# Patent

## Title
RNA interference mediated inhibition of catenin (cadherin-associated protein), beta 1 (CTNNB1) gene expression using short interfering nucleic acid (siNA)

## Abstract

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of CTNNB1 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against CTNNB1 gene expression.

## Background
SEQUENCE LISTING
The sequence listing submitted via EFS, in compliance with 37 CFR §1.52(e)(5), is incorporated herein by reference. The sequence listing text file submitted via EFS contains the file “SequenceListingSIRONC2”, created on Jul. 25, 2011 which is 2,173,912 bytes in size.
BACKGROUND OF THE INVENTION
Beta catenin (also known as cadherin-associated protein and β-catenin), is a member of the catenin family of cytosolic proteins. β-catenin is encoded by the CTNNB1 gene.
β-catenin is a pivotal player in the Wnt/Wg signaling pathway, mediators of several developmental processes. In the absence of Wnt, glycogen synthase kinase 3 (GSK-3β), a serine/threonine protein kinase constitutively phosphorylates the β-catenin protein. When Wnt is present and binds to any of the family members of the frizzled receptors (Fz), an intracellular signaling protein known as dishevelled (Dsh) is recruited to the membrane and phosphorylated. GSK-3β is inhibited by the activation of Dsh. As a result, β-catenin levels increase in the cytosol and are translocated into the nucleus to perform a variety of functions. β-catenin acts together with the transcription factors TCF and LEF to activate specific target genes involved in different processes.
β-catenin undergoes phosphorylation upon growth factor stimulation resulting in reduced cell adhesion, thereby functioning as a component of adherin junctions which are multiprotein complexes that mediate cell adhesion, cell-cell communication and cytoskeletal anchoring. (Willert et al., 1998, Curr. Opin. Genet. Dev. 8:95-102).
Thompson et al. suggest that β-catenin plays an important role in various aspects of liver biology including liver development (both embryonic and postnatal), liver regeneration following partial hepatectomy, hepatocyte growth factor (HGF)-induced hepatomegaly, liver zonation, and pathogenesis of liver cancer. (Thompson M D., 2007, Hepatology May; 45(5):1298-305).
Wang et al. (2008) have shown that β-catenin can function as an oncogene. (Wang et al., 2008, Cancer Epidemiol. Biomarkers Prev. 17 (8):2101-8). In patients with basal cell carcinoma an increased level in β-catenin is present and leads to the increase in proliferation of related tumors. Mutations in the β-catenin gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), hepatoblastoma, and ovarian cancer.
The role of β-catenin in the development of colorectal cancer has been shown to be regulated by the expression product of the APC (adenomatous polyposis of the colon) gene, a tumor suppressor. (Korinek et al., Science, 1997, 275:1784-1787; Morin et al., Science, 1997, 275:1787-1790). The APC protein normally binds β-catenin in conjunction with TCF/LEF forming a transcription factor complex. Morin et al. (Morin et al., Science, 1997, 275:1787-1790) report that APC protein down-regulates the transcriptional activation mediated by β-catenin and Tcf-4 in colon cancer. Their results indicate that the regulation of β-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or β-catenin.
Mutations in the β-catenin gene are either truncations that lead to deletion of part of the N-terminus of β-catenin, or point mutations that affect the serine and threonine residues that are targeted by GSK3α/β or CKIα. These mutant β-catenin proteins are refractory to phosphorylation and thus escape proteasomal degradations. Consequently, β-catenin accumulates within affected cells. Stabilized and nuclear-localized β-catenin is a hallmark of nearly all cases of colon cancer. (Clevers, H., 2006, Cell 127:469-480). Morin et al. demonstrated that mutations of β-catenin that altered phosphorylation sites rendered the cells insensitive to APC-mediated down-regulation of β-catenin and that this disrupted mechanism was critical to colorectal tumorigenesis. (Morin et al., 1997, Science 275:1787-1790).
Other studies also report on the detection of mutations in β-catenin in various cancer cell lines (see e.g., Chan et al., 1999, Nature Genet. 21:410-413; Blaker et al., 1999, Genes Chromosomes Cancer 25:399-402; Sagae et al., 1999, Jpn. J. Cancer Res. 90:510-515; Wang et al., 2008, Cancer Epidemiol. Biomarkers Prev. 17(8):2101-8). Additionally, abnormally high amounts of β-catenin have also been found in melanoma cell lines (see e.g., Rubinfeld et al., 1997, Science, 275:1790-1792).
Likewise other cancers, such as hepatocellular carcinoma (HCC), have also been associated with the Wnt/beta-catenin pathway. HCC is a complex and heterogeneous disease accounting for more than 660,000 new cases per year worldwide. Multiple reports have shown that Wnt signaling components are activated in human HCC patients. Activated Wnt signaling and nuclear beta-catenin correlate with recurrence of disease and poor prognosis (Takigawa et al. 2008, Curr Drug Targets November; 9(11):1013-24). Elevated nuclear beta-catenin staining has been documented in 17-66% of HCC patients (Zulehner et al. 2010, Am J Pathol. January; 176(1):472-81; Yu et al. 2009, J Hepatol. May; 50(5):948-57). Merck's internal dataset on  ̃300 HCC patient tumors generated in collaboration with the Hong Kong University indicates Wnt signaling components are activated in 50% of HCC patients. External data have shown activating beta-catenin mutations in 13-40% of HCC patients, while inactivating Axin 1 or 2 mutations were present in  ̃10% of HCC patients (Lee et al. 2006, Frontiers in Bioscience May 1:11:1901-1915).
Preclinical studies provide evidence that activation of the Wnt/beta-catenin pathway is important in the generation and maintenance of HCC. Liver-targeted disruption of APC in mice activates beta-catenin signaling and leads to the formation of HCC (Colnot et al. 2004, Proc Natl Acad Sci USA. December 7; 101(49):17216-21). Although overexpression of a beta-catenin mutant lacking the GSK-3beta phosphorylation sites alone is not sufficient for hepatocarcinogenesis (Harada et al. 2002, Cancer Res. April 1; 62(7):1971-7.), overexpression of tumorigenic mutant beta-catenin has been shown to make mice susceptible to HCC induced by DEN (diethylnitrosamine), a known carcinogen (Nejak-Bowen et al. 2010, Hepatology 2010 May; 51(5):1603-13. Interestingly, 95% of HCC tumors initiated by overexpression of the human Met receptor in mice (Tre-Met transgenic mouse model) harbor beta-catenin activating mutations (Tward et al. 2007, Proc Natl Acad Sci USA. September 11; 104(37):14771-6). This finding reflects the human disease and suggests that the Wnt pathway cooperates with Met signaling during hepatocarcinogenesis. High rates of beta-catenin activating mutations are also found in other transgenic mouse models for HCC (16% beta-catenin mutations in FGF19, 55% in c-Myc and 41% in H-Ras transgenic mice) (Nicholes et al. 2002, Am J Pathol. June; 160(6):2295-307 de la Coste et al. 1998, Proc Natl Acad Sci USA. July 21; 95(15):8847-51).
Preclinical studies have also shown that beta-catenin is a valid target for HCC. Beta-catenin siRNAs inhibit proliferation and viability of human HCC cell lines (Zeng et al. 2007). Similarly, treatment of human HCC cell lines with an anti-Wnt-1 antibody or TCF4/beta-catenin antagonists induce apoptosis, reduction of c-Myc, cyclin D1 and survivin expression as well as suppress tumor growth in vivo (Wei et al. 2009, Mol Cancer September 24; 8:76; Wei et al. 2010, Int J Cancer. May 15; 126(10):2426-36.2010).
Hepatocellular carcinoma (HCC) is a common and aggressive cancer for which effective therapies are lacking. The Wnt/beta-catenin pathway is activated in a high proportion of HCC cases ( ̃50%), frequently owing to mutations in beta-catenin (i.e. CTNNB1) or in the beta-catenin destruction complex (e.g. Axin1). Moreover, the Wnt pathway as a target has proven to be challenging and is currently undruggable by small molecule inhibitors, making beta-catenin an attractive target for an RNAi-based therapeutic approach (Llovet et al. 2008, Hepatology October: 48: 1312-1327).
Alteration of gene expression, specifically CTNNB1 gene expression, through RNA interference (hereinafter “RNAi”) is one approach for meeting this need. RNAi is induced by short single-stranded RNA (“siRNA”) or double-stranded RNA (“dsRNA”) molecules. The short dsRNA molecules, called “short interfering nucleic acids (“siNA”)” or “short interfering RNA” or “siRNA” or “RNAi inhibitors” silence the expression of messenger RNAs (“mRNAs”) that share sequence homology to the siNA. This can occur via cleavage of the mRNA mediated by an endonuclease complex containing a siNA, commonly referred to as an RNA-induced silencing complex (RISC). Cleavage of the target RNA typically takes place in the middle of the region complementary to the guide sequence of the siNA duplex (Elbashir et al., 2001, Genes Dev., 15:188). In addition, RNA interference can also involve small RNA (e.g., micro-RNA or miRNA) mediated gene silencing, presumably through cellular mechanisms that either inhibit translation or that regulate chromatin structure and thereby prevent transcription of target gene sequences (see for example Allshire, 2002, Science, 297:1818-1819; Volpe et al., 2002, Science, 297:1833-1837; Jenuwein, 2002, Science, 297:2215-2218; and Hall et al., 2002, Science, 297:2232-2237). Despite significant advances in the field of RNAi, there remains a need for agents that can inhibit CTNNB1 gene expression and that can treat disease associated with CTNNB1 expression such as cancer.
SUMMARY OF THE INVENTION
The invention provides a solution to the problem of treating diseases that respond to the modulation of the CTNNB1 gene expression using novel short interfering nucleic acid (siNA) molecules to modulate CTNNB1 expression.
The present invention provides compounds, compositions, and methods useful for modulating the expression of CTNNB1 genes, specifically those CTNNB1 genes associated with cancer and for treating such conditions by RNA interference (RNAi) using small nucleic acid molecules.
In particular, the instant invention features small nucleic acid molecules, i.e., short interfering nucleic acid (siNA) molecules including, but not limited to, short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), short hairpin RNA (shRNA) and circular RNA molecules and methods used to modulate the expression of CTNNB1 genes and/or other genes involved in pathways of CTNNB1 gene expression and/or activity.
In one aspect, the invention provides double-stranded short interfering nucleic acid (siNA) molecules that inhibit the expression of a CTNNB1 gene in a cell or mammal, wherein the double-stranded siNAs comprise a sense and an antisense stand. The antisense strand comprises a sequence that is complementary to at least a part of an RNA associated with the expression of the CTNNB1 gene. The sense strand comprises a sequence that is complementary to the antisense strand. In various embodiments, at least one strand comprises at least a 15 nucleotide sequence selected from the group of sequences consisting of SEQ ID NOS:1-6374. In certain embodiments, the antisense strand comprises at least 15, 16, 17, 18, or 19 nucleotides having sequence complementarity to a target sequence set forth in Table 1a. In other and/or in the same embodiments, the antisense strand comprises at least a 15, 16, 17, 18, or 19 nucleotide sequence of one of the antisense sequences set forth in Table 1b. In some embodiments, the sense strand comprises at least a 15, 16, 17, 18, or 19 nucleotide sequence of a sense strand sequence as set forth in Table 1b.
In certain embodiments of this aspect of the invention, double-stranded short interfering nucleic acid (siNA) molecules are provided wherein the antisense stand comprises a modified sequence as set forth in Table 1c that has sequence complementarity to a target sequence of the invention. In some embodiments, the sense strand also comprises a modified sequence as set forth in Table 1c.
In certain embodiments, the present invention provides a double-stranded short interfering nucleic acid (siNA) molecule that modulates the expression of CTNNB1, wherein the siNA comprises a sense strand and an antisense strand; each strand is independently 15 to 30 nucleotides in length; and the antisense strand comprises at least 15, 16, 17, 18, or 19 nucleotides having sequence complementary to any of:

    
    
        5′-CUGUUGGAUUGAUUCGAAA-3′ (SEQ ID NO: 5);
        5′-ACGACUAGUUCAGUUGCUU-3′ (SEQ ID NO: 194);
        5′-GGAUGAUCCUAGCUAUCGU-3′ (SEQ ID NO: 196); or
        5′-CCAGGAUGAUCCUAGCUAU-3′ (SEQ ID NO: 151).
    
    


In some embodiments of the invention, the antisense strand of a siNA molecule comprises at least a 15, 16, 17, 18, or 19 nucleotide sequence of:

    
    
        5′-UUUCGAAUCAAUCCAACAG-3′ (SEQ ID NO: 4918);
        5′-AAGCAACUGAACUAGUCGU-3′ (SEQ ID NO: 5107);
        5′-ACGAUAGCUAGGAUCAUCC-3′ (SEQ ID NO: 5109); or
        5′-AUAGCUAGGAUCAUCCUGG-3′ (SEQ ID NO: 5064);
    
    


In some embodiments, the sense strand of a siNA molecule of the invention comprises at least a 15, 16, 17, 18, or 19 nucleotide sequence of:

    
    
        5′-CUGUUGGAUUGAUUCGAAA-3′ (SEQ ID NO: 5);
        5′-ACGACUAGUUCAGUUGCUU-3′ (SEQ ID NO: 194);
        5′-GGAUGAUCCUAGCUAUCGU-3′ (SEQ ID NO: 196); or
        5′-CCAGGAUGAUCCUAGCUAU-3′ (SEQ ID NO: 151).
    
    


In some embodiments, a siNA molecule of the invention comprises any of:

    
    
        5′-CUGUUGGAUUGAUUCGAAA-3′ (SEQ ID NO: 5) and 5′-UUUCGAAUCAAUCCAACAG-3′ (SEQ ID NO: 4918); or
        5′-ACGACUAGUUCAGUUGCUU-3′ (SEQ ID NO: 194) and 5′-AAGCAACUGAACUAGUCGU-3′ (SEQ ID NO: 5107); or
        5′-GGAUGAUCCUAGCUAUCGU-3′ (SEQ ID NO: 196) and 5′-ACGAUAGCUAGGAUCAUCC-3′ (SEQ ID NO: 5109); or
        5′-CCAGGAUGAUCCUAGCUAU-3′ (SEQ ID NO: 151) and 5′-AUAGCUAGGAUCAUCCUGG-3′ (SEQ ID NO: 5064).
    
