UCCUACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4884 
                 UAGGAGAAUUCACU 
                  831-849 
                 A- 
                 5150 
                 UGAAAAGUGAATUC 
                  829-849 
               
               
                 1251297.1 
                 2337483.1 
                   
                 UUUCA 
                   
                 2337484.1 
                   
                 UCCUACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4885 
                 AGGAGAAUUCACUU 
                  832-852 
                 A- 
                 5151 
                 UGAAGAAAAGUGA 
                  830-852 
               
               
                 1251354.1 
                 2337567.1 
                   
                 UUCUUCA 
                   
                 2337568.1 
                   
                 AUUCUCCUGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4886 
                 GGAGAAUUCACUUU 
                  833-853 
                 A- 
                 5152 
                 UCGAAGAAAAGUGA 
                  831-853 
               
               
                 1251355.1 
                 2337569.1 
                   
                 UCUUCGA 
                   
                 2337570.1 
                   
                 AUUCUCCUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4887 
                 GGAGAAUUCACUUU 
                  833-853 
                 A- 
                 5153 
                 UCGAAGAAAAGTGA 
                  831-853 
               
               
                 1251356.1 
                 2337571.1 
                   
                 UCUUCGA 
                   
                 2337572.1 
                   
                 AUUCUCCUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4888 
                 GAGAAUUCACUUUU 
                  834-854 
                 A- 
                 5154 
                 UACGAAGAAAAGUG 
                  832-854 
               
               
                 1251357.1 
                 2337573.1 
                   
                 CUUCGUA 
                   
                 2337574.1 
                   
                 AAUUCUCCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4889 
                 CCUGAAGCAUAAAU 
                  1108-1128 
                 A- 
                 5155 
                 UGAAAACAUUUAU 
                 1106-1128 
               
               
                 1251358.1 
                 2337575.1 
                   
                 GUUUUCA 
                   
                 2337576.1 
                   
                 GCUUCAGGUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4890 
                 CUGAAGCAUAAAUG 
                 1109-1129 
                 A- 
                 5156 
                 UCGAAAACAUUUAU 
                 1107-1129 
               
               
                 1251359.1 
                 2337577.1 
                   
                 UUUUCGA 
                   
                 2337578.1 
                   
                 GCUUCAGGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4891 
                 CUGAAGCATAAAUGU 
                 1109-1129 
                 A- 
                 5157 
                 UCGAAAACAUUUAU 
                 1107-1129 
               
               
                 1251360.1 
                 2337579.1 
                   
                 UUUCGA 
                   
                 2337580.1 
                   
                 GCUUCAGGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4892 
                 UGAAGCAUAAAUGU 
                 1153-1173 
                 A- 
                 5158 
                 UUCGAAAACAUTUA 
                 1151-1173 
               
               
                 1251361.1 
                 1852317.1 
                   
                 UUUCGAA 
                   
                 2337581.1 
                   
                 UGCUUCAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4893 
                 GAAGCAUAAAUGUU 
                 1111-1131 
                 A- 
                 5159 
                 UUUCGAAAACATUU 
                 1109-1131 
               
               
                 1251363.1 
                 2337584.1 
                   
                 UUCGAAA 
                   
                 2337585.1 
                   
                 AUGCUUCAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4894 
                 GAAGCAUAAAUGUU 
                 1111-1131 
                 A- 
                 5160 
                 UUUCGAAAACAUU 
                 1109-1131 
               
               
                 1251362.1 
                 2337582.1 
                   
                 UUCGAAA 
                   
                 2337583.1 
                   
                 UAUGCUUCAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4895 
                 AAGCAUAAAUGUUU 
                 1112-1132 
                 A- 
                 5161 
                 UUUUCGAAAACAU 
                 1110-1132 
               
               
                 1251364.1 
                 1812604.1 
                   
                 UCGAAAA 
                   
                 2337586.1 
                   
                 UUAUGCUUCG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4896 
                 AGCAUAAAUGUUUU 
                 1113-1133 
                 A- 
                 5162 
                 UAUUTCGAAAACAU 
                 1111-1133 
               
               
                 1251372.1 
                 2337591.1 
                   
                 CGAAAUA 
                   
                 2337598.1 
                   
                 UUAUGCUUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4897 
                 AGCAUAAAUGUUUU 
                 1113-1133 
                 A- 
                 5163 
                 UAUUUCGAAAACAU 
                 1111-1133 
               
               
                 1251366.1 
                 2337589.1 
                   
                 CGAAAUA 
                   
                 1523300.1 
                   
                 UUAUGCUUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4898 
                 AGCAUAAAUGUUUU 
                 1113-1133 
                 A- 
                 5164 
                 UAUUTCGAAAACAU 
                 1111-1133 
               
               
                 1251367.1 
                 2337589.1 
                   
                 CGAAAUA 
                   
                 2337590.1 
                   
                 UUAUGCUUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 4899 
                 AGCAUAAAUGUUUU 
                 1113-1133 
                 A- 
                 5165 
                 UAUUUCGAAAACAU 
                 1111-1133 
               
               
                 795634.4 
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                 CGAAAUA 
                   
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                 UAAAAUCACUACGA 
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                 UUGCAAA 
                   
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                 GCAAUUA 
                   
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                 ACAAAAGGG 
                   
               
               
                   
               
               
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                 UUAATUGCAAGAUC 
                   
               
               
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                 UACAAAGCC 
                   
               
               
                   
               
               
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                 UACAAAAGG 
                   
               
               
                   
               
               
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                 AAUUACA 
                   
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                 UCUACAAAAG 
                   
               
               
                   
               
               
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                 CUACAAAGG 
                   
               
               
                   
               
               
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                 UCUACAAAGG 
                   
               
               
                   
               
               
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                 AUCUACAAGG 
                   
               
               
                   
               
               
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                 UUGGTAAUUGCAAG 
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                 UUACCAA 
                   
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                 UAAUGGTAAUUGCA 
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                 ACCAUUA 
                   
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                 AGAUCUACG 
                   
               
               
                   
               
               
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                 UUUCACGU 
                   
               
               
                   
               
               
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                 GUGAAACAAACCUUA 
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                 UUCACGTAAGGTUU 
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                 CGUGAA 
                   
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                 GUUUCACGU 
                   
               
               
                   
               
               
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                 UUCACGTAAGGUUU 
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                 GUUUCACGU 
                   
               
               
                   
               
               
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                 UUUCACGUAAGGU 
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                 GAAACAAACCUUACG 
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                 UAUUCACGUAAGG 
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                 UUUGUUUCAC 
                   
               
               
                   
               
               
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                 GAAACAAACCUUACG 
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                 AAACAAACCUUACGU 
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                 GAAUUA 
                   
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                 UUUGUUUCG 
                   
               
               
                   
               
               
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                 UGUGAUAUAUUUUA 
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                 UAUGTUGUAAAAU 
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                 UGUGAUAUAUUUUA 
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                 UAUGTUGUAAAAU 
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                 AUAUCACAGU 
                   
               
               
                   
               
               
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                 GUGAUAUAUUUUAC 
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                 UGAUGUUGUAAAA 
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                 UGAUAUAUUUUACA 
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                 UGGATGUUGUAAA 
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                 ACAUCCA 
                   
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                 AUAUAUCACG 
                   
               
               
                   
               
               
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                 5000 
                 GAUAUAUUUUACAA 
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                 UCGGAUGUUGUAA 
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                 CAUCCGA 
                   
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                 AAUAUAUCGC 
                   
               
               
                   
               
               
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                 GAUAUAUUUUACAA 
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                 UCGGAUGUUGUAA 
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                 CAUCCGA 
                   
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                 5002 
                 AUAUAUUUUACAAC 
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                 5268 
                 UACGGATGUUGTAA 
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                 AUCCGUA 
                   
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                 AAUAUAUCG 
                   
               
               
                   
               
               
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                 AUAUAUUUUACAAC 
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                 UACGGATGUUGUAA 
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                 AAUAUAUCG 
                   
               
               
                   
               
               
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                 UAUAUUUUACAACA 
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                 UAACGGAUGUUGU 
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                 UCCGUUA 
                   
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                 AAAAUAUACC 
                   
               
               
                   
               
               
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                 A- 
                 5005 
                 UAUAUUUUACAACA 
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                 UAACGGAUGUUGU 
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                 UCCGUUA 
                   
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                 UAUAUUUUACAACA 
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                 UAACGGAUGUUGU 
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                 UCCGUUA 
                   
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                 UAUAUUUUACAACA 
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                 UAACGGAUGUUGU 
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                 UCCGUUA 
                   
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                 UAACGGAUGUUGU 
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                 UCCGUUA 
                   
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                 UAACGGAUGUUGU 
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                 UCCGUUA 
                   
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                 UAUAUUUUACAACA 
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                 UAACGGAUGUUGU 
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                 UCCGUUA 
                   
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                 UAUAUUUUACAACA 
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                 UAACGGAUGUUGU 
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                 UCCGUUA 
                   
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                 UAUAUUUUACAACA 
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                 UAACGGAUGUUGU 
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                 UCCGUUA 
                   
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                 AUAUUUUACAACAU 
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                 UUAACGGAUGUUG 
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                 CCGUUAA 
                   
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                 UAAAAUAUGU 
                   
               
               
                   
               
               
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                 AUAUUUUACAACAU 
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                 UUAACGGAUGUTG 
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                 CCGUUAA 
                   
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                 UAAAAUAUGU 
                   
               
               
                   
               
               
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                 UAUUUUACAACAUC 
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                 UAACGGAUGUUGU 
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                 CGUUA 
                   
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                 AAAAUAUG 
                   
               
               
                   
               
               
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                 UAUUUUACAACAUC 
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                 CGUUAUA 
                   
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                 UAAAAUAUG 
                   
               
               
                   
               
               
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                 UAUUUUACAACAUC 
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                 UAACGGAUGUUGU 
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                 CGUUA 
                   
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                 AAAAUAUG 
                   
               
               
                   
               
               
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                 AUUUUACAACAUCCG 
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                 UAAUAACGGAUGU 
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                 UUAUUA 
                   
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                 UGUAAAAUGU 
                   
               
               
                   
               
               
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                 AUUUUACAACAUCCG 
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                 UAAUAACGGAUGU 
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                 UUAUUA 
                   
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                 UGUAAAAUGU 
                   
               
               
                   
               
               
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                 5020 
                 UUUUACAACAUCCG 
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                 UUAATAACGGATGU 
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                 UUAUUAA 
                   
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                 UGUAAAAUG 
                   
               
               
                   
               
               
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                 5021 
                 UUUACAACAUCCGU 
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                 UGUAAUAACGGAU 
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                 UAUUACA 
                   
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                 GUUGUAAAGU 
                   
               
               
                   
               
               
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                 5022 
                 CAACACAAUUUCUUC 
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                 UGCUAAGAAGAAAU 
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                 UUAGCA 
                   
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                 UGUGUUGUU 
                   
               
               
                   
               
               
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                 CAACACAAUUUCUUC 
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                 UGCUAAGAAGAAAU 
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                 UUAGCA 
                   
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                 UGUGUUGUU 
                   
               
               
                   
               
               
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                 CAACACAAUUUCUUC 
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                 UGCUAAGAAGAAAU 
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                 UUAGCA 
                   
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                 UGUGUUGCC 
                   
               
               
                   
               
               
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                 CAACACAAUUUCUUC 
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                 UGCUAAGAAGAAAU 
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                 UUAGCA 
                   
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                 UGUGUUGCC 
                   
               
               
                   
               
               
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                 CAACACAATUTCUUC 
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                 UGCUAAGAAGAAAT 
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                 961334.3 
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                 UUAGCA 
                   
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                 UGUGUUGUU 
                   
               
               
                   
               
               
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                 UGCUAAGAAGAAAU 
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                 UAGCA 
                   
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                 UGUGUUG 
                   
               
               
                   
               
               
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                 GGCUUCAAGUGUUC 
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                 UCAGTAGGAACACU 
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                 CUACUGA 
                   
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                 UGAAGCCGG 
                   
               
               
                   
               
               
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                 UACAGUAGGAACAC 
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                 UACUGUA 
                   
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                 UUGAAGCCG 
                   
               
               
                   
               
               
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                 CUUCAAGUGUUCCU 
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                 UGACAGTAGGAACA 
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                 ACUGUCA 
                   
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                 CUUGAAGCC 
                   
               
               
                   
               
               
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                 UUCAAGUGUUCCUA 
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                 UUGACAGUAGGAAC 
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                 CUGUCAA 
                   
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                 ACUUGAAGC 
                   
               
               
                   
               
               
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                 UUCAAGUGUUCCUA 
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                 UUGACAGUAGGAAC 
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                 CUGUCAA 
                   
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                 ACUUGAAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5033 
                 UCAAGUGUUCCUAC 
                 9103-9123 
                 A- 
                 5299 
                 UAUGACAGUAGGA 
                 9101-9123 
               
               
                 1251482.1 
                 2337761.1 
                   
                 UGUCAUA 
                   
                 2337762.1 
                   
                 ACACUUGAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5034 
                 UCAAGUGUUCCUAC 
                 9103-9123 
                 A- 
                 5300 
                 UAUGACAGUAGGA 
                 9101-9123 
               
               
                 1251483.1 
                 2337761.1 
                   
                 UGUCAUA 
                   
                 2337763.1 
                   
                 ACACUUGAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5035 
                 CAAGUGUUCCUACU 
                 9104-9124 
                 A- 
                 5301 
                 UCAUGACAGUAGGA 
                 9102-9124 
               
               
                 1251492.1 
                 2337764.1 
                   
                 GUCAUGA 
                   
                 2337773.1 
                   
                 ACACUUGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5036 
                 CAAGUGUUCCUACU 
                 9104-9124 
                 A- 
                 5302 
                 UCAUGACAGUAGGA 
                 9102-9124 
               
               
                 1251485.1 
                 2337764.1 
                   
                 GUCAUGA 
                   
                 2337766.1 
                   
                 ACACUUGGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5037 
                 CAAGUGUUCCUACU 
                 9104-9124 
                 A- 
                 5303 
                 UCAUGACAGUAGGA 
                 9102-9124 
               
               
                 802471.4 
                 1536717.1 
                   
                 GUCAUGA 
                   
                 1536718.1 
                   
                 ACACUUGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5038 
                 CAAGUGUUCCUACU 
                 9104-9124 
                 A- 
                 5304 
                 UCAUGACAGUAGGA 
                 9102-9124 
               
               
                 1251486.1 
                 2337764.1 
                   
                 GUCAUGA 
                   
                 1536718.1 
                   
                 ACACUUGAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5039 
                 CAAGUGUUCCUACU 
                 9104-9124 
                 A- 
                 5305 
                 UCAUGACAGUAGGA 
                 9102-9124 
               
               
                 1251484.1 
                 2337764.1 
                   
                 GUCAUGA 
                   
                 2337765.1 
                   
                 ACACUUGGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5040 
                 CAAGUGUUCCUACU 
                 9104-9124 
                 A- 
                 5306 
                 UCAUGACAGUAGGA 
                 9102-9124 
               
               
                 1251491.1 
                 2337764.1 
                   
                 GUCAUGA 
                   
                 2337772.1 
                   
                 ACACUUGGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5041 
                 CAAGUGUUCCUACU 
                 9104-9124 
                 A- 
                 5307 
                 UCAUGACAGUAGGA 
                 9102-9124 
               
               
                 1251487.1 
                 2337764.1 
                   
                 GUCAUGA 
                   
                 2337767.1 
                   
                 ACACUUGGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5042 
                 CAAGUGUUCCUACU 
                 9104-9124 
                 A- 
                 5308 
                 UCAUGACAGUAGGA 
                 9102-9124 
               
               
                 1251488.1 
                 2337764.1 
                   
                 GUCAUGA 
                   
                 2337768.1 
                   
                 ACACUUGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5043 
                 CAAGUGUUCCUACU 
                 9104-9124 
                 A- 
                 5309 
                 UCAUGACAGUAGGA 
                 9102-9124 
               
               
                 1251490.1 
                 2337764.1 
                   
                 GUCAUGA 
                   
                 2337771.1 
                   
                 ACACUUGGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5044 
                 AAGUGUUCCUACUG 
                 9105-9125 
                 A- 
                 5310 
                 UUCATGACAGUAGG 
                 9103-9125 
               
               
                 1251494.1 
                 2337775.1 
                   
                 UCAUGAA 
                   
                 2337776.1 
                   
                 AACACUUGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5045 
                 AGUGUUCCUACUGU 
                 9106-9124 
                 A- 
                 5311 
                 UCAUGACAGUAGGA 
                 9104-9124 
               
               
                 1251493.1 
                 2337769.1 
                   
                 CAUGA 
                   
                 2337774.1 
                   
                 ACACUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5046 
                 AGUGUUCCUACUGU 
                 9106-9124 
                 A- 
                 5312 
                 UCAUGACAGUAGGA 
                 9104-9124 
               
               
                 1251489.1 
                 2337769.1 
                   
                 CAUGA 
                   
                 2337770.1 
                   
                 ACACUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5047 
                 AGUGUUCCUACUGU 
                 9106-9126 
                 A- 
                 5313 
                 UGUCAUGACAGTAG 
                 9104-9126 
               
               
                 1251495.1 
                 2337777.1 
                   
                 CAUGACA 
                   
                 2337778.1 
                   
                 GAACACUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5048 
                 GUGUUCCUACUGUC 
                 9107-9127 
                 A- 
                 5314 
                 UGGUCATGACAGUA 
                 9105-9127 
               
               
                 1251496.1 
                 2337779.1 
                   
                 AUGACCA 
                   
                 2337780.1 
                   
                 GGAACACUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5049 
                 UGUUCCUACUGUCA 
                 9108-9128 
                 A- 
                 5315 
                 UAGGTCAUGACAGU 
                 9106-9128 
               
               
                 1251497.1 
                 2337781.1 
                   
                 UGACCUA 
                   
                 2337782.1 
                   
                 AGGAACACU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5050 
                 GUUCCUACUGUCAU 
                 9109-9129 
                 A- 
                 5316 
                 UCAGGUCAUGACAG 
                 9107-9129 
               
               
                 1251498.1 
                 2337783.1 
                   
                 GACCUGA 
                   
                 2337784.1 
                   
                 UAGGAACGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5051 
                 UUGAUAGUUACCUA 
                 9225-9245 
                 A- 
                 5317 
                 UGCAAACUAGGUAA 
                 9223-9245 
               
               
                 802552.3 
                 1536877.1 
                   
                 GUUUGCA 
                   
                 1536878.1 
                   
                 CUAUCAAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5052 
                 UUGAUAGUTACCUA 
                 9225-9245 
                 A- 
                 5318 
                 UGCAAACUAGGTAA 
                 9223-9245 
               
               
                 1251267.1 
                 2337439.1 
                   
                 GUUUGCA 
                   
                 2337448.1 
                   
                 CUAUCAAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5053 
                 UUGAUAGUTACCUA 
                 9225-9245 
                 A- 
                 5319 
                 UGCAAACUAGGTAA 
                 9223-9245 
               
               
                 1251260.1 
                 2337439.1 
                   
                 GUUUGCA 
                   
                 2337438.1 
                   
                 CUAUCAAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5054 
                 UUGAUAGUUACCUA 
                 9225-9245 
                 A- 
                 5320 
                 UGCAAACUAGGUAA 
                 9223-9245 
               
               
                 1251256.1 
                 2337433.1 
                   
                 GUUUGCA 
                   
                 1536878.1 
                   
                 CUAUCAAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5055 
                 UUGAUAGUUACCUA 
                 9225-9245 
                 A- 
                 5321 
                 UGCAAACUAGGUAA 
                 9223-9245 
               
               
                 1251265.1 
                 2337436.1 
                   
                 GUUUGCA 
                   
                 2337447.1 
                   
                 CUAUCAAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5056 
                 UUGAUAGUUACCUA 
                 9225-9245 
                 A- 
                 5322 
                 UGCAAACUAGGUAA 
                 9223-9245 
               
               
                 1251257.1 
                 2337434.1 
                   
                 GUUUGCA 
                   
                 2337435.1 
                   
                 CUAUCAAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5057 
                 UUGAUAGUUACCUA 
                 9225-9245 
                 A- 
                 5323 
                 UGCAAACUAGGTAA 
                 9223-9245 
               
               
                 1251266.1 
                 2337437.1 
                   
                 GUUUGCA 
                   
                 2337448.1 
                   
                 CUAUCAAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5058 
                 UUGAUAGUUACCUA 
                 9225-9245 
                 A- 
                 5324 
                 UGCAAATUAGGUAA 
                   
               
               
                 1251264.1 
                 2337445.1 
                   
                 AUUUGCA 
                   
                 2337446.1 
                   
                 CUAUCAAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5059 
                 UUGAUAGUUACCUA 
                 9225-9245 
                 A- 
                 5325 
                 UGCAAACUAGGTAA 
                 9223-9245 
               
               
                 1251259.1 
                 2337437.1 
                   
                 GUUUGCA 
                   
                 2337438.1 
                   
                 CUAUCAAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5060 
                 UUGAUAGUUACCUA 
                 9225-9245 
                 A- 
                 5326 
                 UGCAAACUAGGUAA 
                 9223-9245 
               
               
                 1251258.1 
                 2337436.1 
                   
                 GUUUGCA 
                   
                 2337435.1 
                   
                 CUAUCAAGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5061 
                 GAUAGUTACCUAGU 
                 9227-9245 
                 A- 
                 5327 
                 UGCAAACUAGGTAA 
                 9225-9245 
               
               
                 1251263.1 
                 2337444.1 
                   
                 UUGCA 
                   
                 2337443.1 
                   
                 CUAUCGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5062 
                 GAUAGUUACCUAGU 
                 9227-9245 
                 A- 
                 5328 
                 UGCAAACUAGGTAA 
                 9225-9245 
               
               
                 1251262.1 
                 2337442.1 
                   
                 UUGCA 
                   
                 2337443.1 
                   
                 CUAUCGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5063 
                 GAUAGUUACCUAGU 
                 9227-9245 
                 A- 
                 5329 
                 UGCAAACUAGGUAA 
                 9225-9245 
               
               
                 1251261.1 
                 2337440.1 
                   
                 UUGCA 
                   
                 2337441.1 
                   
                 CUAUCGG 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14A 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A siRNA Modified Single Strands and Duplex Sequences 
               
               
                 Column 1 indicates duplex name and the number following the decimal point in a duplex name merely refers to a batch production number. 
               
               
                 Column 2 indicates the name of the sense sequence. Column 3 indicates the sequence ID for the sequence of column 4. Column 4 provides the 
               
               
                 modified sequence of a sense strand suitable for use in a duplex described herein. Column 5 indicates the antisense sequence name. Column 6 
               
               
                 indicates the sequence ID for the sequence of column 7. Column 7 provides the sequence of a modified antisense strand suitable for use in a 
               
               
                 duplex described herein, e.g., a duplex comprising the sense sequence in the same row of the table. Column 8 indicates the position in the 
               
               
                 target mRNA (NM_001365536.1) that is complementary to the antisense strand of Column 7. Column 9 indicated the sequence ID for the sequence 
               
               
                 of column 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 Sense 
                 Seq ID 
                   
                 Antisense 
                 Seq ID 
                   
                 mRNA target 
                 SEQ ID NO: 
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 sequence 
                 NO: 
                 Antisense sequence 
                 sequence in 
                 (mRNA 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 name 
                 (antisense) 
                 (5′-3′) 
                 NM_001365536.1 
                 target) 
               
               
                   
               
               
                 AD- 
                 A- 
                 5330 
                 usgsucg(Ahd)GfuAf 
                 A- 
                 5346 
                 VPusCfsaguAfaAfAfgu 
                 AAUGUCGAGUACACU 
                 5362 
               
               
                 795305.2 
                 1522697.1 
                   
                 CfAfcuuuuacugaL96 
                 1522698.1 
                   
                 guAfcUfcgacasusu 
                 UUUACUGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5331 
                 usgsucgaguAfCfAfc 
                 A- 
                 5347 
                 VPusCfsagdTadAaagu 
                 AAUGUCGAGUACACU 
                 5363 
               
               
                 1251249.1 
                 2337423.1 
                   
                 uuu(Uhd)acugaL96 
                 2337424.1 
                   
                 guAfcUfcgacasusu 
                 UUUACUGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5332 
                 uscsgaguAfCfAfcuu 
                 A- 
                 5348 
                 VPusCfsagdTadAaagu 
                 UGUCGAGUACACUUU 
                 5364 
               
               
                 1251251.1 
                 2337426.1 
                   
                 u(Uhd)acugaL96 
                 2337427.1 
                   
                 guAfcUfcgascsg 
                 UACUGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5333 
                 usgsuag(Ghd)agdAa 
                 A- 
                 5349 
                 VPusdGsaadAadGuga 
                 UGUGUAGGAGAAUUC 
                 5365 
               
               
                 1010663.2 
                 1851796.1 
                   
                 dTucacuuuucaL96 
                 1875201.1 
                   
                 adTudCudCcuacascsa 
                 ACUUUUCU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5334 
                 usgsuaggagdAaUfU 
                 A- 
                 5350 
                 VPudGaadAa(G2p)ug 
                 UGUGUAGGAGAAUUC 
                 5366 
               
               
                 1251301.1 
                 2337482.1 
                   
                 fcac(Uhd)uuucaL96 
                 2337486.1 
                   
                 aadTudCudCcuacascs 
                 ACUUUUCU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5335 
                 asasggg(Ahd)aadAc 
                 A- 
                 5351 
                 VPusdAscgdGadAgau 
                 CAAAGGGAAAACAAU 
                 5367 
               
               
                 961179.3 
                 1812594.1 
                   
                 dAaucuuccguaL96 
                 1812595.1 
                   
                 udGudTudTcccuusus 
                 CUUCCGUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5336 
                 asasgggaaaAfCfAfa 
                 A- 
                 5352 
                 VPudAcgdGa(A2p)ga 
                 CAAAGGGAAAACAAU 
                 5368 
               
               
                 1251317.1 
                 2337506.1 
                   
                 ucu(Uhd)ccguaL96 
                 2337508.1 
                   
                 uudGuUfudTcccuusus 
                 CUUCCGUU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 g 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5337 
                 asgsggaaAfaCfAfAfu 
                 A- 
                 5353 
                 VPusAfsacdGgdAagau 
                 AAAGGGAAAACAAUC 
                 5369 
               
               
                 1251318.1 
                 2337509.1 
                   
                 cuu(Chd)cguuaL96 
                 2337510.1 
                   
                 ugUfuUfucccususu 
                 UUCCGUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5338 
                 gsasaaa(Chd)aaUfCf 
                 A- 
                 5354 
                 VPuUfgadAa(C2p)gga 
                 GGGAAAACAAUCUUC 
                 5370 
               
               
                 1251323.1 
                 2337519.1 
                   
                 UfuccguuucaaL96 
                 2337520.1 
                   
                 agaUfudGuuuucscsc 
                 CGUUUCAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5339 
                 asasaacaauCfUfUfc 
                 A- 
                 5355 
                 VPuUfugdAadAcggad 
                 GGAAAACAAUCUUCC 
                 5371 
               
               
                 1251325.1 
                 2337523.1 
                   
                 cgu(Uhd)ucaaaL96 
                 2337524.1 
                   
                 AgdAuUfguuuuscsc 
                 GUUUCAAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5340 
                 asgscau(Ahd)AfaUf 
                 A- 
                 5356 
                 VPusAfsuuuCfgAfAfaa 
                 GAAGCAUAAAUGUUU 
                 5372 
               
               
                 795634.3 
                 1523299.1 
                   
                 GfUfuuucgaaauaL9 
                 1523300.1 
                   
                 caUfuUfaugcususc 
                 UCGAAAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5341 
                 gsasagcauadAaUfgu 
                 A- 
                 5357 
                 VPuUfucdGadAaacad 
                 CUGAAGCAUAAAUGU 
                 5373 
               
               
                 1251363.1 
                 2337584.1 
                   
                 uu(Uhd)cgaaaL96 
                 2337585.1 
                   
                 TuUfaUfgcuucsasg 
                 UUUCGAAA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5342 
                 asasgca(Uhd)aadAu 
                 A- 
                 5358 
                 VPuUfuudCgdAaaacd 
                 UGAAGCAUAAAUGUU 
                 5374 
               
               
                 1251364.1 
                 1812604.1 
                   
                 dGuuuucgaaaaL96 
                 2337586.1 
                   
                 AuUfudAugcuuscsg 
                 UUCGAAAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5343 
                 asgscauaaaUfgUfuu 
                 A- 
                 5359 
                 VPudAuudTc(G2p)aaa 
                 GAAGCAUAAAUGUUU 
                 5375 
               
               
                 1251373.1 
                 2337591.1 
                   
                 u(Chd)gaaauaL96 
                 2337599.1 
                   
                 adCaUfuUfaugcuscsc 
                 UCGAAAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5344 
                 asusgau(Chd)UfuCf 
                 A- 
                 5360 
                 VPudAcudAcdGacaad 
                 ACAUGAUCUUCUUUG 
                 5376 
               
               
                 1251385.1 
                 1523845.1 
                   
                 UfUfugucguaguaL96 
                 2337618.1 
                   
                 AgdAadGaucausgsu 
                 UCGUAGUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5345 
                 uscsu(Uhd)CfuUfud 
                 A- 
                 5361 
                 VPusUfscadCu(Agn)cg 
                 GAUCUUCUUUGUCGU 
                 5377 
               
               
                 1251391.1 
                 2337625.1 
                   
                 GucguagugaaL96 
                 2337626.1 
                   
                 acdAaAfgAfagasusc 
                 AGUGAU 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14B 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A Unmodified Single Strands and Duplex Sequences. 
               
               
                 Column 1 indicates duplex name; the number following the decimal point in a duplex name merely refers to a batch production number. Column 
               
               
                 2 indicates the sense sequence name. Column 3 indicates the sequence ID for the sequence of column 4. Column 4 provides the unmodified 
               
               
                 sequence of a sense strand suitable for use in a duplex described herein. Column 5 provides the position in the target mRNA (NM_001365536.1) 
               
               
                 of the sense strand of Column 4. Column 6 indicates the antisense sequence name. Column 7 indicates the sequence ID for the sequence of 
               
               
                 column 8. Column 8 provides the sequence of an antisense strand suitable for use in a duplex described herein, without specifying chemical 
               
               
                 modifications. Column 9 indicates the position in the target mRNA (NM_001365536.1) that is complementary to the antisense strand of Column 
               
               
                 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 Sense 
                 Seq ID 
                   
                 mRNA target 
                 Antisense 
                   
                   
                 mRNA target 
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 range in 
                 sequence 
                 Seq ID NO: 
                 antisense sequence 
                 range in 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 NM_001365536.1 
                 name 
                 (antisense) 
                 (5′-3′) 
                 NM_001365536.1 
               
               
                   
               
               
                 AD- 
                 A- 
                 5378 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5394 
                 UCAGUAAAAGUGU 
                  758-780 
               
               
                 795305.2 
                 1522697.1 
                   
                 UUACUGA 
                   
                 1522698.1 
                   
                 ACUCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5379 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5395 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251249.1 
                 2337423.1 
                   
                 UUACUGA 
                   
                 2337424.1 
                   
                 CUCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5380 
                 UCGAGUACACUUUU 
                  762-780 
                 A- 
                 5396 
                 UCAGTAAAAGUGUA 
                  760-780 
               
               
                 1251251.1 
                 2337426.1 
                   
                 ACUGA 
                   
                 2337427.1 
                   
                 CUCGACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5381 
                 UGUAGGAGAATUCA 
                  872-892 
                 A- 
                 5397 
                 UGAAAAGUGAATUC 
                  870-892 
               
               
                 1010663.2 
                 1851796.1 
                   
                 CUUUUCA 
                   
                 1875201.1 
                   
                 UCCUACACA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5382 
                 UGUAGGAGAAUUCA 
                  829-849 
                 A- 
                 5398 
                 UGAAAAGUGAATUC 
                  827-849 
               
               
                 1251301.1 
                 2337482.1 
                   
                 CUUUUCA 
                   
                 2337486.1 
                   
                 UCCUACACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5383 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5399 
                 UACGGAAGAUUGUT 
                  574-596 
               
               
                 961179.3 
                 1812594.1 
                   
                 UCCGUA 
                   
                 1812595.1 
                   
                 UTCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5384 
                 AAGGGAAAACAAUCU 
                  576-596 
                 A- 
                 5400 
                 UACGGAAGAUUGU 
                  574-596 
               
               
                 1251317.1 
                 2337506.1 
                   
                 UCCGUA 
                   
                 2337508.1 
                   
                 UUTCCCUUUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5385 
                 AGGGAAAACAAUCU 
                  577-597 
                 A- 
                 5401 
                 UAACGGAAGAUUG 
                  575-597 
               
               
                 1251318.1 
                 2337509.1 
                   
                 UCCGUUA 
                   
                 2337510.1 
                   
                 UUUUCCCUUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5386 
                 GAAAACAAUCUUCCG 
                  580-600 
                 A- 
                 5402 
                 UUGAAACGGAAGA 
                  578-600 
               
               
                 1251323.1 
                 2337519.1 
                   
                 UUUCAA 
                   
                 2337520.1 
                   
                 UUGUUUUCCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5387 
                 AAAACAAUCUUCCGU 
                  581-601 
                 A- 
                 5403 
                 UUUGAAACGGAAG 
                  579-601 
               
               
                 1251325.1 
                 2337523.1 
                   
                 UUCAAA 
                   
                 2337524.1 
                   
                 AUUGUUUUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5388 
                 AGCAUAAAUGUUUU 
                 1113-1133 
                 A- 
                 5404 
                 UAUUUCGAAAACAU 
                 1111-1133 
               
               
                 795634.3 
                 1523299.1 
                   
                 CGAAAUA 
                   
                 1523300.1 
                   
                 UUAUGCUUC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5389 
                 GAAGCAUAAAUGUU 
                 1111-1131 
                 A- 
                 5405 
                 UUUCGAAAACATUU 
                 1109-1131 
               
               
                 1251363.1 
                 2337584.1 
                   
                 UUCGAAA 
                   
                 2337585.1 
                   
                 AUGCUUCAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5390 
                 AAGCAUAAAUGUUU 
                 1112-1132 
                 A- 
                 5406 
                 UUUUCGAAAACAU 
                 1110-1132 
               
               
                 1251364.1 
                 1812604.1 
                   
                 UCGAAAA 
                   
                 2337586.1 
                   
                 UUAUGCUUCG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5391 
                 AGCAUAAAUGUUUU 
                 1113-1133 
                 A- 
                 5407 
                 UAUUTCGAAAACAU 
                 1111-1133 
               
               
                 1251373.1 
                 2337591.1 
                   
                 CGAAAUA 
                   
                 2337599.1 
                   
                 UUAUGCUCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5392 
                 AUGAUCUUCUUUGU 
                 1433-1453 
                 A- 
                 5408 
                 UACUACGACAAAGA 
                 1431-1453 
               
               
                 1251385.1 
                 1523845.1 
                   
                 CGUAGUA 
                   
                 2337618.1 
                   
                 AGAUCAUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5393 
                 UCUUCUUUGUCGUA 
                 1437-1455 
                 A- 
                 5409 
                 UUCACUACGACAAA 
                 1435-1455 
               
               
                 1251391.1 
                 2337625.1 
                   
                 GUGAA 
                   
                 2337626.1 
                   
                 GAAGAUC 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15A 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A siRNA Modified Single Strands and Duplex Sequences 
               
               
                 Column 1 indicates duplex name and the number following the decimal point in a duplex name merely refers to a batch production number. 
               