    


In some embodiments, a siNA molecule of the invention comprises SEQ ID NOS: 6372 and 6374.
In some embodiments, a siNA molecule of the invention comprises SEQ ID NOS: 6370 and 6369.
In some embodiments, a siNA molecule of the invention comprises SEQ ID NOS: 2021 and 2068.
In some embodiments, a siNA molecule of the invention comprises SEQ ID NOS: 6372 and 6373.
In some embodiments, a siNA molecule of the invention comprises SEQ ID NOS: 2147 and 6368
In some embodiments, the invention features a composition comprising:

    
    
        (a) a double-stranded short interfering nucleic acid (siNA) of the invention;
        (b) a cationic lipid compound having any of compound numbers 1-46 or any combination thereof;
        (c) cholesterol;
        (d) DSPC; and
        (e) PEG-DMG.
    
    


In some embodiments, the invention features a composition comprising:

    
    
        (a) a double-stranded short interfering nucleic acid (siNA) of the invention;
        (b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
        (c) cholesterol;
        (d) DSPC; and
        (e) PEG-DMG.
    
    


In some embodiments, the invention features a composition comprising:

    
    
        (a) a double-stranded short interfering nucleic acid (siNA) having SEQ ID NOS: 6372 and 6374;
        (b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
        (c) cholesterol;
        (d) DSPC; and
        (e) PEG-DMG.
    
    


In some embodiments, the invention features a composition comprising:

    
    
        (a) a double-stranded short interfering nucleic acid (siNA) having SEQ ID NOS: 6370 and 6369;
        (b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
        (c) cholesterol;
        (d) DSPC; and
        (e) PEG-DMG.
    
    


In some embodiments, the invention features a composition comprising:

    
    
        (a) a double-stranded short interfering nucleic acid (siNA) having SEQ ID NOS: 2021 and 2068;
        (b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
        (c) cholesterol;
        (d) DSPC; and
        (e) PEG-DMG.
    
    


In some embodiments, the invention features a composition comprising:

    
    
        (a) a double-stranded short interfering nucleic acid (siNA) having SEQ ID NOS: 6372 and 6373;
        (b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
        (c) cholesterol;
        (d) DSPC; and
        (e) PEG-DMG.
    
    


In some embodiments, the invention features a composition comprising:

    
    
        (a) a double-stranded short interfering nucleic acid (siNA) having SEQ ID NOS: 2147 and 6368;
        (b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
        (c) cholesterol;
        (d) DSPC; and
        (e) PEG-DMG.
    
    


In some embodiments, a composition of the invention comprises any Cationic Lipid having any of compound numbers 1-46 in the following molar ratios:
Cationic Lipid/Cholesterol/PEG-DMG 56.6/38/5.4;
Cationic Lipid/Cholesterol/PEG-DMG 60/38/2;
Cationic Lipid/Cholesterol/PEG-DMG 67.3/29/3.7;
Cationic Lipid/Cholesterol/PEG-DMG 49.3/47/3.7;
Cationic Lipid/Cholesterol/PEG-DMG 50.3/44.3/5.4;
Cationic Lipid/Cholesterol/PEG-C-DMA/DSPC 40/48/2/10;
Cationic Lipid/Cholesterol/PEG-DMG/DSPC 40/48/2/10; and
Cationic Lipid/Cholesterol/PEG-DMG/DSPC 58/30/2/10.
In some embodiments, a composition of the invention comprises (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine, cholesterol, DSPC, and PEG-DMG, having a molar ratio of 50:30:10:2 respectively.
In some embodiments, a composition of the invention further comprises a cryoprotectant. In some embodiments, the cryoprotectant is Sucrose, Trehalose, Raffinose, Stachyose, Verbascose, Mannitol, Glucose, Lactose, Maltose, Maltotriose-heptaose, Dextran, Hydroxyethyl Starch, Insulin, Sorbitol, Glycerol, Arginine, Histidine, Lysine, Proline, Dimethylsulfoxide or any combination thereof. In some embodiments, the cryoprotectant is Sucrose. In some embodiments, the cryoprotectant is Trehalose. In some embodiments, the cryoprotectant is a combination of Sucrose and Trehalose.
In some embodiments of the invention, all of the nucleotides of siNAs of the invention are unmodified. In other embodiments, one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) of the nucleotide positions independently in either one or both strands of an siNA molecule are modified. Modifications include nucleic acid sugar modifications, base modifications, backbone (internucleotide linkage) modifications, non-nucleotide modifications, and/or any combination thereof. In certain instances, purine and pyrimidine nucleotides are differentially modified. For example, purine and pyrimidine nucleotides can be differentially modified at the 2′-sugar position (i.e., at least one purine has a different modification from at least one pyrimidine in the same or different strand at the 2′-sugar position). In certain instances the purines are unmodified in one or both strands, while the pyrimidines in one or both strands are modified. In certain other instances, the pyrimidines are unmodified in one or both strands, while the purines in one or both strands are modified. In some instances, at least one modified nucleotide is a 2′-deoxy-2′-fluoro nucleotide, a 2′-deoxy nucleotide, or a 2′-O-alkyl nucleotide. In some instances, at least 5 or more of the pyrimidine nucleotides in one or both stands are either all 2′-deoxy-2′-fluoro or all 2′-O-methylpyrimidine nucleotides. In some instances, at least 5 or more of the purine nucleotides in one or both stands are either all 2′-deoxy-2′-fluoro or all 2′-O-methyl purine nucleotides. In certain instances, wherein the siNA molecules comprise one or more modifications as described herein, the nucleotides at positions 1, 2, and 3 at the 5′ end of the guide (antisense) strand are unmodified.
In certain embodiments, the siNA molecules of the invention have 3′ overhangs of one, two, three, or four nucleotide(s) on one or both of the strands. In other embodiments, the siNA molecules lack overhangs (i.e., have blunt ends). Preferably, the siNA molecule has 3′ overhangs of two nucleotides on both the sense and antisense strands. The overhangs can be modified or unmodified. Examples of modified nucleotides in the overhangs include, but are not limited to, 2′-O-alkyl nucleotides, 2′-deoxy-2′-fluoro nucleotides, locked nucleic acid (LNA) nucleotides, or 2′-deoxy nucleotides. The overhang nucleotides in the antisense strand can comprise nucleotides that are complementary to nucleotides in the CTNNB1 target sequence. Likewise, the overhangs in the sense stand can comprise nucleotides that are in the CTNNB1 target sequence. In certain instances, the siNA molecules of the invention have two 3′ overhang nucleotides on the antisense stand that are 2′-O-alkyl (e.g., 2′-O-methyl) nucleotides and two 3′ overhang nucleotides on the sense stand that are 2′-deoxy nucleotides. In other instances, the siNA molecules of the invention have two 3′ overhang nucleotides that are 2′-O-alkyl (e.g., 2′-O-methyl) nucleotides on both the antisense stand and on the sense stand. In certain embodiments, the 2′-O-alkyl nucleotides are 2′-O-methyl uridine nucleotides. In certain instances, the overhangs also comprise one or more phosphorothioate linkages between nucleotides of the overhang.
In some embodiments, the siNA molecules of the invention have caps (also referred to herein as “terminal caps.” The cap can be present at the 5′-terminus (5′-cap) or at the 3′-terminus (3′-cap) or can be present on both termini, such as at the 5′ and 3′ termini of the sense strand of the siNA.
In some embodiments, the siNA molecules of the invention are phosphorylated at the 5′ end of the antisense strand. The phosphate group can be a phosphate, a diphosphate or a triphosphate.
The siNA molecules of the invention when double stranded can be symmetric or asymmetric. Each strand of these double stranded siNAs independently can range in nucleotide length between 3 and 30 nucleotides. Generally, each strand of the siNA molecules of the invention is about 15 to 30 (i.e., about 19, 20, 21, 22, 23 or 24) nucleotides in length.
The siNA molecules of the invention, which are double stranded or have a duplex structure, independently comprise about 3 to about 30 (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) base pairs. Generally, the duplex structure of siNAs of the invention is between 15 and 30, more generally between 18 and 25, yet more generally between 19 and 24, and most generally between 19 and 21 base pairs in length.
In certain embodiments, double-stranded short interfering nucleic acid (siNA) molecules are provided, wherein the molecule has a sense strand and an antisense strand and comprises formula (A):




    
    
        wherein, the upper strand is the sense strand and the lower strand is the antisense strand of the double-stranded nucleic acid molecule; wherein the antisense strand comprises at least a 15, 16, 17, 18, or 19 nucleotide sequence of SEQ ID NO: 4918, SEQ ID NO: 5107, SEQ ID NO: 5109, or SEQ ID NO: 5064, and the sense strand comprises a sequence having complementarity to the antisense strand;
        each N is independently a nucleotide which is unmodified or chemically modified or a non-nucleotide;
        each B is a terminal cap that is present or absent;
        (N) represents overhanging nucleotides, each of which is independently unmodified or chemically modified;
        [N] represents nucleotides that are ribonucleotides;
        X1 and X2 are independently integers from 0 to 4;
        X3 is an integer from 15 to 30;
        X4 is an integer from 9 to 30; and
        X5 is an integer from 0 to 6, provided that the sum of X4 and X5 is 15-30.
    
    


In one embodiment, the invention features a double-stranded short interfering nucleic acid (siNA) of formula (A); wherein

    
    
        (a) one or more pyrimidine nucleotides in NX4 positions are independently 2′-deoxy-2′-fluoro nucleotides, 2′-O-alkyl nucleotides, 2′-deoxy nucleotides, ribonucleotides, or any combination thereof;
        (b) one or more purine nucleotides in NX4 positions are independently 2′-deoxy-2′-fluoro nucleotides, 2′-O-alkyl nucleotides, 2′-deoxy nucleotides, ribonucleotides, or any combination thereof;
        (c) one or more pyrimidine nucleotides in NX3 positions are independently 2′-deoxy-2′-fluoro nucleotides, 2′-O-alkyl nucleotides, 2′-deoxy nucleotides, ribonucleotides, or any combination thereof; and
        (d) one or more purine nucleotides in NX3 positions are independently 2′-deoxy-2′-fluoro nucleotides, 2′-O-alkyl nucleotides, 2′-deoxy nucleotides, ribonucleotides,
    
    


The present invention further provides compositions comprising the double-stranded nucleic acid molecules described herein with optionally a pharmaceutically acceptable carrier or diluent.
The administration of the composition can be carried out by known methods, wherein the nucleic acid is introduced into a desired target cell in vitro or in vivo.
Commonly used techniques for introduction of the nucleic acid molecules of the invention into cells, tissues, and organisms include the use of various carrier systems, reagents and vectors. Non-limiting examples of such carrier systems suitable for use in the present invention include conjugates, nucleic-acid-lipid particles, lipid nanoparticles (LNP), liposomes, lipoplexes, micelles, virosomes, virus like particles (VLP), nucleic acid complexes, and mixtures thereof.
The compositions of the invention can be in the form of an aerosol, dispersion, solution (e.g., an injectable solution), a cream, ointment, tablet, powder, suspension or the like. These compositions may be administered in any suitable way, e.g. orally, sublingually, buccally, parenterally, nasally, or topically. In some embodiments, the compositions are aerosolized and delivered via inhalation.
The molecules and compositions of the present invention have utility over a broad range of therapeutic applications. Accordingly another aspect of this invention relates to the use of the compounds and compositions of the invention in treating a subject. The invention thus provides a method for treating a subject, such as a human, suffering from a condition which is mediated by the action, or by the loss of action, of CTNNB1, wherein the method comprises administering to the subject an effective amount of a double-stranded short interfering nucleic acid (siNA) molecule of the invention. In certain embodiments, the condition is cancer.
These and other aspects of the invention will be apparent upon reference to the following detailed description and attached figures. Moreover, it is contemplated that any method or composition described herein can be implemented with respect to any other method or composition described herein and that different embodiments may be combined.
Additionally, patents, patent applications, and other documents are cited throughout the specification to describe and more specifically set forth various aspects of this invention. Each of these references cited herein is hereby incorporated by reference in its entirety, including the drawings.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a non-limiting proposed mechanistic representation of target RNA degradation involved in RNAi. Double-stranded RNA (dsRNA), which is generated by RNA-dependent RNA polymerase (RdRP) from foreign single-stranded RNA, for example viral, transposon, or other exogenous RNA, activates the DICER enzyme that in turn generates siNA duplexes. Alternately, synthetic or expressed siNA can be introduced directly into a cell by appropriate means. An active siNA complex forms that recognizes a target RNA, resulting in degradation of the target RNA by the RISC endonuclease complex or in the synthesis of additional RNA by RNA-dependent RNA polymerase (RdRP), which can activate DICER and result in additional siNA molecules, thereby amplifying the RNAi response.
FIG. 2 shows non-limiting examples of chemically modified siNA constructs of the present invention using a generalized structure of a representative siNA duplex. The specific modifications shown in the figure can be utilized alone or in combination with other modifications of the figure, in addition to other modifications and features described herein with reference to any siNA molecule of the invention. In the figure, N stands for any nucleotide or optionally a non-nucleotide as described here. The upper strand, having B-NX3-(N)X2-B-3′ is the sense (or passenger) strand of the siNA, whereas the lower strand, having B(N)X1-NX4-[N]X5-5′ is the antisense (or guide) strand of the siNA. Nucleotides (or optional non-nucleotides) of internal portions of the sense strand are designated NX3 and nucleotides (or optional non-nucleotides) of internal portions of the antisense strand are designated NX4. Nucleotides (or optional non-nucleotides) of the internal portions are generally base paired between the two strands, but can optionally lack base pairing (e.g. have mismatches or gaps) in some embodiments. Nucleotides (or optional non-nucleotides) of overhang regions are designated by parenthesis (N). Nucleotides of the 5′-terminal portion of the antisense strand are designated [N]. Terminal caps are optionally present at the 5′ and/or 3′ end of the sense strand and further optionally present at the 3′-end of the antisense strand. Generally, each strand can independently range from about 15 to about 30 nucleotides in length, but can vary depending on the presence of any overhang nucleotides. In certain embodiments, X1 and X2 are independently integers from 0 to 4; X3 is an integer from 15 to 30; X4 is an integer from 9 to 30; X5 is an integer from 0 to 6, provided that the sum of X4 and X5 is 15-30. Various modifications are shown for the nucleotides of the sense and antisense strands of the siNA constructs. The (N) overhang nucleotide positions can be chemically modified as described herein (e.g., 2′-O-methyl, 2′-deoxy-2′-fluoro, 2′-deoxy, LNA, universal bases etc.) and can be either derived from a corresponding target nucleic acid sequence or not. The constructs shown in the figure can also comprise phosphorothioate linkages as described herein. For example, phosphorothioate linkages can exist between any N, (N), and/or [N] positions. Such phosphorothioate incorporation can be utilized between purine “R” and pyrimidine “Y” positions, or for stabilization of pyrimidine linkages in general. Furthermore, although not depicted on the Figure, the constructs shown in the figure can optionally include a ribonucleotide at the 9th position from the 5′-end of the sense strand or the 11th position based on the 5′-end of the guide strand by counting 11 nucleotide positions in from the 5′-terminus of the guide strand. Similarly, the antisense strand can include a ribonucleotide at the 14th position from the 5′-end, or alternately can be selected or designed so that a 2′-O-alkyl nucleotide (e.g., a 2′-O-methyl purine) is not present at this position. Furthermore, although not shown in the Figure, the 5′-terminal position of the antisense strand can comprise a terminal phosphate group as described herein. The antisense strand generally comprises sequence complementary to any target nucleic acid sequence of the invention, such as those set forth in Table 1a herein.
FIG. 3 shows non-limiting examples of certain combinations of modifications applied to the representative siNA duplex described in FIG. 2. The table shown below the representative structure provides specific combinations of (N)X1, (N)X2, NX3, NX4, and/or [N]X5 nucleotide (and optional non-nucleotide) positions. For example, combinations of 5 or more (e.g., 5, 6, 7, 8, 9, or 10 or more) NX3 and 5 or more (e.g., 5, 6, 7, 8, 9, or 10 or more) NX4 pyrimidine “Y” and purine “R” nucleotides are specified, each of which can independently have specific (N)X1, and/or (N)X2, substitutions as shown in the figure, in addition to optional phosphorothioate substitutions. The 5′-terminal antisense strand [N] nucleotides are generally ribonucleotides, but can also be modified or unmodified depending on if they are purine “R” or pyrimidine “Y” nucleotides
FIGS. 4A-C shows non-limiting examples of different siNA constructs of the invention. The criteria of the representative structures shown in FIGS. 2 and 3 can be applied to any of the structures shown in FIGS. 4A-C.
The examples shown in FIG. 4A (constructs 1, 2, and 3) have 19 representative base pairs; however, different embodiments of the invention include any number of base pairs described herein. Bracketed regions represent nucleotide overhangs, for example, comprising about 1, 2, 3, or 4 nucleotides in length, preferably about 2 nucleotides. Constructs 1 and 2 can be used independently for RNAi activity. Construct 2 can comprise a polynucleotide or non-nucleotide linker, which can optionally be designed as a biodegradable linker. In one embodiment, the loop structure shown in construct 2 can comprise a biodegradable linker that results in the formation of construct 1 in vivo and/or in vitro. In another example, construct 3 can be used to generate construct 2 under the same principle wherein a linker is used to generate the active siNA construct 2 in vivo and/or in vitro, which can optionally utilize another biodegradable linker to generate the active siNA construct 1 in vivo and/or in vitro. As such, the stability and/or activity of the siNA constructs can be modulated based on the design of the siNA construct for use in vivo or in vitro and/or in vitro.
The examples shown in FIG. 4B represent different variations of double-stranded nucleic acid molecule of the invention, such as microRNA, that can include overhangs, bulges, loops, and stem-loops resulting from partial complementarity. Such motifs having bulges, loops, and stem-loops are generally characteristics of miRNA. The bulges, loops, and stem-loops can result from any degree of partial complementarity, such as mismatches or bulges of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleotides in one or both strands of the double-stranded nucleic acid molecule of the invention.
The example shown in FIG. 4C represents a model double-stranded nucleic acid molecule of the invention comprising a 19 base pair duplex of two 21 nucleotide sequences having dinucleotide 3′-overhangs. The top strand (1) represents the sense strand (passenger strand), the middle strand (2) represents the antisense (guide strand), and the lower strand (3) represents a target polynucleotide sequence. The dinucleotide overhangs (NN) can comprise a sequence derived from the target polynucleotide. For example, the 3′-(NN) sequence in the guide strand can be complementary to the 5′-[NN] sequence of the target polynucleotide. In addition, the 5′-(NN) sequence of the passenger strand can comprise the same sequence as the 5′-[NN] sequence of the target polynucleotide sequence. In other embodiments, the overhangs (NN) are not derived from the target polynucleotide sequence, for example where the 3′-(NN) sequence in the guide strand are not complementary to the 5′-[NN] sequence of the target polynucleotide and the 5′-(NN) sequence of the passenger strand can comprise different sequence from the 5′-[NN] sequence of the target polynucleotide sequence. In additional embodiments, any (NN) nucleotides are chemically modified, e.g., as 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or other modifications herein. Furthermore, the passenger strand can comprise a ribonucleotide position N of the passenger strand. For the representative 19 base pair 21 mer duplex shown, position N can be 9 nucleotides in from the 3′ end of the passenger strand. However, in duplexes of differing length, the position N is determined based on the 5′-end of the guide strand by counting 11 nucleotide positions in from the 5′-terminus of the guide strand and picking the corresponding base paired nucleotide in the passenger strand. Cleavage by Ago2 takes place between positions 10 and 11 as indicated by the arrow. In additional embodiments, there are two ribonucleotides, NN, at positions 10 and 11 based on the 5′-end of the guide strand by counting 10 and 11 nucleotide positions in from the 5′-terminus of the guide strand and picking the corresponding base paired nucleotides in the passenger strand.
FIG. 5 shows non-limiting examples of different stabilization chemistries (1-10) that can be used, for example, to stabilize the 5′ and/or 3′-ends of siNA sequences of the invention, including (1) [3-3′]-inverted deoxyribose; (2) deoxyribonucleotide; (3) [5′-3′]-3′-deoxyribonucleotide; (4) [5′-3]-ribonucleotide; (5) [5′-3]-3′-O-methyl ribonucleotide; (6) 3′-glyceryl; (7) [3′-5′]-3′-deoxyribonucleotide; (8) [3′-3]-deoxyribonucleotide; (9) [5′-2′]-deoxyribonucleotide; and (10) [5-3′]-dideoxyribonucleotide (when X=0). In addition to modified and unmodified backbone chemistries indicated in the figure, these chemistries can be combined with different sugar and base nucleotide modifications as described herein.
FIG. 6 shows a non-limiting example of a strategy used to identify chemically modified siNA constructs of the invention that are nuclease resistant while preserving the ability to mediate RNAi activity. Chemical modifications are introduced into the siNA construct based on educated design parameters (e.g. introducing 2′-modifications, base modifications, backbone modifications, terminal cap modifications etc). The modified construct is tested in an appropriate system (e.g., human serum for nuclease resistance, shown, or an animal model for PK/delivery parameters). In parallel, the siNA construct is tested for RNAi activity, for example in a cell culture system such as a luciferase reporter assay and/or against endogenous mRNA). Lead siNA constructs are then identified which possess a particular characteristic while maintaining RNAi activity, and can be further modified and assayed once again. This same approach can be used to identify siNA-conjugate molecules with improved pharmacokinetic profiles, delivery, and RNAi activity.
FIG. 7 shows non-limiting examples of phosphorylated siNA molecules of the invention, including linear and duplex constructs and asymmetric derivatives thereof.
FIG. 8 shows non-limiting examples of chemically modified terminal phosphate groups of the invention.
FIG. 9 shows a non-limiting example of a cholesterol linked phosphoramidite that can be used to synthesize cholesterol conjugated siNA molecules of the invention. An example is shown with the cholesterol moiety linked to the 5′-end of the sense strand of an siNA molecule.
FIG. 10 depicts an embodiment of 5′ and 3′ inverted abasic cap linked to a nucleic acid strand.