               
                 Column 2 indicates the name of the sense sequence. Column 3 indicates the sequence ID for the sequence of column 4. Column 4 provides the 
               
               
                 modified sequence of a sense strand suitable for use in a duplex described herein. Column 5 indicates the antisense sequence name. Column 6 
               
               
                 indicates the sequence ID for the sequence of column 7. Column 7 provides the sequence of a modified antisense strand suitable for use in a 
               
               
                 duplex described herein, e.g., a duplex comprising the sense sequence in the same row of the table. Column 8 indicates the position in the target 
               
               
                 mRNA (NM_001365536.1) that is complementary to the antisense strand of Column 7. Column 9 indicated the sequence ID for the sequence of 
               
               
                 column 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 Seq ID 
                   
                   
                   
               
               
                   
                 Sense 
                 Seq ID 
                   
                 Antisense 
                 NO: 
                   
                 mRNA target 
                 SEQ ID NO: 
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 sequence 
                 (anti 
                 Antisense sequence 
                 sequence in 
                 (mRNA 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 name 
                 sense) 
                 (5′-3′) 
                 NM_001365536.1 
                 target) 
               
               
                   
               
               
                 AD- 
                 A- 
                 5410 
                 csasagugUfuCfCfUf 
                 A- 
                 5426 
                 VPuCfaudGa(C2p)agu 
                 UUCAAGUGUUCCUAC 
                 5442 
               
               
                 1251492.2 
                 2337764.1 
                   
                 acug(Uhd)caugaL96 
                 2337773.1 
                   
                 aggAfaCfacuugscsc 
                 UGUCAUGA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5411 
                 csasaca(Chd)aadTu 
                 A- 
                 5427 
                 VPusdGscudAadGaag 
                 AACAACACAAUUUCU 
                 5443 
               
               
                 961334.2 
                 1812904.1 
                   
                 dTcuucuuagcaL96 
                 1812905.1 
                   
                 adAadTudGuguugsus 
                 UCUUAGCA 
                   
               
               
                   
                   
                   
                   
                   
                   
                 U 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5412 
                 csasaca(Chd)aaUfUf 
                 A- 
                 5428 
                 VPudGcudAadGaagad 
                 AACAACACAAUUUCU 
                 5444 
               
               
                 1251279.2 
                 2337459.1 
                   
                 UfcuucuuagcaL96 
                 2337464.1 
                   
                 AaUfudGuguugsusu 
                 UCUUAGCA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5413 
                 usgsucgaguAfCfAfc 
                 A- 
                 5429 
                 VPusCfsagdTadAaagu 
                 AAUGUCGAGUACACU 
                 5445 
               
               
                 1251284.2 
                 2337423.1 
                   
                 uuu(Uhd)acugaL96 
                 2337467.1 
                   
                 dGuAfcdTcgacasusu 
                 UUUACUGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5414 
                 ususcug(Uhd)guAfg 
                 A- 
                 5430 
                 VPusdGsugdAa(U2p) 
                 GCUUCUGUGUAGGAG 
                 5446 
               
               
                 1251334.2 
                 2337536.1 
                   
                 dGagaauucacaL96 
                 2337538.1 
                   
                 ucucdCuAfcAfcagaas 
                 AAUUCACU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 gsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5415 
                 asusaaa(Uhd)guUfU 
                 A- 
                 5431 
                 VPusUfsgadAudTucga 
                 GCAUAAAUGUUUUCG 
                 5447 
               
               
                 1251377.2 
                 2337604.1 
                   
                 fUfcgaaauucaaL96 
                 2337606.1 
                   
                 aaAfcAfuuuausgsu 
                 AAAUUCAC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5416 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 5432 
                 VPuUfcadCu(A2p)cga 
                 AUGAUCUUCUUUGUC 
                 5448 
               
               
                 1251398.2 
                 2337622.1 
                   
                 udGucguagugaaL96 
                 2337630.1 
                   
                 cdAaAfgAfagaucsgsu 
                 GUAGUGAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5417 
                 gsasucu(Uhd)CfuUf 
                 A- 
                 5433 
                 VPuUfcadCu(A2p)cga 
                 AUGAUCUUCUUUGUC 
                 5449 
               
               
                 1251399.2 
                 2337628.1 
                   
                 udGUfcguagugaaL96 
                 2337630.1 
                   
                 cdAaAfgAfagaucsgsu 
                 GUAGUGAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5418 
                 csasuga(Uhd)cudTc 
                 A- 
                 5434 
                 VPusdCsuadCgdAcaa 
                 UACAUGAUCUUCUUU 
                 5450 
               
               
                 961188.2 
                 1812612.1 
                   
                 dTuugucguagaL96 
                 1812613.1 
                   
                 adGadAgdAucaugsus 
                 GUCGUAGU 
                   
               
               
                   
                   
                   
                   
                   
                   
                 a 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5419 
                 csasuga(Uhd)cuUfC 
                 A- 
                 5435 
                 VPuCfuadCgdAcaaad 
                 UACAUGAUCUUCUUU 
                 5451 
               
               
                 1251274.3 
                 2337449.1 
                   
                 fUfuugucguagaL96 
                 2337457.1 
                   
                 GadAgdAucaugsusg 
                 GUCGUAGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5420 
                 ususugu(Ahd)GfaUf 
                 A- 
                 5436 
                 VPusGfsuaaUfuGfCfa 
                 CUUUUGUAGAUCUU 
                 5452 
               
               
                 796825.2 
                 1525636.1 
                   
                 CfUfugcaauuacaL96 
                 1257916.1 
                   
                 agaUfcUfacaaasasg 
                 GCAAUUACC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5421 
                 ususuug(Uhd)agAfU 
                 A- 
                 5437 
                 VPusUfsaadTu(G2p)c 
                   
                   
               
               
                 1251411.2 
                 2337650.1 
                   
                 fCfuugcaauuaaL96 
                 2337651.1 
                   
                 aagauCfuAfcaaagscsc 
                   
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5422 
                 gsusaga(Uhd)CfuUf 
                 A- 
                 5438 
                 VPudAugdGudAauug 
                 UUGUAGAUCUUGCAA 
                 5454 
               
               
                 1251419.2 
                 2337662.1 
                   
                 gCfaauuaccauaL96 
                 2337663.1 
                   
                 dCaAfgAfucuacsgsg 
                 UUACCAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5423 
                 usasugu(Ghd)AfaAf 
                 A- 
                 5439 
                 VPusCfsguaAfgGfUfu 
                 AUUAUGUGAAACAAA 
                 5455 
               
               
                 797564.3 
                 1527042.1 
                   
                 CfAfaaccuuacgaL96 
                 1527043.1 
                   
                 uguUfuCfacauasasu 
                 CCUUACGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5424 
                 ususaug(Uhd)gaAfA 
                 A- 
                 5440 
                 VPudGuadAg(G2p)uu 
                 AAUUAUGUGAAACAA 
                 5456 
               
               
                 1251428.2 
                 2337677.1 
                   
                 fCfaaaccuuacaL96 
                 2337678.1 
                   
                 uguuUfcAfcauaasusu 
                 ACCUUACG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5425 
                 usasugugAfaAfCfAf 
                 A- 
                 5441 
                 VPuCfgudAa(G2p)guu 
                 AUUAUGUGAAACAAA 
                 5457 
               
               
                 1251434.2 
                 2337679.1 
                   
                 aacc(Uhd)uacgaL96 
                 2337687.1 
                   
                 uguUfuCfacauasgsu 
                 CCUUACGU 
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15B 
               
             
            
               
                   
               
               
                 Exemplary Human SCN9A Unmodified Single Strands and Duplex Sequences. 
               
               
                 Column 1 indicates duplex name; the number following the decimal point in a duplex name merely refers to a batch production number. Column 
               
               
                 2 indicates the sense sequence name. Column 3 indicates the sequence ID for the sequence of column 4. Column 4 provides the unmodified 
               
               
                 sequence of a sense strand suitable for use in a duplex described herein. Column 5 provides the position in the target mRNA (NM_001365536.1) 
               
               
                 of the sense strand of Column 4. Column 6 indicates the antisense sequence name. Column 7 indicates the sequence ID for the sequence of 
               
               
                 column 8. Column 8 provides the sequence of an antisense strand suitable for use in a duplex described herein, without specifying chemical 
               
               
                 modifications. Column 9 indicates the position in the target mRNA (NM_001365536.1) that is complementary to the antisense strand of Column 
               
               
                 8. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 Sense 
                 Seq ID 
                   
                 mRNA target 
                 Antisense 
                   
                   
                 mRNA target 
               
               
                 Duplex 
                 sequence 
                 NO: 
                 Sense sequence 
                 range in 
                 sequence 
                 Seq ID NO: 
                 antisense sequence 
                 range in 
               
               
                 Name 
                 name 
                 (sense) 
                 (5′-3′) 
                 NM_001365536.1 
                 name 
                 (antisense) 
                 (5′-3′) 
                 NM_001365536.1 
               
               
                   
               
               
                 AD- 
                 A- 
                 5458 
                 CAAGUGUUCCUACU 
                 9104-9124 
                 A- 
                 5474 
                 UCAUGACAGUAGGA 
                 9102-9124 
               
               
                 1251492.2 
                 2337764.1 
                   
                 GUCAUGA 
                   
                 2337773.1 
                   
                 ACACUUGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5459 
                 CAACACAATUTCUUC 
                 8498-8518 
                 A- 
                 5475 
                 UGCUAAGAAGAAAT 
                 8496-8518 
               
               
                 961334.2 
                 1812904.1 
                   
                 UUAGCA 
                   
                 1812905.1 
                   
                 UGUGUUGUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5460 
                 CAACACAAUUUCUUC 
                 8498-8518 
                 A- 
                 5476 
                 UGCUAAGAAGAAAU 
                 8496-8518 
               
               
                 1251279.2 
                 2337459.1 
                   
                 UUAGCA 
                   
                 2337464.1 
                   
                 UGUGUUGUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5461 
                 UGUCGAGUACACUU 
                  760-780 
                 A- 
                 5477 
                 UCAGTAAAAGUGUA 
                  758-780 
               
               
                 1251284.2 
                 2337423.1 
                   
                 UUACUGA 
                   
                 2337467.1 
                   
                 CTCGACAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5462 
                 UUCUGUGUAGGAGA 
                  824-844 
                 A- 
                 5478 
                 UGUGAAUUCUCCU 
                  822-844 
               
               
                 1251334.2 
                 2337536.1 
                   
                 AUUCACA 
                   
                 2337538.1 
                   
                 ACACAGAAGC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5463 
                 AUAAAUGUUUUCGA 
                 1116-1136 
                 A- 
                 5479 
                 UUGAAUTUCGAAAA 
                 1114-1136 
               
               
                 1251377.2 
                 2337604.1 
                   
                 AAUUCAA 
                   
                 2337606.1 
                   
                 CAUUUAUGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5464 
                 GAUCUUCUUUGUCG 
                 1435-1455 
                 A- 
                 5480 
                 UUCACUACGACAAA 
                 1433-1455 
               
               
                 1251398.2 
                 2337622.1 
                   
                 UAGUGAA 
                   
                 2337630.1 
                   
                 GAAGAUCGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5465 
                 GAUCUUCUUUGUCG 
                 1435-1455 
                 A- 
                 5481 
                 UUCACUACGACAAA 
                 1433-1455 
               
               
                 1251399.2 
                 2337628.1 
                   
                 UAGUGAA 
                   
                 2337630.1 
                   
                 GAAGAUCGU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5466 
                 CAUGAUCUTCTUUGU 
                 1432-1452 
                 A- 
                 5482 
                 UCUACGACAAAGAA 
                 1430-1452 
               
               
                 961188.2 
                 1812612.1 
                   
                 CGUAGA 
                   
                 1812613.1 
                   
                 GAUCAUGUA 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5467 
                 CAUGAUCUUCUUUG 
                 1432-1452 
                 A- 
                 5483 
                 UCUACGACAAAGAA 
                 1430-1452 
               
               
                 1251274.3 
                 2337449.1 
                   
                 UCGUAGA 
                   
                 2337457.1 
                   
                 GAUCAUGUG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5468 
                 UUUGUAGAUCUUGC 
                 2531-2551 
                 A- 
                 5484 
                 UGUAAUUGCAAGA 
                 2529-2551 
               
               
                 796825.2 
                 1525636.1 
                   
                 AAUUACA 
                   
                 1257916.1 
                   
                 UCUACAAAAG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5469 
                 UUUUGUAGAUCUUG 
                 2530-2550 
                 A- 
                 5485 
                 UUAATUGCAAGAUC 
                   
               
               
                 1251411.2 
                 2337650.1 
                   
                 CAAUUAA 
                   
                 2337651.1 
                   
                 UACAAAGCC 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5470 
                 GUAGAUCUUGCAAU 
                 2534-2554 
                 A- 
                 5486 
                 UAUGGUAAUUGCA 
                 2532-2554 
               
               
                 1251419.2 
                 2337662.1 
                   
                 UACCAUA 
                   
                 2337663.1 
                   
                 AGAUCUACGG 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5471 
                 UAUGUGAAACAAACC 
                 3299-3319 
                 A- 
                 5487 
                 UCGUAAGGUUUGU 
                 3297-3319 
               
               
                 797564.3 
                 1527042.1 
                   
                 UUACGA 
                   
                 1527043.1 
                   
                 UUCACAUAAU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5472 
                 UUAUGUGAAACAAA 
                 3298-3318 
                 A- 
                 5488 
                 UGUAAGGUUUGUU 
                 3296-3318 
               
               
                 1251428.2 
                 2337677.1 
                   
                 CCUUACA 
                   
                 2337678.1 
                   
                 UCACAUAAUU 
                   
               
               
                   
               
               
                 AD- 
                 A- 
                 5473 
                 UAUGUGAAACAAACC 
                 3299-3319 
                 A- 
                 5489 
                 UCGUAAGGUUUGU 
                 3297-3319 
               
               
                 1251434.2 
                 2337679.1 
                   
                 UUACGA 
                   
                 2337687.1 
                   
                 UUCACAUAGU 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16 
               
             
            
               
                   
               
               
                 SCN9A Lipid-Conjugated Modified Sequences. 
               
               
                 The C16 modifications shown are exemplary modifications. It is understood other lipophilic 
               
               
                 moieties may be used at other locations within the duplex as provided above. 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 SEQ 
                   
                 SEQ 
               
               
                 Duplex 
                   
                 ID 
                   
                 ID 
               
               
                 Name 
                 Modified sense strand sequence 
                 NO: 
                 Modified antisense strand sequence 
                 NO: 
               
               
                   
               
               
                 AD-1479539 
                 gscscca(Ahd)AfaUfAfCfugauaauasgsa 
                 5490 
                 VPusCfsuauUfaUfCfaguaUfuUfugggcsasg 
                 5645 
               
               
                   
               
               
                 AD-1479540 
                 asasggg(Ahd)AfaAfCfAfaucuuccgsusa 
                 5491 
                 VPusAfscggAfaGfAfuuguUfuUfcccuususg 
                 5646 
               
               
                   
               
               
                 AD-1479541 
                 ususugu(Ahd)gadTcdTugcaauuascsa 
                 5492 
                 VPusdGsuadAudTgcaadGadTcdTacaaasasg 
                 5647 
               
               
                   
               
               
                 AD-1479542 
                 asusguc(Ghd)AfgUfAfCfacuuuuacsusa 
                 5493 
                 VPusAfsguaAfaAfGfuguaCfuCfgacaususu 
                 5648 
               
               
                   
               
               
                 AD-1479543 
                 csusaaa(Uhd)UfaUfGfGfaaguaaucsusa 
                 5494 
                 VPusAfsgauUfaCfUfuccaUfaAfuuuagsgsa 
                 5649 
               
               
                   
               
               
                 AD-1479544 
                 usgsaga(Chd)UfgAfCfAfcauuguaasusa 
                 5495 
                 VPusAfsuuaCfaAfUfguguCfaGfucucasasg 
                 5650 
               
               
                   
               
               
                 AD-1479545 
                 asuscuu(Chd)uudTgdTcguagugasusa 
                 5496 
                 VPusdAsucdAcdTacgadCadAadGaagauscsa 
                 5651 
               
               
                   
               
               
                 AD-1479546 
                 usgsguu(Uhd)CfaGfCfAfcagauucasgsa 
                 5497 
                 VPusCfsugaAfuCfUfgugcUfgAfaaccascsa 
                 5652 
               
               
                   
               
               
                 AD-1479547 
                 ascsaug(Ahd)ucdTudCuuugucgusasa 
                 5498 
                 VPusdTsacdGadCaaagdAadGadTcaugusasg 
                 5653 
               
               
                   
               
               
                 AD-1479548 
                 csusucu(Ghd)AfaAfCfAfuccaaacusgsa 
                 5499 
                 VPusCfsaguUfuGfGfauguUfuCfagaagsasa 
                 5654 
               
               
                   
               
               
                 AD-1479549 
                 usasuug(Uhd)GfaCfUfUfuaaguuuasgsa 
                 5500 
                 VPusCfsuaaAfcUfUfaaagUfcAfcaauasasg 
                 5655 
               
               
                   
               
               
                 AD-1479550 
                 csasccu(Uhd)CfuCfCfUfuaaaauucsusa 
                 5501 
                 VPusAfsgaaUfuUfUfaaggAfgAfaggugsasc 
                 5656 
               
               
                   
               
               
                 AD-1479551 
                 ususgug(Ahd)CfuUfUfAfaguuuagusgsa 
                 5502 
                 VPusCfsacuAfaAfCfuuaaAfgUfcacaasusa 
                 5657 
               
               
                   
               
               
                 AD-1479552 
                 gsasucu(Uhd)cudTudGucguagugsasa 
                 5503 
                 VPusdTscadCudAcgacdAadAgdAagaucsasu 
                 5658 
               
               
                   
               
               
                 AD-1479553 
                 ususgcu(Ahd)UfaGfGfAfaauuugguscsa 
                 5504 
                 VPusGfsaccAfaAfUfuuccUfaUfagcaasgsu 
                 5659 
               
               
                   
               
               
                 AD-1479554 
                 csasuga(Uhd)CfuUfCfUfuugucguasgsa 
                 5505 
                 VPusCfsuacGfaCfAfaagaAfgAfucaugsusa 
                 5660 
               
               
                   
               
               
                 AD-1479555 
                 ususgau(Ahd)GfuUfAfCfcuaguuugscsa 
                 5506 
                 VPusGfscaaAfcUfAfgguaAfcUfaucaasasa 
                 5661 
               
               
                   
               
               
                 AD-1479556 
                 ususcug(Uhd)GfuAfGfGfagaauucascsa 
                 5507 
                 VPusGfsugaa(Tgn)ucuccuAfcAfcagaasgsc 
                 5662 
               
               
                   
               
               
                 AD-1479557 
                 usgscua(Uhd)agdGadAauuuggucsusa 
                 5508 
                 VPusdAsgadCcdAaauudTcdCudAuagcasasg 
                 5663 
               
               
                   
               
               
                 AD-1479558 
                 ususcug(Uhd)gudAgdGagaauucascsa 
                 5509 
                 VPusdGsugdAadTucucdCudAcdAcagaasgsc 
                 5664 
               
               
                   
               
               
                 AD-1479559 
                 usgsaua(Ghd)UfuAfCfCfuaguuugcsasa 
                 5510 
                 VPusUfsgcaAfaCfUfagguAfaCfuaucasasa 
                 5665 
               
               
                   
               
               
                 AD-1479560 
                 gsusuug(Ahd)AfcAfCfAfaaucuuucsgsa 
                 5511 
                 VPusCfsgaaAfgAfUfuuguGfuUfcaaacscsu 
                 5666 
               
               
                   
               
               
                 AD-1479561 
                 gsasgau(Ghd)GfaUfUfCfucuucguuscsa 
                 5512 
                 VPusGfsaacGfaAfGfagaaUfcCfaucucscsc 
                 5667 
               
               
                   
               
               
                 AD-1479562 
                 asusgau(Chd)UfuCfUfUfugucguagsusa 
                 5513 
                 VPusAfscuaCfgAfCfaaagAfaGfaucausgsu 
                 5668 
               
               
                   
               
               
                 AD-1479563 
                 asgscuu(Ghd)AfaGfUfAfaaauuagascsa 
                 5514 
                 VPusGfsucuAfaUfUfuuacUfuCfaagcususa 
                 5669 
               
               
                   
               
               
                 AD-1479564 
                 asuscuu(Chd)UfuUfGfUfcguagugasusa 
                 5515 
                 VPusAfsucaCfuAfCfgacaAfaGfaagauscsa 
                 5670 
               
               
                   
               
               
                 AD-1479565 
                 usgsauc(Uhd)ucdTudTgucguagusgsa 
                 5516 
                 VPusdCsacdTadCgacadAadGadAgaucasusg 
                 5671 
               
               
                   
               
               
                 AD-1479566 
                 asuscug(Ahd)gadCudGaauuugccsgsa 
                 5517 
                 VPusdCsggdCadAauucdAgdTcdTcagauscsc 
                 5672 
               
               
                   
               
               
                 AD-1479567 
                 asusgau(Chd)uudCudTugucguagsusa 
                 5518 
                 VPusdAscudAcdGacaadAgdAadGaucausgsu 
                 5673 
               
               
                   
               
               
                 AD-1479568 
                 csasagu(Ghd)UfuCfCfUfacugucausgsa 
                 5519 
                 VPusCfsaugAfcAfGfuaggAfaCfacuugsasa 
                 5674 
               
               
                   
               
               
                 AD-1479569 
                 asusgug(Ahd)AfaCfAfAfaccuuacgsusa 
                 5520 
                 VPusAfscguAfaGfGfuuugUfuUfcacausasa 
                 5675 
               
               
                   
               
               
                 AD-1479570 
                 usgsucg(Ahd)gudAcdAcuuuuacusgsa 
                 5521 
                 VPusdCsagdTadAaagudGudAcdTcgacasusu 
                 5676 
               
               
                   
               
               
                 AD-1479571 
                 usgsuag(Ghd)AfgAfAfUfucacuuuuscsa 
                 5522 
                 VPusGfsaaaAfgUfGfaauuCfuCfcuacascsa 
                 5677 
               
               
                   
               
               
                 AD-1479572 
                 gsgscgu(Uhd)GfuAfGfUfuccuaucuscsa 
                 5523 
                 VPusGfsagaUfaGfGfaacuAfcAfacgccsusu 
                 5678 
               
               
                   
               
               
                 AD-1479573 
                 usasuug(Uhd)gadCudTuaaguuuasgsa 
                 5524 
                 VPusdCsuadAadCuuaadAgdTcdAcaauasasg 
                 5679 
               
               
                   
               
               
                 AD-1479574 
                 ususgug(Ahd)cudTudAaguuuagusgsa 
                 5525 
                 VPusdCsacdTadAacuudAadAgdTcacaasusa 
                 5680 
               
               
                   
               
               
                 AD-1209344 
                 csasaca(Chd)aadTudTcuucuuagscsa 
                 5526 
                 VPusdGscudAadGaagadAadTudGuguugsusu 
                 5681 
               
               
                   
               
               
                 AD-1479575 
                 asasggg(Ahd)aadAcdAaucuuccgsusa 
                 5527 
                 VPusdAscgdGadAgauudGudTudTcccuususg 
                 5682 
               
               
                   
               
               
                 AD-1331347 
                 usgsucg(Ahd)GfuAfCfAfcuuuuacusgsa 
                 5528 
                 VPusCfsaguAfaAfAfguguAfcUfcgacasusu 
                 5683 
               
               
                   
               
               
                 AD-1479576 
                 gsasucu(Uhd)CfuUfUfGfucguagugsasa 
                 5529 
                 VPusUfscacUfaCfGfacaaAfgAfagaucsasu 
                 5684 
               
               
                   
               
               
                 AD-1443073 
                 asgscau(Ahd)AfaUfGfUfuuucgaaasusa 
                 5530 
                 VPusAfsuuuCfgAfAfaacaUfuUfaugcususc 
                 5685 
               
               
                   
               
               
                 AD-1479577 
                 usasugu(Ghd)AfaAfCfAfaaccuuacsgsa 
                 5531 
                 VPusCfsguaAfgGfUfuuguUfuCfacauasasu 
                 5686 
               
               
                   
               
               
                 AD-1479578 
                 usgsuag(Ghd)agdAadTucacuuuuscsa 
                 5532 
                 VPusdGsaadAadGugaadTudCudCcuacascsa 
                 5687 
               
               
                   
               
               
                 AD-1479579 
                 csasuga(Uhd)cudTcdTuugucguasgsa 
                 5533 
                 VPusdCsuadCgdAcaaadGadAgdAucaugsusa 
                 5688 
               
               
                   
               
               
                 AD-1183928 
                 ususcug(Uhd)GfuAfGfGfagaauucascsa 
                 5534 
                 VPusGfsugaAfuUfCfuccuAfcAfcagaasgsc 
                 5689 
               
               
                   
               
               
                 AD-1183930 
                 ususugu(Ahd)GfaUfCfUfugcaauuascsa 
                 5535 
                 VPusGfsuaaUfuGfCfaagaUfcUfacaaasasg 
                 5690 
               
               
                   
               
               
                 AD-1331355 
                 usgsucgaguAfCfAfcuuu(Uhd)acusgsa 
                 5536 
                 VPusCfsagdTadAaaguguAfcUfcgacasusu 
                 5691 
               
               
                   
               
               
                 AD-1479580 
                 uscsgaguAfCfAfcuuu(Uhd)acusgsa 
                 5537 
                 VPusCfsagdTadAaaguguAfcUfcgascsg 
                 5692 
               
               
                   
               
               
                 AD-1331354 
                 csasuga(Uhd)cuUfCfUfuugucguasgsa 
                 5538 
                 VPuCfuadCgdAcaaadGadAgdAucaugsusg 
                 5693 
               
               
                   
               
               
                 AD-1479581 
                 gsasaaa(Chd)aaUfCfUfuccauuucsasa 
                 5539 
                 VPuUfgadAadTggaagaUfudGuuuucscsc 
                 5694 
               
               
                   
               
               
                 AD-1331351 
                 gsasaaa(Chd)aaUfCfUfuccguuucsasa 
                 5540 
                 VPuUfgadAa(C2p)ggaagaUfudGuuuucscsc 
                 5695 
               
               
                   
               
               
                 AD-1479582 
                 asasaacaAfuCfUfUfccgu(Uhd)ucasasa 
                 5541 
                 VPusUfsugdAadAcggaagAfuUfguuuuscsc 
                 5696 
               
               
                   
               
               
                 AD-1331350 
                 asasaacaauCfUfUfccgu(Uhd)ucasasa 
                 5542 
                 VPuUfugdAadAcggadAgdAuUfguuuuscsc 
                 5697 
               
               
                   
               
               
                 AD-1479583 
                 gsgscuu(Chd)UfgUfgUfaggagaaususa 
                 5543 
                 VPudAaudTc(Tgn)ccuadCaCfadGaagccsusc 
                 5698 
               
               
                   
               
               
                 AD-1479584 
                 ususcug(Uhd)guAfgdGagaauucascsa 
                 5544 
                 VPusdGsugdAa(U2p)ucucdCuAfcAfcagaasg 
                 5699 
               
               
                   
                   
                   
                 sc 
                   
               
               
                   
               
               
                 AD-1479585 
                 gsusguaggadGadAuuca(Chd)uuususa 
                 5545 
                 VPudAaadAgdTgaaudTcUfcCfuacacsgsg 
                 5700 
               
               
                   
               
               
                 AD-1479586 
                 usgsuaggagdAaUfucau(Uhd)uuuscsa 
                 5546 
                 VPusdGsaadAadAugaadTuCfuCfcuacascsg 
                 5701 
               
               
                   
               
               
                 AD-1479587 
                 gsgsagaaUfuCfAfCfuuuu(Chd)uucsgsa 
                 5547 
                 VPusCfsgadAgdAaaagugAfaUfucuccsusg 
                 5702 
               
               
                   
               
               
                 AD-1479588 
                 gsgsagaaUfuCfaCfuuuu(Chd)uucsgsa 
                 5548 
                 VPuCfgadAgdAaaagdTgdAaUfucuccsusg 
                 5703 
               
               
                   
               
               
                 AD-1479589 
                 csusgaagCfaUfAfAfaugu(Uhd)uucsgsa 
                 5549 
                 VPusCfsgadAadAcauuuaUfgCfuucagsgsu 
                 5704 
               
               
                   
               
               
                 AD-1479590 
                 usgsaag(Chd)audAadAuguuuucgsasa 
                 5550 
                 VPuUfcgdAadAacaudTuAfudGcuucasgsg 
                 5705 
               
               
                   
               
               
                 AD-1479591 
                 gsasagcaUfaAfAfUfguuu(Uhd)cgasasa 
                 5551 
                 VPusUfsucdGadAaacauuUfaUfgcuucsasg 
                 5706 
               
               
                   
               
               
                 AD-1331349 
                 gsasagcauadAaUfguuu(Uhd)cgasasa 
                 5552 
                 VPuUfucdGadAaacadTuUfaUfgcuucsasg 
                 5707 
               
               
                   
               
               
                 AD-1479592 
                 asasgca(Uhd)aadAudGuuuucgaasasa 
                 5553 
                 VPuUfuudCgdAaaacdAuUfudAugcuuscsg 
                 5708 
               
               
                   
               
               
                 AD-1479593 
                 asgsca(Uhd)aaaUfgUfuuucgaaasusa 
                 5554 
                 VPudAuudTcdGaaaadCaUfuUfaugcususc 
                 5709 
               
               
                   
               
               
                 AD-1479594 
                 asgscauaAfaUfGfUfuuu(Chd)gaaasusa 
                 5555 
                 VPusAfsuuuCfgAfAfaacaUfuUfaugcususc 
                 5710 
               
               
                   
               
               
                 AD-1479595 
                 asgscauaAfaUfGfUfuuu(Chd)gaaasusa 
                 5556 
                 VPusAfsuudTc(G2p)aaaacaUfuUfaugcususc 
                 5711 
               
               
                   
               
               
                 AD-1479596 
                 asgscauaaaUfgUfuuu(Uhd)gaaasusa 
                 5557 
                 VPusAfsuudTcdAaaaadCaUfuUfaugcususc 
                 5712 
               
               
                   
               
               
                 AD-1479597 
                 asgscauaaaUfgUfuuu(Chd)gaaasusa 
                 5558 
                 VPusdAsuudTc(G2p)aaaadCaUfuUfaugcusc 
                 5713 
               
               
                   
                   
                   
                 sc 
                   
               
               
                   
               
               
                 AD-1479598 
                 csasuaaaUfgUfuuu(Chd)gaaasusa 
                 5559 
                 VPusdAsuudTc(G2p)aaaadCaUfuUfaugscsu 
                 5714 
               
               
                   
               
               
                 AD-1479599 
                 asgscauaaaUfgUfuuu(Chd)gaaasusa 
                 5560 
                 VPudAuudTc(G2p)aaaadCaUfuUfaugcususc 
                 5715 
               
               
                   
               
               
                 AD-1479600 
                 gscsa(Uhd)aaaugUfUfuucgaaaususa 
                 5561 
                 VPusdAsaudTu(C2p)gaaaacAfuUfuaugcsusu 
                 5716 
               
               
                   
               
               
                 AD-1479601 
                 asusaaa(Uhd)guUfUfUfcgaaauucsasa 
                 5562 
                 VPusUfsgadAudTucgaaaAfcAfuuuausgsc 
                 5717 
               
               
                   
               
               
                 AD-1479602 
                 asusaaa(Uhd)guUfUfUfcgaaauucsasa 
                 5563 
                 VPusUfsgadAudTucgaaaAfcAfuuuausgsu 
                 5718 
               
               
                   
               
               
                 AD-1479603 
                 usasaaugUfuUfuCfgaaa(Uhd)ucascsa 
                 5564 
                 VPudGugdAadTuucgdAadAaCfauuuasusg 
                 5719 
               
               
                   
               
               
                 AD-1479604 
                 usasca(Uhd)gAfuCfUfUfcuuugucgsusa 
                 5565 
                 VPusAfscgdAcdAaagaagAfuCfauguasgsg 
                 5720 
               
               
                   
               
               
                 AD-1479605 
                 csasuga(Uhd)CfuUfCfUfuugucguasgsa 
                 5566 
                 VPusCfsuadCgdAcaaagaAfgAfucaugsusg 
                 5721 
               
               
                   
               
               
                 AD-1479606 
                 csasuga(Uhd)CfuUfCfUfuugucguasgsa 
                 5567 
                 VPuCfuadCgdAcaaadGadAgdAucaugsusg 
                 5722 
               
               
                   
               
               
                 AD-1331348 
                 asusgau(Chd)UfuCfUfUfugucguagsusa 
                 5568 
                 VPudAcudAcdGacaadAgdAadGaucausgsu 
                 5723 
               
               
                   
               
               
                 AD-1479607 
                 usgsauc(Uhd)UfcUfUfUfgucguagusgsa 
                 5569 
                 VPudCacdTadCgacadAadGadAgaucasusg 
                 5724 
               
               
                   
               
               
                 AD-1479608 
                 uscsu(Uhd)CfuUfudGucguagugsasa 
                 5570 
                 VPusUfscadCu(Agn)cgacdAaAfgAfagasusc 
                 5725 
               
               
                   
               
               
                 AD-1479609 
                 uscsu(Uhd)CfuUfudGucguagugsasa 
                 5571 
                 VPusUfscadCu(A2p)cgacdAaAfgAfagasusc 
                 5726 
               
               
                   
               
               
                 AD-1443072 
                 gsasucu(Uhd)CfuUfudGucguagugsasa 
                 5572 
                 VPuUfcadCu(A2p)cgacdAaAfgAfagaucsgsu 
                 5727 
               
               
                   
               
               
                 AD-1479610 
                 gsasucu(Uhd)CfuUfudGUfcguagugsasa 
                 5573 
                 VPuUfcadCu(A2p)cgacdAaAfgAfagaucsgsu 
                 5728 
               
               
                   
               
               
                 AD-1479611 
                 gsasucu(Uhd)CfuUfUfgUfCfguagugsasa 
                 5574 
                 VPuUfcadCu(A2p)cgacaaAfgAfagaucsgsu 
                 5729 
               
               
                   
               
               
                 AD-1479612 
                 uscsuuugUfcgUfAfguga(Uhd)uuuscsa 
                 5575 
                 VPudGaadAadTcacudAcdGaCfaaagasgsg 
                 5730 
               
               
                   
               
               
                 AD-1479613 
                 asusccu(Uhd)UfugUfAfgaucuugcsasa 
                 5576 
                 VPusUfsgcdAa(G2p)aucuacAfaAfaggauscsc 
                 5731 
               
               
                   
               
               
                 AD-1479614 
                 cscsuuu(Uhd)gudAgdAucuugcaasusa 
                 5577 
                 VPudAuudGc(A2p)agaudCuAfcAfaaaggsgsu 
                 5732 
               
               
                   
               
               
                 AD-1479615 
                 csusuuugUfagAfUfcuug(Chd)aaususa 
                 5578 
                 VPusAfsaudTg(C2p)aagaucUfaCfaaaagsgsg 
                 5733 
               
               
                   
               
               
                 AD-1479616 
                 ususuug(Uhd)AfgAfUfCfuugcaauusasa 
                 5579 
                 VPusUfsaadTu(G2p)caagauCfuAfcaaaasgsg 
                 5734 
               
               
                   
               
               
                 AD-1479617 
                 ususuug(Uhd)agAfUfCfuugcaauusasa 
                 5580 
                 VPusUfsaadTu(G2p)caagauCfuAfcaaagscsc 
                 5735 
               
               
                   
               
               
                 AD-1479618 
                 ususug(Uhd)agaUfCfUfugcaauuascsa 
                 5581 
                 VPusGfsuaaUfuGfCfaagaUfcUfacaaasgsg 
                 5736 
               
               
                   
               
               
                 AD-1479619 
                 ususug(Uhd)agaUfCfUfugcaauuascsa 
                 5582 
                 VPusdGsuadAu(Tgn)gcaagaUfcUfacaaasgsg 
                 5737 
               
               
                   
               
               
                 AD-1479620 
                 ususug(Uhd)agaUfCfUfugcaauuascsa 
                 5583 
                 VPudGuadAu(Tgn)gcaagaUfcUfacaaasgsg 
                 5738 
               
               
                   
               
               
                 AD-1479621 
                 ususguagauCfUfUfgcaa(Uhd)uacscsa 
                 5584 
                 VPusdGsgudAa(U2p)ugcaagAfuCfuacaasgsg 
                 5739 
               
               
                   
               
               
                 AD-1479622 
                 gsusaga(Uhd)CfuUfgCfaauuaccasusa 
                 5585 
                 VPudAugdGudAauugdCaAfgAfucuacsgsg 
                 5740 
               
               
                   
               
               
                 AD-1479623 
                 asasuua(Uhd)gudGadAacaaaccususa 
                 5586 
                 VPudAagdGu(U2p)uguudTcAfcAfuaauususg 
                 5741 
               
               
                   
               
               
                 AD-1479624 
                 asusuaugugdAadAcaaa(Chd)cuusasa 
                 5587 
                 VPuUfaadGg(Tgn)uugudTuCfaCfauaaususu 
                 5742 
               
               
                   
               
               
                 AD-1479625 
                 ususaug(Uhd)gaAfAfCfaaaccuuascsa 
                 5588 
                 VPudGuadAg(G2p)uuuguuUfcAfcauaasusu 
                 5743 
               
               
                   
               
               
                 AD-1331354 
                 csasuga(Uhd)cuUfCfUfuugucguasgsa 
                 5589 
                 VPuCfuadCgdAcaaadGadAgdAucaugsusg 
                 5744 
               
               
                   
               
               
                 AD-1479581 
                 gsasaaa(Chd)aaUfCfUfuccauuucsasa 
                 5590 
                 VPuUfgadAadTggaagaUfudGuuuucscsc 
                 5745 
               
               
                   
               
               
                 AD-1331351 
                 gsasaaa(Chd)aaUfCfUfuccguuucsasa 
                 5591 
                 VPuUfgadAa(C2p)ggaagaUfudGuuuucscsc 
                 5746 
               
               
                   
               
               
                 AD-1331350 
                 asasaacaauCfUfUfccgu(Uhd)ucasasa 
                 5592 
                 VPuUfugdAadAcggadAgdAuUfguuuuscsc 
                 5747 
               
               
                   
               
               
                 AD-1479583 
                 gsgscuu(Chd)UfgUfgUfaggagaaususa 
                 5593 
                 VPudAaudTc(Tgn)ccuadCaCfadGaagccsusc 
                 5748 
               
               
                   
               
               
                 AD-1479585 
                 gsusguaggadGadAuuca(Chd)uuususa 
                 5594 
                 VPudAaadAgdTgaaudTcUfcCfuacacsgsg 
                 5749 
               
               
                   
               
               
                 AD-1479588 
                 gsgsagaaUfuCfaCfuuuu(Chd)uucsgsa 
                 5595 
                 VPuCfgadAgdAaaagdTgdAaUfucuccsusg 
                 5750 
               
               
                   
               
               
                 AD-1479590 
                 usgsaag(Chd)audAadAuguuuucgsasa 
                 5596 
                 VPuUfcgdAadAacaudTuAfudGcuucasgsg 
                 5751 
               
               
                   
               
               
                 AD-1331349 
                 gsasagcauadAaUfguuu(Uhd)cgasasa 
                 5597 
                 VPuUfucdGadAaacadTuUfaUfgcuucsasg 
                 5752 
               
               
                   
               
               
                 AD-1479592 
                 asasgca(Uhd)aadAudGuuuucgaasasa 
                 5598 
                 VPuUfuudCgdAaaacdAuUfudAugcuuscsg 
                 5753 
               
               
                   
               
               
                 AD-1479593 
                 asgsca(Uhd)aaaUfgUfuuucgaaasusa 
                 5599 
                 VPudAuudTcdGaaaadCaUfuUfaugcususc 
                 5754 
               
               
                   
               
               
                 AD-1479599 
                 asgscauaaaUfgUfuuu(Chd)gaaasusa 
                 5600 
                 VPudAuudTc(G2p)aaaadCaUfuUfaugcususc 
                 5755 
               
               
                   
               
               
                 AD-1479603 
                 usasaaugUfuUfuCfgaaa(Uhd)ucascsa 
                 5601 
                 VPudGugdAadTuucgdAadAaCfauuuasusg 
                 5756 
               
               
                   
               
               
                 AD-1479606 
                 csasuga(Uhd)CfuUfCfUfuugucguasgsa 
                 5602 
                 VPuCfuadCgdAcaaadGadAgdAucaugsusg 
                 5757 
               
               
                   
               
               
                 AD-1331348 
                 asusgau(Chd)UfuCfUfUfugucguagsusa 
                 5603 
                 VPudAcudAcdGacaadAgdAadGaucausgsu 
                 5758 
               
               
                   
               
               
                 AD-1479607 
                 usgsauc(Uhd)UfcUfUfUfgucguagusgsa 
                 5604 
                 VPudCacdTadCgacadAadGadAgaucasusg 
                 5759 
               
               
                   
               
               
                 AD-1443072 
                 gsasucu(Uhd)CfuUfudGucguagugsasa 
                 5605 
                 VPuUfcadCu(A2p)cgacdAaAfgAfagaucsgsu 
                 5760 
               
               
                   
               
               
                 AD-1479610 
                 gsasucu(Uhd)CfuUfudGUfcguagugsasa 
                 5606 
                 VPuUfcadCu(A2p)cgacdAaAfgAfagaucsgsu 
                 5761 
               
               
                   
               
               
                 AD-1479611 
                 gsasucu(Uhd)CfuUfUfgUfCfguagugsasa 
                 5607 
                 VPuUfcadCu(A2p)cgacaaAfgAfagaucsgsu 
                 5762 
               
               
                   
               
               
                 AD-1479612 
                 uscsuuugUfcgUfAfguga(Uhd)uuuscsa 
                 5608 
                 VPudGaadAadTcacudAcdGaCfaaagasgsg 
                 5763 
               
               
                   
               
               
                 AD-1479614 
                 cscsuuu(Uhd)gudAgdAucuugcaasusa 
                 5609 
                 VPudAuudGc(A2p)agaudCuAfcAfaaaggsgsu 
                 5764 
               
               
                   
               
               
                 AD-1479620 
                 ususug(Uhd)agaUfCfUfugcaauuascsa 
                 5610 
                 VPudGuadAu(Tgn)gcaagaUfcUfacaaasgsg 
                 5765 
               
               
                   
               
               
                 AD-1479622 
                 gsusaga(Uhd)CfuUfgCfaauuaccasusa 
                 5611 
                 VPudAugdGudAauugdCaAfgAfucuacsgsg 
                 5766 
               
               
                   
               
               
                 AD-1479623 
                 asasuua(Uhd)gudGadAacaaaccususa 
                 5612 
                 VPudAagdGu(U2p)uguudTcAfcAfuaauususg 
                 5767 
               
               
                   
               
               
                 AD-1479624 
                 asusuaugugdAadAcaaa(Chd)cuusasa 
                 5613 
                 VPuUfaadGg(Tgn)uugudTuCfaCfauaaususu 
                 5768 
               
               
                   
               
               
                 AD-1479625 
                 ususaug(Uhd)gaAfAfCfaaaccuuascsa 
                 5614 
                 VPudGuadAg(G2p)uuuguuUfcAfcauaasusu 
                 5769 
               
               
                   
               
               
                 AD-1481938 
                 gsusaga(Uhd)CfuUfgCfaauuaccasusa 
                 5615 
                 VPusdAsugdGudAauugdCaAfgAfucuacsgsg 
                 5770 
               
               
                   
               
               
                 AD-1481939 
                 asasuua(Uhd)gudGadAacaaaccususa 
                 5616 
                 VPusdAsagdGu(U2p)uguudTcAfcAfuaauusu 
                 5771 
               
               
                   
                   
                   
                 sg 
                   
               
               
                   
               
               
                 AD-1481940 
                 asusuaugugdAadAcaaa(Chd)cuusasa 
                 5617 
                 VPusUfsaadGg(Tgn)uugudTuCfaCfauaausu 
                 5772 
               
               
                   
                   
                   
                 su 
                   
               
               
                   
               
               
                 AD-1481941 
                 ususaug(Uhd)gaAfAfCfaaaccuuascsa 
                 5618 
                 VPusdGsuadAg(G2p)uuuguuUfcAfcauaasusu 
                 5773 
               
               
                   
               
               
                 AD-1481942 
                 csasuga(Uhd)cuUfCfUfuugucguasgsa 
                 5619 
                 VPusCfsuadCgdAcaaadGadAgdAucaugsusg 
                 5774 
               
               
                   
               
               
                 AD-1481943 
                 gsasaaa(Chd)aaUfCfUfuccauuucsasa 
                 5620 
                 VPusUfsgadAadTggaagaUfudGuuuucscsc 
                 5775 
               
               
                   
               
               
                 AD-1481944 
                 gsasaaa(Chd)aaUfCfUfuccguuucsasa 
                 5621 
                 VPusUfsgadAa(C2p)ggaagaUfudGuuuucscsc 
                 5776 
               
               
                   
               
               
                 AD-1481945 
                 asasaacaauCfUfUfccgu(Uhd)ucasasa 
                 5622 
                 VPusUfsugdAadAcggadAgdAuUfguuuuscsc 
                 5777 
               
               
                   
               
               
                 AD-1481946 
                 gsgscuu(Chd)UfgUfgUfaggagaaususa 
                 5623 
                 VPusdAsaudTc(Tgn)ccuadCaCfadGaagccsu 
                 5778 
               
               
                   
                   
                   
                 sc 
                   
               
               
                   
               
               
                 AD-1481947 
                 gsusguaggadGadAuuca(Chd)uuususa 
                 5624 
                 VPusdAsaadAgdTgaaudTcUfcCfuacacsgsg 
                 5779 
               
               
                   
               
               
                 AD-1481948 
                 gsgsagaaUfuCfaCfuuuu(Chd)uucsgsa 
                 5625 
                 VPusCfsgadAgdAaaagdTgdAaUfucuccsusg 
                 5780 
               
               
                   
               
               
                 AD-1481949 
                 usgsaag(Chd)audAadAuguuuucgsasa 
                 5626 
                 VPuslIfscgdAadAacaudTuAfudGcuucasgsg 
                 5781 
               
               
                   
               
               
                 AD-1481950 
                 gsasagcauadAaUfguuu(Uhd)cgasasa 
                 5627 
                 VPusUfsucdGadAaacadTuUfaUfgcuucsasg 
                 5782 
               
               
                   
               
               
                 AD-1481951 
                 asasgca(Uhd)aadAudGuuuucgaasasa 
                 5628 
                 VPusUfsuudCgdAaaacdAuUfudAugcuuscsg 
                 5783 
               
               
                   
               
               
                 AD-1481952 
                 asgsca(Uhd)aaaUfgUfuuucgaaasusa 
                 5629 
                 VPusdAsuudTcdGaaaadCaUfuUfaugcususc 
                 5784 
               
               
                   
               
               
                 AD-1481953 
                 asgscauaaaUfgUfuuu(Chd)gaaasusa 
                 5630 
                 VPusdAsuudTc(G2p)aaaadCaUfuUfaugcusu 
                 5785 
               
               
                   
                   
                   
                 sc 
                   
               
               
                   
               
               
                 AD-1481954 
                 usasaaugUfuUfuCfgaaa(Uhd)ucascsa 
                 5631 
                 VPusdGsugdAadTuucgdAadAaCfauuuasusg 
                 5786 
               
               
                   
               
               
                 AD-1481955 
                 csasuga(Uhd)CfuUfCfUfuugucguasgsa 
                 5632 
                 VPusCfsuadCgdAcaaadGadAgdAucaugsusg 
                 5787 
               
               
                   
               
               
                 AD-1481956 
                 asusgau(Chd)UfuCfUfUfugucguagsusa 
                 5633 
                 VPusdAscudAcdGacaadAgdAadGaucausgsu 
                 5788 
               
               
                   
               
               
                 AD-1481957 
                 usgsauc(Uhd)UfcUfUfUfgucguagusgsa 
                 5634 
                 VPusdCsacdTadCgacadAadGadAgaucasusg 
                 5789 
               
               
                   
               
               
                 AD-1481958 
                 gsasucu(Uhd)CfuUfudGucguagugsasa 
                 5635 
                 VPusUfscadCu(A2p)cgacdAaAfgAfagaucsg 
                 5790 
               
               
                   
                   
                   
                 su 
                   
               
               
                   
               
               
                 AD-1481959 
                 gsasucu(Uhd)CfuUfudGUfcguagugsasa 
                 5636 
                 VPusUfscadCu(A2p)cgacdAaAfgAfagaucsg 
                 5791 
               
               
                   
                   
                   
                 su 
                   
               
               
                   
               
               
                 AD-1481960 
                 gsasucu(Uhd)CfuUfUfgUfCfguagugsasa 
                 5637 
                 VPusUfscadCu(A2p)cgacaaAfgAfagaucsgsu 
                 5792 
               
               
                   
               
               
                 AD-1481961 
                 uscsuuugUfcgUfAfguga(Uhd)uuuscsa 
                 5638 
                 VPusdGsaadAadTcacudAcdGaCfaaagasgsg 
                 5793 
               
               
                   
               
               
                 AD-1481962 
                 cscsuuu(Uhd)gudAgdAucuugcaasusa 
                 5639 
                 VPusdAsuudGc(A2p)agaudCuAfcAfaaaggsg 
                 5794 
               
               
                   
                   
                   
                 su 
                   
               
               
                   
               
               
                 AD-1479619 
                 ususug(Uhd)agaUfCfUfugcaauuascsa 
                 5640 
                 VPusdGsuadAu(Tgn)gcaagaUfcUfacaaasgsg 
                 5795 
               
               
                   
               
               
                 AD-1481938 
                 gsusaga(Uhd)CfuUfgCfaauuaccasusa 
                 5641 
                 VPusdAsugdGudAauugdCaAfgAfucuacsgsg 
                 5796 
               
               
                   
               
               
                 AD-1481939 
                 asasuua(Uhd)gudGadAacaaaccususa 
                 5642 
                 VPusdAsagdGu(U2p)uguudTcAfcAfuaauusu 
                 5797 
               
               
                   
                   
                   
                 sg 
                   
               
               
                   
               
               
                 AD-1481940 
                 asusuaugugdAadAcaaa(Chd)cuusasa 
                 5643 
                 VPusUfsaadGg(Tgn)uugudTuCfaCfauaausu 
                 5798 
               
               
                   
                   
                   
                 su 
                   
               
               
                   
               
               
                 AD-1481941 
                 ususaug(Uhd)gaAfAfCfaaaccuuascsa 
                 5644 
                 VPusdGsuadAg(G2p)uuuguuUfcAfcauaasusu 
                 5799 
               
               
                   
               
               
                 AD-1331352 
                 usgsucgaguAfCfAfcuuu(Uhd)acusgsa 
                 5800 
                 VPusCfsagdTadAaagudGuAfcdTcgacasusu 
                 5801 
               
               
                   
               
            
           
         
       
     
     Example 2. In Vitro Screening of SCN9A siRNA 
     Experimental Methods 
     Dual-Glo® Luciferase Assay 
     Hepa1-6 cells (ATCC) were grown to near confluence at 37° C. in an atmosphere of 5% CO 2  in DMEM (ATCC) supplemented with 10% FBS, before being released from the plate by trypsinization. A single-dose experiment was performed at 10 nM final duplex concentration. Three different siRNA and psiCHECK2-SCN9A plasmid transfections were carried out with each plasmid containing the 3′ untranslated region (UTR). The three plasmids were referred to as SCN9A-1, SCN9A-2, and SCN9A-3. Transfection was carried out by adding 10 nM of siRNA duplexes and 30-75 ng of one of the three psiCHECK2-SCN9A plasmids per well along with 4.9 μL of Opti-MEM plus 0.5 μL of Lipofectamine 2000 per well (Invitrogen, Carlsbad Calif. cat #13778-150) and then incubated at room temperature for 15 minutes. The mixture was then added to the cells (approximately 15,000 per well), which were re-suspended in 35 μL of fresh complete media. The transfected cells were incubated at 37° C. in an atmosphere of 5% CO 2 . 
     Twenty-four hours after the siRNAs and psiCHECK2-SCN9A plasmid were transfected; Firefly (transfection control) and  Renilla  (fused to SCN9A target sequence) luciferase were measured. First, media was removed from cells. Then Firefly luciferase activity was measured by adding 20 μL of Dual-Glo® Luciferase Reagent (Promega) equal to the culture medium volume to each well and mixing. The mixture was incubated at room temperature for 30 minutes before luminescence (500 nm) was measured on a Spectramax (Molecular Devices) to detect the Firefly luciferase signal.  Renilla  luciferase activity was measured by adding 20 μL of room temperature of Dual-Glo® Stop &amp; Glo® Reagent (Promega) were added to each well and the plates were incubated for 10-15 minutes before luminescence was again measured to determine the  Renilla  luciferase signal. The Dual-Glo® Stop &amp; Glo® Reagent quenched the firefly luciferase signal and sustained luminescence for the  Renilla  luciferase reaction. siRNA activity was determined by normalizing the  Renilla  (SCN9A) signal to the Firefly (control) signal within each well. The magnitude of siRNA activity was then assessed relative to cells that were transfected with the same vector but were not treated with siRNA or were treated with a non-SCN9A targeting siRNA. All transfections are done with n=4. 
     Results 
     The results of the single-dose dual luciferase screen in Hepa1-6 cells transfected with either the SCN9A-1 (added at 30 ng/well), SCN9A-2 (added at 75 ng/well), or SCN9A-3 plasmid (added at 30 ng/well) and treated with an exemplary set of SCN9A siRNAs is shown in Table 3 (correspond to siRNAs in Table 2A). The single-dose experiment was performed at a 10 nM final duplex concentration and the data are expressed as percent SCN9A luciferase signal remaining relative to cells treated with a non-targeting control. 
     Of the siRNA duplexes evaluated in cells transfected with SCN9A-1, 2 achieved ≥80% knockdown of SCN9A, 34 achieved ≥60% knockdown of SCN9A, 92 achieved ≥30% knockdown of SCN9A, and 95 achieved ≥20% knockdown of SCN9A. 
     Of the siRNA duplexes evaluated in cells transfected with SCN9A-2, 9 achieved ≥80% knockdown of SCN9A, 90 achieved ≥60% knockdown of SCN9A, 130 achieved ≥30% knockdown of SCN9A, and 132 achieved ≥20% knockdown of SCN9A. 
     Of the siRNA duplexes evaluated in cells transfected with SCN9A-3, 7 achieved ≥60% knockdown of SCN9A, 34 achieved ≥30% knockdown of SCN9A, and 47 achieved ≥20% knockdown of SCN9A. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 SCN9A in vitro dual luciferase 10 nM screen 
               
               
                 with one set of exemplary human SCN9A siRNAs 
               
            
           
           
               
               
            
               
                   
                 10 nM 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 % of SCN9A Luciferase 
                   
               
               
                 Duplex ID* 
                 Plasmid 
                 signal Remaining 
                 StDev 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 AD-887232.1 
                 SCN9A-1 
                 93.8 
                 0.080 
               