DETAILED DESCRIPTION OF THE INVENTION
A. Terms and Definitions
The following terminology and definitions apply as used in the present application.
The term “abasic” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to sugar moieties lacking a nucleobase or having a hydrogen atom (H) or other non-nucleobase chemical groups in place of a nucleobase at the 1′ position of the sugar moiety, see for example Adamic et al., U.S. Pat. No. 5,998,203. In one embodiment, an abasic moiety of the invention is a ribose, deoxyribose, or dideoxyribose sugar.
The term “acyclic nucleotide” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to any nucleotide having an acyclic ribose sugar, for example where any of the ribose carbon/carbon or carbon/oxygen bonds are independently or in combination absent from the nucleotide.
The term “alkyl” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to a saturated or unsaturated hydrocarbons, including straight-chain, branched-chain, alkenyl, alkynyl groups and cyclic groups, but excludes aromatic groups. Notwithstanding the foregoing, alkyl also refers to non-aromatic heterocyclic groups. Preferably, the alkyl group has 1 to 12 carbons. More preferably, it is a lower alkyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkyl group can be substituted or unsubstituted. When substituted, the substituted group(s) is preferably, hydroxyl, halogen, cyano, C1-C4 alkoxy, ═O, ═S, NO2, SH, NH2, or NR1R2, where R1 and R2 independently are H or C1-C4 alkyl.
The phrase “agents that interfere with cell cycle checkpoints” refers to compounds that inhibit protein kinases that transduce cell cycle checkpoint signals, thereby sensitizing the cancer cell to DNA damaging agents.
The phrase “agents that interfere with receptor tyrosine kinases (RTKs)” refers to compounds that inhibit RTKs and therefore inhibit mechanisms involved in oncogenesis and tumor progression.
The phrase “androgen receptor modulators” refers to compounds that interfere or inhibit the binding of androgens to the receptor, regardless of mechanism.
The phrase “angiogenesis inhibitors” refers to compounds that inhibit the formation of new blood vessels, regardless of mechanism.
The term “aryl” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to an aromatic group that has at least one ring having a conjugated pi electron system and includes carbocyclic aryl, heterocyclic aryl and biaryl groups, all of which can be optionally substituted. The preferred substituent(s) of aryl groups are halogen, trihalomethyl, hydroxyl, SH, OH, cyano, C1-C4 alkoxy, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, NH2, and NR1R2 groups, where R1 and R2 independently are H or C1-C4 alkyl.
The term “alkylaryl” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to an alkyl group (as described above) covalently joined to an aryl group (as described above). Carbocyclic aryl groups are groups wherein the ring atoms on the aromatic ring are all carbon atoms. The carbon atoms are optionally substituted. Heterocyclic aryl groups are groups having from 1 to 3 heteroatoms as ring atoms in the aromatic ring and the remainder of the ring atoms are carbon atoms. Suitable heteroatoms include oxygen, sulfur, and nitrogen, and examples of heterocyclic aryl groups having such heteroatoms include furanyl, thienyl, pyridyl, pyrrolyl, N-lower alkyl pyrrolo, pyrimidyl, pyrazinyl, imidazolyl and the like, all optionally substituted. Preferably, the alkyl group is a C1-C4 alkyl group.
The term “amide” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to an —C(O)—NH—R, where R is either alkyl, aryl, alkylaryl or hydrogen.
The phrase “antisense region” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the term refers to a nucleotide sequence of an siNA molecule having complementarity to a target nucleic acid sequence. In addition, the antisense region of an siNA molecule can optionally comprise a nucleic acid sequence having complementarity to a sense region of the siNA molecule. In one embodiment, the antisense region of the siNA molecule is referred to as the antisense strand or guide strand.
The phrase “asymmetric hairpin” refers to a linear siNA molecule comprising an antisense region, a loop portion that can comprise nucleotides or non-nucleotides, and a sense region that comprises fewer nucleotides than the antisense region to the extent that the sense region has enough complementary nucleotides to base pair with the antisense region and form a duplex with loop. For example, an asymmetric hairpin siNA molecule of the invention can comprise an antisense region having length sufficient to mediate RNAi in a cell or in vitro system (e.g. about 15 to about 30, or about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides) and a loop region comprising about 4 to about 12 (e.g., about 4, 5, 6, 7, 8, 9, 10, 11, or 12) nucleotides, and a sense region having about 3 to about 25 (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25) nucleotides that are complementary to the antisense region. The asymmetric hairpin siNA molecule can also comprise a 5′-terminal phosphate group that can be chemically modified. The loop portion of the asymmetric hairpin siNA molecule can comprise nucleotides, non-nucleotides, linker molecules, or conjugate molecules as described herein.
The term “biodegradable” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to degradation in a biological system, for example, enzymatic degradation or chemical degradation.
The term “biodegradable linker” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the term refers to a linker molecule that is designed to connect one molecule to another molecule, and which is susceptible to degradation in a biological system. The linker can be a nucleic acid or non-nucleic acid based linker. For example, a biodegradable linker can be used to attach a ligand or biologically active molecule to an siNA molecule of the invention. Alternately, a biodegradable linker can be used to connect the sense and antisense strands of an siNA molecule of the invention. The biodegradable linker is designed such that its stability can be modulated for a particular purpose, such as delivery to a particular tissue or cell type. The stability of a nucleic acid-based biodegradable linker molecule can be modulated by using various chemistries, for example combinations of ribonucleotides, deoxyribonucleotides, and chemically modified nucleotides, such as 2′-O-methyl, 2′-fluoro, 2′-amino, 2′-O-amino, 2′-C-allyl, 2′-O-allyl, and other 2′-modified or base modified nucleotides. The biodegradable nucleic acid linker molecule can be a dimer, trimer, tetramer or longer nucleic acid molecule, for example, an oligonucleotide of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides in length, or can comprise a single nucleotide with a phosphorus-based linkage, for example, a phosphoramidate or phosphodiester linkage. The biodegradable nucleic acid linker molecule can also comprise nucleic acid backbone, nucleic acid sugar, or nucleic acid base modifications.
The phrase “biologically active molecule” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the term refers to compounds or molecules that are capable of eliciting or modifying a biological response in a system and/or are capable of modulating the pharmacokinetics and/or pharmacodynamics of other biologically active molecules. Examples of biologically active molecules, include siNA molecules alone or in combination with other molecules including, but not limited to therapeutically active molecules such as antibodies, cholesterol, hormones, antivirals, peptides, proteins, chemotherapeutics, small molecules, vitamins, co-factors, nucleosides, nucleotides, oligonucleotides, enzymatic nucleic acids, antisense nucleic acids, triplex forming oligonucleotides, polyamines, polyamides, polyethylene glycol, other polyethers, 2-5A chimeras, siNA, dsRNA, allozymes, aptamers, decoys and analogs thereof.
The phrase “biological system” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to material, in a purified or unpurified form, from biological sources including, but not limited to, human or animal, wherein the system comprises the components required for RNAi activity. Thus, the phrase includes, for example, a cell, tissue, subject, or organism, or extract thereof. The term also includes reconstituted material from a biological source.
The phrase “blunt end” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the term refers to termini of a double-stranded siNA molecule having no overhanging nucleotides. For example, the two strands of a double-stranded siNA molecule having blunt ends align with each other with matched base-pairs without overhanging nucleotides at the termini. A siNA duplex molecule of the invention can comprise blunt ends at one or both termini of the duplex, such as termini located at the 5′-end of the antisense strand, the 5′-end of the sense strand, or both termini of the duplex.
The term “cap” also referred to herein as “terminal cap,” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the term refers to a moiety, which can be a chemically modified nucleotide or non-nucleotide that can be incorporated at one or more termini of one or more nucleic acid molecules of the invention. These terminal modifications protect the nucleic acid molecule from exonuclease degradation, and can help in delivery and/or localization within a cell. The cap can be present at the 5′-terminus (5′-cap) or at the 3′-terminal (3′-cap) or can be present on both termini of any nucleic acid molecule of the invention. A cap can be present at the 5′-end, 3-end and/or 5′ and 3′-ends of the sense strand of a nucleic acid molecule of the invention. Additionally, a cap can optionally be present at the 3′-end of the antisense strand of a nucleic acid molecule of the invention. In non-limiting examples, the 5′-cap includes, but is not limited to, LNA; glyceryl; inverted deoxy abasic residue (moiety); 4′,5′-methylene nucleotide; 1-(beta-D-erythrofuranosyl) nucleotide, 4′-thio nucleotide; carbocyclic nucleotide; 1,5-anhydrohexitol nucleotide; L-nucleotides; alpha-nucleotides; modified base nucleotide; phosphorodithioate linkage; threo-pentofuranosyl nucleotide; acyclic 3′,4′-seco nucleotide; acyclic 3,4-dihydroxybutyl nucleotide; acyclic 3,5-dihydroxypentyl nucleotide; 3′-3′-inverted nucleotide moiety; 3′-3′-inverted abasic moiety; 3′-2′-inverted nucleotide moiety; 3′-2′-inverted abasic moiety; 1,4-butanediol phosphate; 3′-phosphoramidate; hexylphosphate; aminohexyl phosphate; 3′-phosphate; 3′-phosphorothioate; phosphorodithioate; or bridging or non-bridging methylphosphonate moiety. Non-limiting examples of the 3′-cap include, but are not limited to, LNA; glyceryl; inverted deoxy abasic residue (moiety); 4′,5′-methylene nucleotide; 1-(beta-D-erythrofuranosyl) nucleotide; 4′-thio nucleotide; carbocyclic nucleotide; 5′-amino-alkyl phosphate; 1,3-diamino-2-propyl phosphate; 3-aminopropyl phosphate; 6-aminohexyl phosphate; 1,2-aminododecyl phosphate; hydroxypropyl phosphate; 1,5-anhydrohexitol nucleotide; L-nucleotide; alpha-nucleotide; modified base nucleotide; phosphorodithioate; threo-pentofuranosyl nucleotide; acyclic 3′,4′-seco nucleotide; 3,4-dihydroxybutyl nucleotide; 3,5-dihydroxypentyl nucleotide, 5′-5′-inverted nucleotide moiety; 5′-5′-inverted abasic moiety; 5′-phosphoramidate; 5′-phosphorothioate; 1,4-butanediol phosphate; 5′-amino; bridging and/or non-bridging 5′-phosphoramidate; phosphorothioate and/or phosphorodithioate; bridging or non bridging methylphosphonate; and 5′-mercapto moieties (for more details see Beaucage and Iyer, 1993, Tetrahedron 49, 1925; incorporated by reference herein). FIG. 5 shows some non-limiting examples of various caps.
The term “cell” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the term is used in its usual biological sense, and does not refer to an entire multicellular organism, e.g., specifically does not refer to a human being. The cell can be present in an organism, e.g., birds, plants and mammals, such as humans, cows, sheep, apes, monkeys, swine, dogs, and cats. The cell can be prokaryotic (e.g., bacterial cell) or eukaryotic (e.g., mammalian or plant cell). The cell can be of somatic or germ line origin, totipotent or pluripotent, dividing or non-dividing. The cell can also be derived from or can comprise a gamete or embryo, a stem cell, or a fully differentiated cell.
The phrase “chemical modification” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the term refers to any modification of the chemical structure of the nucleotides that differs from nucleotides of native siRNA or RNA in general. The term “chemical modification” encompasses the addition, substitution, or modification of native siRNA or RNA at the sugar, base, or internucleotide linkage, as described herein or as is otherwise known in the art. In certain embodiments, the term “chemical modification” can refer to certain forms of RNA that are naturally occurring in certain biological systems, for example 2′-O-methyl modifications or inosine modifications.
The term “CTNNB1” refers to catenin (cadherin-associated protein), beta 1 which is gene that encodes CTNNB1 proteins, CTNNB1 peptides, CTNNB1 polypeptides, CTNNB1 regulatory polynucleotides (e.g., CTNNB1 miRNAs and siNAs), mutant CTNNB1 genes, and splice variants of a CTNNB1 genes, as well as other genes involved in CTNNB1 pathways of gene expression and/or activity. Thus, each of the embodiments described herein with reference to the term “CTNNB1” are applicable to all of the protein, peptide, polypeptide, and/or polynucleotide molecules covered by the term “CTNNB1”, as that term is defined herein. Comprehensively, such gene targets are also referred to herein generally as “target” sequences (including the target sequences listed in Table 1a).
The term “complementarity” or “complementary” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the terms generally refer to the formation or existence of hydrogen bond(s) between one nucleic acid sequence and another nucleic acid sequence by either traditional Watson-Crick or other non-traditional types of bonding as described herein. In reference to the nucleic molecules of the present invention, the binding free energy for a nucleic acid molecule with its complementary sequence is sufficient to allow the relevant function of the nucleic acid to proceed, e.g., RNAi activity. Determination of binding free energies for nucleic acid molecules is well known in the art (see, e.g., Turner et al., 1987, CSH Symp. Quant. Biol. LII pp. 123-133; Frier et al., 1986, Proc. Nat. Acad. Sci. USA 83:9373-9377; Turner et al., 1987, J. Am. Chem. Soc. 109:3783-3785). Perfect complementary means that all the contiguous residues of a nucleic acid sequence will hydrogen bond with the same number of contiguous residues in a second nucleic acid sequence. Partial complementarity can include various mismatches or non-based paired nucleotides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more mismatches, non-nucleotide linkers, or non-based paired nucleotides) within the nucleic acid molecule, which can result in bulges, loops, or overhangs that result between the sense strand or sense region and the antisense strand or antisense region of the nucleic acid molecule or between the antisense strand or antisense region of the nucleic acid molecule and a corresponding target nucleic acid molecule. Such partial complementarity can be represented by a % complementarity that is determined by the number of non-base paired nucleotides, i.e., about 50%, 60%, 70%, 80%, 90% etc. depending on the total number of nucleotides involved. Such partial complementarity is permitted to the extent that the nucleic acid molecule (e.g., siNA) maintains its function, for example the ability to mediate sequence specific RNAi.
The terms “composition” or “formulation” as used herein refer to their generally accepted meaning in the art. These terms generally refer to a composition or formulation, such as in a pharmaceutically acceptable carrier or diluent, in a form suitable for administration, e.g., systemic or local administration, into a cell or subject, including, for example, a human. Suitable forms, in part, depend upon the use or the route of entry, for example oral, transdermal, inhalation, or by injection. Such forms should not prevent the composition or formulation from reaching a target cell (i.e., a cell to which the negatively charged nucleic acid is desirable for delivery). For example, compositions injected into the blood stream should be soluble. Other factors are known in the art, and include considerations such as toxicity and forms that prevent the composition or formulation from exerting its effect. As used herein, pharmaceutical formulations include formulations for human and veterinary use. Non-limiting examples of agents suitable for formulation with the nucleic acid molecules of the instant invention include: Lipid Nanoparticles (see for example Semple et al., 2010, Nat Biotechnol., February; 28(2):172-6.); P-glycoprotein inhibitors (such as Pluronic P85); biodegradable polymers, such as poly(DL-lactide-coglycolide) microspheres for sustained release delivery (Emerich, D F et al, 1999, Cell Transplant, 8, 47-58); and loaded nanoparticles, such as those made of polybutylcyanoacrylate. Other non-limiting examples of delivery strategies for the nucleic acid molecules of the instant invention include material described in Boado et al., 1998, J. Pharm. Sci., 87, 1308-1315; Tyler et al., 1999, FEBS Lett., 421, 280-284; Pardridge et al., 1995, PNAS USA., 92, 5592-5596; Boado, 1995, Adv. Drug Delivery Rev., 15, 73-107; Aldrian-Herrada et al., 1998, Nucleic Acids Res., 26, 4910-4916; and Tyler et al., 1999, PNAS USA., 96, 7053-7058. A “pharmaceutically acceptable composition” or “pharmaceutically acceptable formulation” can refer to a composition or formulation that allows for the effective distribution of the nucleic acid molecules of the instant invention to the physical location most suitable for their desired activity.
The phrase “cytotoxic/cytostatic agents” refer to compounds that cause cell death or inhibit cell proliferation primarily by interfering directly with the cell's functioning or inhibit or interfere with cell mytosis, including alkylating agents, tumor necrosis factors, intercalators, hypoxia activatable compounds, microtubule inhibitors/microtubule-stabilizing agents, inhibitors of mitotic kinesins, inhibitors of histone deacetylase, inhibitors of kinases involved in mitotic progression, antimetabolites; biological response modifiers; hormonal/anti-hormonal therapeutic agents, hematopoietic growth factors, monoclonal antibody targeted therapeutic agents, topoisomerase inhibitors, proteasome inhibitors and ubiquitin ligase inhibitors.
The phrase “estrogen receptor modulators” refers to compounds that interfere with or inhibit the binding of estrogen to the receptor, regardless of mechanism.
The term “gene” or “target gene” as used herein refers to their meaning as is generally accepted in the art. The terms generally refer a nucleic acid (e.g., DNA or RNA) sequence that comprises partial length or entire length coding sequences necessary for the production of a polypeptide. The target gene can also include the UTR or non-coding region of the nucleic acid sequence. A gene or target gene can also encode a functional RNA (fRNA) or non-coding RNA (ncRNA), such as small temporal RNA (stRNA), micro RNA (miRNA), small nuclear RNA (snRNA), short interfering RNA (siRNA), small nucleolar RNA (snRNA), ribosomal RNA (rRNA), transfer RNA (tRNA) and precursor RNAs thereof. Such non-coding RNAs can serve as target nucleic acid molecules for siNA mediated RNA interference in modulating the activity of fRNA or ncRNA involved in functional or regulatory cellular processes. Aberrant fRNA or ncRNA activity leading to disease can therefore be modulated by siNA molecules of the invention. siNA molecules targeting fRNA and ncRNA can also be used to manipulate or alter the genotype or phenotype of a subject, organism or cell, by intervening in cellular processes such as genetic imprinting, transcription, translation, or nucleic acid processing (e.g., transamination, methylation etc.). The target gene can be a gene derived from a cell, an endogenous gene, a transgene, or exogenous genes such as genes of a pathogen, for example a virus, which is present in the cell after infection thereof. The cell containing the target gene can be derived from or contained in any organism, for example a plant, animal, protozoan, virus, bacterium, or fungus. Non-limiting examples of plants include monocots, dicots, or gymnosperms. Non-limiting examples of animals include vertebrates or invertebrates. Non-limiting examples of fungi include molds or yeasts. For a review, see for example Snyder and Gerstein, 2003, Science, 300, 258-260.
The phrase “HMG-CoA reductase inhibitors” refers to inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase. The term HMG-CoA reductase inhibitor as used herein includes all pharmaceutically acceptable lactone and open-acid forms (i.e., where the lactone ring is opened to form the free acid) as well as salt and ester forms of compounds that have HMG-CoA reductase inhibitory activity, and therefore the use of such salts, esters, open-acid and lactone forms is included within the scope of this invention.
The phrase “homologous sequence” as used herein refers to its meaning as is generally accepted in the art. The term generally refers a nucleotide sequence that is shared by one or more polynucleotide sequences, such as genes, gene transcripts and/or non-coding polynucleotides. For example, a homologous sequence can be a nucleotide sequence that is shared by two or more genes encoding related but different proteins, such as different members of a gene family, different protein epitopes, different protein isoforms or completely divergent genes. A homologous sequence can be a nucleotide sequence that is shared by two or more non-coding polynucleotides, such as noncoding DNA or RNA, regulatory sequences, introns, and sites of transcriptional control or regulation. Homologous sequences can also include sequence regions shared by more than one polynucleotide sequence. Homology does not need to be perfect identity (100%), as partially homologous sequences are also contemplated by and within the scope of the instant invention (e.g., at least 95%, 94%, 93%, 92%, 91%, 90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 81%, 80% etc.). Percent homology is the number of matching nucleotides between two sequences divided by the total length being compared, multiplied by 100.
The phrase “improved RNAi activity” refers to an increase in RNAi activity measured in vitro and/or in vivo, where the RNAi activity is a reflection of both the ability of the siNA to mediate RNAi and the stability of the siNAs of the invention. In this invention, the product of these activities can be increased in vitro and/or in vivo compared to an all RNA siNA or an siNA containing a plurality of ribonucleotides. In some cases, the activity or stability of the siNA molecule can be decreased (i.e., less than ten-fold), but the overall activity of the siNA molecule is enhanced in vitro and/or in vivo.
The terms “inhibit,” “down-regulate,” or “reduce” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the term generally refers the reduction in the expression of the gene, or level of RNA molecules or equivalent RNA molecules encoding one or more proteins or protein subunits, or activity of one or more proteins or protein subunits, below that observed in the absence of the nucleic acid molecules (e.g., siNA) of the invention. Down-regulation can also be associated with post-transcriptional silencing, such as, RNAi mediated cleavage or by alteration in DNA methylation patterns or DNA chromatin structure Inhibition, down-regulation or reduction with an siNA molecule can be in reference to an inactive molecule, an attenuated molecule, an siNA molecule with a scrambled sequence, or an siNA molecule with mismatches or alternatively, it can be in reference to the system in the absence of the nucleic acid.
The phrase “inhibitors of cell proliferation and survival signaling pathway” refers to pharmaceutical agents that inhibit cell surface receptors and signal transduction cascades downstream of those surface receptors.