               
                 AD-887233.1 
                   
                 20.6 
                 0.038 
               
               
                 AD-887234.1 
                   
                 42.8 
                 0.086 
               
               
                 AD-887235.1 
                   
                 20.6 
                 0.035 
               
               
                 AD-887236.1 
                   
                 21.9 
                 0.037 
               
               
                 AD-887237.1 
                   
                 24.8 
                 0.018 
               
               
                 AD-887238.1 
                   
                 57.6 
                 0.040 
               
               
                 AD-887239.1 
                   
                 28.7 
                 0.014 
               
               
                 AD-887240.1 
                   
                 60.8 
                 0.043 
               
               
                 AD-887241.1 
                   
                 35.2 
                 0.014 
               
               
                 AD-887242.1 
                   
                 58.7 
                 0.092 
               
               
                 AD-887243.1 
                   
                 65.6 
                 0.099 
               
               
                 AD-887244.1 
                   
                 23.7 
                 0.019 
               
               
                 AD-887245.1 
                   
                 15.9 
                 0.020 
               
               
                 AD-887246.1 
                   
                 20.4 
                 0.022 
               
               
                 AD-887247.1 
                   
                 20.1 
                 0.018 
               
               
                 AD-887248.1 
                   
                 19.9 
                 0.011 
               
               
                 AD-887249.1 
                   
                 24.1 
                 0.045 
               
               
                 AD-887250.1 
                   
                 31.5 
                 0.039 
               
               
                 AD-887251.1 
                   
                 27.1 
                 0.040 
               
               
                 AD-887252.1 
                   
                 22.4 
                 0.026 
               
               
                 AD-887253.1 
                   
                 23.1 
                 0.015 
               
               
                 AD-887254.1 
                   
                 24.6 
                 0.033 
               
               
                 AD-887255.1 
                   
                 44.5 
                 0.072 
               
               
                 AD-887256.1 
                   
                 51.4 
                 0.082 
               
               
                 AD-887257.1 
                   
                 21.8 
                 0.025 
               
               
                 AD-887258.1 
                   
                 51.7 
                 0.124 
               
               
                 AD-887259.1 
                   
                 30.2 
                 0.046 
               
               
                 AD-887260.1 
                   
                 26.8 
                 0.043 
               
               
                 AD-887261.1 
                   
                 27.9 
                 0.030 
               
               
                 AD-887262.1 
                   
                 33.3 
                 0.094 
               
               
                 AD-887263.1 
                   
                 40.6 
                 0.042 
               
               
                 AD-887264.1 
                   
                 31.2 
                 0.047 
               
               
                 AD-887265.1 
                   
                 37.0 
                 0.045 
               
               
                 AD-887266.1 
                   
                 44.5 
                 0.131 
               
               
                 AD-887267.1 
                   
                 46.4 
                 0.059 
               
               
                 AD-887268.1 
                   
                 36.7 
                 0.035 
               
               
                 AD-887269.1 
                   
                 35.2 
                 0.038 
               
               
                 AD-887270.1 
                   
                 34.1 
                 0.046 
               
               
                 AD-887271.1 
                   
                 71.6 
                 0.036 
               
               
                 AD-887272.1 
                   
                 49.4 
                 0.018 
               
               
                 AD-887273.1 
                   
                 50.6 
                 0.041 
               
               
                 AD-887274.1 
                   
                 36.7 
                 0.099 
               
               
                 AD-887275.1 
                   
                 89.3 
                 0.041 
               
               
                 AD-887276.1 
                   
                 49.8 
                 0.036 
               
               
                 AD-887277.1 
                   
                 97.5 
                 0.152 
               
               
                 AD-887278.1 
                   
                 49.3 
                 0.052 
               
               
                 AD-887279.1 
                   
                 86.3 
                 0.086 
               
               
                 AD-887280.1 
                   
                 45.5 
                 0.025 
               
               
                 AD-887281.1 
                   
                 42.7 
                 0.086 
               
               
                 AD-887282.1 
                   
                 105.3 
                 0.240 
               
               
                 AD-887283.1 
                   
                 121.4 
                 0.208 
               
               
                 AD-887284.1 
                   
                 82.6 
                 0.116 
               
               
                 AD-887285.1 
                   
                 54.7 
                 0.147 
               
               
                 AD-887286.1 
                   
                 122.0 
                 0.057 
               
               
                 AD-887287.1 
                   
                 44.2 
                 0.090 
               
               
                 AD-887288.1 
                   
                 40.7 
                 0.026 
               
               
                 AD-887289.1 
                   
                 54.0 
                 0.083 
               
               
                 AD-887290.1 
                   
                 51.4 
                 0.094 
               
               
                 AD-887291.1 
                   
                 52.5 
                 0.112 
               
               
                 AD-887292.1 
                   
                 37.5 
                 0.061 
               
               
                 AD-887293.1 
                   
                 41.8 
                 0.083 
               
               
                 AD-887294.1 
                   
                 103.6 
                 0.109 
               
               
                 AD-887295.1 
                   
                 46.0 
                 0.100 
               
               
                 AD-887296.1 
                   
                 60.7 
                 0.049 
               
               
                 AD-887297.1 
                   
                 42.3 
                 0.072 
               
               
                 AD-887298.1 
                   
                 47.6 
                 0.035 
               
               
                 AD-887299.1 
                   
                 65.9 
                 0.068 
               
               
                 AD-887300.1 
                   
                 89.9 
                 0.040 
               
               
                 AD-887301.1 
                   
                 66.6 
                 0.078 
               
               
                 AD-887302.1 
                   
                 59.6 
                 0.053 
               
               
                 AD-887303.1 
                   
                 31.3 
                 0.032 
               
               
                 AD-887304.1 
                   
                 37.5 
                 0.055 
               
               
                 AD-887305.1 
                   
                 73.2 
                 0.056 
               
               
                 AD-887306.1 
                   
                 35.5 
                 0.021 
               
               
                 AD-887307.1 
                   
                 36.7 
                 0.032 
               
               
                 AD-887308.1 
                   
                 97.6 
                 0.098 
               
               
                 AD-887309.1 
                   
                 60.5 
                 0.066 
               
               
                 AD-887310.1 
                   
                 45.8 
                 0.018 
               
               
                 AD-887311.1 
                   
                 40.8 
                 0.037 
               
               
                 AD-887312.1 
                   
                 44.9 
                 0.113 
               
               
                 AD-887313.1 
                   
                 48.3 
                 0.077 
               
               
                 AD-887314.1 
                   
                 45.3 
                 0.056 
               
               
                 AD-887315.1 
                   
                 44.2 
                 0.029 
               
               
                 AD-887316.1 
                   
                 55.0 
                 0.054 
               
               
                 AD-887317.1 
                   
                 51.3 
                 0.045 
               
               
                 AD-887318.1 
                   
                 55.8 
                 0.053 
               
               
                 AD-887319.1 
                   
                 44.2 
                 0.020 
               
               
                 AD-887320.1 
                   
                 50.9 
                 0.060 
               
               
                 AD-887321.1 
                   
                 50.3 
                 0.093 
               
               
                 AD-887322.1 
                   
                 104.1 
                 0.129 
               
               
                 AD-887323.1 
                   
                 99.3 
                 0.064 
               
               
                 AD-887324.1 
                   
                 94.8 
                 0.083 
               
               
                 AD-887325.1 
                   
                 36.2 
                 0.063 
               
               
                 AD-887326.1 
                   
                 42.4 
                 0.033 
               
               
                 AD-887327.1 
                   
                 57.2 
                 0.104 
               
               
                 AD-887328.1 
                   
                 57.9 
                 0.036 
               
               
                 AD-887329.1 
                   
                 65.0 
                 0.124 
               
               
                 AD-887330.1 
                   
                 61.0 
                 0.026 
               
               
                 AD-887331.1 
                   
                 89.2 
                 0.079 
               
               
                 AD-887332.1 
                   
                 44.3 
                 0.078 
               
               
                 AD-887333.1 
                   
                 42.7 
                 0.135 
               
               
                 AD-887334.1 
                   
                 57.7 
                 0.035 
               
               
                 AD-887335.1 
                   
                 59.8 
                 0.088 
               
               
                 AD-887336.1 
                   
                 75.3 
                 0.098 
               
               
                 AD-887337.1 
                   
                 47.5 
                 0.080 
               
               
                 AD-887338.1 
                   
                 51.8 
                 0.056 
               
               
                 AD-887339.1 
                   
                 60.2 
                 0.068 
               
               
                 AD-887340.1 
                   
                 126.3 
                 0.223 
               
               
                 AD-887341.1 
                   
                 109.1 
                 0.127 
               
               
                 AD-887342.1 
                   
                 53.1 
                 0.101 
               
               
                 AD-887343.1 
                   
                 55.3 
                 0.042 
               
               
                 AD-887344.1 
                 SCN9A-2 
                 13.5 
                 0.039 
               
               
                 AD-887345.1 
                   
                 21.4 
                 0.006 
               
               
                 AD-887346.1 
                   
                 13.0 
                 0.026 
               
               
                 AD-887347.1 
                   
                 27.0 
                 0.041 
               
               
                 AD-887348.1 
                   
                 34.9 
                 0.039 
               
               
                 AD-887349.1 
                   
                 13.6 
                 0.045 
               
               
                 AD-887350.1 
                   
                 18.4 
                 0.033 
               
               
                 AD-887351.1 
                   
                 12.8 
                 0.021 
               
               
                 AD-887352.1 
                   
                 14.6 
                 0.034 
               
               
                 AD-887353.1 
                   
                 84.0 
                 0.081 
               
               
                 AD-887354.1 
                   
                 12.8 
                 0.028 
               
               
                 AD-887355.1 
                   
                 25.5 
                 0.051 
               
               
                 AD-887356.1 
                   
                 17.7 
                 0.040 
               
               
                 AD-887357.1 
                   
                 17.3 
                 0.009 
               
               
                 AD-887358.1 
                   
                 22.6 
                 0.033 
               
               
                 AD-887359.1 
                   
                 35.0 
                 0.032 
               
               
                 AD-887360.1 
                   
                 23.8 
                 0.048 
               
               
                 AD-887361.1 
                   
                 21.7 
                 0.026 
               
               
                 AD-887362.1 
                   
                 21.5 
                 0.027 
               
               
                 AD-887363.1 
                   
                 25.6 
                 0.044 
               
               
                 AD-887364.1 
                   
                 33.5 
                 0.038 
               
               
                 AD-887365.1 
                   
                 28.2 
                 0.037 
               
               
                 AD-887366.1 
                   
                 25.6 
                 0.015 
               
               
                 AD-887367.1 
                   
                 23.4 
                 0.028 
               
               
                 AD-887368.1 
                   
                 21.5 
                 0.033 
               
               
                 AD-887369.1 
                   
                 30.8 
                 0.032 
               
               
                 AD-887370.1 
                   
                 28.8 
                 0.034 
               
               
                 AD-887371.1 
                   
                 27.6 
                 0.050 
               
               
                 AD-887372.1 
                   
                 27.0 
                 0.053 
               
               
                 AD-887373.1 
                   
                 39.0 
                 0.042 
               
               
                 AD-887374.1 
                   
                 78.8 
                 0.037 
               
               
                 AD-887375.1 
                   
                 37.0 
                 0.056 
               
               
                 AD-887376.1 
                   
                 30.0 
                 0.069 
               
               
                 AD-887377.1 
                   
                 28.1 
                 0.032 
               
               
                 AD-887378.1 
                   
                 20.8 
                 0.025 
               
               
                 AD-887379.1 
                   
                 26.2 
                 0.023 
               
               
                 AD-887380.1 
                   
                 39.9 
                 0.086 
               
               
                 AD-887381.1 
                   
                 34.5 
                 0.007 
               
               
                 AD-887382.1 
                   
                 25.5 
                 0.027 
               
               
                 AD-887383.1 
                   
                 29.2 
                 0.040 
               
               
                 AD-887384.1 
                   
                 27.2 
                 0.043 
               
               
                 AD-887385.1 
                   
                 33.6 
                 0.044 
               
               
                 AD-887386.1 
                   
                 29.4 
                 0.020 
               
               
                 AD-887387.1 
                   
                 28.8 
                 0.060 
               
               
                 AD-887388.1 
                   
                 45.3 
                 0.087 
               
               
                 AD-887389.1 
                   
                 32.6 
                 0.062 
               
               
                 AD-887390.1 
                   
                 27.0 
                 0.055 
               
               
                 AD-887391.1 
                   
                 43.3 
                 0.039 
               
               
                 AD-887392.1 
                   
                 35.7 
                 0.019 
               
               
                 AD-887393.1 
                   
                 30.5 
                 0.017 
               
               
                 AD-887394.1 
                   
                 33.3 
                 0.022 
               
               
                 AD-887395.1 
                   
                 32.9 
                 0.051 
               
               
                 AD-887396.1 
                   
                 39.5 
                 0.028 
               
               
                 AD-887397.1 
                   
                 33.7 
                 0.040 
               
               
                 AD-887398.1 
                   
                 37.0 
                 0.020 
               
               
                 AD-887399.1 
                   
                 36.5 
                 0.069 
               
               
                 AD-887400.1 
                   
                 42.4 
                 0.042 
               
               
                 AD-887401.1 
                   
                 44.3 
                 0.074 
               
               
                 AD-887402.1 
                   
                 35.2 
                 0.070 
               
               
                 AD-887403.1 
                   
                 35.7 
                 0.027 
               
               
                 AD-887404.1 
                   
                 45.5 
                 0.126 
               
               
                 AD-887405.1 
                   
                 37.8 
                 0.065 
               
               
                 AD-887406.1 
                   
                 36.6 
                 0.064 
               
               
                 AD-887407.1 
                   
                 37.9 
                 0.036 
               
               
                 AD-887408.1 
                   
                 41.0 
                 0.049 
               
               
                 AD-887409.1 
                   
                 39.5 
                 0.044 
               
               
                 AD-887410.1 
                   
                 47.0 
                 0.031 
               
               
                 AD-887411.1 
                   
                 39.3 
                 0.014 
               
               
                 AD-887412.1 
                   
                 34.6 
                 0.052 
               
               
                 AD-887413.1 
                   
                 42.1 
                 0.057 
               
               
                 AD-887414.1 
                   
                 34.1 
                 0.051 
               
               
                 AD-887415.1 
                   
                 32.0 
                 0.036 
               
               
                 AD-887416.1 
                   
                 34.1 
                 0.032 
               
               
                 AD-887417.1 
                   
                 35.4 
                 0.041 
               
               
                 AD-887418.1 
                   
                 42.5 
                 0.078 
               
               
                 AD-887419.1 
                   
                 46.2 
                 0.067 
               
               
                 AD-887420.1 
                   
                 53.0 
                 0.047 
               
               
                 AD-887421.1 
                   
                 37.1 
                 0.025 
               
               
                 AD-887422.1 
                   
                 38.0 
                 0.099 
               
               
                 AD-887423.1 
                   
                 29.6 
                 0.038 
               
               
                 AD-887424.1 
                   
                 44.5 
                 0.077 
               
               
                 AD-887425.1 
                   
                 50.5 
                 0.065 
               
               
                 AD-887426.1 
                   
                 49.4 
                 0.026 
               
               
                 AD-887427.1 
                   
                 38.5 
                 0.067 
               
               
                 AD-887428.1 
                   
                 34.0 
                 0.033 
               
               
                 AD-887429.1 
                   
                 33.5 
                 0.035 
               
               
                 AD-887430.1 
                   
                 33.4 
                 0.046 
               
               
                 AD-887431.1 
                   
                 25.2 
                 0.045 
               
               
                 AD-887432.1 
                   
                 43.8 
                 0.055 
               
               
                 AD-887433.1 
                   
                 34.8 
                 0.043 
               
               
                 AD-887434.1 
                   
                 67.0 
                 0.075 
               
               
                 AD-887435.1 
                   
                 49.0 
                 0.021 
               
               
                 AD-887436.1 
                   
                 35.6 
                 0.099 
               
               
                 AD-887437.1 
                   
                 36.8 
                 0.076 
               
               
                 AD-887438.1 
                   
                 34.1 
                 0.096 
               
               
                 AD-887439.1 
                   
                 32.6 
                 0.031 
               
               
                 AD-887440.1 
                   
                 37.9 
                 0.016 
               
               
                 AD-887441.1 
                   
                 35.9 
                 0.065 
               
               
                 AD-887442.1 
                   
                 46.6 
                 0.085 
               
               
                 AD-887443.1 
                   
                 40.5 
                 0.027 
               
               
                 AD-887444.1 
                   
                 42.6 
                 0.028 
               
               
                 AD-887445.1 
                   
                 63.9 
                 0.129 
               
               
                 AD-887446.1 
                   
                 41.0 
                 0.105 
               
               
                 AD-887447.1 
                   
                 56.1 
                 0.053 
               
               
                 AD-887448.1 
                   
                 37.8 
                 0.101 
               
               
                 AD-887449.1 
                   
                 38.8 
                 0.041 
               
               
                 AD-887450.1 
                   
                 45.4 
                 0.057 
               
               
                 AD-887451.1 
                   
                 61.1 
                 0.024 
               
               
                 AD-887452.1 
                   
                 36.3 
                 0.034 
               
               
                 AD-887453.1 
                   
                 40.6 
                 0.028 
               
               
                 AD-887454.1 
                   
                 45.3 
                 0.081 
               
               
                 AD-887455.1 
                   
                 42.7 
                 0.097 
               
               
                 AD-887456.1 
                   
                 36.1 
                 0.068 
               
               
                 AD-887457.1 
                   
                 54.0 
                 0.057 
               
               
                 AD-887458.1 
                   
                 45.0 
                 0.056 
               
               
                 AD-887459.1 
                   
                 55.9 
                 0.041 
               
               
                 AD-887460.1 
                   
                 37.2 
                 0.023 
               
               
                 AD-887461.1 
                   
                 70.7 
                 0.120 
               
               
                 AD-887462.1 
                   
                 63.4 
                 0.050 
               
               
                 AD-887463.1 
                   
                 28.7 
                 0.015 
               
               
                 AD-887464.1 
                   
                 39.9 
                 0.043 
               
               
                 AD-887465.1 
                   
                 30.2 
                 0.046 
               
               
                 AD-887466.1 
                   
                 43.0 
                 0.056 
               
               
                 AD-887467.1 
                   
                 27.8 
                 0.032 
               
               
                 AD-887468.1 
                   
                 27.2 
                 0.021 
               
               
                 AD-887469.1 
                   
                 49.1 
                 0.052 
               
               
                 AD-887470.1 
                   
                 39.3 
                 0.067 
               
               
                 AD-887471.1 
                   
                 46.1 
                 0.074 
               
               
                 AD-887472.1 
                   
                 40.3 
                 0.071 
               
               
                 AD-887473.1 
                   
                 52.3 
                 0.055 
               
               
                 AD-887474.1 
                   
                 61.7 
                 0.079 
               
               
                 AD-887475.1 
                   
                 55.7 
                 0.020 
               
               
                 AD-887476.1 
                   
                 57.8 
                 0.026 
               
               
                 AD-887477.1 
                 SCN9A-3 
                 45.3 
                 0.027 
               
               
                 AD-887478.1 
                   
                 26.4 
                 0.033 
               
               
                 AD-887479.1 
                   
                 69.3 
                 0.083 
               
               
                 AD-887480.1 
                   
                 24.3 
                 0.035 
               
               
                 AD-887481.1 
                   
                 28.9 
                 0.054 
               
               
                 AD-887482.1 
                   
                 32.8 
                 0.077 
               
               
                 AD-887483.1 
                   
                 31.6 
                 0.044 
               
               
                 AD-887484.1 
                   
                 39.4 
                 0.012 
               
               
                 AD-887485.1 
                   
                 38.0 
                 0.044 
               
               
                 AD-887486.1 
                   
                 46.3 
                 0.049 
               
               
                 AD-887487.1 
                   
                 50.4 
                 0.087 
               
               
                 AD-887488.1 
                   
                 47.2 
                 0.076 
               
               
                 AD-887489.1 
                   
                 54.9 
                 0.050 
               
               
                 AD-887490.1 
                   
                 65.3 
                 0.052 
               
               
                 AD-887491.1 
                   
                 74.5 
                 0.080 
               
               
                 AD-887492.1 
                   
                 63.8 
                 0.105 
               
               
                 AD-887493.1 
                   
                 89.2 
                 0.223 
               
               
                 AD-887494.1 
                   
                 43.8 
                 0.085 
               
               
                 AD-887495.1 
                   
                 71.7 
                 0.140 
               
               
                 AD-887496.1 
                   
                 85.9 
                 0.069 
               
               
                 AD-887497.1 
                   
                 72.9 
                 0.025 
               
               
                 AD-887498.1 
                   
                 52.9 
                 0.083 
               
               
                 AD-887499.1 
                   
                 78.7 
                 0.071 
               
               
                 AD-887500.1 
                   
                 70.3 
                 0.062 
               
               
                 AD-887501.1 
                   
                 60.9 
                 0.073 
               
               
                 AD-887502.1 
                   
                 59.3 
                 0.077 
               
               
                 AD-887503.1 
                   
                 55.1 
                 0.068 
               
               
                 AD-887504.1 
                   
                 63.9 
                 0.087 
               
               
                 AD-887505.1 
                   
                 63.0 
                 0.031 
               
               
                 AD-887506.1 
                   
                 62.3 
                 0.062 
               
               
                 AD-887507.1 
                   
                 70.9 
                 0.095 
               
               
                 AD-887508.1 
                   
                 56.3 
                 0.072 
               
               
                 AD-887509.1 
                   
                 78.4 
                 0.065 
               
               
                 AD-887510.1 
                   
                 50.9 
                 0.038 
               
               
                 AD-887511.1 
                   
                 75.0 
                 0.029 
               
               
                 AD-887512.1 
                   
                 81.5 
                 0.154 
               
               
                 AD-887513.1 
                   
                 65.7 
                 0.039 
               
               
                 AD-887514.1 
                   
                 53.4 
                 0.036 
               
               
                 AD-887515.1 
                   
                 55.2 
                 0.084 
               
               
                 AD-887516.1 
                   
                 69.7 
                 0.099 
               
               
                 AD-887517.1 
                   
                 68.3 
                 0.057 
               
               
                 AD-887518.1 
                   
                 91.5 
                 0.134 
               
               
                 AD-887519.1 
                   
                 101.2 
                 0.188 
               
               
                 AD-887520.1 
                   
                 72.9 
                 0.082 
               
               
                 AD-887521.1 
                   
                 75.7 
                 0.048 
               
               
                 AD-887522.1 
                   
                 70.8 
                 0.082 
               
               
                 AD-887523.1 
                   
                 89.9 
                 0.104 
               
               
                 AD-887524.1 
                   
                 54.1 
                 0.062 
               
               
                 AD-887525.1 
                   
                 61.5 
                 0.034 
               
               
                 AD-887526.1 
                   
                 58.1 
                 0.098 
               
               
                 AD-887527.1 
                   
                 66.2 
                 0.138 
               
               
                 AD-887528.1 
                   
                 72.5 
                 0.096 
               
               
                 AD-887529.1 
                   
                 80.7 
                 0.122 
               
               
                 AD-887530.1 
                   
                 73.8 
                 0.018 
               
               
                 AD-887531.1 
                   
                 81.8 
                 0.090 
               
               
                   
               
               
                 (*the number following the decimal point in a duplex name merely refers to a batch production number) 
               
            
           
         
       
     
     Example 3. In Vitro Screening of SCN9A siRNA 
     Experimental Methods 
     Cell Culture and Transfections: 
     Human neuroblastoma BE(2)-C cells expressing a SC9NA gene were transfected independently by adding 5 μl of Opti-MEM plus 0.1 μl of Lipofectamine RNAiMax per well (Invitrogen, Carlsbad Calif. cat #13778-150) to 5.1 μl of siRNA duplexes per well into a 384-well plate and are incubated at room temperature for 15 minutes. 40 μl of InVitroGRO CP Medium (BioIVT Cat #Z99029) containing 5×10 3  BE(2)-C cells were then added to the siRNA mixture. Cells were incubated for 24 hours prior to RNA purification. Experiments were performed at 0.1 nM, 1 nM, 10 nM, and 50 nM final duplex concentrations and the results are shown in Table 8. 
     In a second experiment, BE(2)-C cells expressing a SC9NA gene were transfected independently by adding 5 μl of Opti-MEM plus 0.1 μl of Lipofectamine RNAiMax per well (Invitrogen, Carlsbad Calif. cat #13778-150) to 5.1 μl of siRNA duplexes per well into a 384-well plate and are incubated at room temperature for 15 minutes. 40 μl of InVitroGRO CP Medium (BioIVT Cat #Z99029) containing 5×10 3  BE(2)-C cells were then added to the siRNA mixture. Cells were incubated for 24 hours prior to RNA purification. Experiments were performed at 0.1 nM, 1 nM, 10 nM, and 50 nM final duplex concentrations and the results are shown in Table 17. 
     RNA Isolation: 
     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: 
     cDNA was synthesized using ABI High capacity cDNA reverse transcription kit (Applied Biosystems, Foster City, Calif., Cat #4368813). 10 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 5 μl 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 SCN9A Human probe 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 BE(2)-C cells transfected with SCN9A and treated with an exemplary set of SCN9A siRNAs is shown in Table 8 (correspond to siRNAs in Table 4A, 4B, 5A, 5B, 6A, and 6B). The experiment was performed at a 0.1 nM, 1 nM, 10 nM, and 50 nM final duplex concentrations and the data are expressed as percent message remaining relative to non-targeting control. 
     Of the siRNA duplexes evaluated at 50 nM, 5 achieved ≥80% knockdown of SCN9A, 86 achieved ≥60% knockdown of SCN9A, 266 achieved ≥30% knockdown of SCN9A, 298 achieved ≥20% knockdown of SCN9A, and 314 achieved ≥10% knockdown of SCN9A. 
     Of the siRNA duplexes evaluated at 10 nM, 2 achieved ≥80% knockdown of SCN9A, 104 achieved ≥60% knockdown of SCN9A, 290 achieved ≥30% knockdown of SCN9A, 316 achieved ≥20% knockdown of SCN9A, and 324 achieved ≥10% knockdown of SCN9A. 
     Of the siRNA duplexes evaluated at 1 nM, 32 achieved ≥60% knockdown of SCN9A, 203 achieved ≥30% knockdown of SCN9A, 256 achieved ≥20% knockdown of SCN9A, and 296 achieved ≥10% knockdown of SCN9A. 
     Of the siRNA duplexes evaluated at 0.1 nM, 6 achieved ≥60% knockdown of SCN9A, 111 achieved ≥30% knockdown of SCN9A, 167 achieved ≥20% knockdown of SCN9A, and 213 achieved ≥10% knockdown of SCN9A. 
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 SCN9A in vitro multidose-dose screen with one set of exemplary human  
               
               
                 SCN9A siRNA duplexes (*the number following the decimal point  
               
               
                 in a duplex name merely refers to a batch production number) 
               
            
           
           
               
               
               
               
               
            
               
                   
                 50 nM 
                 10 nM 
                 1 nM 
                 0.1 nM 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 % message 
                 St. 
                 % message 
                 St.  
                 % message 
                 St. 
                 % message 
                 St. 
               
               
                 Duplex Name* 
                 remaining 
                 Dev. 
                 remaining 
                 Dev. 
                 remaining 
                 Dev. 
                 remaining 
                 Dev. 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 AD-1010663.1 
                 20.4 
                 3.1 
                 22.0 
                 3.4 
                 32.2 
                 3.3 
                 29.7 
                 6.2 
               
               
                 AD-802123.1 
                 25.2 
                 4.1 
                 31.1 
                 2.6 
                 27.8 
                 2.8 
                 34.8 
                 5.0 
               
               
                 AD-961342.1 
                 44.6 
                 9.2 
                 28.8 
                 3.5 
                 46.6 
                 3.0 
                 37.3 
                 1.3 
               
               
                 AD-961334.1 
                 40.1 
                 15.1 
                 29.6 
                 3.2 
                 42.0 
                 1.2 
                 39.5 
                 8.9 
               
               
                 AD-961179.1 
                 26.1 
                 1.9 
                 28.8 
                 3.1 
                 38.8 
                 1.4 
                 39.6 
                 2.9 
               
               
                 AD-1010661.1 
                 22.6 
                 2.8 
                 24.1 
                 5.0 
                 39.5 
                 4.4 
                 39.8 
                 5.5 
               
               
                 AD-1010662.1 
                 27.0 
                 4.9 
                 21.1 
                 3.0 
                 44.6 
                 7.0 
                 40.5 
                 7.3 
               
               
                 AD-961192.1 
                 29.4 
                 2.2 
                 28.9 
                 2.4 
                 53.5 
                 2.4 
                 40.8 
                 4.0 
               
               
                 AD-961189.1 
                 23.7 
                 6.1 
                 24.3 
                 5.6 
                 37.6 
                 1.4 
                 40.9 
                 7.4 
               
               
                 AD-961188.1 
                 19.0 
                 0.6 
                 22.0 
                 4.6 
                 34.3 
                 5.6 
                 41.6 
                 1.0 
               
               
                 AD-1010665.1 
                 48.8 
                 5.4 
                 36.9 
                 1.7 
                 69.6 
                 4.1 
                 42.2 
                 3.8 
               
               
                 AD-802853.2 
                 35.3 
                 3.2 
                 36.9 
                 6.4 
                 40.1 
                 4.2 
                 44.1 
                 5.2 
               
               
                 AD-802471.2 
                 23.7 
                 5.7 
                 26.1 
                 4.9 
                 24.5 
                 2.6 
                 44.5 
                 4.4 
               
               
                 AD-1010664.1 
                 31.0 
                 3.8 
                 29.9 
                 2.3 
                 54.2 
                 4.4 
                 45.0 
                 5.2 
               
               
                 AD-802552.1 
                 27.9 
                 5.0 
                 34.3 
                 2.6 
                 37.9 
                 5.3 
                 45.1 
                 5.5 
               
               
                 AD-802625.2 
                 37.8 
                 5.1 
                 36.4 
                 8.7 
                 36.9 
                 4.0 
                 45.2 
                 1.4 
               
               
                 AD-802503.1 
                 26.6 
                 1.1 
                 33.7 
                 4.0 
                 34.4 
                 4.0 
                 45.3 
                 6.4 
               
               
                 AD-1010700.1 
                 63.7 
                 5.0 
                 32.4 
                 1.4 
                 50.5 
                 1.4 
                 45.4 
                 6.4 
               
               
                 AD-961207.1 
                 19.3 
                 1.9 
                 21.0 
                 4.8 
                 43.9 
                 10.2 
                 45.5 
                 10.5 
               
               
                 AD-1010671.1 
                 23.7 
                 4.0 
                 26.8 
                 4.0 
                 52.8 
                 7.8 
                 45.6 
                 2.5 
               
               
                 AD-1002101.1 
                 33.4 
                 7.3 
                 39.2 
                 3.0 
                 50.1 
                 6.3 
                 45.8 
                 4.9 
               
               
                 AD-961208.1 
                 18.6 
                 1.9 
                 20.9 
                 1.5 
                 45.8 
                 10.4 
                 46.6 
                 6.8 
               
               
                 AD-1010693.1 
                 44.0 
                 9.9 
                 29.5 
                 2.5 
                 54.2 
                 6.6 
                 46.6 
                 9.2 
               
               
                 AD-802553.1 
                 26.7 
                 2.6 
                 32.2 
                 3.2 
                 39.1 
                 5.6 
                 46.9 
                 1.3 
               
               
                 AD-961190.1 
                 24.7 
                 1.0 
                 28.4 
                 5.3 
                 49.4 
                 5.0 
                 47.5 
                 4.4 
               
               
                 AD-802946.1 
                 29.8 
                 3.8 
                 35.8 
                 4.1 
                 41.1 
                 6.2 
                 48.0 
                 4.5 
               
               
                 AD-961191.1 
                 28.3 
                 1.1 
                 29.0 
                 3.0 
                 62.2 
                 5.6 
                 48.9 
                 4.8 
               
               
                 AD-801647.1 
                 31.3 
                 4.1 
                 31.6 
                 3.6 
                 45.0 
                 6.6 
                 48.9 
                 6.2 
               
               
                 AD-961279.1 
                 42.0 
                 9.7 
                 33.9 
                 5.3 
                 44.2 
                 4.5 
                 50.0 
                 12.3 
               
               
                 AD-1010697.1 
                 33.1 
                 4.3 
                 29.8 
                 1.2 
                 54.9 
                 6.5 
                 50.0 
                 15.7 
               
               
                 AD-799938.1 
                 26.4 
                 3.5 
                 27.5 
                 8.3 
                 38.6 
                 4.0 
                 51.0 
                 9.2 
               
               
                 AD-797636.2 
                 34.7 
                 6.4 
                 25.7 
                 2.7 
                 53.2 
                 9.9 
                 52.4 
                 8.4 
               
               
                 AD-961326.1 
                 57.6 
                 9.4 
                 45.9 
                 12.6 
                 48.8 
                 3.2 
                 52.6 
                 7.4 
               
               
                 AD-802945.2 
                 46.1 
                 6.1 
                 50.0 
                 3.4 
                 46.1 
                 8.6 
                 52.7 
                 5.3 
               
               
                 AD-802206.2 
                 37.4 
                 2.7 
                 43.6 
                 2.8 
                 40.6 
                 9.1 
                 53.0 
                 2.6 
               
               
                 AD-1002409.1 
                 40.8 
                 11.4 
                 43.9 
                 2.2 
                 48.4 
                 7.1 
                 53.3 
                 6.3 
               
               
                 AD-801263.1 
                 29.9 
                 2.8 
                 33.1 
                 7.1 
                 36.9 
                 4.3 
                 53.4 
                 5.0 
               
               
                 AD-961201.1 
                 35.3 
                 3.4 
                 40.8 
                 9.3 
                 66.4 
                 8.6 
                 53.9 
                 7.0 
               
               
                 AD-795371.1 
                 22.4 
                 3.7 
                 21.4 
                 1.9 
                 31.9 
                 1.9 
                 54.0 
                 3.8 
               
               
                 AD-799587.1 
                 45.6 
                 4.9 
                 40.8 
                 2.1 
                 45.6 
                 4.1 
                 54.4 
                 2.5 
               
               
                 AD-802014.1 
                 43.0 
                 2.7 
                 41.3 
                 1.7 
                 46.1 
                 4.2 
                 54.8 
                 4.1 
               
               
                 AD-961182.1 
                 32.5 
                 3.1 
                 33.2 
                 5.5 
                 39.8 
                 3.8 
                 54.8 
                 26.8 
               
               
                 AD-800966.1 
                 33.8 
                 3.3 
                 36.4 
                 2.5 
                 52.5 
                 2.7 
                 54.9 
                 5.2 
               
               
                 AD-795305.1 
                 24.5 
                 1.5 
                 24.8 
                 2.0 
                 38.9 
                 6.0 
                 55.0 
                 9.3 
               
               
                 AD-798584.2 
                 45.7 
                 5.5 
                 33.7 
                 3.7 
                 55.1 
                 5.8 
                 55.2 
                 7.5 
               
               
                 AD-795366.1 
                 17.1 
                 2.2 
                 19.4 
                 2.7 
                 28.5 
                 3.2 
                 56.2 
                 4.1 
               
               
                 AD-1002051.1 
                 38.2 
                 6.7 
                 33.0 
                 5.6 
                 40.3 
                 7.5 
                 56.3 
                 6.6 
               
               
                 AD-961321.1 
                 65.9 
                 6.7 
                 33.8 
                 7.4 
                 57.5 
                 5.1 
                 56.7 
                 7.8 
               
               
                 AD-797565.2 
                 23.0 
                 1.2 
                 20.6 
                 4.3 
                 43.1 
                 4.8 
                 56.8 
                 3.7 
               
               
                 AD-1010698.1 
                 57.0 
                 8.8 
                 30.9 
                 2.7 
                 49.6 
                 2.3 
                 56.8 
                 12.7 
               
               
                 AD-799223.1 
                 31.0 
                 3.2 
                 26.8 
                 7.1 
                 36.6 
                 5.3 
                 57.2 
                 5.8 
               
               
                 AD-801883.2 
                 42.9 
                 6.3 
                 43.7 
                 8.6 
                 36.9 
                 7.0 
                 57.2 
                 7.5 
               
               
                 AD-961155.1 
                 58.5 
                 4.5 
                 50.1 
                 5.2 
                 54.9 
                 9.4 
                 57.5 
                 8.8 
               
               
                 AD-1002100.1 
                 45.6 
                 11.2 
                 48.9 
                 6.3 
                 58.7 
                 6.6 
                 57.9 
                 11.8 
               
               
                 AD-801658.2 
                 52.9 
                 11.9 
                 51.7 
                 5.9 
                 54.5 
                 5.6 
                 57.9 
                 5.4 
               
               
                 AD-800110.1 
                 44.3 
                 8.0 
                 38.6 
                 5.0 
                 44.2 
                 2.1 
                 58.2 
                 3.5 
               
               
                 AD-800819.1 
                 32.8 
                 1.7 
                 32.9 
                 6.5 
                 48.0 
                 7.8 
                 58.5 
                 4.3 
               
               
                 AD-796618.1 
                 20.8 
                 2.1 
                 23.4 
                 2.2 
                 31.7 
                 3.0 
                 58.6 
                 7.9 
               
               
                 AD-797564.2 
                 21.6 
                 3.1 
                 22.7 
                 5.7 
                 48.6 
                 9.8 
                 58.9 
                 7.8 
               
               
                 AD-796825.1 
                 13.9 
                 1.4 
                 18.5 
                 2.1 
                 26.3 
                 2.6 
                 59.0 
                 6.8 
               
               
                 AD-800297.2 
                 63.1 
                 6.1 
                 51.5 
                 6.4 
                 79.9 
                 8.4 
                 59.3 
                 6.8 
               
               
                 AD-801304.1 
                 28.5 
                 2.6 
                 35.0 
                 3.7 
                 46.5 
                 3.5 
                 59.5 
                 3.2 
               
               
                 AD-801708.2 
                 48.9 
                 5.3 
                 46.0 
                 7.2 
                 57.8 
                 5.5 
                 59.7 
                 9.0 
               
               
                 AD-1010673.1 
                 27.2 
                 4.7 
                 28.8 
                 4.3 
                 52.6 
                 17.0 
                 59.9 
                 8.6 
               
               
                 AD-1010699.1 
                 72.3 
                 3.2 
                 33.3 
                 4.7 
                 53.4 
                 2.3 
                 59.9 
                 10.1 
               
               
                 AD-1001246.1 
                 40.3 
                 4.9 
                 40.0 
                 1.2 
                 51.9 
                 7.1 
                 60.1 
                 10.8 
               
               
                 AD-796209.1 
                 31.6 
                 5.6 
                 26.7 
                 3.0 
                 42.6 
                 3.6 
                 60.5 
                 8.6 
               
               
                 AD-801835.1 
                 45.7 
                 2.8 
                 48.9 
                 3.6 
                 55.6 
                 3.5 
                 60.6 
                 3.2 
               
               
                 AD-1010677.1 
                 40.4 
                 4.5 
                 49.1 
                 5.8 
                 61.3 
                 13.3 
                 61.1 
                 7.1 
               
               
                 AD-802141.2 
                 51.4 
                 7.1 
                 50.8 
                 3.7 
                 54.8 
                 3.8 
                 61.9 
                 1.8 
               
               
                 AD-802153.2 
                 67.9 
                 2.2 
                 73.0 
                 4.5 
                 64.5 
                 9.1 
                 63.0 
                 4.7 
               
               
                 AD-1010670.1 
                 34.8 
                 4.1 
                 45.0 
                 6.9 
                 58.9 
                 3.2 
                 63.3 
                 15.2 
               
               
                 AD-800661.1 
                 42.7 
                 5.7 
                 40.6 
                 2.9 
                 48.7 
                 2.1 
                 63.3 
                 4.1 
               
               
                 AD-800058.1 
                 50.9 
                 6.3 
                 42.3 
                 2.5 
                 46.1 
                 1.2 
                 63.8 
                 3.0 
               
               
                 AD-795910.1 
                 28.0 
                 1.8 
                 34.2 
                 7.6 
                 39.7 
                 2.7 
                 64.0 
                 5.4 
               
               
                 AD-961200.1 
                 52.8 
                 6.6 
                 92.3 
                 36.4 
                 75.1 
                 9.5 
                 64.1 
                 11.1 
               
               
                 AD-799939.1 
                 34.8 
                 3.9 
                 36.8 
                 0.3 
                 39.9 
                 3.7 
                 64.1 
                 3.8 
               
               
                 AD-1010660.1 
                 42.2 
                 1.5 
                 48.5 
                 9.5 
                 70.2 
                 10.6 
                 64.3 
                 10.0 
               
               
                 AD-961093.1 
                 54.9 
                 9.5 
                 53.1 
                 1.9 
                 59.8 
                 4.7 
                 64.4 
                 3.5 
               
               
                 AD-1000916.1 
                 42.0 
                 3.3 
                 44.1 
                 2.9 
                 52.6 
                 2.9 
                 64.4 
                 7.3 
               
               
                 AD-801681.2 
                 45.4 
                 2.6 
                 43.0 
                 4.6 
                 68.1 
                 5.1 
                 64.5 
                 2.9 
               
               
                 AD-995116.1 
                 27.9 
                 6.6 
                 25.8 
                 2.9 
                 48.1 
                 13.4 
                 64.7 
                 3.7 
               
               
                 AD-800461.1 
                 40.2 
                 4.1 
                 42.2 
                 1.6 
                 51.0 
                 5.8 
                 64.7 
                 5.6 
               
               
                 AD-996318.1 
                 34.1 
                 4.7 
                 23.8 
                 2.0 
                 48.5 
                 7.4 
                 64.8 
                 15.1 
               
               
                 AD-795634.2 
                 23.4 
                 6.1 
                 23.2 
                 7.2 
                 46.2 
                 15.6 
                 65.0 
                 9.2 
               
               
                 AD-795911.1 
                 26.3 
                 3.0 
                 27.9 
                 4.3 
                 38.4 
                 2.1 
                 65.0 
                 7.0 
               
               
                 AD-797036.1 
                 28.3 
                 4.7 
                 27.8 
                 3.2 
                 36.2 
                 3.2 
                 65.1 
                 8.0 
               
               
                 AD-961137.1 
                 44.6 
                 5.1 
                 45.9 
                 1.2 
                 63.0 
                 7.1 
                 65.1 
                 5.8 
               
               
                 AD-801884.2 
                 41.9 
                 2.3 
                 49.3 
                 3.0 
                 60.9 
                 11.5 
                 65.2 
                 11.4 
               
               
                 AD-801490.2 
                 54.0 
                 5.7 
                 56.2 
                 5.9 
                 56.4 
                 6.6 
                 65.3 
                 4.7 
               
               
                 AD-802145.2 
                 47.7 
                 1.9 
                 54.3 
                 4.7 
                 45.5 
                 8.3 
                 65.6 
                 10.6 
               
               
                 AD-961146.1 
                 54.6 
                 6.1 
                 55.3 
                 2.4 
                 72.6 
                 10.4 
                 65.8 
                 7.3 
               
               
                 AD-795909.1 
                 31.2 
                 7.9 
                 30.8 
                 2.9 
                 35.2 
                 2.7 
                 65.9 
                 1.8 
               
               
                 AD-1010690.1 
                 75.9 
                 12.7 
                 49.3 
                 12.4 
                 57.5 
                 3.7 
                 66.0 
                 12.8 
               
               
                 AD-802071.2 
                 64.9 
                 7.0 
                 58.4 
                 6.1 
                 70.0 
                 2.7 
                 66.2 
                 5.9 
               
               
                 AD-795913.1 
                 23.9 
                 3.0 
                 23.3 
                 2.3 
                 35.0 
                 2.5 
                 66.4 
                 8.4 
               
               
                 AD-800334.1 
                 37.2 
                 4.7 
                 35.3 
                 6.1 
                 50.8 
                 8.2 
                 66.4 
                 6.1 
               
               
                 AD-795739.1 
                 29.0 
                 5.7 
                 24.7 
                 2.4 
                 42.3 
                 6.4 
                 66.6 
                 2.8 
               
               
                 AD-796619.1 
                 33.1 
                 2.9 
                 31.4 
                 5.2 
                 39.4 
                 3.1 
                 66.7 
                 4.7 
               
               
                 AD-800400.1 
                 31.8 
                 1.9 
                 40.7 
                 3.5 
                 47.8 
                 1.4 
                 66.9 
                 4.9 
               
               
                 AD-800414.2 
                 53.0 
                 5.0 
                 45.4 
                 1.9 
                 66.4 
                 4.2 
                 67.5 
                 3.4 
               
               
                 AD-801886.2 
                 49.6 
                 4.0 
                 50.2 
                 4.5 
                 59.2 
                 3.6 
                 67.5 
                 7.9 
               
               
                 AD-961187.1 
                 28.8 
                 2.4 
                 31.2 
                 4.7 
                 51.7 
                 4.6 
                 68.4 
                 17.7 
               
               
                 AD-799594.1 
                 47.2 
                 2.9 
                 40.6 
                 4.0 
                 47.2 
                 3.6 
                 69.0 
                 2.2 
               
               
                 AD-798579.1 
                 43.3 
                 3.6 
                 39.4 
                 1.9 
                 44.3 
                 2.3 
                 69.1 
                 6.9 
               
               
                 AD-802105.2 
                 36.1 
                 7.1 
                 40.4 
                 6.5 
                 37.8 
                 9.7 
                 69.5 
                 6.2 
               
               
                 AD-798588.2 
                 40.3 
                 3.4 
                 31.2 
                 2.7 
                 66.5 
                 8.6 
                 69.5 
                 4.1 
               
               
                 AD-797034.1 
                 28.6 
                 4.1 
                 30.3 
                 1.7 
                 35.2 
                 5.9 
                 69.5 
                 13.4 
               
               
                 AD-961203.1 
                 30.2 
                 6.1 
                 29.8 
                 5.7 
                 39.5 
                 6.4 
                 69.6 
                 9.5 
               
               
                 AD-961259.1 
                 58.2 
                 9.8 
                 40.3 
                 6.0 
                 53.0 
                 5.0 
                 69.7 
                 18.2 
               
               
                 AD-798580.1 
                 35.5 
                 1.6 
                 33.4 
                 4.7 
                 41.5 
                 3.4 
                 69.9 
                 4.9 
               
               
                 AD-1010696.1 
                 78.4 
                 6.6 
                 33.4 
                 6.3 
                 49.7 
                 3.9 
                 70.3 
                 14.2 
               
               
                 AD-802205.2 
                 49.5 
                 6.6 
                 61.7 
                 3.0 
                 55.9 
                 6.6 
                 70.4 
                 11.7 
               
               
                 AD-801724.1 
                 36.5 
                 4.2 
                 37.2 
                 2.9 
                 51.0 
                 5.0 
                 70.4 
                 5.4 
               