The term “integrin blockers” refers to compounds which selectively antagonize, inhibit or counteract binding of a physiological ligand to the α ωβ3 integrin, to compounds which selectively antagonize, inhibit or counteract binding of a physiological ligand to the α ωβ5 integrin, to compounds which antagonize, inhibit or counteract binding of a physiological ligand to both the α ωβ3 integrin and the α ωβ5 integrin, and to compounds which antagonize, inhibit or counteract the activity of the particular integrin(s) expressed on capillary endothelial cells. The term also refers to antagonists of the α ω6 α ω8 α11 α21 α51 α6β1 and α6β4 integrins. The term also refers to antagonists of any combination of α ωβ3, α ωβ5, α ω6, α ω8, α11, α21, α51, α6β1, and α6β4 integrins.
The terms “intermittent” or “intermittently” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to periodic stopping and starting at either regular or irregular intervals.
The terms “internucleoside linkage” or “internucleoside linker” or “internucleotide linkage” or “internucleotide linker” are used herein interchangeably and refer to any linker or linkage between two nucleoside units, as is known in the art, including, for example, but not limitation, phosphate, analogs of phosphate, phosphonate, guanidium, hydroxylamine, hydroxylhydrazinyl, amide, carbamate, alkyl, and substituted alkyl linkages. The internucleoside linkages constitute the backbone of a nucleic acid molecule.
The terms “mammalian” or “mammal” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to any warm blooded vertebrate species, such as a human, mouse, rat, dog, cat, hamster, guinea pig, rabbit, livestock, and the like.
The phrase “metered dose inhaler” or MDI refers to a unit comprising a can, a secured cap covering the can and a formulation metering valve situated in the cap. MDI systems includes a suitable channeling device. Suitable channeling devices comprise for example, a valve actuator and a cylindrical or cone-like passage through which medicament can be delivered from the filled canister via the metering valve to the nose or mouth of a patient such as a mouthpiece actuator.
The term “microRNA” or “miRNA” as used herein refers to its meaning as is generally accepted in the art. The term generally refers a small double-stranded RNA that regulates the expression of target messenger RNAs either by mRNA cleavage, translational repression/inhibition or heterochromatic silencing (see for example Ambros, 2004, Nature, 431, 350-355; Bartel, 2004, Cell, 116, 281-297; Cullen, 2004, Virus Research., 102, 3-9; He et al., 2004, Nat. Rev. Genet., 5, 522-531; Ying et al., 2004, Gene, 342, 25-28; and Sethupathy et al., 2006, RNA, 12:192-197).
The term “modulate” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the term refers to when the expression of a gene, or level of one or more RNA molecules (coding or non-coding), or activity of one or more RNA molecules or proteins or protein subunits, is up-regulated or down-regulated, such that expression, level, or activity is greater than or less than that observed in the absence of the molecule that effects modulation. For example, the term “modulate” in some embodiments can refer to inhibition and in other embodiments can refer to potentiation or up-regulation, e.g., of gene expression.
The phrase “modified nucleotide” as used herein refers to its meaning as is generally accepted in the art. The term generally refers a nucleotide, which contains a modification in the chemical structure of the base, sugar and/or phosphate of the unmodified (or natural) nucleotide as is generally known in the art. Non-limiting examples of modified nucleotides are described herein and in U.S. application Ser. No. 12/064,014.
The phrase “NSAIDs that are selective COX-2 inhibitors” for purposes herein, refers to NSAIDs, which possess a specificity for inhibiting COX-2 over COX-1 of at least 100 fold as measured by the ratio of IC50 for COX-2 over IC50 for COX-1 evaluated by cell or microsomal assays.
The phrase “non-base paired” refers to nucleotides that are not base paired between the sense strand or sense region and the antisense strand or antisense region of an double-stranded siNA molecule; and can include for example, but not limitation, mismatches, overhangs, single stranded loops, etc.
The term “non-nucleotide” refers to any group or compound which can be incorporated into a nucleic acid chain in the place of one or more nucleotide units, such as for example but not limitation abasic moieties or alkyl chains. The group or compound is “abasic” in that it does not contain a commonly recognized nucleotide base, such as adenosine, guanine, cytosine, uracil or thymine and therefore lacks a nucleobase at the 1′-position.
The term “nucleotide” is used as is generally recognized in the art. Nucleotides generally comprise a nucleobase, a sugar, and an internucleoside linkage, e.g., a phosphate. The base can be a natural bases (standard), modified bases, or a base analog, as are well known in the art. Such bases are generally located at the 1′ position of a nucleotide sugar moiety. Additionally, the nucleotides can be unmodified or modified at the sugar, internucleoside linkage, and/or base moiety, (also referred to interchangeably as nucleotide analogs, modified nucleotides, non-natural nucleotides, non-standard nucleotides and others; see, for example, U.S. application Ser. No. 12/064,014.
The term “overhang” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary double stranded nucleic acid molecules, the term generally refers to the terminal portion of a nucleotide sequence that is not base paired between the two strands of a double-stranded nucleic acid molecule (see for example, FIG. 4). Overhangs, when present, are typically at the 3′-end of one or both strands in a siNA duplex.
The term “parenteral” as used herein refers to its meaning as is generally accepted in the art. The term generally refers methods or techniques of administering a molecule, drug, agent, or compound in a manner other than through the digestive tract, and includes epicutaneous, subcutaneous, intravascular (e.g., intravenous), intramuscular, or intrathecal injection or infusion techniques and the like.
The phrase “pathway target” refers to any target involved in pathways of gene expression or activity. For example, any given target can have related pathway targets that can include upstream, downstream, or modifier genes in a biologic pathway. These pathway target genes can provide additive or synergistic effects in the treatment of diseases, conditions, and traits herein.
The term “phosphorothioate” refers to an internucleotide phosphate linkage comprising one or more sulfur atoms in place of an oxygen atom. Hence, the term phosphorothioate refers to both phosphorothioate and phosphorodithioate internucleotide linkages.
“Prenyl-protein transferase inhibitor” refers to a compound that inhibits any one or any combination of the prenyl-protein transferase enzymes, including farnesyl-protein transferase (FPTase), geranylgeranyl-protein transferase type I (GGPTase-I), and geranylgeranyl-protein transferase type-II (GGPTase-II, also called Rab GGPTase).
The phrase “retinoid receptor modulators” refers to compounds that interfere or inhibit the binding of retinoids to the receptor, regardless of mechanism.
The term “ribonucleotide” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to a nucleotide with a hydroxyl group at the 2′ position of a β-D-ribofuranose moiety.
The term “RNA” as used herein refers to its generally accepted meaning in the art. Generally, the term RNA refers to a molecule comprising at least one ribofuranoside moiety. The term can include double-stranded RNA, single-stranded RNA, isolated RNA such as partially purified RNA, essentially pure RNA, synthetic RNA, recombinantly produced RNA, as well as altered RNA that differs from naturally occurring RNA by the addition, deletion, substitution and/or alteration of one or more nucleotides. Such alterations can include addition of non-nucleotide material, such as to the end(s) of the siNA or internally, for example at one or more nucleotides of the RNA. Nucleotides in the RNA molecules of the instant invention can also comprise non-standard nucleotides, such as non-naturally occurring nucleotides or chemically synthesized nucleotides or deoxynucleotides. These altered RNAs can be referred to as analogs or analogs of naturally-occurring RNA.
The phrase “RNA interference” or term “RNAi” refer to the biological process of inhibiting or down regulating gene expression in a cell, as is generally known in the art, and which is mediated by short interfering nucleic acid molecules, see for example Zamore and Haley, 2005, Science, 309, 1519-1524; Vaughn and Martienssen, 2005, Science, 309, 1525-1526; Zamore et al., 2000, Cell, 101, 25-33; Bass, 2001, Nature, 411, 428-429; Elbashir et al., 2001, Nature, 411, 494-498; and Kreutzer et al., International PCT Publication No. WO 00/44895; Zernicka-Goetz et al., International PCT Publication No. WO 01/36646; Fire, International PCT Publication No. WO 99/32619; Plaetinck et al., International PCT Publication No. WO 00/01846; Mello and Fire, International PCT Publication No. WO 01/29058; Deschamps-Depaillette, International PCT Publication No. WO 99/07409; and Li et al., International PCT Publication No. WO 00/44914; Allshire, 2002, Science, 297, 1818-1819; Volpe et al., 2002, Science, 297, 1833-1837; Jenuwein, 2002, Science, 297, 2215-2218; and Hall et al., 2002, Science, 297, 2232-2237; Hutvagner and Zamore, 2002, Science, 297, 2056-60; McManus et al., 2002, RNA, 8, 842-850; Reinhart et al., 2002, Gene & Dev., 16, 1616-1626; and Reinhart & Bartel, 2002, Science, 297, 1831). Additionally, the term RNAi is meant to be equivalent to other terms used to describe sequence specific RNA interference, such as post transcriptional gene silencing, translational inhibition, transcriptional inhibition, or epigenetics. For example, siNA molecules of the invention can be used to epigenetically silence genes at either the post-transcriptional level or the pre-transcriptional level. In a non-limiting example, epigenetic modulation of gene expression by siNA molecules of the invention can result from siNA mediated modification of chromatin structure or methylation patterns to alter gene expression (see, for example, Verdel et al., 2004, Science, 303, 672-676; Pal-Bhadra et al., 2004, Science, 303, 669-672; Allshire, 2002, Science, 297, 1818-1819; Volpe et al., 2002, Science, 297, 1833-1837; Jenuwein, 2002, Science, 297, 2215-2218; and Hall et al., 2002, Science, 297, 2232-2237). In another non-limiting example, modulation of gene expression by siNA molecules of the invention can result from siNA mediated cleavage of RNA (either coding or non-coding RNA) via RISC, or via translational inhibition, as is known in the art or modulation can result from transcriptional inhibition (see for example Janowski et al., 2005, Nature Chemical Biology, 1, 216-222).
The phrase “RNAi inhibitor” refers to any molecule that can down regulate, reduce or inhibit RNA interference function or activity in a cell or organism. An RNAi inhibitor can down regulate, reduce or inhibit RNAi (e.g., RNAi mediated cleavage of a target polynucleotide, translational inhibition, or transcriptional silencing) by interaction with or interfering with the function of any component of the RNAi pathway, including protein components such as RISC, or nucleic acid components such as miRNAs or siRNAs. A RNAi inhibitor can be an siNA molecule, an antisense molecule, an aptamer, or a small molecule that interacts with or interferes with the function of RISC, a miRNA, or an siRNA or any other component of the RNAi pathway in a cell or organism. By inhibiting RNAi (e.g., RNAi mediated cleavage of a target polynucleotide, translational inhibition, or transcriptional silencing), a RNAi inhibitor of the invention can be used to modulate (e.g., up-regulate or down regulate) the expression of a target gene.
The phrase “sense region” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the term refers to a nucleotide sequence of an siNA molecule having complementarity to an antisense region of the siNA molecule. In addition, the sense region of an siNA molecule can comprise a nucleic acid sequence having homology or sequence identity with a target nucleic acid sequence. In one embodiment, the sense region of the siNA molecule is also referred to as the sense strand or passenger strand.
The phrases “short interfering nucleic acid”, “siNA”, “short interfering RNA”, “siRNA”, “short interfering nucleic acid molecule”, “short interfering oligonucleotide molecule”, or “chemically modified short interfering nucleic acid molecule” refer to any nucleic acid molecule capable of inhibiting or down regulating gene expression or viral replication by mediating RNA interference (“RNAi”) or gene silencing in a sequence-specific manner. These terms can refer to both individual nucleic acid molecules, a plurality of such nucleic acid molecules, or pools of such nucleic acid molecules. The siNA can be a double-stranded nucleic acid molecule comprising self-complementary sense and antisense strands, wherein the antisense strand comprises a nucleotide sequence that is complementary to a nucleotide sequence in a target nucleic acid molecule or a portion thereof and the sense strand comprises a nucleotide sequence corresponding to the target nucleic acid sequence or a portion thereof. The siNA can be a polynucleotide with a duplex, asymmetric duplex, hairpin or asymmetric hairpin secondary structure, having self-complementary sense and antisense regions, wherein the antisense region comprises a nucleotide sequence that is complementary to a nucleotide sequence in a separate target nucleic acid molecule or a portion thereof and the sense region comprises a nucleotide sequence corresponding to the target nucleic acid sequence or a portion thereof. The siNA can be a circular single-stranded polynucleotide having two or more loop structures and a stem comprising self-complementary sense and antisense regions, wherein the antisense region comprises nucleotide sequence that is complementary to a nucleotide sequence in a target nucleic acid molecule or a portion thereof and the sense region comprises a nucleotide sequence corresponding to the target nucleic acid sequence or a portion thereof, and wherein the circular polynucleotide can be processed either in vivo or in vitro to generate an active siNA molecule capable of mediating RNAi. The siNA can also comprise a single-stranded polynucleotide having a nucleotide sequence complementary to nucleotide sequence in a target nucleic acid molecule or a portion thereof (for example, where such siNA molecule does not require the presence within the siNA molecule of a nucleotide sequence corresponding to the target nucleic acid sequence or a portion thereof), wherein the single-stranded polynucleotide can further comprise a terminal phosphate group, such as a 5′-phosphate (see for example, Martinez et al., 2002, Cell, 110, 563-574 and Schwarz et al., 2002, Molecular Cell, 10, 537-568), or 5′,3′-diphosphate.
The term “subject” as used herein refers to its meaning as is generally accepted in the art. The term generally refers an organism to which the nucleic acid molecules of the invention can be administered. A subject can be a mammal or mammalian cells, including a human or human cells. The term also refers to an organism, which is a donor or recipient of explanted cells or the cells themselves.
The phrase “systemic administration” as used herein refers to its meaning as is generally accepted in the art. The term generally refers in vivo systemic absorption or accumulation of drugs in the blood stream followed by distribution throughout the entire body.
The term “target” as it refers to CTNNB1 refers to any CTNNB1 target protein, peptide, or polypeptide, such as encoded by Genbank Accession Nos. shown in Table 5. The term also refers to nucleic acid sequences or target polynucleotide sequence encoding any target protein, peptide, or polypeptide, such as proteins, peptides, or polypeptides encoded by sequences having Genbank Accession Nos. shown in Table 5. The target of interest can include target polynucleotide sequences, such as target DNA or target RNA. The term “target” is also meant to include other sequences, such as differing isoforms, mutant target genes, splice variants of target polynucleotides, target polymorphisms, and non-coding (e.g., ncRNA, miRNA, stRNA, sRNA) or other regulatory polynucleotide sequences as described herein.
The phrase “target site” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to a sequence within a target nucleic acid molecule, (e.g., RNA) that is “targeted”, e.g., for cleavage mediated by an siNA construct, which contains sequences within its antisense region that are complementary to the target sequence.
The phrase “therapeutically effective amount” as used herein refers to its meaning as is generally accepted in the art. The term generally refers to the amount of the compound or composition that will elicit the biological or medical response of a cell, tissue, system, animal or human that is be sought by the researcher, veterinarian, medical doctor or other clinician. For example, if a given clinical treatment is considered effective when there is at least a 25% 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 that amount necessary to effect at least a 25% reduction in that parameter.
The phrase “universal base” as used herein refers to its meaning as is generally accepted in the art. The term universal base generally refers to nucleotide base analogs that form base pairs with each of the natural DNA/RNA bases with little or no discrimination between them. Non-limiting examples of universal bases include C-phenyl, C-naphthyl and other aromatic derivatives, inosine, azole carboxamides, and nitroazole derivatives such as 3-nitropyrrole, 4-nitroindole, 5-nitroindole, and 6-nitroindole as known in the art (see for example, Loakes, 2001, Nucleic Acids Research, 29, 2437-2447).
The term “up-regulate” as used herein refers to its meaning as is generally accepted in the art. With reference to exemplary nucleic acid molecules of the invention, the term refers to an increase in the expression of a gene, or level of RNA molecules or equivalent RNA molecules encoding one or more proteins or protein subunits, or activity of one or more RNAs, proteins or protein subunits, above that observed in the absence of the nucleic acid molecules (e.g., siNA) of the invention. In certain instances, up-regulation or promotion of gene expression with an siNA molecule is above that level observed in the presence of an inactive or attenuated molecule. In other instances, up-regulation or promotion of gene expression with siNA molecules is above that level observed in the presence of, for example, an siNA molecule with scrambled sequence or with mismatches. In still other instances, up-regulation or promotion of gene expression with a nucleic acid molecule of the instant invention is greater in the presence of the nucleic acid molecule than in its absence. In some instances, up-regulation or promotion of gene expression is associated with inhibition of RNA mediated gene silencing, such as RNAi mediated cleavage or silencing of a coding or non-coding RNA target that down regulates, inhibits, or silences the expression of the gene of interest to be up-regulated. The down regulation of gene expression can, for example, be induced by a coding RNA or its encoded protein, such as through negative feedback or antagonistic effects. The down regulation of gene expression can, for example, be induced by a non-coding RNA having regulatory control over a gene of interest, for example by silencing expression of the gene via translational inhibition, chromatin structure, methylation, RISC mediated RNA cleavage, or translational inhibition. As such, inhibition or down regulation of targets that down regulate, suppress, or silence a gene of interest can be used to up-regulate expression of the gene of interest toward therapeutic use.
The term “vector” as used herein refers to its meaning as is generally accepted in the art. The term vector generally refers to any nucleic acid- and/or viral-based expression system or technique used to deliver one or more nucleic acid molecules.
B. siNA Molecules of the Invention
The present invention provides compositions and methods comprising siNAs targeted to CTNNB1 that can be used to treat diseases, e.g., malignancies and/or cancers associated with CTNNB1 expression. In particular aspects and embodiments of the invention, the nucleic acid molecules of the invention comprise at least a 15 nucleotide sequence of the sequences shown in Table 1a and Table 1b. The siNAs can be provided in several forms. For example, the siNA can be isolated as one or more siNA compounds, or it may be in the form of a transcriptional cassette in a DNA plasmid. The siNA may also be chemically synthesized and can include modifications as shown, for example, but not limitation, in Table 1c and Table 6. Thus, in various embodiments, at least one strand or region of the nucleic acids of the invention comprises at least a 15 nucleotide sequence selected from the group of sequences consisting of SEQ ID NOS:1-6374. The siNAs can be administered alone or co-administered with other siNA molecules or with conventional agents that treat a CTNNB1 related disease or condition.
The siNA molecules of the invention can be used to mediate gene silencing, specifically CTNNB1, via interaction with RNA transcripts or alternately by interaction with particular gene sequences, wherein such interaction results in modulation of gene silencing either at the transcriptional level or post-transcriptional level such as, for example, but not limited to, RNAi or through cellular processes that modulate the chromatin structure or methylation patterns of the target and prevent transcription of the target gene, with the nucleotide sequence of the target thereby mediating silencing. More specifically, the target is any of CTNNB1 RNA, DNA, or mRNA,
In one aspect, the invention provides short interfering nucleic acid (siNA) molecules for inhibiting the expression of the CTNNB1 gene in a cell or mammal. The siNA can be single-stranded or double-stranded. When double-stranded, the siNA comprising a sense and an antisense stand. The antisense strand is complementary to at least a part of an mRNA formed in the expression of the CTNNB1 gene. The sense strand comprises a region that is complementary to the antisense strand. In specific embodiments, the antisense strand comprises at least a 15 nucleotide sequence of an antisense sequence listed in Table 1b. Generally, the double-stranded siNA comprises at least a 15 nucleotide sequence of the sense strand in Table 1b and at least a 15 nucleotide sequence of the antisense strand in Table 1b. One or more of the nucleotides of the siNAs of the invention are optionally modified. In further embodiments having modifications, some siNAs of the invention comprises at least one nucleotide sequence selected from the groups of sequences provide in Table 1c. In other embodiments, the siNA comprises at least two sequences selected from the group of sequences provided in Table 1c, wherein one of the at least two sequences is complementary to another of the at least two sequences and one of the at least two sequences is complementary to a sequence of a mRNA generated in the expression of the CTNNB1 gene. Examples of certain modified siNAs of the invention are in Table 1c.
The double stranded RNA molecules of the invention can comprise two distinct and separate strands that can be symmetric or asymmetric and are complementary, i.e., two single-stranded RNA molecules, or can comprise one single-stranded molecule in which two complementary portions, e.g., a sense region and an antisense region, are base-paired, and are covalently linked by one or more single-stranded “hairpin” areas (i.e. loops) resulting in, for example, a single-stranded short-hairpin polynucleotide or a circular single-stranded polynucleotide.