               
                 AD-801738.2 
                 51.2 
                 2.1 
                 63.5 
                 4.7 
                 65.4 
                 3.2 
                 70.4 
                 5.5 
               
               
                 AD-801064.1 
                 48.5 
                 9.8 
                 45.5 
                 2.6 
                 53.6 
                 4.4 
                 70.5 
                 8.3 
               
               
                 AD-995486.1 
                 36.1 
                 3.1 
                 27.0 
                 4.4 
                 52.9 
                 6.8 
                 70.9 
                 7.8 
               
               
                 AD-961163.1 
                 50.2 
                 9.8 
                 60.6 
                 16.2 
                 58.8 
                 14.9 
                 71.1 
                 2.7 
               
               
                 AD-961138.1 
                 63.7 
                 4.3 
                 68.4 
                 7.2 
                 71.9 
                 4.3 
                 71.1 
                 3.8 
               
               
                 AD-799231.2 
                 40.6 
                 3.3 
                 44.5 
                 8.0 
                 60.1 
                 7.3 
                 71.3 
                 7.9 
               
               
                 AD-1000046.1 
                 40.3 
                 4.2 
                 41.6 
                 3.5 
                 62.9 
                 5.8 
                 71.4 
                 8.7 
               
               
                 AD-800273.2 
                 52.4 
                 3.2 
                 43.9 
                 5.5 
                 68.2 
                 6.6 
                 71.5 
                 14.9 
               
               
                 AD-800487.1 
                 51.9 
                 2.7 
                 48.7 
                 4.4 
                 59.8 
                 3.7 
                 71.6 
                 8.4 
               
               
                 AD-800069.1 
                 56.3 
                 4.7 
                 46.9 
                 2.3 
                 52.3 
                 3.1 
                 71.6 
                 3.0 
               
               
                 AD-1010694.1 
                 81.7 
                 6.5 
                 50.5 
                 9.8 
                 67.0 
                 4.5 
                 71.6 
                 19.8 
               
               
                 AD-799221.1 
                 48.7 
                 4.7 
                 41.8 
                 4.1 
                 50.5 
                 3.6 
                 71.8 
                 7.9 
               
               
                 AD-961257.1 
                 47.5 
                 3.9 
                 52.3 
                 4.9 
                 70.0 
                 22.0 
                 71.8 
                 12.1 
               
               
                 AD-961014.1 
                 58.5 
                 4.4 
                 40.6 
                 3.0 
                 78.8 
                 5.4 
                 72.0 
                 3.1 
               
               
                 AD-961300.1 
                 96.3 
                 24.0 
                 59.2 
                 5.3 
                 60.8 
                 4.2 
                 72.3 
                 20.0 
               
               
                 AD-800492.2 
                 60.4 
                 8.3 
                 45.2 
                 4.5 
                 70.2 
                 6.9 
                 72.4 
                 8.3 
               
               
                 AD-801957.2 
                 53.6 
                 4.6 
                 68.1 
                 8.0 
                 59.3 
                 7.1 
                 72.4 
                 5.8 
               
               
                 AD-799937.1 
                 48.1 
                 6.0 
                 42.2 
                 4.1 
                 50.9 
                 5.6 
                 72.4 
                 6.8 
               
               
                 AD-800709.2 
                 63.6 
                 4.5 
                 64.5 
                 4.7 
                 79.1 
                 9.5 
                 72.5 
                 8.7 
               
               
                 AD-801832.1 
                 42.6 
                 4.7 
                 50.5 
                 6.9 
                 55.1 
                 2.1 
                 72.6 
                 5.5 
               
               
                 AD-999598.1 
                 46.5 
                 5.4 
                 38.9 
                 4.2 
                 65.0 
                 5.0 
                 72.7 
                 12.7 
               
               
                 AD-800956.1 
                 30.7 
                 1.7 
                 42.5 
                 3.5 
                 65.7 
                 14.9 
                 72.8 
                 9.8 
               
               
                 AD-961225.1 
                 36.2 
                 0.4 
                 36.1 
                 3.6 
                 60.2 
                 8.7 
                 73.3 
                 10.4 
               
               
                 AD-801063.1 
                 40.5 
                 4.5 
                 46.1 
                 2.5 
                 53.2 
                 7.8 
                 73.4 
                 5.5 
               
               
                 AD-801676.2 
                 42.2 
                 0.7 
                 51.9 
                 2.3 
                 57.8 
                 5.1 
                 73.5 
                 14.7 
               
               
                 AD-799942.1 
                 38.6 
                 5.7 
                 41.7 
                 4.3 
                 47.1 
                 3.9 
                 73.5 
                 5.7 
               
               
                 AD-802016.2 
                 51.8 
                 1.8 
                 59.8 
                 6.8 
                 61.6 
                 5.6 
                 73.7 
                 9.2 
               
               
                 AD-1000585.1 
                 55.5 
                 8.8 
                 59.6 
                 5.4 
                 76.8 
                 6.6 
                 73.8 
                 8.8 
               
               
                 AD-1010674.1 
                 32.5 
                 2.1 
                 43.9 
                 4.0 
                 76.7 
                 12.1 
                 74.1 
                 12.7 
               
               
                 AD-801725.1 
                 42.2 
                 2.6 
                 44.5 
                 2.8 
                 58.5 
                 1.2 
                 74.2 
                 6.3 
               
               
                 AD-961350.1 
                 62.6 
                 6.5 
                 31.3 
                 2.6 
                 57.5 
                 2.6 
                 74.5 
                 10.7 
               
               
                 AD-799959.1 
                 46.2 
                 8.8 
                 45.7 
                 2.2 
                 52.0 
                 2.9 
                 74.5 
                 7.1 
               
               
                 AD-800486.1 
                 46.9 
                 3.0 
                 53.4 
                 6.3 
                 54.7 
                 1.5 
                 74.6 
                 10.4 
               
               
                 AD-961245.1 
                 52.3 
                 10.7 
                 53.5 
                 10.2 
                 54.0 
                 2.9 
                 74.6 
                 13.1 
               
               
                 AD-995121.1 
                 35.1 
                 7.6 
                 28.8 
                 3.3 
                 46.8 
                 6.8 
                 75.2 
                 6.8 
               
               
                 AD-995521.1 
                 81.9 
                 13.8 
                 53.3 
                 6.1 
                 87.0 
                 13.5 
                 75.3 
                 8.9 
               
               
                 AD-800849.2 
                 57.0 
                 4.8 
                 47.4 
                 6.3 
                 80.3 
                 3.5 
                 75.5 
                 11.3 
               
               
                 AD-801654.2 
                 52.5 
                 4.4 
                 55.3 
                 5.1 
                 71.1 
                 2.6 
                 75.6 
                 5.7 
               
               
                 AD-802070.2 
                 53.7 
                 2.3 
                 57.9 
                 3.4 
                 63.2 
                 5.1 
                 75.8 
                 10.7 
               
               
                 AD-797699.1 
                 43.6 
                 5.1 
                 37.5 
                 4.4 
                 54.0 
                 4.5 
                 76.1 
                 15.5 
               
               
                 AD-1001409.1 
                 54.0 
                 3.1 
                 58.0 
                 4.5 
                 65.7 
                 6.5 
                 76.3 
                 1.6 
               
               
                 AD-801062.1 
                 43.7 
                 8.3 
                 42.1 
                 5.3 
                 64.3 
                 3.7 
                 76.3 
                 5.5 
               
               
                 AD-801675.2 
                 52.4 
                 2.7 
                 66.7 
                 4.3 
                 65.1 
                 1.9 
                 76.4 
                 9.3 
               
               
                 AD-797964.1 
                 53.2 
                 10.9 
                 56.6 
                 3.8 
                 54.4 
                 4.3 
                 76.7 
                 5.5 
               
               
                 AD-795914.1 
                 24.8 
                 1.7 
                 24.4 
                 0.6 
                 38.2 
                 4.2 
                 77.6 
                 19.2 
               
               
                 AD-796041.1 
                 45.7 
                 2.5 
                 116.1 
                 16.4 
                 66.8 
                 10.4 
                 77.8 
                 10.4 
               
               
                 AD-798667.1 
                 47.4 
                 6.7 
                 55.7 
                 20.4 
                 55.6 
                 5.1 
                 78.1 
                 12.0 
               
               
                 AD-799225.1 
                 48.5 
                 10.3 
                 42.3 
                 6.9 
                 54.2 
                 3.9 
                 79.1 
                 4.6 
               
               
                 AD-961000.1 
                 43.8 
                 5.3 
                 37.5 
                 5.3 
                 65.4 
                 1.0 
                 79.2 
                 4.8 
               
               
                 AD-800490.1 
                 50.9 
                 6.5 
                 45.3 
                 5.8 
                 53.9 
                 4.9 
                 79.5 
                 8.8 
               
               
                 AD-961040.1 
                 57.2 
                 11.3 
                 35.3 
                 4.7 
                 77.3 
                 11.3 
                 79.8 
                 11.7 
               
               
                 AD-795304.1 
                 30.0 
                 2.9 
                 32.1 
                 6.3 
                 43.3 
                 5.5 
                 79.9 
                 17.9 
               
               
                 AD-798577.1 
                 53.6 
                 3.6 
                 45.7 
                 6.7 
                 51.5 
                 3.6 
                 79.9 
                 8.8 
               
               
                 AD-801132.1 
                 48.0 
                 2.8 
                 45.2 
                 2.7 
                 58.5 
                 4.6 
                 80.2 
                 8.5 
               
               
                 AD-961106.1 
                 71.2 
                 14.7 
                 78.0 
                 8.6 
                 89.8 
                 6.5 
                 80.2 
                 17.7 
               
               
                 AD-801747.2 
                 49.5 
                 5.9 
                 49.7 
                 4.3 
                 75.9 
                 6.8 
                 80.2 
                 4.6 
               
               
                 AD-1010667.1 
                 71.4 
                 16.0 
                 71.0 
                 15.6 
                 73.6 
                 3.0 
                 80.3 
                 21.0 
               
               
                 AD-961085.1 
                 60.0 
                 3.9 
                 49.2 
                 1.1 
                 66.3 
                 7.8 
                 80.5 
                 5.7 
               
               
                 AD-961267.1 
                 77.9 
                 4.6 
                 96.8 
                 63.6 
                 52.3 
                 2.5 
                 80.6 
                 8.3 
               
               
                 AD-961221.1 
                 57.2 
                 12.8 
                 66.5 
                 7.7 
                 79.9 
                 23.0 
                 80.9 
                 20.1 
               
               
                 AD-795920.1 
                 39.6 
                 9.3 
                 36.6 
                 5.6 
                 52.4 
                 6.9 
                 81.3 
                 6.4 
               
               
                 AD-1000678.1 
                 54.1 
                 6.6 
                 59.0 
                 5.2 
                 68.5 
                 7.5 
                 81.5 
                 10.9 
               
               
                 AD-796396.1 
                 32.3 
                 2.9 
                 31.3 
                 4.6 
                 43.5 
                 3.1 
                 81.8 
                 9.8 
               
               
                 AD-1010695.1 
                 100.2 
                 23.6 
                 57.9 
                 20.2 
                 56.9 
                 3.8 
                 82.2 
                 31.8 
               
               
                 AD-1010679.1 
                 44.4 
                 2.9 
                 50.8 
                 6.2 
                 84.4 
                 19.0 
                 82.6 
                 9.3 
               
               
                 AD-999715.1 
                 60.0 
                 9.6 
                 58.4 
                 10.7 
                 71.5 
                 5.0 
                 83.1 
                 6.2 
               
               
                 AD-796304.1 
                 39.4 
                 6.4 
                 37.9 
                 2.9 
                 48.4 
                 6.1 
                 83.3 
                 2.9 
               
               
                 AD-795132.1 
                 30.6 
                 1.6 
                 28.3 
                 2.9 
                 45.1 
                 3.5 
                 83.3 
                 11.6 
               
               
                 AD-800060.1 
                 54.7 
                 4.2 
                 50.5 
                 5.9 
                 56.5 
                 3.9 
                 83.4 
                 3.9 
               
               
                 AD-1000106.1 
                 75.0 
                 7.6 
                 59.6 
                 11.5 
                 80.3 
                 9.4 
                 83.5 
                 7.7 
               
               
                 AD-795912.1 
                 32.2 
                 5.7 
                 33.5 
                 3.9 
                 49.4 
                 4.4 
                 83.6 
                 5.2 
               
               
                 AD-961056.1 
                 51.2 
                 4.5 
                 50.5 
                 0.9 
                 74.5 
                 11.3 
                 83.8 
                 9.1 
               
               
                 AD-1010684.1 
                 48.0 
                 5.6 
                 59.3 
                 8.8 
                 83.1 
                 16.0 
                 83.9 
                 7.8 
               
               
                 AD-801601.2 
                 58.6 
                 2.8 
                 57.9 
                 1.8 
                 75.3 
                 11.2 
                 84.0 
                 6.1 
               
               
                 AD-1010666.1 
                 64.5 
                 9.2 
                 72.3 
                 15.1 
                 78.2 
                 5.2 
                 84.1 
                 21.0 
               
               
                 AD-801746.2 
                 62.8 
                 3.2 
                 60.7 
                 2.7 
                 77.7 
                 2.2 
                 84.7 
                 7.9 
               
               
                 AD-796919.1 
                 28.1 
                 1.1 
                 29.9 
                 2.8 
                 43.1 
                 8.4 
                 84.8 
                 5.2 
               
               
                 AD-1000130.1 
                 71.1 
                 11.5 
                 74.5 
                 5.6 
                 81.1 
                 9.7 
                 85.2 
                 5.8 
               
               
                 AD-800387.2 
                 53.1 
                 4.4 
                 49.7 
                 4.9 
                 75.4 
                 3.1 
                 85.6 
                 15.5 
               
               
                 AD-801680.2 
                 57.5 
                 1.7 
                 61.9 
                 6.1 
                 73.5 
                 2.5 
                 85.8 
                 12.0 
               
               
                 AD-1010692.1 
                 76.4 
                 9.2 
                 54.3 
                 4.3 
                 57.8 
                 7.2 
                 86.2 
                 26.9 
               
               
                 AD-801540.2 
                 52.6 
                 3.2 
                 54.5 
                 4.7 
                 65.3 
                 4.2 
                 86.6 
                 9.7 
               
               
                 AD-801251.1 
                 58.6 
                 4.9 
                 50.9 
                 2.1 
                 61.0 
                 6.8 
                 86.6 
                 12.2 
               
               
                 AD-996733.1 
                 63.0 
                 13.1 
                 45.7 
                 5.2 
                 88.0 
                 6.5 
                 86.7 
                 16.2 
               
               
                 AD-961013.1 
                 47.9 
                 5.1 
                 36.5 
                 3.8 
                 65.6 
                 10.8 
                 86.8 
                 7.5 
               
               
                 AD-1000679.1 
                 78.4 
                 6.9 
                 93.8 
                 3.9 
                 89.7 
                 7.8 
                 86.9 
                 9.2 
               
               
                 AD-800389.2 
                 63.3 
                 4.4 
                 56.9 
                 6.5 
                 81.1 
                 11.2 
                 87.2 
                 9.5 
               
               
                 AD-961049.1 
                 48.2 
                 5.6 
                 49.7 
                 10.0 
                 74.6 
                 5.9 
                 87.3 
                 13.2 
               
               
                 AD-961320.1 
                 78.9 
                 8.5 
                 59.3 
                 5.6 
                 56.5 
                 2.4 
                 87.5 
                 19.6 
               
               
                 AD-801491.2 
                 59.2 
                 3.2 
                 71.8 
                 8.3 
                 75.2 
                 13.8 
                 87.7 
                 2.1 
               
               
                 AD-800706.2 
                 65.7 
                 1.9 
                 60.7 
                 6.0 
                 81.8 
                 3.6 
                 87.8 
                 11.6 
               
               
                 AD-801723.2 
                 61.3 
                 8.1 
                 71.3 
                 2.1 
                 81.4 
                 5.5 
                 88.0 
                 3.2 
               
               
                 AD-800606.2 
                 54.0 
                 3.4 
                 50.0 
                 10.3 
                 89.4 
                 4.4 
                 88.6 
                 13.6 
               
               
                 AD-801721.2 
                 49.3 
                 4.6 
                 61.3 
                 5.5 
                 70.1 
                 5.1 
                 89.5 
                 5.3 
               
               
                 AD-1000747.1 
                 52.2 
                 7.4 
                 57.5 
                 6.7 
                 68.7 
                 6.0 
                 89.6 
                 12.2 
               
               
                 AD-797963.1 
                 61.3 
                 8.6 
                 51.2 
                 5.4 
                 63.7 
                 6.8 
                 89.7 
                 9.3 
               
               
                 AD-995055.1 
                 44.4 
                 3.0 
                 37.0 
                 3.6 
                 66.9 
                 11.9 
                 89.8 
                 6.6 
               
               
                 AD-800470.1 
                 61.6 
                 8.8 
                 62.7 
                 4.0 
                 71.1 
                 3.2 
                 89.9 
                 5.1 
               
               
                 AD-961226.1 
                 47.0 
                 10.8 
                 34.8 
                 4.4 
                 65.4 
                 15.8 
                 90.0 
                 14.2 
               
               
                 AD-801678.2 
                 56.3 
                 3.0 
                 62.9 
                 5.8 
                 68.2 
                 2.7 
                 90.2 
                 10.6 
               
               
                 AD-801677.2 
                 59.8 
                 1.9 
                 70.7 
                 7.4 
                 79.4 
                 9.1 
                 90.3 
                 8.1 
               
               
                 AD-801035.2 
                 63.3 
                 3.1 
                 64.8 
                 5.2 
                 84.3 
                 7.3 
                 90.4 
                 8.0 
               
               
                 AD-800386.2 
                 49.6 
                 1.5 
                 50.3 
                 3.0 
                 67.6 
                 9.5 
                 91.1 
                 5.7 
               
               
                 AD-798332.1 
                 59.2 
                 12.3 
                 50.5 
                 2.3 
                 63.2 
                 6.8 
                 91.1 
                 7.1 
               
               
                 AD-802106.2 
                 78.8 
                 2.3 
                 93.0 
                 9.7 
                 84.6 
                 13.3 
                 91.5 
                 7.9 
               
               
                 AD-798614.1 
                 70.8 
                 15.0 
                 64.3 
                 8.5 
                 89.6 
                 14.2 
                 91.7 
                 12.9 
               
               
                 AD-798672.1 
                 63.7 
                 7.8 
                 53.8 
                 6.3 
                 65.7 
                 6.2 
                 91.8 
                 5.5 
               
               
                 AD-961196.1 
                 48.3 
                 5.6 
                 74.3 
                 44.2 
                 77.1 
                 9.4 
                 91.9 
                 11.8 
               
               
                 AD-799230.2 
                 48.7 
                 3.2 
                 46.1 
                 4.7 
                 68.2 
                 6.2 
                 92.1 
                 6.1 
               
               
                 AD-961206.1 
                 43.2 
                 2.7 
                 45.8 
                 7.5 
                 58.2 
                 4.8 
                 92.1 
                 5.2 
               
               
                 AD-800667.2 
                 64.2 
                 3.4 
                 59.5 
                 4.7 
                 88.0 
                 17.1 
                 92.6 
                 9.3 
               
               
                 AD-961022.1 
                 39.3 
                 2.1 
                 31.1 
                 2.7 
                 62.9 
                 5.8 
                 92.7 
                 11.1 
               
               
                 AD-796920.1 
                 32.8 
                 3.1 
                 38.5 
                 6.0 
                 48.3 
                 3.4 
                 92.8 
                 14.5 
               
               
                 AD-801888.2 
                 57.3 
                 4.9 
                 64.7 
                 1.1 
                 78.4 
                 15.3 
                 92.9 
                 3.8 
               
               
                 AD-961239.1 
                 52.9 
                 5.5 
                 45.9 
                 9.3 
                 57.9 
                 6.1 
                 93.0 
                 10.8 
               
               
                 AD-800008.2 
                 61.9 
                 9.1 
                 59.8 
                 2.5 
                 84.5 
                 10.6 
                 93.0 
                 15.5 
               
               
                 AD-800494.2 
                 64.5 
                 3.2 
                 64.2 
                 6.0 
                 69.1 
                 8.2 
                 93.7 
                 2.0 
               
               
                 AD-961296.1 
                 92.8 
                 5.4 
                 67.6 
                 5.6 
                 99.0 
                 54.9 
                 94.1 
                 18.4 
               
               
                 AD-796827.1 
                 37.3 
                 3.3 
                 33.9 
                 3.8 
                 53.6 
                 9.2 
                 94.2 
                 11.7 
               
               
                 AD-961270.1 
                 91.7 
                 10.3 
                 81.5 
                 22.7 
                 65.3 
                 8.8 
                 94.3 
                 17.1 
               
               
                 AD-961012.1 
                 116.4 
                 6.8 
                 82.2 
                 2.8 
                 122.2 
                 12.1 
                 94.6 
                 14.2 
               
               
                 AD-800382.2 
                 60.6 
                 5.2 
                 46.6 
                 5.8 
                 76.2 
                 11.6 
                 94.7 
                 18.1 
               
               
                 AD-799683.1 
                 56.0 
                 4.2 
                 52.2 
                 2.8 
                 58.6 
                 6.3 
                 95.0 
                 9.7 
               
               
                 AD-799549.1 
                 63.4 
                 4.6 
                 60.6 
                 3.7 
                 67.2 
                 2.5 
                 95.0 
                 4.3 
               
               
                 AD-801655.2 
                 65.3 
                 7.5 
                 55.8 
                 5.0 
                 86.9 
                 9.4 
                 95.1 
                 10.5 
               
               
                 AD-801679.2 
                 60.1 
                 4.0 
                 69.5 
                 1.9 
                 73.1 
                 5.1 
                 95.6 
                 15.9 
               
               
                 AD-961011.1 
                 47.8 
                 4.4 
                 42.2 
                 3.6 
                 73.7 
                 11.5 
                 95.6 
                 4.4 
               
               
                 AD-961058.1 
                 65.7 
                 3.6 
                 55.0 
                 7.5 
                 78.8 
                 12.6 
                 95.7 
                 16.0 
               
               
                 AD-800968.2 
                 61.3 
                 3.7 
                 58.7 
                 3.1 
                 76.2 
                 7.2 
                 96.0 
                 16.7 
               
               
                 AD-961010.1 
                 43.1 
                 5.8 
                 37.5 
                 1.9 
                 72.8 
                 11.0 
                 96.6 
                 10.3 
               
               
                 AD-1000864.1 
                 107.1 
                 13.4 
                 95.5 
                 6.0 
                 97.1 
                 2.3 
                 96.7 
                 13.9 
               
               
                 AD-796087.1 
                 36.1 
                 3.3 
                 36.1 
                 6.2 
                 53.6 
                 2.7 
                 96.7 
                 8.6 
               
               
                 AD-961251.1 
                 110.4 
                 13.6 
                 67.3 
                 15.3 
                 80.3 
                 15.8 
                 96.8 
                 7.9 
               
               
                 AD-800495.2 
                 64.7 
                 6.5 
                 67.3 
                 7.1 
                 82.9 
                 7.5 
                 97.2 
                 7.5 
               
               
                 AD-799936.1 
                 58.4 
                 2.6 
                 49.1 
                 4.7 
                 62.2 
                 3.6 
                 97.3 
                 3.7 
               
               
                 AD-801539.2 
                 53.2 
                 1.9 
                 63.5 
                 3.2 
                 72.3 
                 6.5 
                 97.4 
                 10.1 
               
               
                 AD-996130.1 
                 61.5 
                 4.0 
                 58.1 
                 7.9 
                 87.1 
                 8.9 
                 97.4 
                 11.1 
               
               
                 AD-1010669.1 
                 42.6 
                 4.8 
                 61.2 
                 10.8 
                 71.8 
                 10.7 
                 97.4 
                 21.9 
               
               
                 AD-1000115.1 
                 81.7 
                 6.2 
                 74.8 
                 14.4 
                 85.0 
                 3.0 
                 97.5 
                 9.0 
               
               
                 AD-796088.1 
                 37.4 
                 6.2 
                 36.8 
                 4.3 
                 50.2 
                 1.8 
                 97.7 
                 8.5 
               
               
                 AD-795841.1 
                 54.9 
                 4.4 
                 39.4 
                 5.1 
                 61.5 
                 4.4 
                 97.9 
                 12.5 
               
               
                 AD-999259.1 
                 56.4 
                 9.1 
                 52.2 
                 3.5 
                 78.0 
                 10.3 
                 98.3 
                 24.5 
               
               
                 AD-999762.1 
                 65.0 
                 12.5 
                 49.0 
                 7.1 
                 82.6 
                 12.1 
                 98.4 
                 9.3 
               
               
                 AD-801653.1 
                 54.6 
                 4.6 
                 58.3 
                 7.0 
                 75.1 
                 4.0 
                 98.5 
                 5.8 
               
               
                 AD-796138.1 
                 28.7 
                 5.8 
                 29.5 
                 4.0 
                 44.4 
                 1.9 
                 98.6 
                 13.1 
               
               
                 AD-1010676.1 
                 56.7 
                 10.5 
                 76.0 
                 8.7 
                 101.2 
                 44.8 
                 98.7 
                 14.9 
               
               
                 AD-801744.2 
                 65.2 
                 2.8 
                 74.7 
                 4.6 
                 76.3 
                 4.7 
                 98.8 
                 5.9 
               
               
                 AD-795774.1 
                 38.0 
                 5.1 
                 30.6 
                 5.0 
                 55.3 
                 10.0 
                 99.2 
                 8.4 
               
               
                 AD-999601.1 
                 75.3 
                 4.1 
                 61.4 
                 2.9 
                 97.2 
                 18.3 
                 99.3 
                 19.7 
               
               
                 AD-961078.1 
                 62.3 
                 4.2 
                 65.4 
                 9.3 
                 76.8 
                 19.5 
                 99.4 
                 15.9 
               
               
                 AD-798984.1 
                 75.3 
                 6.8 
                 67.0 
                 2.9 
                 82.7 
                 7.3 
                 99.8 
                 12.7 
               
               
                 AD-800007.2 
                 68.0 
                 5.0 
                 69.4 
                 7.5 
                 98.3 
                 9.2 
                 100.6 
                 7.6 
               
               
                 AD-801228.2 
                 68.9 
                 4.0 
                 66.9 
                 6.9 
                 77.7 
                 10.6 
                 101.0 
                 10.6 
               
               
                 AD-961109.1 
                 101.8 
                 15.6 
                 98.2 
                 19.2 
                 97.9 
                 13.9 
                 101.1 
                 14.5 
               
               
                 AD-961057.1 
                 57.9 
                 7.9 
                 47.1 
                 5.7 
                 79.8 
                 8.2 
                 101.9 
                 10.1 
               
               
                 AD-801745.2 
                 72.4 
                 9.2 
                 74.1 
                 4.5 
                 89.2 
                 6.6 
                 102.0 
                 16.4 
               
               
                 AD-801489.2 
                 72.9 
                 6.2 
                 69.0 
                 5.9 
                 84.2 
                 5.7 
                 102.3 
                 6.5 
               
               
                 AD-800388.2 
                 71.5 
                 1.7 
                 57.6 
                 3.1 
                 95.3 
                 3.6 
                 102.9 
                 9.8 
               
               
                 AD-796936.1 
                 37.1 
                 3.5 
                 40.9 
                 3.8 
                 61.3 
                 1.8 
                 103.7 
                 9.8 
               
               
                 AD-796318.1 
                 44.4 
                 7.3 
                 47.3 
                 3.3 
                 66.9 
                 8.6 
                 103.9 
                 6.5 
               
               
                 AD-801397.2 
                 64.6 
                 4.3 
                 69.9 
                 11.1 
                 80.7 
                 2.8 
                 104.1 
                 7.6 
               
               
                 AD-961004.1 
                 89.4 
                 11.4 
                 88.5 
                 8.5 
                 107.5 
                 19.2 
                 104.7 
                 9.5 
               
               
                 AD-961202.1 
                 53.4 
                 5.1 
                 49.3 
                 15.0 
                 71.3 
                 8.2 
                 104.8 
                 10.1 
               
               
                 AD-995873.1 
                 40.1 
                 1.2 
                 34.6 
                 6.0 
                 78.2 
                 9.9 
                 105.0 
                 18.1 
               
               
                 AD-801022.2 
                 62.7 
                 2.8 
                 63.0 
                 5.3 
                 88.2 
                 7.8 
                 105.3 
                 11.8 
               
               
                 AD-800496.2 
                 68.4 
                 1.8 
                 63.4 
                 5.7 
                 90.2 
                 7.0 
                 105.5 
                 11.7 
               
               
                 AD-1010668.1 
                 54.7 
                 6.4 
                 50.1 
                 10.3 
                 61.7 
                 4.4 
                 105.6 
                 30.8 
               
               
                 AD-801399.2 
                 61.6 
                 4.5 
                 68.1 
                 6.4 
                 78.8 
                 4.5 
                 106.3 
                 6.9 
               
               
                 AD-961227.1 
                 70.7 
                 13.2 
                 62.4 
                 18.3 
                 69.4 
                 13.2 
                 106.6 
                 24.6 
               
               
                 AD-961285.1 
                 84.7 
                 4.3 
                 58.6 
                 4.4 
                 57.0 
                 4.0 
                 106.8 
                 12.3 
               
               
                 AD-799010.2 
                 72.4 
                 3.2 
                 63.8 
                 6.6 
                 88.7 
                 8.9 
                 107.6 
                 22.6 
               
               
                 AD-961243.1 
                 64.6 
                 17.0 
                 66.4 
                 9.0 
                 60.3 
                 13.3 
                 107.8 
                 12.8 
               
               
                 AD-800974.2 
                 62.8 
                 3.6 
                 69.2 
                 4.8 
                 80.5 
                 5.3 
                 108.5 
                 6.8 
               
               
                 AD-800850.2 
                 68.8 
                 7.6 
                 64.0 
                 1.7 
                 83.0 
                 5.1 
                 110.0 
                 9.7 
               
               
                 AD-961066.1 
                 64.2 
                 6.4 
                 68.6 
                 9.0 
                 94.8 
                 8.0 
                 110.6 
                 11.9 
               
               
                 AD-961220.1 
                 91.6 
                 11.9 
                 97.9 
                 17.5 
                 106.8 
                 19.0 
                 111.3 
                 15.8 
               
               
                 AD-1010683.1 
                 91.9 
                 9.3 
                 84.9 
                 13.1 
                 91.8 
                 11.9 
                 111.6 
                 15.8 
               
               
                 AD-961009.1 
                 86.0 
                 8.0 
                 64.8 
                 11.9 
                 94.8 
                 15.3 
                 111.9 
                 10.9 
               
               
                 AD-961269.1 
                 91.7 
                 11.5 
                 69.7 
                 4.0 
                 74.8 
                 15.5 
                 112.3 
                 11.0 
               
               
                 AD-961271.1 
                 54.8 
                 11.6 
                 66.8 
                 8.6 
                 63.9 
                 4.8 
                 112.5 
                 10.4 
               
               
                 AD-961042.1 
                 131.0 
                 17.7 
                 104.1 
                 14.8 
                 132.1 
                 19.7 
                 113.1 
                 16.1 
               
               
                 AD-961233.1 
                 86.8 
                 2.7 
                 92.3 
                 11.2 
                 115.2 
                 12.0 
                 113.5 
                 24.6 
               
               
                 AD-1010691.1 
                 83.2 
                 13.4 
                 70.3 
                 12.5 
                 70.5 
                 20.0 
                 114.3 
                 9.2 
               
               
                 AD-1010680.1 
                 75.5 
                 14.3 
                 62.1 
                 20.6 
                 69.2 
                 3.6 
                 115.3 
                 9.3 
               
               
                 AD-997386.1 
                 75.4 
                 11.9 
                 54.6 
                 2.2 
                 102.7 
                 5.3 
                 115.7 
                 10.0 
               
               
                 AD-801140.2 
                 81.4 
                 2.3 
                 73.8 
                 7.3 
                 110.3 
                 8.9 
                 115.8 
                 18.3 
               
               
                 AD-996618.1 
                 49.0 
                 6.8 
                 40.5 
                 1.0 
                 83.2 
                 17.7 
                 115.9 
                 14.5 
               
               
                 AD-1000451.1 
                 102.3 
                 7.4 
                 100.7 
                 10.4 
                 117.9 
                 11.6 
                 116.1 
                 6.2 
               
               
                 AD-961024.1 
                 102.3 
                 1.9 
                 90.5 
                 8.4 
                 129.4 
                 9.6 
                 116.2 
                 7.7 
               
               
                 AD-1010688.1 
                 81.2 
                 10.5 
                 68.2 
                 16.2 
                 76.2 
                 10.5 
                 116.4 
                 5.1 
               
               
                 AD-999721.1 
                 88.2 
                 14.5 
                 74.3 
                 8.8 
                 105.7 
                 7.6 
                 117.0 
                 15.7 
               
               
                 AD-999986.1 
                 92.1 
                 7.1 
                 68.3 
                 4.2 
                 103.6 
                 25.5 
                 117.7 
                 4.4 
               
               
                 AD-961252.1 
                 76.5 
                 5.7 
                 71.6 
                 8.5 
                 93.7 
                 5.0 
                 118.3 
                 8.2 
               
               
                 AD-1000133.1 
                 108.6 
                 9.9 
                 104.8 
                 4.5 
                 103.4 
                 14.8 
                 118.4 
                 22.2 
               
               
                 AD-1010672.1 
                 47.9 
                 7.7 
                 34.5 
                 10.1 
                 67.6 
                 14.0 
                 119.1 
                 14.0 
               
               
                 AD-961039.1 
                 63.3 
                 8.9 
                 50.4 
                 6.3 
                 92.7 
                 18.6 
                 119.5 
                 8.3 
               
               
                 AD-800384.2 
                 109.7 
                 11.6 
                 107.5 
                 11.0 
                 157.3 
                 12.1 
                 119.8 
                 16.6 
               
               
                 AD-998897.1 
                 95.0 
                 7.2 
                 80.0 
                 8.1 
                 113.6 
                 10.8 
                 119.8 
                 13.0 
               
               
                 AD-996319.1 
                 50.5 
                 3.3 
                 41.7 
                 4.8 
                 93.7 
                 5.9 
                 119.9 
                 18.3 
               
               
                 AD-996635.1 
                 69.5 
                 5.3 
                 60.3 
                 5.6 
                 107.1 
                 1.9 
                 120.2 
                 14.4 
               