The linker can be polynucleotide linker or a non-nucleotide linker. In some embodiments, the linker is a non-nucleotide linker. In some embodiments, a hairpin or circular siNA molecule of the invention contains one or more loop motifs, wherein at least one of the loop portions of the siNA molecule is biodegradable. For example, a single-stranded hairpin siNA molecule of the invention is designed such that degradation of the loop portion of the siNA molecule in vivo can generate a double-stranded siNA molecule with 3′-terminal overhangs, such as 3′-terminal nucleotide overhangs comprising 1, 2, 3 or 4 nucleotides. Or alternatively, a circular siNA molecule of the invention is designed such that degradation of the loop portions of the siNA molecule in vivo can generate a double-stranded siNA molecule with 3′-terminal overhangs, such as 3′-terminal nucleotide overhangs comprising about 2 nucleotides.
In symmetric siNA molecules of the invention, each strand, the sense (passenger) strand and antisense (guide) strand, are independently about 15 to about 30 (e.g., about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) nucleotides in length. Generally, each strand of the symmetric siNA molecules of the invention are about 19-24 (e.g., about 19, 20, 21, 22, 23 or 24) nucleotides in length.
In asymmetric siNA molecules, the antisense region or strand of the molecule is about 15 to about 30 (e.g., about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) nucleotides in length, wherein the sense region is about 3 to about 25 (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25) nucleotides in length. Generally, each strand of the asymmetric siNA molecules of the invention is about 19-24 (e.g., about 19, 20, 21, 22, 23 or 24) nucleotides in length.
In yet other embodiments, siNA molecules of the invention comprise single stranded hairpin siNA molecules, wherein the siNA molecules are about 25 to about 70 (e.g., about 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 40, 45, 50, 55, 60, 65, or 70) nucleotides in length.
In still other embodiments, siNA molecules of the invention comprise single-stranded circular siNA molecules, wherein the siNA molecules are about 38 to about 70 (e.g., about 38, 40, 45, 50, 55, 60, 65, or 70) nucleotides in length.
In still other embodiments, siNA molecules of the invention comprise single-stranded non-circular siNA molecules, wherein the siNA molecules are independently about 15 to about 30 (e.g., about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) nucleotides in length.
In various symmetric embodiments, the siNA duplexes of the invention independently comprise about 15 to about 30 (e.g., about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) base pairs. Generally, the duplex structure of siNAs of the invention is between 15 and 30, more generally between 18 and 25, yet more generally between 19 and 24, and most generally between 19 and 21 base pairs in length.
In yet other embodiments, where the duplex siNA molecules of the invention are asymmetric, the siNA molecules comprise about 3 to 25 (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25) base pairs. Generally, the duplex structure of siNAs of the invention is between 15 and 25, more generally between 18 and 25, yet more generally between 19 and 24, and most generally between 19 and 21 base pairs in length.
In still other embodiments, where the siNA molecules of the invention are hairpin or circular structures, the siNA molecules comprise about 15 to about 30 (e.g., about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) base pairs.
The sense strand and antisense strand, or the sense region and antisense region, of the siNA molecules of the invention can be complementary. Also, the antisense strand or antisense region can be complementary to a nucleotide sequence or a portion thereof of the CTNNB1 target RNA. The sense strand or sense region of the siNA can comprise a nucleotide sequence of a CTNNB1 gene or a portion thereof. In certain embodiments, the sense region or sense strand of an siNA molecule of the invention is complementary to that portion of the antisense region or antisense strand of the siNA molecule that is complementary to a CTNNB1 target polynucleotide sequence, such as for example, but not limited to, those sequences represented by GENBANK Accession Nos. shown in Table 5.
In some embodiments, siNA molecules of the invention have perfect complementarity between the sense strand or sense region and the antisense strand or antisense region of the siNA molecule. In other or the same embodiments, the antisense strand of the siNA molecules of the invention are perfectly complementary to a corresponding target nucleic acid molecule.
In yet other embodiments, siNA molecules of the invention have partial complementarity (i.e., less than 100% complementarity) between the sense strand or sense region and the antisense strand or antisense region of the siNA molecule or between the antisense strand or antisense region of the siNA molecule and a corresponding target nucleic acid molecule. Thus, in some embodiments, the double-stranded nucleic acid molecules of the invention, have between about 15 to about 30 (e.g., about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) nucleotides in one strand that are complementary to the nucleotides of the other strand. In other embodiments, the molecules have between about 15 to about 30 (e.g., about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) nucleotides in the sense region that are complementary to the nucleotides of the antisense region. of the double-stranded nucleic acid molecule. In certain embodiments, the double-stranded nucleic acid molecules of the invention have between about 15 to about 30 (e.g., about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) nucleotides in the antisense strand that are complementary to a nucleotide sequence of its corresponding target nucleic acid molecule.
In other embodiments, the siNA molecule can contain one or more nucleotide deletions, substitutions, mismatches and/or additions; provided, however, that the siNA molecule maintains its activity, for example, to mediate RNAi. In a non-limiting example, the deletion, substitution, mismatch and/or addition can result in a loop or bulge, or alternately a wobble or other alternative (non Watson-Crick) base pair. Thus, in some embodiments, for example, the double-stranded nucleic acid molecules of the invention, have 1 or more (e.g., 1, 2, 3, 4, 5, or 6) nucleotides, in one strand or region that are mismatches or non-base-paired with the other strand or region. In other embodiments, the double-stranded nucleic acid molecules of the invention, have 1 or more (e.g., 1, 2, 3, 4, 5, or 6) nucleotides in each strand or region that are mismatches or non-base-paired with the other strand or region. In a preferred embodiment, the siNA of the invention contains no more than 3 mismatches. If the antisense strand of the siNA contains mismatches to a target sequence, it is preferable that the area of mismatch not be located in the center of the region of complementarity.
In other embodiments, the siNA molecule can contain one or more nucleotide deletions, substitutions, mismatches and/or additions to a sequence in Table 1b provided, however, that the siNA molecule maintains its activity, for example, to mediate RNAi. In a non-limiting example, the deletion, substitution, mismatch and/or addition can result in a loop or bulge, or alternately a wobble or other alternative (non Watson-Crick) base pair.
The invention also comprises double-stranded nucleic acid (siNA) molecules as otherwise described hereinabove in which the first strand and second strand are complementary to each other and wherein at least one strand is hybridisable to the polynucleotide sequence of a sequence in Table 1b under conditions of high stringency, and wherein any of the nucleotides is unmodified or chemically modified.
Hybridization techniques are well known to the skilled artisan (see for instance, Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989)). Preferred stringent hybridization conditions include overnight incubation at 42° C. in a solution comprising: 50% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5×Denhardt's solution, 10% dextran sulfate, and 20 microgram/ml denatured, sheared salmon sperm DNA; followed by washing the filters in 0.1×SSC at about 65° C.
In one specific embodiment, the first strand has about 15, 16, 17, 18, 19, 20 or 21 nucleotides that are complementary to the nucleotides of the other strand and at least one strand is hybridisable to a polynucleotide sequence in Table 1b. In a more preferred embodiment, the first strand has about 15, 16, 17, 18, 19, 20 or 21 nucleotides that are complementary to the nucleotides of the other strand and at least one strand is hybridisable to SEQ ID NO: 1, SEQ ID NO: 1049, SEQ ID NO: 43, SEQ ID NO: 1091, SEQ ID NO: 51, SEQ ID NO: 1099, SEQ ID NO: 53, or SEQ ID NO:1101; under conditions of high stringency, and wherein any of the nucleotides is unmodified or chemically modified.
In certain embodiments, the siNA molecules of the invention comprise overhangs of about 1 to about 4 (e.g., about 1, 2, 3 or 4) nucleotides. The nucleotides in the overhangs can be the same or different nucleotides. In some embodiments, the overhangs occur at the 3′-end at one or both strands of the double-stranded nucleic acid molecule. For example, a double-stranded nucleic acid molecule of the invention can comprise a nucleotide or non-nucleotide overhang at the 3′-end of the antisense strand/region, the 3′-end of the sense strand/region, or both the antisense strand/region and the sense strand/region of the double-stranded nucleic acid molecule.
In some embodiments, the nucleotides comprising the overhang portion of an siNA molecule of the invention comprise sequences based on the CTNNB1 target polynucleotide sequence in which nucleotides comprising the overhang portion of the antisense strand/region of an siNA molecule of the invention can be complementary to nucleotides in the CTNNB1 target polynucleotide sequence and/or nucleotides comprising the overhang portion of the sense strand/region of an siNA molecule of the invention can comprise the nucleotides in the CTNNB1 target polynucleotide sequence. Thus, in some embodiments, the overhang comprises a two nucleotide overhang that is complementary to a portion of the CTNNB1 target polynucleotide sequence. In other embodiments, however, the overhang comprises a two nucleotide overhang that is not complementary to a portion of the CTNNB1 target polynucleotide sequence. In certain embodiments, the overhang comprises a 3′-UU overhang that is not complementary to a portion of the CTNNB1 target polynucleotide sequence. In other embodiments, the overhang comprises a UU overhang at the 3′ end of the antisense strand and a TT overhang at the 3′ end of the sense strand. In other embodiments, the overhang comprises nucleotides as described in the examples, Tables, and Figures herein.
In any of the embodiments of the siNA molecules described herein having 3′-terminal nucleotide overhangs, the overhangs are optionally chemically modified at one or more nucleic acid sugar, base, or backbone positions. Representative, but not limiting examples of modified nucleotides in the overhang portion of a double-stranded nucleic acid (siNA) molecule of the invention include: 2′-O-alkyl (e.g., 2′-O-methyl), 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-deoxy-2′-fluoroarabino (FANA), 4′-thio, 2′-O-trifluoromethyl, 2′-O-ethyl-trifluoromethoxy, 2′-O-difluoromethoxy-ethoxy, universal base, acyclic, or 5-C-methyl nucleotides. In more preferred embodiments, the overhang nucleotides are each independently, a 2′-O-alkyl nucleotide, a 2′-O-methyl nucleotide, a 2′-dexoy-2-fluoro nucleotide, or a 2′-deoxy ribonucleotide. In some instances the overhang nucleotides are linked by a one or more phosphorothioate linkages.
In yet other embodiments, siNA molecules of the invention comprise duplex nucleic acid molecules with blunt ends (i.e., without nucleotide overhangs), where both ends are blunt, or alternatively, where one of the ends is blunt. In some embodiments, the siNA molecules of the invention can comprises one blunt end, for example wherein the 5′-end of the antisense strand and the 3′-end of the sense strand do not have any overhanging nucleotides. In another example, the siNA molecule comprises one blunt end, for example wherein the 3′-end of the antisense strand and the 5′-end of the sense strand do not have any overhanging nucleotides. In other embodiments, siNA molecules of the invention comprise two blunt ends, for example wherein the 3′-end of the antisense strand and the 5′-end of the sense strand as well as the 5′-end of the antisense strand and 3′-end of the sense strand do not have any overhanging nucleotides.
In any of the embodiments or aspects of the siNA molecules of the invention, the sense strand and/or the antisense strand can further have a cap, such as described herein or as known in the art, at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense strand and/or antisense strand. Or as in the case of a hairpin siNA molecule, the cap can be at either one or both of the terminal nucleotides of the polynucleotide. In some embodiments, the cap is at one of both of the ends of the sense strand of a double-stranded siNA molecule. In other embodiments, the cap is at the 3′-end of antisense (guide) strand. In preferred embodiments, the caps are at the 3′-end of the sense strand and the 5′-end of the sense strand.
Representative, but non-limiting examples of such terminal caps include an inverted abasic nucleotide, an inverted deoxy abasic nucleotide, an inverted nucleotide moiety, a group shown in FIG. 5, a glyceryl modification, an alkyl or cycloalkyl group, a heterocycle, or any other cap as is generally known in the art.
Any of the embodiments of the siNA molecules of the invention can have a 5′ phosphate termini. In some embodiments, the siNA molecules lack terminal phosphates.
Any siNA molecule or construct of the invention can comprise one or more chemical modifications. Modifications can be used to improve in vitro or in vivo characteristics such as stability, activity, toxicity, immune response (e.g., prevent stimulation of an interferon response, an inflammatory or pro-inflammatory cytokine response, or a Toll-like Receptor (TlF) response), and/or bioavailability.
Applicants describe herein chemically modified siNA molecules with improved RNAi activity and/or stability compared to corresponding unmodified siNA molecules. Various chemically modified siNA motifs disclosed herein provide the capacity to maintain RNAi activity that is substantially similar to unmodified or minimally modified active siRNA (see for example Elbashir et al., 2001, EMBO J., 20:6877-6888) while at the same time providing nuclease resistance and pharmacokinetic properties suitable for use in therapeutic applications.
In various embodiments, the siNA molecules of the invention comprise modifications wherein any (e.g., one or more or all) nucleotides present in the sense and/or antisense strand are modified nucleotides (e.g., wherein one nucleotide is modified, some nucleotides (i.e., plurality or more than one) are modified, or all nucleotides are modified nucleotides. In some embodiments, the siNA molecules of the invention are partially modified (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 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, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, or 59 nucleotides are modified) with chemical modifications. In some embodiments, an siNA molecule of the invention comprises at least about 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, or 60 nucleotides that are modified nucleotides. In other embodiments, the siNA molecules of the invention are completely modified (e.g., 100% modified) with chemical modifications, i.e., the siNA molecule does not contain any ribonucleotides. In some of embodiments, one or more of the nucleotides in the sense strand of the siNA molecules of the invention are modified. In the same or other embodiments, one or more of the nucleotides in the antisense strand of the siNA molecules of the invention are modified.
The chemical modification within a single siNA molecule can be the same or different. In some embodiments, at least one strand has at least one chemical modification. In other embodiments, each strand has at least one chemical modifications, which can be the same or different, such as, sugar, base, or backbone (i.e., internucleotide linkage) modifications. In other embodiments, siNA molecules of the invention contain at least 2, 3, 4, 5, or more different chemical modifications.
Non-limiting examples of chemical modifications that are suitable for use in the present invention, are disclosed in U.S. patent application Ser. Nos. 10/444,853; 10/981,966; 12/064,014 and in references cited therein and include sugar, base, and phosphate, non-nucleotide modifications, and/or any combination thereof.
In certain specific embodiments of the invention, at least one modified nucleotide is a 2′-deoxy-2-fluoro nucleotide, a 2′-deoxy nucleotide, a 2′-O-alkyl (e.g., 2′-O-methyl) nucleotide, or a locked nucleic acid (LNA) nucleotide as is generally recognized in the art.
In yet other embodiment of the invention, at least one nucleotide has a ribo-like, Northern or A form helix configuration (see e.g., Saenger, Principles of Nucleic Acid Structure, Springer-Verlag ed., 1984). Non-limiting examples of nucleotides having a Northern configuration include locked nucleic acid (LNA) nucleotides (e.g., 2′-O, 4′-C-methylene-(D-ribofuranosyl) nucleotides); 2′-methoxyethoxy (MOE) nucleotides; 2′-methyl-thio-ethyl nucleotides, 2′-deoxy-2′-fluoro nucleotides; 2′-deoxy-2′-chloro nucleotides; 2′-azido nucleotides; 2′-O-trifluoromethyl nucleotides; 2′-O-ethyl-trifluoromethoxy nucleotides; 2′-O-difluoromethoxy-ethoxy nucleotides; 4′-thio nucleotides and 2′-O-methyl nucleotides.
In various embodiments, a majority (e.g., greater than 50%) of the pyrimidine nucleotides present in the double-stranded siNA molecule comprises a sugar modification. In some of the same and/or other embodiments, a majority (e.g., greater than 50%) of the purine nucleotides present in the double-stranded siNA molecule comprises a sugar modification.
In some embodiments, the pyrimidine nucleotides in the antisense strand are 2′-O-methyl or 2′-deoxy-2′-fluoro pyrimidine nucleotides and the purine nucleotides present in the antisense strand are 2′-O-methyl nucleotides or 2′-deoxy nucleotides. In other embodiments, the pyrimidine nucleotides in the sense strand are 2′-deoxy-2′-fluoro pyrimidine nucleotides and the purine nucleotides present in the sense strand are 2′-O-methyl or 2′-deoxy purine nucleotides.
In certain embodiments of the invention, all the pyrimidine nucleotides in the complementary region on the sense strand are 2′-deoxy-2′-fluoro pyrimidine nucleotides. In certain embodiments, all of the pyrimidine nucleotides in the complementary region of the antisense strand are 2′-deoxy-2′-fluoro pyrimidine nucleotides. In certain embodiments, all the purine nucleotides in the complementary region on the sense strand are 2′-deoxy purine nucleotides. In certain embodiments, all of the purines in the complementary region on the antisense strand are 2′-O-methyl purine nucleotides. In certain embodiments, all of the pyrimidine nucleotides in the complementary regions on the sense strand are 2′-deoxy-2′-fluoro pyrimidine nucleotides; all of the pyrimidine nucleotides in the complementary region of the antisense strand are 2′-deoxy-2′-fluoro pyrimidine nucleotides; all the purine nucleotides in the complementary region on the sense strand are 2′-deoxy purine nucleotides and all of the purines in the complementary region on the antisense strand are 2′-O-methyl purine nucleotides.
In some embodiments, at least 5 or more of the pyrimidine nucleotides in one or both stands are 2′-deoxy-2′-fluoro pyrimidine nucleotides. In some embodiments, at least 5 or more of the pyrimidine nucleotides in one or both stands are 2′-O-methylpyrimidine nucleotides. In some embodiments, at least 5 or more of the purine nucleotides in one or both stands are 2′-deoxy-2′-fluoro purine nucleotides In some embodiments, at least 5 or more of the purine nucleotides in one or both stands are 2′-O-methyl purine nucleotides.
In certain embodiments, the purines and pyrimidines are differentially modified at the 2′-sugar position (i.e., at least one purine has a different modification from at least one pyrimidine in the same or different strand at the 2′-sugar position). For example, in some instances, at least 5 or more of the pyrimidine nucleotides in one or both stands are 2′-deoxy-2′-fluoro pyrimidine nucleotides and at least 5 or more purine nucleotides in one or both strands are 2′-O-methyl purine nucleotides. In other instances at least 5 or more of the pyrimidine nucleotides in one or both stands are 2′-O-methylpyrimidine nucleotides and at least 5 or more purine nucleotides in one or both strands are 2′-deoxy-2′-fluoro purine nucleotides.
Further non-limiting examples of sense and antisense strands of such siNA molecules having various modifications and modifications patterns are shown in FIGS. 2 and 3.
Any of the above described modifications, or combinations thereof, including those in the references cited, can be applied to any of the siNA molecules of the invention.
The modified siNA molecules of the invention can comprise modifications at various locations within the siNA molecule. In some embodiments, the double-stranded siNA molecule of the invention comprises modified nucleotides at internal base paired positions within the siNA duplex. In other embodiments, a double-stranded siNA molecule of the invention comprises modified nucleotides at non-base paired or overhang regions of the siNA molecule. In yet other embodiments, a double-stranded siNA molecule of the invention comprises modified nucleotides at terminal positions of the siNA molecule. For example, such terminal regions include the 3′-position and/or 5′-position of the sense and/or antisense strand or region of the siNA molecule. Additionally, any of the modified siNA molecules of the invention can have a modification in one or both oligonucleotide strands of the siNA duplex, for example in the sense strand, the antisense strand, or both strands. Moreover, with regard to chemical modifications of the siNA molecules of the invention, each strand of the double-stranded siNA molecules of the invention can have one or more chemical modifications, such that each strand comprises a different pattern of chemical modifications.
In certain embodiments each strand of a double-stranded siNA molecule of the invention comprises a different pattern of chemical modifications, such as any Stab modification chemistries described herein (see Table 9) or any combination thereof, i.e., different combinations of defined Stabilzation chemistry (Stab) sense and antisense strands. Further, non-limiting examples of modification schemes that could give rise to different patterns of modifications are shown in Table 9. The stabilization chemistries referred to in Table 9 as Stab, can be combined in any combination of sense/antisense chemistries, such as Stab 7/8, Stab 7/11, Stab 8/8, Stab 18/8, Stab 18/11, Stab 12/13, Stab 7/13, Stab 18/13, Stab 7/19, Stab 8/19, Stab 18/19, Stab 7/20, Stab 8/20, Stab 18/20, Stab 7/32, Stab 8/32, or Stab 18/32 or any other combination of Stabilization chemistries.
In any of the siNAs of the invention, one or more (for example 1, 2, 3, 4 or 5) nucleotides at the 5′-end of the guide strand or guide region (also known as antisense strand or antisense region) of the siNA molecule are ribonucleotides.
In certain embodiments, the present invention provides a double-stranded short interfering nucleic acid (siNA) molecule that modulates the expression of CTNNB1, wherein the siNA comprises a sense strand and an antisense strand; each strand is independently 15 to 30 nucleotides in length; and the antisense strand comprises at least 15, 16, 17, 18, or 19 nucleotides having sequence complementary to any of:

    
    
        5′-CUGUUGGAUUGAUUCGAAA-3′ (SEQ ID NO: 5);
        5′-ACGACUAGUUCAGUUGCUU-3′ (SEQ ID NO: 194);
        5′-GGAUGAUCCUAGCUAUCGU-3′ (SEQ ID NO: 196); or
        5′-CCAGGAUGAUCCUAGCUAU-3′ (SEQ ID NO: 151).
    
    


In some embodiments, the antisense strand of a siNA molecule of the invention comprises at least a 15, 16, 17, 18, or 19 nucleotide sequence of:

    
    
        5′-UUUCGAAUCAAUCCAACAG-3′ (SEQ ID NO: 4918);
        5′-AAGCAACUGAACUAGUCGU-3′ (SEQ ID NO: 5107);
        5′-ACGAUAGCUAGGAUCAUCC-3′ (SEQ ID NO: 5109); or
        5′-AUAGCUAGGAUCAUCCUGG-3′ (SEQ ID NO: 5064).
    
    


In some embodiments, the sense strand of a siNA molecule of the invention comprises at least a 15, 16, 17, 18, or 19 nucleotide sequence of:

    
    
        5′-CUGUUGGAUUGAUUCGAAA-3′ (SEQ ID NO: 5);
        5′-ACGACUAGUUCAGUUGCUU-3′ (SEQ ID NO: 194);
        5′-GGAUGAUCCUAGCUAUCGU-3′ (SEQ ID NO: 196); or
        5′-CCAGGAUGAUCCUAGCUAU-3′ (SEQ ID NO: 151).
    
    


In some embodiments, a siNA molecule of the invention comprises any of:

    
    
        5′-CUGUUGGAUUGAUUCGAAA-3′ (SEQ ID NO: 5) and 5′-UUUCGAAUCAAUCCAACAG-3′ (SEQ ID NO: 4918); or
        5′-ACGACUAGUUCAGUUGCUU-3′ (SEQ ID NO: 194) and 5′-AAGCAACUGAACUAGUCGU-3′ (SEQ ID NO: 5107); or
        5′-GGAUGAUCCUAGCUAUCGU-3′ (SEQ ID NO: 196) and 5′-ACGAUAGCUAGGAUCAUCC-3′ (SEQ ID NO: 5109); or
        5′-CCAGGAUGAUCCUAGCUAU-3′ (SEQ ID NO: 151) and 5′-AUAGCUAGGAUCAUCCUGG-3′ (SEQ ID NO: 5064).
    