               
                 AD-1010678.1 
                 88.1 
                 12.5 
                 85.5 
                 10.6 
                 89.0 
                 17.2 
                 121.1 
                 15.0 
               
               
                 AD-1010685.1 
                 111.6 
                 15.7 
                 108.7 
                 12.2 
                 78.0 
                 7.2 
                 122.2 
                 7.9 
               
               
                 AD-961044.1 
                 97.5 
                 9.6 
                 88.4 
                 12.2 
                 134.5 
                 10.9 
                 122.7 
                 22.2 
               
               
                 AD-1010686.1 
                 78.7 
                 6.5 
                 76.7 
                 7.0 
                 86.1 
                 26.9 
                 123.1 
                 19.5 
               
               
                 AD-1010687.1 
                 117.9 
                 15.8 
                 115.2 
                 30.5 
                 107.5 
                 26.3 
                 124.7 
                 19.7 
               
               
                 AD-994670.1 
                 129.5 
                 59.3 
                 134.9 
                 46.8 
                 118.4 
                 32.5 
                 124.8 
                 42.9 
               
               
                 AD-996052.1 
                 91.5 
                 4.9 
                 72.6 
                 13.5 
                 121.3 
                 21.0 
                 125.5 
                 29.0 
               
               
                 AD-961244.1 
                 76.7 
                 11.0 
                 77.3 
                 12.3 
                 86.9 
                 17.0 
                 125.7 
                 11.9 
               
               
                 AD-1010689.1 
                 97.6 
                 12.4 
                 70.6 
                 13.0 
                 72.1 
                 13.8 
                 125.7 
                 12.1 
               
               
                 AD-998894.1 
                 99.2 
                 7.1 
                 92.6 
                 8.1 
                 127.6 
                 21.1 
                 126.2 
                 23.1 
               
               
                 AD-995824.1 
                 79.3 
                 6.1 
                 79.4 
                 5.6 
                 132.8 
                 21.0 
                 127.8 
                 17.2 
               
               
                 AD-998346.1 
                 63.5 
                 10.6 
                 50.5 
                 11.1 
                 83.0 
                 29.0 
                 127.9 
                 17.0 
               
               
                 AD-995660.1 
                 136.0 
                 20.1 
                 113.3 
                 16.3 
                 138.8 
                 21.7 
                 128.3 
                 27.5 
               
               
                 AD-961204.1 
                 131.2 
                 6.3 
                 120.0 
                 23.3 
                 93.0 
                 6.9 
                 128.4 
                 16.1 
               
               
                 AD-998261.1 
                 92.0 
                 5.8 
                 69.2 
                 3.7 
                 120.4 
                 14.9 
                 128.8 
                 10.2 
               
               
                 AD-800975.2 
                 68.4 
                 14.1 
                 70.0 
                 14.9 
                 93.4 
                 23.3 
                 128.9 
                 30.2 
               
               
                 AD-794914.1 
                 54.4 
                 20.5 
                 45.0 
                 8.5 
                 85.8 
                 5.5 
                 129.1 
                 22.5 
               
               
                 AD-1010682.1 
                 74.2 
                 13.6 
                 73.0 
                 10.6 
                 77.2 
                 11.2 
                 129.5 
                 7.4 
               
               
                 AD-961246.1 
                 74.2 
                 5.9 
                 67.8 
                 8.9 
                 104.0 
                 16.8 
                 130.0 
                 10.2 
               
               
                 AD-961037.1 
                 73.0 
                 6.1 
                 55.0 
                 6.2 
                 97.9 
                 11.1 
                 130.1 
                 15.6 
               
               
                 AD-961043.1 
                 113.8 
                 12.2 
                 101.4 
                 8.0 
                 136.2 
                 19.6 
                 131.8 
                 6.0 
               
               
                 AD-798031.1 
                 80.4 
                 12.9 
                 69.9 
                 8.2 
                 86.4 
                 19.4 
                 132.3 
                 18.6 
               
               
                 AD-961232.1 
                 106.8 
                 22.1 
                 102.7 
                 18.1 
                 127.4 
                 26.3 
                 132.5 
                 16.0 
               
               
                 AD-996036.1 
                 110.9 
                 9.5 
                 102.8 
                 7.5 
                 123.2 
                 6.6 
                 132.5 
                 11.3 
               
               
                 AD-995573.1 
                 144.5 
                 17.9 
                 109.1 
                 8.6 
                 139.9 
                 28.2 
                 132.8 
                 12.3 
               
               
                 AD-995587.1 
                 141.8 
                 15.3 
                 112.6 
                 18.3 
                 141.1 
                 16.7 
                 133.9 
                 11.4 
               
               
                 AD-961295.1 
                 100.5 
                 8.5 
                 78.2 
                 5.3 
                 76.0 
                 6.5 
                 135.3 
                 15.9 
               
               
                 AD-999596.1 
                 102.6 
                 5.7 
                 93.6 
                 13.8 
                 131.0 
                 1.9 
                 136.1 
                 27.0 
               
               
                 AD-996619.1 
                 94.9 
                 5.1 
                 96.5 
                 13.6 
                 118.2 
                 17.2 
                 136.6 
                 10.8 
               
               
                 AD-795826.1 
                 70.1 
                 11.1 
                 56.1 
                 13.8 
                 100.3 
                 7.9 
                 136.7 
                 18.9 
               
               
                 AD-998015.1 
                 82.1 
                 2.8 
                 63.8 
                 3.4 
                 107.7 
                 11.0 
                 137.3 
                 5.5 
               
               
                 AD-1010675.1 
                 90.0 
                 16.1 
                 76.8 
                 13.1 
                 99.9 
                 24.3 
                 137.7 
                 24.0 
               
               
                 AD-1010681.1 
                 102.6 
                 13.3 
                 91.2 
                 26.3 
                 119.3 
                 18.8 
                 138.2 
                 22.6 
               
               
                 AD-995823.1 
                 77.4 
                 5.2 
                 69.6 
                 8.2 
                 127.3 
                 13.1 
                 138.3 
                 14.2 
               
               
                 AD-999215.1 
                 97.0 
                 18.5 
                 87.0 
                 4.4 
                 113.7 
                 16.5 
                 139.4 
                 19.5 
               
               
                 AD-801020.2 
                 78.5 
                 6.5 
                 66.2 
                 5.4 
                 101.1 
                 4.1 
                 139.7 
                 11.6 
               
               
                 AD-999348.1 
                 87.0 
                 12.7 
                 80.6 
                 3.6 
                 111.4 
                 12.2 
                 141.1 
                 13.3 
               
               
                 AD-996533.1 
                 110.0 
                 6.7 
                 110.4 
                 11.6 
                 148.8 
                 15.8 
                 146.0 
                 22.6 
               
               
                 AD-961036.1 
                 129.0 
                 17.9 
                 106.4 
                 13.8 
                 135.2 
                 13.4 
                 149.0 
                 12.0 
               
               
                 AD-961231.1 
                 131.4 
                 20.6 
                 127.4 
                 10.6 
                 126.4 
                 31.6 
                 155.5 
                 24.9 
               
               
                 AD-997715.1 
                 117.7 
                 16.6 
                 110.1 
                 14.6 
                 129.0 
                 20.5 
                 157.2 
                 35.0 
               
               
                 AD-801309.2 
                 59.4 
                 6.8 
                 63.1 
                 7.3 
                 83.8 
                 4.8 
                 158.4 
                 66.9 
               
               
                   
               
            
           
         
       
     
     The results of the multi-dose screen in BE(2)-C cells expressing a SCN9A gene and treated with an exemplary set of SCN9A siRNAs is shown in Table 17 (correspond to siRNAs in Table 13A). The experiment was performed at a 0.1 nM, 1 nM, 10 nM, and 50 nM final duplex concentrations and the data are expressed as percent message remaining relative to non-targeting control. 
     Of the siRNA duplexes evaluated at 50 nM in Table 17, 5 achieved ≥90% knockdown of SCN9A, 52 achieved ≥80% knockdown of SCN9A, 180 achieved ≥60% knockdown of SCN9A, 254 achieved ≥30% knockdown of SCN9A, 261 achieved ≥20% knockdown of SCN9A, and 264 achieved ≥10% knockdown of SCN9A. 
     Of the siRNA duplexes evaluated at 10 nM in Table 17, 3 achieved ≥90% knockdown of SCN9A, 59 achieved ≥80% knockdown of SCN9A, 174 achieved ≥60% knockdown of SCN9A, 233 achieved ≥30% knockdown of SCN9A, 249 achieved ≥20% knockdown of SCN9A, and 255 achieved ≥10% knockdown of SCN9A. 
     Of the siRNA duplexes evaluated at 1 nM in Table 17, 2 achieved ≥90% knockdown of SCN9A, 15 achieved ≥80% knockdown of SCN9A, 109 achieved ≥60% knockdown of SCN9A, 228 achieved ≥30% knockdown of SCN9A, 247 achieved ≥20% knockdown of SCN9A, and 258 achieved ≥10% knockdown of SCN9A. 
     Of the siRNA duplexes evaluated at 0.1 nM in Table 17, 9 achieved ≥70% knockdown of SCN9A, 30 achieved ≥60% knockdown of SCN9A, 77 achieved ≥50% knockdown of SCN9A, 178 achieved ≥30% knockdown of SCN9A, 203 achieved ≥20% knockdown of SCN9A, and 225 achieved ≥10% knockdown of SCN9A. 
     
       
         
           
               
             
               
                 TABLE 17 
               
             
            
               
                   
               
               
                 SCN9A in vitro multidose-dose screen with one set of exemplary human SCN9A siRNA duplexes (*the 
               
               
                 number following the decimal point in a duplex name merely refers to a batch production number) 
               
            
           
           
               
               
               
               
               
            
               
                   
                 50 nM 
                 10 nM 
                 1 nM 
                 0.1 nM 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Mis- 
                 % message 
                   
                 % message 
                   
                 % message 
                   
                 % message 
                   
               
               
                 Duplex 
                 SC9NA 
                 match 
                 remaining 
                 St. Dev. 
                 remaining 
                 St. Dev. 
                 remaining 
                 St. Dev. 
                 remaining 
                 St. Dev. 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 AD-1251302.1 
                 HsSCN9A_ORF1rp 
                 3 
                 88.2 
                 15.4 
                 75.7 
                 19.8 
                 81.6 
                 6.1 
                 70.8 
                 2.7 
               
               
                 AD-1251303.1 
                 HsSCN9A_ORF1rp 
                 2 
                 73.2 
                 8.7 
                 84.2 
                 27.4 
                 61.9 
                 8.6 
                 68.2 
                 3.6 
               
               
                 AD-1251304.1 
                 HsSCN9A_ORF1rp 
                 1 
                 25.8 
                 4.0 
                 53.2 
                 23.0 
                 44.2 
                 5.1 
                 43.9 
                 1.7 
               
               
                 AD-1251305.1 
                 HsSCN9A_ORF1rp 
                 1 
                 25.6 
                 4.7 
                 18.8 
                 3.3 
                 38.3 
                 6.9 
                 49.1 
                 3.4 
               
               
                 AD-1251306.1 
                 HsSCN9A_ORF1rp 
                 1 
                 27.7 
                 5.2 
                 20.7 
                 2.1 
                 40.2 
                 9.0 
                 55.6 
                 5.5 
               
               
                 AD-1251307.1 
                 HsSCN9A_ORF1rp 
                 1 
                 40.5 
                 2.1 
                 64.0 
                 22.8 
                 56.1 
                 4.4 
                 68.3 
                 4.1 
               
               
                 AD-1251315.1 
                 HsSCN9A_ORF1rp 
                 1 
                 26.6 
                 1.3 
                 24.7 
                 1.5 
                 44.7 
                 4.8 
                 46.9 
                 2.6 
               
               
                 AD-1251310.1 
                 HsSCN9A_ORF1rp 
                 1 
                 32.0 
                 1.1 
                 28.3 
                 2.0 
                 48.9 
                 5.1 
                 59.8 
                 5.1 
               
               
                 AD-961179.3 
                 HsSCN9A_ORF1rp 
                 1 
                 33.9 
                 2.9 
                 29.3 
                 3.2 
                 42.5 
                 4.8 
                 49.9 
                 3.7 
               
               
                 AD-1251308.1 
                 HsSCN9A_ORF1rp 
                 1 
                 40.3 
                 3.7 
                 29.4 
                 2.8 
                 49.1 
                 6.4 
                 58.1 
                 3.5 
               
               
                 AD-1251314.1 
                 HsSCN9A_ORF1rp 
                 1 
                 41.7 
                 3.0 
                 34.1 
                 2.9 
                 58.0 
                 8.3 
                 58.8 
                 3.4 
               
               
                 AD-1251309.2 
                 HsSCN9A_ORF1rp 
                 1 
                 48.4 
                 3.9 
                 34.4 
                 1.1 
                 66.1 
                 10.1 
                 60.3 
                 4.9 
               
               
                 AD-1251316.1 
                 HsSCN9A_ORF1rp 
                 1 
                 43.4 
                 2.5 
                 37.1 
                 6.7 
                 49.8 
                 1.7 
                 72.8 
                 16.2 
               
               
                 AD-1251317.1 
                 HsSCN9A_ORF1rp 
                 1 
                 27.2 
                 2.9 
                 58.7 
                 43.5 
                 34.3 
                 2.0 
                 40.3 
                 2.7 
               
               
                 AD-1251311.1 
                 HsSCN9A_ORF1rp 
                 1 
                 45.9 
                 14.8 
                 58.9 
                 37.2 
                 59.2 
                 4.8 
                 69.3 
                 24.8 
               
               
                 AD-1251309.1 
                 HsSCN9A_ORF1rp 
                 1 
                 53.5 
                 3.2 
                 80.0 
                 46.2 
                 57.9 
                 4.1 
                 64.7 
                 5.8 
               
               
                 AD-1251318.1 
                 HsSCN9A_ORF1rp 
                 1 
                 23.3 
                 1.3 
                 18.0 
                 2.7 
                 30.2 
                 5.3 
                 37.7 
                 7.8 
               
               
                 AD-1251319.1 
                 HsSCN9A_ORF1rp 
                 1 
                 25.4 
                 0.9 
                 21.3 
                 1.9 
                 48.0 
                 13.8 
                 46.8 
                 1.6 
               
               
                 AD-1251313.1 
                 HsSCN9A_ORF1rp 
                 1 
                 36.3 
                 1.6 
                 30.8 
                 7.3 
                 53.0 
                 4.0 
                 65.6 
                 4.2 
               
               
                 AD-1251312.1 
                 HsSCN9A_ORF1rp 
                 1 
                 54.4 
                 6.9 
                 38.8 
                 2.4 
                 66.9 
                 5.4 
                 69.3 
                 3.5 
               
               
                 AD-1251320.1 
                 HsSCN9A_ORF1rp 
                 1 
                 26.5 
                 2.0 
                 43.2 
                 29.5 
                 39.8 
                 5.2 
                 47.7 
                 5.3 
               
               
                 AD-1251321.1 
                 HsSCN9A_ORF1rp 
                 0 
                 19.3 
                 3.3 
                 15.3 
                 3.5 
                 38.1 
                 12.7 
                 36.2 
                 2.4 
               
               
                 AD-1251323.1 
                 HsSCN9A_ORF1rp 
                 0 
                 17.3 
                 4.1 
                 18.9 
                 9.8 
                 27.2 
                 4.7 
                 35.9 
                 5.5 
               
               
                 AD-1251322.1 
                 HsSCN9A_ORF1rp 
                 1 
                 16.3 
                 2.4 
                 22.5 
                 10.0 
                 27.5 
                 1.2 
                 40.8 
                 5.4 
               
               
                 AD-1251325.1 
                 HsSCN9A_ORF1rp 
                 1 
                 19.6 
                 2.8 
                 30.6 
                 15.0 
                 29.2 
                 5.3 
                 35.4 
                 1.6 
               
               
                 AD-1251324.1 
                 HsSCN9A_ORF1rp 
                 1 
                 22.0 
                 9.0 
                 33.4 
                 14.4 
                 27.5 
                 6.9 
                 33.2 
                 2.7 
               
               
                 AD-1251249.1 
                 HsSCN9A_ORF1rp 
                 1 
                 25.0 
                 2.2 
                 15.0 
                 1.3 
                 29.6 
                 6.1 
                 36.6 
                 5.4 
               
               
                 AD-1251254.1 
                 HsSCN9A_ORF1rp 
                 1 
                 19.3 
                 1.3 
                 17.6 
                 2.9 
                 30.4 
                 4.1 
                 43.8 
                 20.0 
               
               
                 AD-1251248.1 
                 HsSCN9A_ORF1rp 
                 1 
                 29.8 
                 5.2 
                 17.8 
                 2.4 
                 35.8 
                 4.6 
                 47.0 
                 6.4 
               
               
                 AD-1251284.1 
                 HsSCN9A_ORF1rp 
                 1 
                 21.8 
                 1.9 
                 19.0 
                 2.4 
                 30.1 
                 3.3 
                 32.2 
                 1.8 
               
               
                 AD-1251253.1 
                 HsSCN9A_ORF1rp 
                 1 
                 28.6 
                 2.0 
                 22.0 
                 3.0 
                 48.2 
                 5.9 
                 102.4 
                 47.0 
               
               
                 AD-1251286.1 
                 HsSCN9A_ORF1rp 
                 1 
                 25.4 
                 4.1 
                 22.6 
                 3.5 
                 36.5 
                 5.9 
                 37.3 
                 3.7 
               
               
                 AD-1251282.1 
                 HsSCN9A_ORF1rp 
                 1 
                 30.9 
                 8.8 
                 22.8 
                 9.3 
                 36.9 
                 5.5 
                 50.8 
                 3.4 
               
               
                 AD-1010661.3 
                 HsSCN9A_ORF1rp 
                 1 
                 34.2 
                 4.6 
                 23.1 
                 5.5 
                 48.8 
                 11.5 
                 56.1 
                 6.3 
               
               
                 AD-795305.3 
                 HsSCN9A_ORF1rp 
                 1 
                 23.6 
                 3.8 
                 23.4 
                 16.3 
                 47.7 
                   
                 36.0 
                 2.0 
               
               
                 AD-1251250.1 
                 HsSCN9A_ORF1rp 
                 1 
                 22.9 
                 1.8 
                 24.6 
                 12.5 
                 30.6 
                 3.7 
                 43.6 
                 4.7 
               
               
                 AD-1251283.1 
                 HsSCN9A_ORF1rp 
                 1 
                 28.9 
                 6.0 
                 26.8 
                 9.0 
                 36.5 
                 7.8 
                 45.0 
                 5.7 
               
               
                 AD-1251281.1 
                 HsSCN9A_ORF1rp 
                 1 
                 33.7 
                 11.0 
                 26.8 
                 5.7 
                 54.1 
                 5.9 
                 61.1 
                 2.6 
               
               
                 AD-1251255.1 
                 HsSCN9A_ORF1rp 
                 1 
                 30.5 
                 1.9 
                 26.9 
                 10.7 
                 49.1 
                 8.5 
                 63.8 
                 5.7 
               
               
                 AD-1251289.1 
                 HsSCN9A_ORF1rp 
                 1 
                 26.4 
                 1.6 
                 35.1 
                 5.9 
                 49.0 
                 4.2 
                 68.1 
                 9.7 
               
               
                 AD-1251252.1 
                 HsSCN9A_ORF1rp 
                 1 
                 28.1 
                 1.9 
                 44.5 
                 31.9 
                 44.9 
                 4.2 
                 58.8 
                 6.1 
               
               
                 AD-1251285.1 
                 HsSCN9A_ORF1rp 
                 1 
                 34.3 
                 5.6 
                 47.3 
                 33.3 
                 50.0 
                 5.3 
                 60.3 
                 8.1 
               
               
                 AD-1251291.1 
                 HsSCN9A_ORF1rp 
                 1 
                 39.7 
                 7.7 
                 48.5 
                 18.9 
                 64.0 
                 15.2 
                 64.5 
                 3.5 
               
               
                 AD-1251290.1 
                 HsSCN9A_ORF1rp 
                 1 
                 23.7 
                 2.0 
                 66.4 
                 27.7 
                 36.9 
                 2.3 
                 42.2 
                 3.7 
               
               
                 AD-1251251.1 
                 HsSCN9A_ORF1rp 
                 1 
                 17.9 
                 0.8 
                 13.9 
                 1.9 
                 27.8 
                 4.8 
                 35.4 
                 3.9 
               
               
                 AD-1251287.1 
                 HsSCN9A_ORF1rp 
                 1 
                 27.9 
                 7.8 
                 25.9 
                 0.7 
                 49.1 
                 10.2 
                 55.2 
                 7.4 
               
               
                 AD-1251288.1 
                 HsSCN9A_ORF1rp 
                 1 
                 21.3 
                 4.1 
                 29.0 
                 7.5 
                 51.3 
                 18.3 
                 41.2 
                 2.0 
               
               
                 AD-1251326.1 
                 HsSCN9A_ORF1rp 
                 1 
                 32.0 
                 5.4 
                 24.4 
                 0.2 
                 52.9 
                 3.2 
                 63.0 
                 3.0 
               
               
                 AD-1251327.1 
                 HsSCN9A_ORF1rp 
                 1 
                 67.9 
                 7.7 
                 74.9 
                 27.8 
                 69.2 
                 9.1 
                 69.9 
                 2.9 
               
               
                 AD-1251328.1 
                 HsSCN9A_ORF1rp 
                 1 
                 19.3 
                 2.3 
                 25.3 
                 4.0 
                 27.3 
                 6.1 
                 66.1 
                 5.8 
               
               
                 AD-1251329.1 
                 HsSCN9A_ORF1rp 
                 0 
                 34.9 
                 1.9 
                 101.9 
                 3.9 
                 55.1 
                 4.7 
                 91.4 
                 8.7 
               
               
                 AD-1251330.1 
                 HsSCN9A_ORF1rp 
                 1 
                 54.9 
                 5.1 
                 48.1 
                 3.6 
                 55.2 
                 9.0 
                 77.1 
                 10.3 
               
               
                 AD-795366.3 
                 HsSCN9A_ORF1rp 
                 1 
                 18.6 
                 5.7 
                 15.7 
                 2.4 
                 26.1 
                 8.5 
                 42.8 
                 7.0 
               
               
                 AD-1251331.1 
                 HsSCN9A_ORF1rp 
                 1 
                 17.6 
                 2.0 
                 20.9 
                 1.5 
                 30.8 
                 6.1 
                 56.5 
                 4.6 
               
               
                 AD-1251334.1 
                 HsSCN9A_ORF1rp 
                 1 
                 20.1 
                 5.8 
                 26.4 
                 2.8 
                 24.2 
                 2.8 
                 37.1 
                 6.4 
               
               
                 AD-1251333.1 
                 HsSCN9A_ORF1rp 
                 1 
                 27.0 
                 1.6 
                 28.8 
                 4.2 
                 40.8 
                 4.7 
                 59.1 
                 6.6 
               
               
                 AD-1251338.1 
                 HsSCN9A_ORF1rp 
                 1 
                 28.5 
                 2.0 
                 31.6 
                 6.3 
                 47.9 
                 0.7 
                 92.7 
                 10.2 
               
               
                 AD-1251337.1 
                 HsSCN9A_ORF1rp 
                 1 
                 39.3 
                 2.5 
                 41.6 
                 5.2 
                 65.7 
                 13.5 
                 98.8 
                 6.2 
               
               
                 AD-1251336.1 
                 HsSCN9A_ORF1rp 
                 1 
                 45.9 
                 3.6 
                 54.4 
                 6.2 
                 72.8 
                 7.3 
                 106.0 
                 11.0 
               
               
                 AD-1251335.1 
                 HsSCN9A_ORF1rp 
                 1 
                 52.5 
                 6.1 
                 71.4 
                 5.5 
                 66.2 
                 6.9 
                 101.9 
                 22.0 
               
               
                 AD-1251339.1 
                 HsSCN9A_ORF1rp 
                 1 
                 25.4 
                 1.0 
                 28.3 
                 2.1 
                 51.9 
                 2.0 
                 78.1 
                 7.9 
               
               
                 AD-1251340.1 
                 HsSCN9A_ORF1rp 
                 1 
                 34.1 
                 3.9 
                 29.5 
                 5.2 
                 45.8 
                 1.2 
                 65.6 
                 8.5 
               
               
                 AD-1251341.1 
                 HsSCN9A_ORF1rp 
                 1 
                 51.9 
                 2.9 
                 48.3 
                 5.0 
                 51.3 
                 3.3 
                 60.1 
                 7.4 
               
               
                 AD-1251342.1 
                 HsSCN9A_ORF1rp 
                 1 
                 18.3 
                 4.3 
                 20.8 
                 1.3 
                 20.2 
                 2.5 
                 27.9 
                 2.1 
               
               
                 AD-1251347.1 
                 HsSCN9A_ORF1rp 
                 1 
                 25.4 
                 4.3 
                 15.9 
                 5.6 
                 34.8 
                 4.4 
                 55.2 
                 6.2 
               
               
                 AD-795371.3 
                 HsSCN9A_ORF1rp 
                 1 
                 17.3 
                 3.2 
                 19.0 
                 4.2 
                 24.1 
                 8.2 
                 43.4 
                 5.8 
               
               
                 AD-1010663.3 
                 HsSCN9A_ORF1rp 
                 1 
                 28.3 
                 2.4 
                 20.4 
                 1.6 
                 32.5 
                 3.5 
                 45.2 
                 5.2 
               
               
                 AD-1251301.1 
                 HsSCN9A_ORF1rp 
                 1 
                 26.4 
                 1.3 
                 20.4 
                 1.5 
                 39.6 
                 3.0 
                 47.9 
                 5.8 
               
               
                 AD-1251348.1 
                 HsSCN9A_ORF1rp 
                 2 
                 17.5 
                 8.4 
                 22.8 
                 2.1 
                 29.8 
                 6.8 
                 41.0 
                 5.3 
               
               
                 AD-1251343.1 
                 HsSCN9A_ORF1rp 
                 1 
                 23.1 
                 1.6 
                 23.3 
                 4.6 
                 41.3 
                 7.1 
                 63.7 
                 11.5 
               
               
                 AD-1251346.1 
                 HsSCN9A_ORF1rp 
                 1 
                 29.4 
                 3.4 
                 26.2 
                 4.3 
                 46.1 
                 2.1 
                 68.6 
                 14.2 
               
               
                 AD-1251299.1 
                 HsSCN9A_ORF1rp 
                 1 
                 32.4 
                 7.9 
                 29.5 
                 14.3 
                 48.7 
                 3.5 
                 58.7 
                 3.8 
               
               
                 AD-1251345.1 
                 HsSCN9A_ORF1rp 
                 2 
                 30.4 
                 2.1 
                 29.7 
                 3.6 
                 47.7 
                 6.3 
                 78.9 
                 7.2 
               
               
                 AD-1251349.1 
                 HsSCN9A_ORF1rp 
                 1 
                 23.8 
                 4.4 
                 31.2 
                 6.1 
                 33.6 
                 11.0 
                 55.6 
                 10.1 
               
               
                 AD-1251292.1 
                 HsSCN9A_ORF1rp 
                 1 
                 27.0 
                 3.7 
                 31.8 
                 12.7 
                 42.1 
                 6.7 
                 128.8 
                 66.1 
               
               
                 AD-1251293.1 
                 HsSCN9A_ORF1rp 
                 1 
                 32.4 
                 4.6 
                 32.5 
                 13.1 
                 43.9 
                 4.9 
                 58.5 
                 4.1 
               
               
                 AD-1251294.1 
                 HsSCN9A_ORF1rp 
                 2 
                 44.6 
                 3.5 
                 33.3 
                 3.3 
                 54.8 
                 5.2 
                 65.1 
                 0.8 
               
               
                 AD-1251344.1 
                 HsSCN9A_ORF1rp 
                 1 
                 30.0 
                 2.9 
                 33.5 
                 2.0 
                 47.0 
                 4.6 
                 81.8 
                 7.0 
               
               
                 AD-1251300.1 
                 HsSCN9A_ORF1rp 
                 1 
                 32.2 
                 4.4 
                 39.5 
                 21.6 
                 42.6 
                 3.6 
                 58.2 
                 4.4 
               
               
                 AD-1251295.1 
                 HsSCN9A_ORF1rp 
                 1 
                 31.6 
                 5.8 
                 43.2 
                 12.4 
                 64.8 
                 4.1 
                 62.3 
                 3.7 
               
               
                 AD-1251296.1 
                 HsSCN9A_ORF1rp 
                 1 
                 37.2 
                 7.3 
                 60.8 
                 31.7 
                 52.5 
                 11.4 
                 60.4 
                 7.7 
               
               
                 AD-1251350.1 
                 HsSCN9A_ORF1rp 
                 1 
                 28.0 
                 2.9 
                 29.3 
                 3.3 
                 36.9 
                 4.9 
                 67.8 
                 7.3 
               
               
                 AD-1251351.1 
                 HsSCN9A_ORF1rp 
                 1 
                 26.3 
                 2.2 
                 31.5 
                 3.6 
                 52.4 
                 5.5 
                 80.5 
                 10.0 
               
               
                 AD-1251353.1 
                 HsSCN9A_ORF1rp 
                 1 
                 25.4 
                 0.8 
                 26.4 
                 5.8 
                 39.2 
                 5.0 
                 60.7 
                 4.0 
               
               
                 AD-1251352.1 
                 HsSCN9A_ORF1rp 
                 1 
                 27.1 
                 1.4 
                 28.1 
                 3.9 
                 38.7 
                 4.4 
                 79.3 
                 7.7 
               
               
                 AD-1251298.1 
                 HsSCN9A_ORF1rp 
                 1 
                 58.5 
                 11.3 
                 34.5 
                 6.3 
                 61.7 
                 6.7 
                 61.1 
                 3.2 
               
               
                 AD-1251297.1 
                 HsSCN9A_ORF1rp 
                 1 
                 50.7 
                 9.4 
                 45.4 
                 19.9 
                 64.9 
                 11.2 
                 68.5 
                 3.1 
               
               
                 AD-1251354.1 
                 HsSCN9A_ORF1rp 
                 1 
                 25.6 
                 3.7 
                 25.2 
                 4.1 
                 36.5 
                 3.5 
                 61.3 
                 10.9 
               
               
                 AD-1251355.1 
                 HsSCN9A_ORF1rp 
                 1 
                 12.9 
                 6.8 
                 15.5 
                 5.4 
                 14.6 
                 2.6 
                 27.9 
                 3.6 
               
               
                 AD-1251356.1 
                 HsSCN9A_ORF1rp 
                 1 
                 21.4 
                 6.6 
                 30.9 
                 2.2 
                 21.2 
                 13.2 
                 45.7 
                 5.6 
               
               
                 AD-1251357.1 
                 HsSCN9A_ORF1rp 
                 1 
                 29.0 
                 1.0 
                 31.8 
                 4.9 
                 49.7 
                 14.6 
                 60.1 
                 17.7 
               
               
                 AD-1251358.1 
                 HsSCN9A_ORF1rp 
                 1 
                 19.3 
                 1.3 
                 26.5 
                 6.7 
                 52.1 
                 6.5 
                 76.8 
                 36.1 
               
               
                 AD-1251359.1 
                 HsSCN9A_ORF1rp 
                 0 
                 16.3 
                 2.0 
                 16.5 
                 3.6 
                 26.8 
                 12.1 
                 47.0 
                 25.6 
               
               
                 AD-1251360.1 
                 HsSCN9A_ORF1rp 
                 0 
                 23.5 
                 2.1 
                 23.0 
                 3.3 
                 33.2 
                 9.9 
                 62.8 
                 5.0 
               
               
                 AD-1251361.1 
                 HsSCN9A_ORF1rp 
                 0 
                 20.0 
                 1.2 
                 19.8 
                 4.4 
                 29.8 
                 8.5 
                 46.8 
                 5.4 
               
               
                 AD-1251363.1 
                 HsSCN9A_ORF1rp 
                 0 
                 9.4 
                 3.0 
                 10.9 
                 1.9 
                 14.7 
                 2.8 
                 34.0 
                 12.5 
               
               
                 AD-1251362.1 
                 HsSCN9A_ORF1rp 
                 0 
                 12.5 
                 1.7 
                 13.3 
                 1.5 
                 24.3 
                 5.1 
                 36.3 
                 7.1 
               
               
                 AD-1251364.1 
                 HsSCN9A_ORF1rp 
                 1 
                 12.5 
                 4.1 
                 14.8 
                 1.7 
                 11.8 
                 6.0 
                 25.0 
                 1.5 
               
               
                 AD-1251372.1 
                 HsSCN9A_ORF1rp 
                 1 
                 21.3 
                 3.1 
                 11.0 
                 6.1 
                 23.6 
                 4.6 
                 58.5 
                 8.3 
               
               
                 AD-1251366.1 
                 HsSCN9A_ORF1rp 
                 1 
                 14.5 
                 0.6 
                 13.8 
                 3.9 
                 25.6 
                 3.5 
                 62.5 
                 3.0 
               
               
                 AD-1251367.1 
                 HsSCN9A_ORF1rp 
                 1 
                 15.0 
                 2.6 
                 16.2 
                 1.0 
                 27.2 
                 5.6 
                 56.8 
                 4.9 
               
               
                 AD-795634.4 
                 HsSCN9A_ORF1rp 
                 1 
                 14.1 
                 0.7 
                 16.8 
                 1.9 
                 28.4 
                 7.4 
                 64.4 
                 2.7 
               
               
                 AD-1251369.1 
                 HsSCN9A_ORF1rp 
                 2 
                 19.5 
                 0.8 
                 17.4 
                 2.7 
                 20.9 
                 6.9 
                 41.7 
                 11.7 
               
               
                 AD-1251368.1 
                 HsSCN9A_ORF1rp 
                 1 
                 17.8 
                 1.5 
                 19.2 
                 2.7 
                 33.2 
                 2.1 
                 50.7 
                 2.7 
               
               
                 AD-1251373.1 
                 HsSCN9A_ORF1rp 
                 1 
                 25.3 
                 1.3 
                 22.3 
                 2.8 
                 30.5 
                 15.1 
                 42.5 
                 22.0 
               
               
                 AD-1251365.1 
                 HsSCN9A_ORF1rp 
                 1 
                 17.8 
                 1.2 
                 22.4 
                 2.2 
                 28.4 
                 4.6 
                 49.9 
                 11.6 
               
               
                 AD-1251370.1 
                 HsSCN9A_ORF1rp 
                 1 
                 26.1 
                 3.8 
                 24.4 
                 3.3 
                 10.0 
                 2.8 
                 49.2 
                 12.9 
               
               
                 AD-1251374.1 
                 HsSCN9A_ORF1rp 
                 1 
                 23.6 
                 4.5 
                 27.5 
                 6.8 
                 20.9 
                 9.6 
                 69.2 
                 12.6 
               
               
                 AD-1251375.1 
                 HsSCN9A_ORF1rp 
                 0 
                 22.3 
                 1.0 
                 21.8 
                 9.4 
                 30.5 
                 14.9 
                 63.2 
                 2.8 
               
               
                 AD-1251371.1 
                 HsSCN9A_ORF1rp 
                 1 
                 29.4 
                 2.4 
                 27.1 
                 2.4 
                 25.0 
                 6.3 
                 65.7 
                 8.7 
               
               
                 AD-1251376.1 
                 HsSCN9A_ORF1rp 
                 1 
                 15.5 
                 2.3 
                 14.2 
                 4.8 
                 16.8 
                 4.7 
                 27.4 
                 7.1 
               
               
                 AD-1251377.1 
                 HsSCN9A_ORF1rp 
                 1 
                 10.7 
                 6.8 
                 15.6 
                 2.6 
                 10.1 
                 3.8 
                 22.6 
                 5.2 
               
               
                 AD-1251378.1 
                 HsSCN9A_ORF1rp 
                 1 
                 20.9 
                 1.8 
                 21.1 
                 3.7 
                 10.0 
                 5.3 
                 48.6 
                 19.4 
               
               
                 AD-1251379.1 
                 HsSCN9A_ORF1rp 
                 1 
                 39.1 
                 4.1 
                 42.8 
                 3.2 
                 53.8 
                 8.1 
                 96.8 
                 2.1 
               
               
                 AD-1251380.1 
                 HsSCN9A_ORF1rp 
                 0 
                 22.4 
                 3.5 
                 21.1 
                 1.1 
                 22.0 
                 4.9 
                 50.0 
                 2.7 
               
               
                 AD-1251381.1 
                 HsSCN9A_ORF1rp 
                 0 
                 22.0 
                 1.9 
                 22.1 
                 2.9 
                 32.0 
                 8.8 
                 51.8 
                 2.8 
               
               
                 AD-1251382.1 
                 HsSCN9A_ORF1rp 
                 1 
                 25.7 
                 2.1 
                 20.8 
                 4.3 
                 40.1 
                 15.4 
                 76.5 
                 9.5 
               
               
                 AD-1251384.1 
                 HsSCN9A_ORF1rp 
                 1 
                 15.0 
                 0.8 
                 11.8 
                 4.4 
                 20.7 
                 1.8 
                 40.7 
                 1.4 
               
               
                 AD-1251274.2 
                 HsSCN9A_ORF1rp 
                 1 
                 22.3 
                 1.4 
                 14.2 
                 5.0 
                 29.3 
                 2.4 
                 38.5 
                 4.7 
               
               
                 AD-961188.3 
                 HsSCN9A_ORF1rp 
                 1 
                 20.9 
                 1.1 
                 14.8 
                 1.8 
                 35.5 
                 5.8 
                 49.9 
                 4.7 
               
               
                 AD-1251383.1 
                 HsSCN9A_ORF1rp 
                 1 
                 16.6 
                 2.2 
                 14.8 
                 3.3 
                 27.8 
                 6.5 
                 47.5 
                 6.1 
               
               
                 AD-1251269.1 
                 HsSCN9A_ORF1rp 
                 1 
                 23.0 
                 6.7 
                 15.5 
                 1.4 
                 41.6 
                 17.6 
                 43.6 
                 4.3 
               
               
                 AD-1251270.1 
                 HsSCN9A_ORF1rp 
                 1 
                 22.1 
                 2.9 
                 16.8 
                 4.6 
                 47.0 
                 8.0 
                 60.8 
                 4.2 
               
               
                 AD-1251268.1 
                 HsSCN9A_ORF1rp 
                 1 
                 20.3 
                 3.0 
                 17.1 
                 6.6 
                 46.2 
                 12.4 
                 46.8 
                 4.1 
               
               
                 AD-1251274.1 
                 HsSCN9A_ORF1rp 
                 1 
                 16.9 
                 3.7 
                 17.9 
                 6.9 
                 34.3 
                 5.2 
                 104.5 
                 47.1 
               
               
                 AD-1251271.1 
                 HsSCN9A_ORF1rp 
                 1 
                 23.6 
                 2.1 
                 19.9 
                 3.1 
                 35.2 
                 1.9 
                 53.7 
                 5.6 
               
               
                 AD-1251275.2 
                 HsSCN9A_ORF1rp 
                 1 
                 23.0 
                 4.1 
                 26.0 
                 7.7 
                 54.8 
                 20.9 
                 51.3 
                 2.6 
               
               
                 AD-1251275.1 
                 HsSCN9A_ORF1rp 
                 1 
                 21.0 
                 3.5 
                 38.9 
                 22.9 
                 43.9 
                 15.8 
                 51.1 
                 6.7 
               
               
                 AD-1251385.1 
                 HsSCN9A_ORF1rp 
                 1 
                 8.9 
                 3.7 
                 9.4 
                 4.8 
                 11.9 
                 6.0 
                 30.3 
                 5.2 
               
               
                 AD-1251272.1 
                 HsSCN9A_ORF1rp 
                 1 
                 22.0 
                 2.4 
                 19.3 
                 6.8 
                 31.8 
                 2.2 
                 54.8 
                 4.8 
               
               
                 AD-1251386.1 
                 HsSCN9A_ORF1rp 
                 0 
                 24.8 
                 2.7 
                 26.0 
                 2.1 
                 27.1 
                 13.8 
                 47.2 
                 17.2 
               
               
                 AD-1251273.1 
                 HsSCN9A_ORF1rp 
                 1 
                 24.4 
                 1.5 
                 50.5 
                 19.9 
                 35.7 
                 7.0 
                 49.2 
                 1.9 
               
               
                 AD-1251390.1 
                 HsSCN9A_ORF1rp 
                 1 
                 23.4 
                 1.8 
                 13.0 
                 4.8 
                 37.9 
                 11.8 
                 59.5 
                 9.9 
               
               
                 AD-1251398.1 
                 HsSCN9A_ORF1rp 
                 1 
                 19.9 
                 10.8 
                 16.2 
                 3.1 
                 14.6 
                 6.5 
                 47.5 
                 8.8 
               
               
                 AD-1251396.1 
                 HsSCN9A_ORF1rp 
                 1 
                 23.8 
                 1.5 
                 17.1 
                 4.6 
                 31.1 
                 8.8 
                 55.7 
                 3.6 
               
               
                 AD-1251399.1 
                 HsSCN9A_ORF1rp 
                 1 
                 20.2 
                 4.6 
                 17.6 
                 3.9 
                 19.9 
                 6.1 
                 39.4 
                 17.9 
               
               
                 AD-795913.3 
                 HsSCN9A_ORF1rp 
                 1 
                 19.2 
                 1.0 
                 18.1 
                 2.2 
                 31.3 
                 8.2 
                 62.2 
                 3.8 
               
               
                 AD-1251400.1 
                 HsSCN9A_ORF1rp 
                 1 
                 22.4 
                 3.4 
                 19.1 
                 2.1 
                 29.6 
                 14.6 
                 58.7 
                 5.9 
               
               
                 AD-1251388.1 
                 HsSCN9A_ORF1rp 
                 1 
                 21.1 
                 1.8 
                 21.5 
                 2.8 
                 33.9 
                 13.3 
                 62.8 
                 6.4 
               
               
                 AD-1251397.1 
                 HsSCN9A_ORF1rp 
                 1 
                 30.5 
                 2.0 
                 24.4 
                 12.3 
                 51.6 
                 11.2 
                 63.9 
                 12.3 
               
               
                 AD-1251395.1 
                 HsSCN9A_ORF1rp 
                 1 
                 29.4 
                 4.9 
                 26.1 
                 5.4 
                 40.4 
                 12.2 
                 66.6 
                 8.5 
               
               
                 AD-1251387.1 
                 HsSCN9A_ORF1rp 
                 1 
                 27.9 
                 1.4 
                 28.4 
                 3.1 
                 43.0 
                 18.2 
                 80.9 
                 9.0 
               
               
                 AD-1251389.1 
                 HsSCN9A_ORF1rp 
                 1 
                 37.3 
                 2.3 
                 35.9 
                 9.6 
                 60.0 
                 7.4 
                 87.0 
                 15.3 
               
               
                 AD-1251393.1 
                 HsSCN9A_ORF1rp 
                 1 
                 39.6 
                 2.8 
                 41.8 
                 6.2 
                 60.0 
                 21.7 
                 105.3 
                 8.9 
               
               
                 AD-1251394.1 
                 HsSCN9A_ORF1rp 
                 1 
                 50.4 
                 2.6 
                 42.5 
                 11.2 
                 83.4 
                 17.4 
                 98.1 
                 10.9 
               
               
                 AD-1251401.1 
                 HsSCN9A_ORF1rp 
                 1 
                 59.1 
                 3.9 
                 46.0 
                 9.7 
                 51.5 
                 22.8 
                 77.7 
                 15.2 
               
               
                 AD-1251391.1 
                 HsSCN9A_ORF1rp 
                 1 
                 10.1 
                 6.8 
                 16.4 
                 8.0 
                 15.4 
                 3.1 
                 47.9 
                 20.6 
               
               
                 AD-1251392.1 
                 HsSCN9A_ORF1rp 
                 1 
                 22.9 
                 2.8 
                 20.8 
                 5.9 
                 21.1 
                 5.7 
                 71.0 
                 16.2 
               
               
                 AD-1251402.1 
                 HsSCN9A_ORF1rp 
                 1 
                 45.1 
                 7.4 
                 40.7 
                 6.9 
                 87.2 
                 6.8 
                 86.2 
                 10.2 
               
               
                 AD-1251403.1 
                 HsSCN9A_ORF1rp 
                 1 
                 35.1 
                 2.3 
                 31.3 
                 3.4 
                 47.0 
                 8.7 
                 62.7 
                 3.4 
               
               
                 AD-1251404.1 
                 HsSCN9A_ORF1rp 
                 1 
                 55.3 
                 6.4 
                 58.0 
                 15.5 
                 48.7 
                 18.2 
                 73.5 
                 8.5 
               
               
                 AD-1251405.1 
                 HsSCN9A_ORF1rp 
                 1 
                 22.8 
                 2.4 
                 25.5 
                 5.8 
                 25.1 
                 12.5 
                 37.4 
                 19.6 
               
               
                 AD-1251406.1 
                 HsSCN9A_ORF2rp 
                 0 
                 29.5 
                 11.4 
                 34.2 
                 5.4 
                 26.3 
                 4.9 
                 38.7 
                 13.3 
               
               
                 AD-1251407.1 
                 HsSCN9A_ORF2rp 
                 1 
                 26.6 
                 2.6 
                 26.2 
                 2.1 
                 43.8 
                 8.8 
                 63.4 
                 16.8 
               
               
                 AD-1251408.1 
                 HsSCN9A_ORF2rp 
                 1 
                 14.1 
                 4.2 
                 17.4 
                 4.7 
                 22.3 
                 6.1 
                 54.1 
                 14.5 
               
               
                 AD-1251409.1 
                 HsSCN9A_ORF2rp 
                 0 
                 17.7 
                 2.5 
                 17.5 
                 5.5 
                 28.9 
                 7.3 
                 55.6 
                 9.0 
               
               
                 AD-1251411.1 
                 HsSCN9A_ORF2rp 
                 1 
                 11.9 
                 0.5 
                 11.5 
                 2.5 
                 16.2 
                 2.1 
                 29.2 
                 3.6 
               
               
                 AD-1251410.1 
                 HsSCN9A_ORF2rp 
                 1 
                 12.0 
                 2.1 
                 11.7 
                 2.9 
                 17.7 
                 2.5 
                 29.6 
                 7.2 
               
               
                 AD-1251412.1 
                 HsSCN9A_ORF2rp 
                 1 
                 4.7 
                 1.7 
                 7.6 
                 3.0 
                 15.2 
                 3.4 
                 23.1 
                 9.5 
               
               
                 AD-796825.3 
                 HsSCN9A_ORF2rp 
                 1 
                 5.2 
                 2.5 
                 9.6 
                 2.6 
                 16.6 
                 3.1 
                 35.0 
                 7.7 
               
               
                 AD-1251413.1 
                 HsSCN9A_ORF2rp 
                 1 
                 14.2 
                 2.9 
                 12.0 
                 1.9 
                 26.6 
                 7.3 
                 46.9 
                 4.2 
               
               
                 AD-1251414.1 
                 HsSCN9A_ORF2rp 
                 1 
                 13.6 
                 1.7 
                 15.4 
                 2.7 
                 31.7 
                 4.6 
                 64.8 
                 9.0 
               
               
                 AD-1251415.1 
                 HsSCN9A_ORF2rp 
                 1 
                 13.5 
                 0.7 
                 15.9 
                 2.4 
                 23.0 
                 3.6 
                 51.2 
                 6.1 
               
               
                 AD-1251416.1 
                 HsSCN9A_ORF2rp 
                 1 
                 12.8 
                 2.2 
                 17.3 
                 2.6 
                 31.1 
                 2.8 
                 57.0 
                 6.5 
               
               
                 AD-1251417.1 
                 HsSCN9A_ORF2rp 
                 0 
                 11.3 
                 2.4 
                 13.5 
                 3.9 
                 23.6 
                 2.2 
                 42.4 
                 10.3 
               
               
                 AD-1251418.1 
                 HsSCN9A_ORF2rp 
                 1 
                 46.4 
                 5.0 
                 48.1 
                 2.6 
                 50.6 
                 2.9 
                 57.6 
                 9.0 
               
               
                 AD-1251419.1 
                 HsSCN9A_ORF2rp 
                 1 
                 8.7 
                 1.3 
                 12.9 
                 1.4 
                 23.0 
                 2.3 
                 27.2 
                 3.2 
               
               
                 AD-1251420.1 
                 HsSCN9A_ORF2rp 
                 1 
                 15.3 
                 1.1 
                 18.7 
                 1.3 
                 35.5 
                 2.9 
                 44.8 
                 3.1 
               
               
                 AD-1251421.1 
                 HsSCN9A_ORF2rp 
                 1 
                 16.5 
                 1.2 
                 18.2 
                 2.7 
                 32.3 
                 4.0 
                 56.2 
                 6.1 
               
               
                 AD-1251422.1 
                 HsSCN9A_ORF2rp 
                 1 
                 21.9 
                 2.5 
                 23.5 
                 4.6 
                 36.5 
                 3.7 
                 68.5 
                 4.2 
               
               
                 AD-1251423.1 
                 HsSCN9A_ORF2rp 
                 1 
                 48.6 
                 3.7 
                 45.7 
                 3.8 
                 62.7 
                 3.8 
                 84.1 
                 8.5 
               
               
                 AD-1251425.1 
                 HsSCN9A_ORF2rp 
                 0 
                 18.0 
                 2.3 
                 25.7 
                 3.4 
                 28.3 
                 2.9 
                 45.7 
                 2.3 
               
               
                 AD-1251427.1 
                 HsSCN9A_ORF2rp 
                 1 
                 18.5 
                 2.3 
                 22.0 
                 1.3 
                 29.6 
                 1.3 
                 42.5 
                 3.1 
               
               
                 AD-1251426.1 
                 HsSCN9A_ORF2rp 
                 1 
                 29.7 
                 1.9 
                 29.7 
                 3.0 
                 38.7 
                 3.9 
                 67.0 
                 10.6 
               
               
                 AD-1251428.1 
                 HsSCN9A_ORF2rp 
                 1 
                 12.5 
                 0.8 
                 17.5 
                 1.9 
                 23.6 
                 0.1 
                 30.9 
                 3.4 
               
               
                 AD-797564.4 
                 HsSCN9A_ORF2rp 
                 1 
                 21.2 
                 3.5 
                 23.9 
                 6.1 
                 39.4 
                 2.3 
                 69.2 
                 7.9 
               
               
                 AD-1251434.1 
                 HsSCN9A_ORF2rp 
                 1 
                 16.3 
                 1.0 
                 25.1 
                 4.2 
                 34.4 
                 3.1 
                 39.1 
                 2.5 
               
               
                 AD-1251431.1 
                 HsSCN9A_ORF2rp 
                 2 
                 21.3 
                 3.5 
                 27.4 
                 5.5 
                 34.6 
                 5.4 
                 62.8 
                 3.1 
               
               
                 AD-1251433.1 
                 HsSCN9A_ORF2rp 
                 1 
                 22.1 
                 6.3 
                 28.4 
                 2.7 
                 39.3 
                 2.2 
                 48.6 
                 7.5 
               
               
                 AD-1251430.1 
                 HsSCN9A_ORF2rp 
                 1 
                 32.1 
                 3.3 
                 30.9 
                 4.2 
                 49.6 
                 7.5 
                 81.5 
                 6.4 
               
               
                 AD-1251429.1 
                 HsSCN9A_ORF2rp 
                 1 
                 30.0 
                 4.6 
                 33.3 
                 9.9 
                 52.0 
                 3.4 
                 92.1 
                 4.8 
               
               
                 AD-1251435.1 
                 HsSCN9A_ORF2rp 
                 1 
                 34.9 
                 6.3 
                 47.8 
                 8.5 
                 58.1 
                 7.4 
                 93.2 
                 14.2 
               
               
                 AD-1251438.1 
                 HsSCN9A_ORF2rp 
                 1 
                 20.1 
                 3.8 
                 25.1 
                 5.2 
                 35.5 
                 3.8 
                 55.5 
                 2.9 
               
               
                 AD-1251436.1 
                 HsSCN9A_ORF2rp 
                 1 
                 25.0 
                 3.0 
                 33.4 
                 11.1 
                 47.7 
                 9.8 
                 86.2 
                 24.0 
               
               
                 AD-1251437.1 
                 HsSCN9A_ORF2rp 
                 1 
                 24.6 
                 3.9 
                 34.4 
                 3.9 
                 41.8 
                 7.1 
                 65.3 
                 7.3 
               
               
                 AD-797565.4 
                 HsSCN9A_ORF2rp 
                 1 
                 28.2 
                 6.0 
                 39.3 
                 8.0 
                 54.4 
                 0.0 
                 76.1 
                 7.2 
               
               
                 AD-1251443.1 
                 HsSCN9A_ORF2rp 
                 1 
                 43.2 
                 4.4 
                 52.4 
                 3.6 
                 63.0 
                 4.0 
                 94.7 
                 10.5 
               
               
                 AD-1251444.1 
                 HsSCN9A_ORF2rp 
                 1 
                 39.3 
                 7.9 
                 54.5 
                 13.1 
                 59.8 
                 14.9 
                 72.2 
                 9.9 
               
               
                 AD-1251442.1 
                 HsSCN9A_ORF2rp 
                 1 
                 44.2 
                 5.8 
                 61.1 
                 9.7 
                 76.8 
                 8.9 
                 102.9 
                 5.6 
               
               
                 AD-1251441.1 
                 HsSCN9A_ORF2rp 
                 1 
                 51.0 
                 10.9 
                 71.0 
                 14.2 
                 78.9 
                 12.0 
                 119.7 
                 14.5 
               
               
                 AD-1251445.1 
                 HsSCN9A_ORF2rp 
                 0 
                 56.7 
                 7.7 
                 57.9 
                 1.8 
                 84.7 
                 14.2 
                 101.1 
                 18.9 
               
               
                 AD-1251439.1 
                 HsSCN9A_ORF2rp 
                 1 
                 21.7 
                 4.1 
                 30.7 
                 2.6 
                 35.2 
                 0.3 
                 49.0 
                 4.9 
               
               
                 AD-1251447.1 
                 HsSCN9A_ORF2rp 
                 0 
                 34.1 
                 3.4 
                 32.8 
                 4.6 
                 47.4 
                 1.8 
                 77.8 
                 6.3 
               
               
                 AD-1251446.1 
                 HsSCN9A_ORF2rp 
                 0 
                 29.8 
                 4.3 
                 34.6 
                 0.9 
                 46.9 
                 9.3 
                 64.0 
                 8.0 
               
               
                 AD-1251448.1 
                 HsSCN9A_ORF2rp 
                 1 
                 21.7 
                 3.3 
                 24.6 
                 3.4 
                 36.2 
                 2.3 
                 57.2 
                 8.1 
               
               
                 AD-1251450.1 
                 HsSCN9A_ORF2rp 
                 1 
                 45.4 
                 5.5 
                 64.0 
                 8.0 
                 80.5 
                 11.1 
                 90.5 
                 5.5 
               
               
                 AD-1251449.1 
                 HsSCN9A_ORF2rp 
                 1 
                 39.5 
                 1.9 
                 66.5 
                 8.8 
                 70.0 
                 13.7 
                 79.7 
                 8.7 
               
               
                 AD-1251451.1 
                 HsSCN9A_ORF2rp 
                 1 
                 151.3 
                 26.1 
                 173.5 
                 16.6 
                 134.6 
                 12.6 
                 112.4 
                 20.9 
               
               
                 AD-1251453.1 
                 HsSCN9A_3UTR2 
                 1 
                 63.7 
                 11.4 
                 79.2 
                 7.3 
                 88.9 
                 12.9 
                 94.1 
                 6.4 
               
               
                 AD-1251452.1 
                 HsSCN9A_3UTR2 
                 1 
                 71.3 
                 4.8 
                 81.2 
                 9.3 
                 85.0 
                 10.8 
                 82.6 
                 5.4 
               
               
                 AD-1251454.1 
                 HsSCN9A_3UTR2 
                 1 
                 63.5 
                 13.3 
                 79.3 
                 9.2 
                 75.8 
                 9.3 
                 97.6 
                 6.8 
               
               
                 AD-1251455.1 
                 HsSCN9A_3UTR2 
                 1 
                 51.7 
                 9.1 
                 46.1 
                 4.9 
                 63.5 
                 3.0 
                 80.6 
                 2.1 
               
               
                 AD-1251456.1 
                 HsSCN9A_3UTR2 
                 1 
                 64.3 
                 6.0 
                 90.5 
                 11.6 
                 78.4 
                 4.2 
                 101.9 
                 20.7 
               
               
                 AD-1251457.1 
                 HsSCN9A_3UTR2 
                 1 
                 79.1 
                 14.7 
                 110.0 
                 9.9 
                 115.5 
                 20.4 
                 112.2 
                 12.8 
               
               
                 AD-1251459.1 
                 HsSCN9A_3UTR2 
                 1 
                 67.9 
                 17.2 
                 95.3 
                 3.1 
                 98.0 
                 8.5 
                 98.4 
                 13.2 
               
               
                 AD-1251458.1 
                 HsSCN9A_3UTR2 
                 1 
                 65.7 
                 8.9 
                 96.7 
                 5.2 
                 89.7 
                 8.1 
                 92.6 
                 19.5 
               
               
                 AD-1251462.1 
                 HsSCN9A_3UTR2 
                 0 
                 53.7 
                 11.0 
                 45.4 
                 8.0 
                 69.1 
                 7.1 
                 92.5 
                 10.8 
               
               
                 AD-1251461.1 
                 HsSCN9A_3UTR2 
                 0 
                 39.5 
                 4.4 
                 52.2 
                 9.5 
                 52.4 
                 10.0 
                 73.4 
                 7.2 
               
               
                 AD-1251468.1 
                 HsSCN9A_3UTR2 
                 0 
                 57.2 
                 11.7 
                 69.7 
                 6.9 
                 69.9 
                 27.8 
                 96.3 
                 13.0 
               
               
                 AD-1251463.1 
                 HsSCN9A_3UTR2 
                 0 
                 59.0 
                 6.0 
                 71.0 
                 7.3 
                 76.1 
                 25.4 
                 84.5 
                 0.7 
               
               
                 AD-1251460.1 
                 HsSCN9A_3UTR2 
                 0 
                 51.7 
                 11.9 
                 76.8 
                 8.3 
                 73.0 
                 13.5 
                 78.6 
                 10.6 
               
               
                 AD-1251469.1 
                 HsSCN9A_3UTR2 
                 0 
                 58.2 
                 6.4 
                 80.9 
                 6.3 
                 86.4 
                 9.0 
                 93.7 
                 7.8 
               
               
                 AD-801647.3 
                 HsSCN9A_3UTR2 
                 0 
                 64.5 
                 11.9 
                 83.8 
                 8.1 
                 78.4 
                 5.2 
                 80.1 
                 7.9 
               
               
                 AD-1251467.1 
                 HsSCN9A_3UTR2 
                 0 
                 56.8 
                 15.2 
                 100.9 
                 15.2 
                 104.8 
                 8.8 
                 86.3 
                 15.7 
               
               
                 AD-1251466.1 
                 HsSCN9A_3UTR2 
                 0 
                 72.3 
                 18.5 
                 105.2 
                 10.0 
                 112.2 
                 10.3 
                 113.0 
                 13.4 
               
               
                 AD-1251470.1 
                 HsSCN9A_3UTR2 
                 1 
                 44.9 
                 7.9 
                 52.3 
                 9.7 
                 61.4 
                 3.7 
                 63.6 
                 4.1 
               
               
                 AD-1251471.1 
                 HsSCN9A_3UTR2 
                 1 
                 51.3 
                 2.7 
                 69.5 
                 5.1 
                 54.2 
                 3.3 
                 80.1 
                 11.2 
               
               
                 AD-1251465.1 
                 HsSCN9A_3UTR2 
                 0 
                 66.1 
                 11.7 
                 76.8 
                 7.3 
                 84.5 
                 9.8 
                 94.9 
                 20.2 
               
               
                 AD-1251472.1 
                 HsSCN9A_3UTR2 
                 1 
                 86.2 
                 4.2 
                 98.3 
                 12.9 
                 76.8 
                 8.6 
                 109.5 
                 6.7 
               
               
                 AD-1251464.1 
                 HsSCN9A_3UTR2 
                 0 
                 77.4 
                 9.8 
                 108.6 
                 13.9 
                 115.7 
                 4.2 
                 106.4 
                 8.1 
               
               
                 AD-1251473.1 
                 HsSCN9A_3UTR2 
                 0 
                 57.3 
                 1.8 
                 68.9 
                 6.8 
                 76.5 
                 6.6 
                 84.0 
                 8.0 
               
               
                 AD-1251474.1 
                 HsSCN9A_3UTR2 
                 0 
                 57.4 
                 9.3 
                 74.5 
                 4.4 
                 71.6 
                 7.7 
                 84.8 
                 1.6 
               
               
                 AD-1251475.1 
                 HsSCN9A_3UTR2 
                 1 
                 57.3 
                 6.3 
                 64.7 
                 8.7 
                 70.6 
                 9.1 
                 80.0 
                 9.0 
               
               
                 AD-1251476.1 
                 HsSCN9A_3UTR2 
                 1 
                 55.1 
                 8.6 
                 88.3 
                 7.1 
                 79.4 
                 6.6 
                 90.9 
                 18.5 
               
               
                 AD-1251279.1 
                 HsSCN9A_3UTR2 
                 0 
                 41.1 
                 2.9 
                 30.9 
                 2.1 
                 38.7 
                 4.8 
                 46.6 
                 2.3 
               
               
                 AD-1251276.1 
                 HsSCN9A_3UTR2 
                 0 
                 39.0 
                 7.0 
                 33.4 
                 11.2 
                 49.1 
                 7.2 
                 54.6 
                 8.2 
               
               
                 AD-1251280.1 
                 HsSCN9A_3UTR2 
                 0 
                 43.9 
                 2.9 
                 41.1 
                 13.8 
                 43.0 
                 4.2 
                 46.3 
                 3.9 
               
               
                 AD-1251277.1 
                 HsSCN9A_3UTR2 
                 0 
                 42.6 
                 6.4 
                 47.0 
                 24.3 
                 51.8 
                 8.4 
                 52.3 
                 4.9 
               
               
                 AD-961334.3 
                 HsSCN9A_3UTR2 
                 0 
                 52.6 
                 8.4 
                 68.4 
                 20.0 
                 52.5 
                 7.6 
                 59.3 
                 5.8 
               
               
                 AD-1251278.1 
                 HsSCN9A_3UTR2 
                 0 
                 36.6 
                 3.1 
                 45.6 
                 20.8 
                 44.7 
                 4.7 
                 47.2 
                 2.1 
               
               
                 AD-1251477.1 
                 HsSCN9A_3UTR2 
                 1 
                 46.1 
                 17.5 
                 58.6 
                 8.4 
                 90.9 
                 1.7 
                 93.4 
                 12.8 
               
               
                 AD-1251478.1 
                 HsSCN9A_3UTR2 
                 1 
                 78.6 
                 3.2 
                 82.8 
                 1.1 
                 77.7 
                 8.7 
                 112.7 
                 15.5 
               
               
                 AD-1251479.1 
                 HsSCN9A_3UTR2 
                 0 
                 81.1 
                 10.6 
                 103.1 
                 8.9 
                 91.1 
                 9.8 
                 115.5 
                 10.6 
               
               
                 AD-1251481.1 
                 HsSCN9A_3UTR2 
                 1 
                 65.0 
                 4.7 
                 76.1 
                 9.1 
                 73.4 
                 3.7 
                 98.6 
                 9.3 
               
               
                 AD-1251480.1 
                 HsSCN9A_3UTR2 
                 1 
                 69.5 
                 4.9 
                 76.6 
                 2.6 
                 88.1 
                 8.3 
                 117.5 
                 12.9 
               
               
                 AD-1251482.1 
                 HsSCN9A_3UTR2 
                 1 
                 60.8 
                 2.9 
                 65.6 
                 13.3 
                 72.6 
                 8.4 
                 91.2 
                 14.0 
               
               
                 AD-1251483.1 
                 HsSCN9A_3UTR2 
                 1 
                 62.5 
                 12.5 
                 75.6 
                 7.9 
                 75.4 
                 6.0 
                 91.5 
                 12.7 
               
               
                 AD-1251492.1 
                 HsSCN9A_3UTR2 
                 0 
                 22.3 
                 2.6 
                 29.1 
                 3.3 
                 33.3 
                 3.4 
                 52.8 
                 7.6 
               
               
                 AD-1251485.1 
                 HsSCN9A_3UTR2 
                 0 
                 27.9 
                 3.7 
                 33.9 
                 7.3 
                 41.4 
                 5.4 
                 56.2 
                 6.4 
               
               
                 AD-802471.4 
                 HsSCN9A_3UTR2 
                 0 
                 38.5 
                 4.6 
                 39.0 
                 5.3 
                 57.9 
                 8.0 
                 82.7 
                 17.2 
               
               
                 AD-1251486.1 
                 HsSCN9A_3UTR2 
                 0 
                 38.5 
                 2.8 
                 39.8 
                 8.1 
                 51.6 
                 4.4 
                 78.1 
                 11.1 
               
               
                 AD-1251484.1 
                 HsSCN9A_3UTR2 
                 0 
                 33.7 
                 2.8 
                 39.9 
                 9.1 
                 72.9 
                 27.3 
                 76.1 
                 3.9 
               
               
                 AD-1251491.1 
                 HsSCN9A_3UTR2 
                 0 
                 33.7 
                 7.5 
                 45.6 
                 5.7 
                 48.4 
                 6.8 
                 61.9 
                 11.3 
               
               
                 AD-1251487.1 
                 HsSCN9A_3UTR2 
                 0 
                 46.0 
                 7.1 
                 50.1 
                 12.4 
                 61.6 
                 10.6 
                 82.9 
                 8.4 
               
               
                 AD-1251488.1 
                 HsSCN9A_3UTR2 
                 0 
                 47.9 
                 6.4 
                 52.1 
                 6.6 
                 57.2 
                 8.0 
                 82.0 
                 7.7 
               
               
                 AD-1251490.1 
                 HsSCN9A_3UTR2 
                 0 
                 46.5 
                 12.0 
                 53.9 
                 17.4 
                 52.6 
                 4.1 
                 79.0 
                 5.3 
               
               
                 AD-1251494.1 
                 HsSCN9A_3UTR2 
                 1 
                 51.7 
                 6.1 
                 42.6 
                 2.8 
                 51.8 
                 7.3 
                 80.5 
                 5.4 
               
               
                 AD-1251493.1 
                 HsSCN9A_3UTR2 
                 0 
                 28.2 
                 1.2 
                 30.4 
                 2.3 
                 38.7 
                 3.8 
                 53.6 
                 2.8 
               
               
                 AD-1251489.1 
                 HsSCN9A_3UTR2 
                 0 
                 38.9 
                 4.4 
                 54.3 
                 8.1 
                 59.3 
                 13.6 
                 83.7 
                 16.5 
               
               
                 AD-1251495.1 
                 HsSCN9A_3UTR2 
                 1 
                 67.8 
                 6.5 
                 58.8 
                 3.1 
                 68.8 
                 14.7 
                 77.6 
                 25.9 
               
               
                 AD-1251496.1 
                 HsSCN9A_3UTR2 
                 1 
                 61.6 
                 7.8 
                 48.6 
                 5.8 
                 64.2 
                 7.1 
                 78.7 
                 7.9 
               
               
                 AD-1251497.1 
                 HsSCN9A_3UTR2 
                 1 
                 78.9 
                 10.4 
                 71.3 
                 9.4 
                 67.7 
                 5.5 
                 93.1 
                 6.0 
               
               
                 AD-1251498.1 
                 HsSCN9A_3UTR2 
                 1 
                 91.0 
                 6.2 
                 79.9 
                 14.1 
                 79.0 
                 11.5 
                 89.1 
                 10.4 
               
               
                 AD-802552.3 
                 HsSCN9A_3UTR2 
                 0 
                 45.8 
                 3.9 
                 31.8 
                 4.5 
                 60.8 
                 9.9 
                 51.1 
                 3.4 
               
               
                 AD-1251267.1 
                 HsSCN9A_3UTR2 
                 0 
                 44.9 
                 2.7 
                 32.2 
                 2.1 
                 48.4 
                 2.2 
                 55.7 
                 3.8 
               
               
                 AD-1251260.1 
                 HsSCN9A_3UTR2 
                 0 
                 48.1 
                 7.6 
                 33.0 
                 6.6 
                 59.5 
                 10.8 
                 58.4 
                 1.8 
               
               
                 AD-1251256.1 
                 HsSCN9A_3UTR2 
                 0 
                 42.3 
                 4.0 
                 33.6 
                 8.3 
                 47.5 
                 3.2 
                 52.8 
                 3.1 
               
               
                 AD-1251265.1 
                 HsSCN9A_3UTR2 
                 0 
                 50.9 
                 6.8 
                 34.5 
                 10.1 
                 60.0 
                 16.7 
                 58.4 
                 4.3 
               
               
                 AD-1251257.1 
                 HsSCN9A_3UTR2 
                 0 
                 50.0 
                 5.2 
                 40.8 
                 7.9 
                 50.1 
                 4.1 
                 65.8 
                 11.6 
               
               
                 AD-1251266.1 
                 HsSCN9A_3UTR2 
                 0 
                 52.4 
                 7.1 
                 41.8 
                 6.8 
                 58.0 
                 5.5 
                 70.0 
                 16.1 
               
               
                 AD-1251264.1 
                 HsSCN9A_3UTR2 
                 1 
                 49.2 
                 3.0 
                 47.6 
                 11.3 
                 64.5 
                 5.4 
                 71.7 
                 10.0 
               
               
                 AD-1251259.1 
                 HsSCN9A_3UTR2 
                 0 
                 49.0 
                 4.7 
                 48.9 
                 23.0 
                 49.1 
                 3.1 
                 64.4 
                 1.8 
               
               
                 AD-1251258.1 
                 HsSCN9A_3UTR2 
                 0 
                 47.3 
                 8.8 
                 54.9 
                 42.4 
                 52.1 
                 7.1 
                 52.7 
                 4.2 
               
               
                 AD-1251263.1 
                 HsSCN9A_3UTR2 
                 0 
                 30.4 
                 1.6 
                 22.8 
                 4.0 
                 67.4 
                 15.5 
                 71.5 
                 24.2 
               
               
                 AD-1251262.1 
                 HsSCN9A_3UTR2 
                 0 
                 45.1 
                 3.6 
                 30.5 
                 4.3 
                 57.8 
                 3.6 
                 57.4 
                 1.7 
               
               
                 AD-1251261.1 
                 HsSCN9A_3UTR2 
                 0 
                 43.1 
                 5.3 
                 34.1 
                 10.0 
                 47.5 
                 5.0 
                 51.5 
                 4.8 
               
               
                   
               
            
           
         
       
     
     Example 4. In Vivo Screening of SCN9A siRNA 
     Experimental Methods 
     Wildtype B6/C57 mice (Charles Rivers Laboratory) were retro-orbitally injected with human SCN9A constructs designed to span various regions of human SCN9A (e.g., the 3′ UTR_AAV1 (positions 6266 to 7998), 3′UTR-AAV2 (positions 7999 to 9750) and two open reading frames (ORF-1 (positions 299 to 2441) or ORF-2 (positions 2392 to 4354)) packaged in AAV particles (2×10 10  gc/mouse). After two weeks, mice were injected subcutaneously with 3 mg/kg of exemplary siRNAs (C16, VCP, or GalNAc) (Tables 4A, 5A, 6A, 18 (also summarized in  FIGS.  1 A- 1 C ) or 20 (also summarized in  FIGS.  3 A- 3 D ), or a PBS or non-targeting siRNA control (Table 9). On day 14 post-treatment, livers were harvested for qPCR analysis with a probe specifically recognizing SCN9A. Mouse GAPDH was used as normalization control. Relative levels of SCN9A mRNA in the liver were calculated with the delta/delta Ct method, normalized to the control groups, and is depicted as the percent message remaining in Tables 10-12, 19, and 21 below. 
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 Control siRNA Sequences 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Duplex 
                   
                   
                 Seq ID No: 
                 Modified 
                 Seq ID No: 
                 Unmodified 
               
               
                 Name 
                 Target 
                 Strand 
                 (modified) 
                 Sequences 
                 (unmodified) 
                 Sequences 
               
               
                   
               
               
                 AD- 
                 none 
                 Sense 
                 3695 
                 asascaguGfuUfCfUf 
                 3696 
                 AACAGUGUUC 
               
               
                 64228.39 
                   
                   
                   
                 ugcucuauaaL96 
                   
                 UUGCUCUAUA 
               
               
                   
                   
                   
                   
                   
                   
                 A 
               
               
                   
               
               
                 AD- 
                 mTTR 
                 Antisense 
                 3697 
                 usUfsauaGfaGfCfaa 
                 3698 
                 UUAUAGAGCA 
               
               
                 86460 
                   
                   
                   
                 gaAfcAfcuguususu 
                   
                 AGAACACUGU 
               
               
                   
                   
                   
                   
                   
                   
                 UUU 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18 
               
             
            
               
                   
               
               
                 Exemplary SCN9A duplexes investigated and corresponding chemistry that target ORF-1 
               
               
                 of SCN9A (e.g., positions 299-2441). 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. 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 SEQ ID 
                   
               
               
                 Duplex Name 
                 Strand 
                 NO: 
                 Modified Sequence 
               
               
                   
               
               
                 AD-795305.2 
                 sense 
                 5330 
                 usgsucg(Ahd)GfuAfCfAfcuuuuacugaL96 
               
               
                 (parent) 
                 anti- 
                 5346 
                 VPusCfsaguAfaAfAfguguAfcUfcgacasusu 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251249.1 
                 sense 
                 5331 
                 usgsucgaguAfCfAfcuuu(Uhd)acugaL96 
               
               
                   
                 anti- 
                 5347 
                 VPusCfsagdTadAaaguguAfcUfcgacasusu 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251251.1 
                 sense 
                 5332 
                 uscsgaguAfCfAfcuuu(Uhd)acugaL96 
               
               
                   
                 anti- 
                 5348 
                 VPusCfsagdTadAaaguguAfcUfcgascsg 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1010663.2 
                 sense 
                 5333 
                 usgsuag(Ghd)agdAadTucacuuuucaL96 
               
               
                 (parent) 
                 anti- 
                 5349 
                 VPusdGsaadAadGugaadTudCudCcuacascsa 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251301.1 
                 sense 
                 5334 
                 usgsuaggagdAaUfUfcac(Uhd)uuucaL96 
               
               
                   
                 anti- 
                 5350 
                 VPudGaadAa(G2p)ugaadTudCudCcuacascsg 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-961179.3 
                 sense 
                 5335 
                 asasggg(Ahd)aadAcdAaucuuccguaL96 
               
               
                 (parent) 
                 anti- 
                 5351 
                 VPusdAscgdGadAgauudGudTudTcccuususg 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251317.1 
                 sense 
                 5336 
                 asasgggaaaAfCfAfaucu(Uhd)ccguaL96 
               
               
                   
                 anti- 
                 5352 
                 VPudAcgdGa(A2p)gauudGuUfudTcccuususg 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251318.1 
                 sense 
                 5337 
                 asgsggaaAfaCfAfAfucuu(Chd)cguuaL96 
               
               
                   
                 anti- 
                 5353 
                 VPusAfsacdGgdAagauugUfuUfucccususu 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251323.1 
                 sense 
                 5338 
                 gsasaaa(Chd)aaUfCfUfuccguuucaaL96 
               
               
                   
                 anti- 
                 5354 
                 VPuUfgadAa(C2p)ggaagaUfudGuuuucscsc 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251325.1 
                 sense 
                 5339 
                 asasaacaauCfUfUfccgu(Uhd)ucaaaL96 
               
               
                   
                 anti- 
                 5355 
                 VPuUfugdAadAcggadAgdAuUfguuuuscsc 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-795634.3 
                 sense 
                 5340 
                 asgscau(Ahd)AfaUfGfUfuuucgaaauaL96 
               
               
                 (parent) 
                 anti- 
                 5356 
                 VPusAfsuuuCfgAfAfaacaUfuUfaugcususc 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251363.1 
                 sense 
                 5341 
                 gsasagcauadAaUfguuu(Uhd)cgaaaL96 
               
               
                   
                 anti- 
                 5357 
                 VPuUfucdGadAaacadTuUfaUfgcuucsasg 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251364.1 
                 sense 
                 5342 
                 asasgca(Uhd)aadAudGuuuucgaaaaL96 
               
               
                   
                 anti- 
                 5358 
                 VPuUfuudCgdAaaacdAuUfudAugcuuscsg 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251373.1 
                 sense 
                 5343 
                 asgscauaaaUfgUfuuu(Chd)gaaauaL96 
               
               
                   
                 anti- 
                 5359 
                 VPudAuudTc(G2p)aaaadCaUfuUfaugcuscsc 
               
               
                   
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251385.1 
                 sense 
                 5344 
                 asusgau(Chd)UfuCfUfUfugucguaguaL96 
               
               
                 (parent: AD- 
                 anti- 
                 5360 
                 VPudAcudAcdGacaadAgdAadGaucausgsu 
               
               
                 795913) 
                 sense 
                   
                   
               
               
                   
               
               
                 AD-1251391.1 
                 sense 
                 5345 
                 uscsu(Uhd)CfuUfudGucguagugaaL96 
               
               
                 (parent: AD- 
                 anti- 
                 5361 
                 VPusUfscadCu(Agn)cgacdAaAfgAfagasusc 
               
               
                 795913) 
                 sense 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 20 
               
             
            
               
                   
               
               
                 Exemplary SCN9A duplexes investigated and corresponding chemistry that target region 
               
               
                 2 of the 3′ UTR of SCN9A (HsSCN9A_3UTR2, e.g., positions 7999 to 9750), ORF-1 of SCN9A 
               
               
                 (HsSCN9A_ORF1rp, e.g., positions 299-2441), and ORF2 of SCN9A (HsSCN9A_ORF2rp, e.g., 
               
               
                 positions 2392-4345). 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) 
               
               
                 production number. The suffix can be omitted from the duplex name without changing the 
               
               
                 that merely refers to a batch chemical structure. 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Duplex 
                   
                 SEQ ID 
                   
                 Parent 
               
               
                 AAV 
                 Name 
                 Strand 
                 NO: 
                 Modified Sequence 
               
               
                   
               
               
                 HsSCN9A_ 
                 AD- 
                 sense 
                 5410 
                 csasagugUfuCfCfUfacug(Uhd) 
                 AD- 
               
               
                 3UTR2 
                 1251492.2 
                   
                   
                 caugaL96 
                 802471 
               
               
                   
                   
                 anti- 
                 5426 
                 VPuCfaudGa(C2p)aguaggAfaC 
                   
               
               
                   
                   
                 sense 
                   
                 facuugscsc 
                   
               
               
                   
                 AD- 
                 sense 
                 5411 
                 csasaca(Chd)aadTudTcuucuua 
                 Self 
               
               
                   
                 961334.2 
                   
                   
                 gcaL96 
                   
               
               
                   
                 (Parent) 
                 anti- 
                 5427 
                 VPusdGscudAadGaagadAadTu 
                   
               
               
                   
                   
                 sense 
                   
                 dGuguugsusu 
                   
               
               
                   
                 AD- 
                 sense 
                 5412 
                 csasaca(Chd)aaufUfUfcuucuu 
                 AD- 
               
               
                   
                 1251279.2 
                   
                   
                 agcaL96 
                 961334 
               
               
                   
                   
                 anti- 
                 5428 
                 VPudGcudAadGaagadAaufud 
                   
               
               
                   
                   
                 sense 
                   
                 Guguugsusu 
                   
               
               
                   
               
               
                 HsSCN9A_ 
                 AD- 
                 sense 
                 5413 
                 usgsucgaguAfCfAfcuuu(Uhd)a 
                 AD- 
               
               
                 ORF1rp 
                 1251284.2 
                   
                   
                 cugaL96 
                 1010661 
               
               
                   
                   
                 anti- 
                 5429 
                 VPusCfsagdTadAaagudGuAfcd 
                   
               
               
                   
                   
                 sense 
                   
                 Tcgacasusu 
                   
               
               
                   
                 AD- 
                 sense 
                 5414 
                 ususcug(Uhd)guAfgdGagaauu 
                 AD- 
               
               
                   
                 1251334.2 
                   
                   
                 cacaL96 
                 795366 
               
               
                   
                   
                 anti- 
                 5430 
                 VPusdGsugdAa(U2p)ucucdCu 
                   
               
               
                   
                   
                 sense 
                   
                 AfcAfcagaasgsc 
                   
               
               
                   
                 AD- 
                 sense 
                 5415 
                 asusaaa(Uhd)guUfUfUfcgaaau 
                 AD- 
               
               
                   
                 1251377.2 
                   
                   
                 ucaaL96 
                 795634 
               
               
                   
                   
                 anti- 
                 5431 
                 VPusufsgadAudTucgaaaAfcAf 
                   
               
               
                   
                   
                 sense 
                   
                 uuuausgsu 
                   
               
               
                   
                 AD- 
                 sense 
                 5416 
                 gsasucu(Uhd)CfuUfudGucgua 
                 AD- 
               
               
                   
                 1251398.2 
                   
                   
                 gugaaL96 
                 795913 
               
               
                   
                   
                 anti- 
                 5432 
                 VPuufcadCu(A2p)cgacdAaAfg 
                   
               
               
                   
                   
                 sense 
                   
                 Afagaucsgsu 
                   
               
               
                   
                 AD- 
                 sense 
                 5417 
                 gsasucu(Uhd)CfuUfudGUfcgu 
                 AD- 
               
               
                   
                 1251399.2 
                   
                   
                 agugaaL96 
                 795913 
               
               
                   
                   
                 anti- 
                 5433 
                 VPuufcadCu(A2p)cgacdAaAfg 
                   
               
               
                   
                   
                 sense 
                   
                 Afagaucsgsu 
                   
               
               
                   
                 AD- 
                 sense 
                 5418 
                 csasuga(Uhd)cudTcdTuugucgu 
                 Self 
               
               
                   
                 961188.2 
                   
                   
                 agaL96 
                   
               
               
                   
                 (Parent) 
                 anti- 
                 5434 
                 VPusdCsuadCgdAcaaadGadAg 
                   
               
               
                   
                   
                 sense 
                   
                 dAucaugsusa 
                   
               
               
                   
                 AD- 
                 sense 
                 5419 
                 csasuga(Uhd)cuufCfUfuugucg 
                 AD- 
               
               
                   
                 1251274.3 
                   
                   
                 uagaL96 
                 961188 
               
               
                   
                   
                 anti- 
                 5435 
                 VPuCfuadCgdAcaaadGadAgdA 
                   
               
               
                   
                   
                 sense 
                   
                 ucaugsusg 
                   
               
               
                   
               
               
                 HsSCN9A_ 
                 AD- 
                 sense 
                 5420 
                 ususugu(Ahd)GfaufCfUfugcaa 
                 Self 
               
               
                 ORF2rp 
                 796825.2 
                   
                   
                 uuacaL96 
                   
               
               
                   
                 (Parent) 
                 anti- 
                 5436 
                 VPusGfsuaaUfuGfCfaagaUfcUf 
                   
               
               
                   
                   
                 sense 
                   
                 acaaasasg 
                   
               
               
                   
                 AD- 
                 sense 
                 5421 
                 ususuug(Uhd)agAfUfCfuugcaa 
                 AD- 
               
               
                   
                 1251411.2 
                   
                   
                 uuaaL96 
                 796825 
               
               
                   
                   
                 anti- 
                 5437 
                 VPusufsaadTu(G2p)caagauCfu 
                   
               
               
                   
                   
                 sense 
                   
                 Afcaaagscsc 
                   
               
               
                   
                 AD- 
                 sense 
                 5422 
                 gsusaga(Uhd)CfuufgCfaauuac 
                 AD- 
               
               
                   
                 1251419.2 
                   
                   
                 cauaL96 
                 796825 
               
               
                   
                   
                 anti- 
                 5438 
                 VPudAugdGudAauugdCaAfgAf 
                   
               
               
                   
                   
                 sense 
                   
                 ucuacsgsg 
                   
               
               
                   
                 AD- 
                 sense 
                 5423 
                 usasugu(Ghd)AfaAfCfAfaaccu 
                 Self 
               
               
                   
                 797564.3 
                   
                   
                 uacgaL96 
                   
               
               
                   
                 (Parent) 
                 anti- 
                 5439 
                 VPusCfsguaAfgGfUfuuguUfuCf 
                   
               
               
                   
                   
                 sense 
                   
                 acauasasu 
                   
               
               
                   
                 AD- 
                 sense 
                 5424 
                 ususaug(Uhd)gaAfAfCfaaaccu 
                 AD- 
               
               
                   
                 1251428.2 
                   
                   
                 uacaL96 
                 1251428 
               
               
                   
                   
                 anti- 
                 5440 
                 VPudGuadAg(G2p)uuuguuufc 
                   
               
               
                   
                   
                 sense 
                   
                 Afcauaasusu 
                   
               
               
                   
                 AD- 
                 sense 
                 5425 
                 usasugugAfaAfCfAfaacc(Uhd) 
                 AD- 
               
               
                   
                 1251434.2 
                   
                   
                 uacgaL96 
                 1251428 
               
               
                   
                   
                 anti- 
                 5441 
                 VPuCfgudAa(G2p)guuuguUfu 
                   
               
               
                   
                   
                 sense 
                   
                 Cfacauasgsu 
               
               
                   
               
            
           
         
       
     
     Results 
     Table 10 (siRNA duplexes correspond to siRNA sequences in Tables 4A and 5A) demonstrates the results of the in vivo screen for the ORF-1 targeting duplexes, and includes siRNA duplexes with Fluoro and Non-Fluoro chemistries. Of the siRNA duplexes evaluated in the in vivo screen shown in Table 10, 1 achieved ≥80% knockdown of SCN9A, 8 achieved ≥60% knockdown of SCN9A, 13 achieved ≥40% knockdown of SCN9A, and 15 achieved ≥20% knockdown of SCN9A. 
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 Efficacy and duration of exemplary ORF-1 
               
               
                 targeting SCN9A siRNAs in mice 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 % message remaining at 
                   
               
               
                 Treatment* 
                 Chemistry 
                 day 14 post-treatment 
                 St. Dev. 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 PBS 
                 N/A 
                 100.00 
                 19.46 
               
               
                 Naïve (AAV-only) 
                   
                 115.79 
                 22.37 
               
               
                 AD-64228.39 (AAV- 
                 Fluoro 
                 59.06 
                 27.45 
               
               
                 control) 
               
               
                 AD-961179.2 
                 NonFluoro 
                 20.49 
                 0.95 
               
               
                 AD-795305.2 
                 Fluoro 
                 21.96 
                 5.16 
               
               
                 AD-1010661.2 
                 NonFluoro 
                 41.08 
                 6.19 
               
               
                 AD-795366.2 
                 Fluoro 
                 29.15 
                 4.74 
               
               
                 AD-1010662.2 
                 NonFluoro 
                 52.17 
                 4.57 
               
               
                 AD-795371.2 
                 Fluoro 
                 16.30 
                 6.34 
               
               
                 AD-1010663.2 
                 NonFluoro 
                 21.60 
                 1.20 
               
               
                 AD-795634.3 
                 Fluoro 
                 20.80 
                 6.50 
               
               
                 AD-795739.2 
                 Fluoro 
                 41.18 
                 10.45 
               
               
                 AD-1010664.2 
                 NonFluoro 
                 71.93 
                 4.59 
               
               
                 AD-961188.2 
                 NonFluoro 
                 38.51 
                 0.36 
               
               
                 AD-961189.2 
                 NonFluoro 
                 55.25 
                 14.04 
               
               
                 AD-795913.2 
                 Fluoro 
                 26.74 
                 5.61 
               
               
                 AD-795914.2 
                 Fluoro 
                 76.20 
                 11.80 
               
               
                 AD-961192.2 
                 NonFluoro 
                 104.26 
                 12.37 
               
               
                 AD-1010671.2 
                 NonFluoro 
                 98.29 
                 17.97 
               
               
                 AD-796618.2 
                 Fluoro 
                 57.42 
                 1.30 
               
               
                   
               
               
                 (*the number following the decimal point in a duplex name merely refers to a batch production number) 
               
            
           
         
       
     
     Table 11 (siRNA duplexes correspond to siRNA sequences in Tables 4A, 5A, and 6A) demonstrates the results of the in vivo screen for the ORF-2-targeting duplexes as well as the 3′UTR_AAV1 and 3′UTR_AAV2 targeting duplexes and includes siRNA duplexes with Fluoro, Non-Fluoro, Fluoro+GNA chemistries. Of the ORF-2 targeting siRNA duplexes evaluated in the in vivo screen shown in Table 11, 3 achieved ≥80% knockdown of SCN9A, 4 achieved ≥30% knockdown of SCN9A, and 5 achieved ≥20% knockdown of SCN9A. Of the 3′UTR_AAV1 targeting siRNA duplexes (positions 6266 to 7998) evaluated in this screen shown in Table 11, 2 achieved ≥20% knockdown of SCN9A. Of the 3′UTR_AAV2 targeting siRNA duplexes (positions 7999 to 9750) evaluated in this screen shown in Table 11, 2 achieved ≥60% knockdown of SCN9A, and 5 achieved ≥30% knockdown of SCN9A. 
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 Efficacy and duration of exemplary ORF-2 
               
               
                 and 3′UTR targeting SCN9A siRNAs in mice 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                 % message 
                   
               
               
                   
                   
                   
                 remaining at 
               
               
                   
                   
                   
                 day 14 post- 
                 St. 
               
               
                 AAV 
                 Treatment* 
                 Chemistry 
                 treatment 
                 Dev. 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 HsSCN9A_ORF2rp 
                 PBS 
                 n/a 
                 100.00 
                 13.04 
               
               
                   
                 naïve (AAV-only) 
                   
                 96.31 
                 19.26 
               
               
                   
                 AD-796825.1 
                 Fluoro 
                 12.49 
                 2.90 
               
               
                   
                 AD-961207.1 
                 NonFluoro 
                 71.01 
                 17.81 
               
               
                   
                 AD-961208.1 
                 NonFluoro 
                 66.66 
                 10.33 
               
               
                   
                 AD-797564.2 
                 Fluoro 
                 13.59 
                 5.19 
               
               
                   
                 AD-797565.2 
                 Fluoro 
                 12.26 
                 1.86 
               
               
                 3′UTR_AAV1 
                 PBS 
                 n/a 
                 100.00 
                 21.53 
               
               
                   
                 naïve (AAV-only) 
                   
                 117.95 
                 19.80 
               
               
                   
                 AD-800819.1 
                 Fluoro 
                 79.02 
                 5.13 
               
               
                   
                 AD-1010693.1 
                 NonFluoro 
                 70.89 
                 9.77 
               
               
                 3′UTR_AAV2 
                 PBS 
                 n/a 
                 100.00 
                 28.24 
               
               
                   
                 naïve (AAV-only) 
                   
                 114.62 
                 35.06 
               
               
                   
                 AD-802503.1 
                 Fluoro 
                 50.95 
                 7.80 
               
               
                   
                 AD-802552.1 
                 Fluoro 
                 31.59 
                 5.19 
               
               
                   
                 AD-1002101.1 
                 Fluoro + 
                 55.04 
                 23.31 
               
               
                   
                   
                 GNA 
               
               
                   
                 AD-802625.2 
                 Fluoro 
                 47.78 
                 4.47 
               
               
                   
                 AD-802853.2 
                 Fluoro 
                 35.44 
                 5.41 
               
               
                   
               
               
                 (*the number following the decimal point in a duplex name merely refers to a batch production number) 
               
            
           
         
       
     
     Table 12 (siRNA duplexes correspond to siRNA sequences in Tables 4A, 5A, and 6A) demonstrates the results of the in vivo screen for 3′UTR AAV2 targeting siRNA duplexes (positions 7999 to 9750), and includes siRNA duplexes with alternate chemistries. Of the 3′UTR_AAV2 targeting siRNA duplexes (positions 7999 to 9750) evaluated in the in vivo screen shown in Table 12, 1 achieved ≥80% knockdown of SCN9A, 4 achieved ≥60% knockdown of SCN9A, 6 achieved ≥30% knockdown of SCN9A, and 7 achieved ≥20% knockdown of SCN9A. 
     
       
         
           
               
             
               
                 TABLE 12 
               
             
            
               
                   
               
               
                 Efficacy and duration of exemplary distal 3′UTR 
               
               
                 targeting SCN9A siRNAs (positions 7999 to 9750) in mice 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 % Message 
                   
               
               
                   
                   
                 Remaining at Day 
                 St. 
               
               
                 Treatment* 
                 Chemistry 
                 14 post treatment 
                 Dev. 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 PBS 
                 n/a 
                 100.00 
                 9.16 
               
               
                 AAV-only 
                   
                 109.27 
                 7.75 
               
               
                 AD-64228.39 
                 (AAV control) Fluoro 
                 64.03 
                 9.62 
               
               
                 (TTR control) 
               
               
                 AD-802471.2 
                 N6-C16 + VP + Fluoro 
                 28.30 
                 3.24 
               
               
                 AD-961342.2 
                 N6-C16 + VP + Non-Fluoro 
                 42.46 
                 6.81 
               
               
                 AD-961334.2 
                 N6-C16 + VP + Non-Fluoro 
                 29.65 
                 2.41 
               
               
                 AD-1010697.2 
                 N6-C16 + VP + Non-Fluoro 
                 84.05 
                 13.41 
               
               
                 AD-1010698.2 
                 N6-C16 + VP + Non-Fluoro 
                 72.76 
                 10.07 
               
               
                 AD-802123.2 
                 N6-C16 + VP + Fluoro 
                 36.01 
                 1.91 
               
               
                 AD-801647.2 
                 N6-C16 + VP + Fluoro 
                 10.26 
                 0.94 
               
               
                 AD-961163.2 
                 N6-C16 + VP + Fluoro + 
                 61.24 
                 15.34 
               
               
                   
                 GNA 
               
               
                   
               
               
                 (*the number following the decimal point in a duplex name merely refers to a batch production number) 
               
            
           
         
       
     
     Table 19 and  FIG.  2    (siRNA duplexes correspond to siRNA sequences in Table 18 and  FIGS.  1 A- 1 C ) demonstrate the results of the in vivo screen for the ORF-1-targeting duplexes with the chemistries described in Table 18 and shown in  FIGS.  1 A- 1 C . Of the ORF-1 targeting duplexes evaluated in the in vivo screen shown in Table 19, 1 achieved ≥80% knockdown of SCN9A, 8 achieved ≥70% knockdown of SCN9A, 13 achieved ≥60% knockdown of SCN9A, 14 achieved ≥50% knockdown of SCN9A, and 15 achieved ≥30% knockdown of SCN9A. The results summarized in Table 19 also demonstrate that several modifications were tolerable in vivo with similar or improved potency compared to parent duplexes. 
     
       
         
           
               
             
               
                 TABLE 19 
               
             
            
               
                   
               
               
                 Efficacy of exemplary SCN9A siRNA duplexes in mice. In this 
               
               
                 table, the column “Duplex Name” provides the numerical 
               
               
                 part of the duplex name without a suffix (e.g., number following 
               
               
                 the decimal point that can be included in a duplex name). The 
               
               
                 suffix 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-795305 in Table 19 refers 
               
               
                 to the same duplex as AD-795305.2 in Table 18. 
               
            
           
           
               
               
            
               
                 Duplex Name 
                 Day 14 post-treatment 
               
            
           
           
               
               
               
            
               
                 (Administered at 3 mg/kg) 
                 % SCN9A Message Remaining 
                 StDev 
               
               
                   
               
            
           
           
               
               
               
            
               
                 PBS 
                 100.00 
                 4.16 
               
               
                 AD-795305 (parent) 
                 31.56 
                 2.46 
               
               
                 AD-1251249 
                 23.56 
                 3.45 
               
               
                 AD-1251251 
                 19.56 
                 1.28 
               
               
                 AD-1010663 (parent) 
                 34.01 
                 4.55 
               
               
                 AD-1251301 
                 64.01 
                 6.65 
               
               
                 AD-961179 (parent) 
                 35.99 
                 21.51 
               
               
                 AD-1251317 
                 36.50 
                 6.98 
               
               
                 AD-1251318 
                 23.35 
                 2.38 
               
               
                 AD-1251323 
                 33.32 
                 5.62 
               
               
                 AD-1251325 
                 27.82 
                 2.14 
               
               
                 AD-795634 (parent) 
                 25.39 
                 5.54 
               
               
                 AD-1251363 
                 20.81 
                 6.51 
               
               
                 AD-1251364 
                 26.37 
                 6.88 
               
               
                 AD-1251373 
                 41.23 
                 5.94 
               
               
                 AD-1251385 
                 29.05 
                 12.32 
               
               
                 AD-1251391 
                 86.58 
                 13.78 
               
               
                   
               
            
           
         
       
     
     Following in vitro testing in Example 3 and the results in Table 17, a subset of duplexes were selected and placed in two groups: screen 1, which included AD-1010663.3, AD-1251301.1, AD-1251249.1, AD-1251251.1, AD-795305.3, AD-1251363.1, AD-1251364.1, AD-1251373.1, AD-795634.4, AD-1251385.1, AD-1251391.1, AD-1251317.1, AD-1251318.1, AD-1251323.1, AD-1251325.1, and AD-961179.3, screen 2 which included AD-1251492.1, AD-1251279.1, AD-961334.3, AD-1251284.1, AD-1251334.1, AD-1251377.1, AD-1251398.1, AD-1251399.1, AD-1251274.2, AD-961188.3, AD-1251411.1, AD-1251419.1, AD-796825, AD-1251428.1, AD-797564.4, and AD-1251434.1. The percent SCN9A message remaining when these duplexes were tested at a 0.1 nM ( FIG.  4 A ), 1 nM ( FIG.  4 B ), and 10 nM ( FIG.  4 C ) was graphed versus the position in the target SCN9A mRNA of the sense strand of the tested duplex. From these graphs, a set of duplexes was selected for in vivo investigation, which are shown in Table 20 and  FIGS.  3 A- 3 D . 
     Table 21 and  FIG.  5    (siRNA duplexes correspond to siRNA sequences in Table 20 and  FIGS.  3 A- 3 D ) demonstrate the results of the in vivo screen for the duplexes targeting region 2 of the 3′ UTR of SCN9A (HsSCN9A_3 UTR2, e.g., positions 7999 to 9750), ORF-1 of SCN9A (HsSCN9A_ORF1rp, e.g., positions 299-2441), and ORF2 of SCN9A (HsSCN9A_ORF2rp, e.g., positions 2392-4345), with the chemistries described in Table 20 and shown in  FIGS.  3 A- 3 D . Of the exemplary duplexes investigated in the in vivo screen shown in Table 20, 4 achieved ≥80% knockdown of SCN9A, 11 achieved ≥70% knockdown of SCN9A, 13 achieved ≥50% knockdown of SCN9A, 14 achieved ≥30% knockdown of SCN9A, 15 achieved ≥20% knockdown of SCN9A, and 16 achieved ≥10% knockdown of SCN9A. The results summarized in Table 19 also demonstrate that several modifications were tolerable in vivo with similar potency compared to parent duplexes. 
     
       
         
           
               
             
               
                 TABLE 21 
               
             
            
               
                   
               
               
                 Efficacy of exemplary SCN9A siRNA duplexes in mice. In this table, the exemplary duplexes investigated 
               
               
                 correspond to those summarized in Table 20 and FIGS. 3A-3D. The prior parent data corresponds to 
               
               
                 duplexes tested with data summarized in Tables 10-12. The column “Parent Duplex Name” provides 
               
               
                 the numerical part of the duplex name without a suffix (e.g., number following the decimal point 
               
               
                 that can be included in a duplex name). The suffix 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-802471 in Table 21 refers to the same duplex as AD-802471.2 in Table 12. 
               
            
           
           
               
               
               
            
               
                   
                 Exemplary Duplexes Investigated 
                 Prior Parent Data (see, Tables 10-12) 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Duplex Name 
                 Day 14 post-treatment 
                   
                 Day 14 post-treatment 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 (Administered 
                 % SCN9A Message 
                   
                 Parent Duplex 
                 % SCN9A Message 
                   
               
               
                 AAV 
                 at 3 mg/kg) 
                 Remaining 
                 StDev 
                 Name 
                 Remaining 
                 StDev 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 3UTR2 
                 PBS 
                 100.00 
                 17.39 
                   
                   
                   
               
               
                   
                 AD-1251492.2* 
                 19.42 
                 13.58 
                 AD-802471 
                 28.30 
                 3.24 
               
               
                   
                 AD-961334.2 (Parent) 
                 17.15 
                 1.96 
                 AD-961334 (self) 
                 29.65 
                 2.41 
               
               
                   
                 AD-1251279.2 
                 13.34 
                 3.34 
                 AD-961334 
                 29.65 
                 2.41 
               
               
                 ORF1rp 
                 PBS 
                 100.00 
                 29.22 
               
               
                   
                 AD-1251284.2* 
                 14.43 
                 2.84 
                 AD-1010661 
                 41.08 
                 6.19 
               
               
                   
                 AD-1251334.2* 
                 65.74 
                 28.11 
                 AD-795366 
                 29.15 
                 4.74 
               
               
                   
                 AD-1251377.2* 
                 28.53 
                 17.61 
                 AD-795634 
                 20.80 
                 6.50 
               
               
                   
                 AD-1251398.2* 
                 81.26 
                 6.35 
                 AD-795913 
                 26.74 
                 5.61 
               
               
                   
                 AD-1251399.2* 
                 75.63 
                 37.43 
                 AD-795913 
                 26.74 
                 5.61 
               
               
                   
                 AD-961188.2 (Parent) 
                 44.91 
                 20.18 
                 AD-961188 (self) 
                 38.51 
                 0.36 
               
               
                   
                 AD-1251274.2 
                 27.38 
                 2.23 
                 AD-961188 
                 38.51 
                 0.36 
               
               
                 ORF2rp 
                 PBS 
                 100.00 
                 21.48 
               
               
                   
                 AD-796825.2 (Parent) 
                 20.38 
                 2.13 
                 AD-796825 Self) 
                 12.49 
                 2.90 
               
               
                   
                 AD-1251411.2 
                 24.57 
                 5.44 
                 AD-796825 
                 12.49 
                 2.90 
               
               
                   
                 AD-1251419.2 
                 28.49 
                 4.48 
                 AD-796825 
                 12.49 
                 2.90 
               
               
                   
                 AD-797564.3 (Parent) 
                 22.90 
                 5.49 
                 AD-797564 (self) 
                 13.59 
                 5.19 
               
               
                   
                 AD-1251428.2 
                 43.00 
                 7.98 
                 AD-797564 
                 13.59 
                 5.19 
               
               
                   
                 AD-1251434.2 
                 26.85 
                 10.83 
                 AD-797564 
                 13.59 
                 5.19 
               
               
                   
               
               
                 *parents not screened in this study