    


Any of the above described modifications, or combinations thereof, including those in the references cited, can be applied to any of these embodiments.
In certain embodiments, the nucleotides of the at least a 15, 16, 17, 18, or 19 nucleotide sequence of SEQ ID NO: 5, SEQ ID NO: 4918, SEQ ID NO: 194, SEQ ID NO: 5107, SEQ ID NO: 196, SEQ ID NO: 5109, SEQ ID NO: 151, or SEQ ID NO: 5064 form a contiguous stretch of nucleotides.
In some embodiments, the siNA molecule can contain one or more nucleotide deletions, substitutions, mismatches and/or additions to the at least 15, 16, 17, 18, or 19 nucleotide sequence of SEQ ID NO: 5, SEQ ID NO: 4918, SEQ ID NO: 194, SEQ ID NO: 5107, SEQ ID NO: 196, SEQ ID NO: 5109, SEQ ID NO: 151, or SEQ ID NO: 5064; provided, however, that the siNA molecule maintains its activity, for example, to mediate RNAi. In a non-limiting example, the deletion, substitution, mismatch and/or addition can result in a loop or bulge, or alternately a wobble or other alternative (non Watson-Crick) base pair.
In certain embodiments of the invention, double-stranded siNA molecules are provided, wherein the molecule has a sense strand and an antisense strand and comprises the following formula (A):




    
    
        wherein, the upper strand is the sense strand and the lower strand is the antisense strand of the double-stranded nucleic acid molecule; wherein the antisense strand comprises at least a 15, 16, 17, 18, or 19 nucleotide sequence of SEQ ID NO: 4918, SEQ ID NO: 5107, SEQ ID NO: 5109, or SEQ ID NO: 5064, and the sense strand comprises a sequence having complementarity to the antisense strand;
        each N is independently a nucleotide which is unmodified or chemically modified or a non-nucleotide;
        each B is a terminal cap that is present or absent;
        (N) represents overhanging nucleotides, each of which is independently unmodified or chemically modified;
        [N] represents nucleotides that are ribonucleotides;
        X1 and X2 are independently integers from 0 to 4;
        X3 is an integer from 15 to 30;
        X4 is an integer from 9 to 30; and
        X5 is an integer from 0 to 6, provided that the sum of X4 and X5 is 15-30.
    
    


In certain embodiments, the nucleotides of the at least a 15, 16, 17, 18, or 19 nucleotide sequence of SEQ ID NO: 4918, SEQ ID NO: 5107, SEQ ID NO: 5109, or SEQ ID NO: 5064 form a contiguous stretch of nucleotides.
In some embodiments, the siNA molecule of formula A can contain one or more nucleotide deletions, substitutions, mismatches and/or additions to the at least 15, 16, 17, 18, or 19 nucleotide sequence of SEQ ID NO: 4918, SEQ ID NO: 5107, SEQ ID NO: 5109, or SEQ ID NO: 5064; provided, however, that the siNA molecule maintains its activity, for example, to mediate RNAi. In a non-limiting example, the deletion, substitution, mismatch and/or addition can result in a loop or bulge, or alternately a wobble or other alternative (non Watson-Crick) base pair.
In one embodiment, the invention features a double-stranded short interfering nucleic acid (siNA) of formula (A); wherein

    
    
        (a) one or more pyrimidine nucleotides in NX4 positions are independently 2′-deoxy-2′-fluoro nucleotides, 2′-O-alkyl nucleotides, 2′-deoxy nucleotides, ribonucleotides, or any combination thereof;
        (b) one or more purine nucleotides in NX4 positions are independently 2′-deoxy-2′-fluoro nucleotides, 2′-O-alkyl nucleotides, 2′-deoxy nucleotides, ribonucleotides, or any combination thereof;
        (c) one or more pyrimidine nucleotides in NX3 positions are independently 2′-deoxy-2′-fluoro nucleotides, 2′-O-alkyl nucleotides, 2′-deoxy nucleotides, ribonucleotides, or any combination thereof; and
        (d) one or more purine nucleotides in NX3 positions are independently 2′-deoxy-2′-fluoro nucleotides, 2′-O-alkyl nucleotides, 2′-deoxy nucleotides, ribonucleotides, or any combination thereof.
    
    


In certain embodiments, the invention features a double-stranded short interfering nucleic acid (siNA) molecule of formula (A); wherein

    
    
        (a) 1, 2, 3, 4, 5 or more pyrimidine nucleotides in NX4 positions are 2′-deoxy-2′-fluoro nucleotides;
        (b) 1, 2, 3, 4, 5 or more purine nucleotides in NX4 positions are 2′-O-alkyl nucleotides;
        (c) 1, 2, 3, 4, 5 or more pyrimidine nucleotides in NX3 positions are 2′-deoxy-2′-fluoro nucleotides; and
        (d) 1, 2, 3, 4, 5 or more purine nucleotides in NX3 positions are 2′-deoxy nucleotides.
    
    


In certain embodiments, the invention features a double-stranded short interfering nucleic acid (siNA) molecule of formula (A); wherein

    
    
        (a) 1, 2, 3, 4, 5 or more pyrimidine nucleotides in NX4 positions are 2′-O-alkyl nucleotides;
        (b) 1, 2, 3, 4, 5 or more purine nucleotides in NX4 positions are ribonucleotides;
        (c) 1, 2, 3, 4, 5 or more pyrimidine nucleotides in NX3 positions are 2′-O-alkyl nucleotides; and
        (d) 1, 2, 3, 4, 5 or more purine nucleotides in NX3 positions are ribonucleotides.
    
    


In certain embodiments, the invention features a double-stranded short interfering nucleic acid (siNA) molecule of formula (A); wherein

    
    
        (a) 1, 2, 3, 4, 5 or more pyrimidine nucleotides in NX4 positions are 2′-deoxy-2′-fluoro nucleotides;
        (b) 1, 2, 3, 4, 5 or more purine nucleotides in NX4 positions are 2′-O-alkyl nucleotides;
        (c) 1, 2, 3, 4, 5 or more pyrimidine nucleotides in NX3 positions are 2′-O-alkyl nucleotides; and
        (d) 1, 2, 3, 4, 5 or more purine nucleotides in NX3 positions are 2′-deoxy-2′-fluoro nucleotides.
    
    


In certain embodiments, the invention features a double-stranded short interfering nucleic acid (siNA) molecule of formula (A) further comprising one or more phosphorothioate internucleotide linkages.
In some embodiments, siNA molecules having formula A comprise a terminal phosphate group at the 5′-end of the antisense strand or antisense region of the nucleic acid molecule.
In various embodiments, siNA molecules having formula A comprise X5=0, 1, 2, or 3; each X1 and X2=1 or 2; X3=18, 19, 20, 21, 22, or 23, and X4=17, 18, 19, 20, 21, 22, or 23.
In certain embodiments, siNA molecules having formula A comprise X5=3. In other embodiments siNA molecules having formula A comprise X5=0.
In certain embodiments, siNA molecules having formula A comprise X1=2 and X2=2.
In various embodiments, siNA molecules having formula A comprise X5=0, X1=2, and X2=2. In other embodiments, siNA molecules having formula A comprise X5=3, X1=2, and X2=2.
In one specific embodiment, an siNA molecule having formula A comprises X5=3; each X1 and X2=2; X3=19, and X4=16.
In another specific embodiment, an siNA molecule having formula A comprises X5=0; each X1 and X2=2; X3=19, and X4=19.
In certain embodiments, siNA molecules having formula A comprise caps (B) at the 3′ and 5′ ends of the sense strand or sense region.
In certain embodiments, siNA molecules having formula A comprise caps (B) at the 3′-end of the antisense strand or antisense region.
In various embodiments, siNA molecules having formula A comprise caps (B) at the 3′ and 5′ ends of the sense strand or sense region and caps (B) at the 3′-end of the antisense strand or antisense region.
In yet other embodiments, siNA molecules having formula A comprise caps (B) only at the 5′-end of the sense (upper) strand of the double-stranded nucleic acid molecule.
In some embodiments, siNA molecules having formula A further comprise one or more phosphorothioate internucleotide linkages between the nucleotides. In certain embodiments, siNA molecules having formula A comprise one or more phosphorothioate internucleotide linkages between the first terminal (N) and the adjacent nucleotide on the 3′ end of the sense strand, antisense strand, or both sense strand and antisense strands of the nucleic acid molecule. For example, a double-stranded nucleic acid molecule can comprise X1 and/or X2=2 having overhanging nucleotide positions with a phosphorothioate internucleotide linkage, e.g., (NsN) where “s” indicates phosphorothioate.
In some embodiments, one or more of the nucleotides of siNA molecules having formula A have a universal base.
In certain embodiments, siNA molecules having formula A have at position 14 from the 5′-end of the antisense strand a ribonucleotide when the nucleotide at that position 14 is a purine. In other embodiments, siNA molecules having formula A have at position 14 from the 5′-end of the antisense strand a ribonucleotide, a 2′-deoxy-2′-fluoro nucleotide or a 2′-O-methyl nucleotide when the nucleotide at that position 14 is a pyrimidine nucleotide.
In some embodiments, siNA molecules having formula A comprises (N) nucleotides in the antisense strand (lower strand) that are complementary to nucleotides in a CTNNB1 target polynucleotide sequence, which also has complementarity to the N and [N] nucleotides of the antisense (lower) strand.
In certain embodiments, one or more siNA molecules of the invention are modified according to modification criteria as shown and described in U.S. Ser. No. 61/408,428 and U.S. Ser. No. 61/408,303, both of which are incorporated by reference herein.
Any of the above described modifications, or combinations thereof, discussed above as applicable to siNAs of the invention, including those in the references cited, can be applied to any of the embodiments to siNA molecules of the present invention.
C. Generation/Synthesis of siNA Molecules
The siNAs of the invention can be obtained using a number of techniques known to those of skill in the art. For example the siNA can be chemically synthesized or may be encoded by plasmid (e.g., transcribed as sequences that automatically fold into duplexes with hairpin loops.). siNA can also be generated by cleavage of longer dsRNA (e.g., dsRNA greater than about 25 nucleotides in length) by the E coli RNase II or Dicer. These enzymes process the dsRNA into biologically active siNA (see, e.g., Yang et al., PNAS USA 99:9942-9947 (2002); Calegari et al. PNAS USA 99:14236 (2002) Byron et al. Ambion Tech Notes; 10 (1):4-6 (2009); Kawaski et al., Nucleic Acids Res., 31:981-987 (2003), Knight and Bass, Science, 293:2269-2271 (2001) and Roberston et al., J. Biol. Chem 243:82 (1969).
1. Chemical Synthesis
Preferably, siNA of the invention are chemically synthesized. Oligonucleotides (e.g., certain modified oligonucleotides or portions of oligonucleotides lacking ribonucleotides) are synthesized using protocols known in the art, for example as described in Caruthers et al., 1992, Methods in Enzymology 211, 3-19, Thompson et al., International PCT Publication No. WO 99/54459, Wincott et al., 1995, Nucleic Acids Res. 23, 2677-2684, Wincott et al., 1997, Methods Mol. Bio., 74, 59, Brennan et al., 1998, Biotechnol Bioeng., 61, 33-45, and Brennan, U.S. Pat. No. 6,001,311. The synthesis of oligonucleotides makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end.
siNA molecules without modifications are synthesized using procedures as described in Usman et al., 1987, J. Am. Chem. Soc., 109, 7845; Scaringe et al., 1990, Nucleic Acids Res., 18, 5433. These syntheses makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end that can be used for certain siNA molecules of the invention.
In certain embodiments, the siNA molecules of the invention are synthesized, deprotected, and analyzed according to methods described in U.S. Pat. Nos. 6,995,259, 6,686,463, 6,673,918, 6,649,751, 6,989,442, and U.S. patent application Ser. No. 10/190,359.
In a non-limiting synthesis example, small scale syntheses are conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 μmol scale protocol with a 2.5 min coupling step for 2′-O-methylated nucleotides and a 45 second coupling step for 2′-deoxy nucleotides or 2′-deoxy-2′-fluoro nucleotides. Table 10 outlines the amounts and the contact times of the reagents used in the synthesis cycle.
Alternatively, the siNA molecules of the present invention can be synthesized separately and joined together post-synthetically, for example, by ligation (Moore et al., 1992, Science 256, 9923; Draper et al., International PCT Publication No. WO 93/23569; Shabarova et al., 1991, Nucleic Acids Research 19, 4247; Bellon et al., 1997, Nucleosides & Nucleotides, 16, 951; Bellon et al., 1997, Bioconjugate Chem. 8, 204), or by hybridization following synthesis and/or deprotection.
Various siNA molecules of the invention can also be synthesized using the teachings of Scaringe et al., U.S. Pat. Nos. 5,889,136; 6,008,400; and 6,111,086.
2. Vector Expression
Alternatively, siNA molecules of the invention that interact with and down-regulate gene encoding target CTNNB1 molecules can be expressed and delivered from transcription units (see for example Couture et al., 1996, TIG., 12, 510) inserted into DNA or RNA vectors. The recombinant vectors can be DNA plasmids or viral vectors. siNA expressing viral vectors can be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus.
In some embodiments, pol III based constructs are used to express nucleic acid molecules of the invention. Transcription of the siNA molecule sequences can be driven from a promoter for eukaryotic RNA polymerase I (pol I), RNA polymerase II (pol II), or RNA polymerase III (pol III). (see for example, Thompson, U.S. Pat. Nos. 5,902,880 and 6,146,886). (See also, Izant and Weintraub, 1985, Science, 229, 345; McGarry and Lindquist, 1986, Proc. Natl. Acad. Sci., USA 83, 399; Scanlon et al., 1991, Proc. Natl. Acad. Sci. USA, 88, 10591-5; Kashani-Sabet et al., 1992, Antisense Res. Dev., 2, 3-15; Dropulic et al., 1992, J. Virol., 66, 1432-41; Weerasinghe et al., 1991, J. Virol., 65, 5531-4; Ojwang et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 10802-6; Chen et al., 1992, Nucleic Acids Res., 20, 4581-9; Sarver et al., 1990 Science, 247, 1222-1225; Thompson et al., 1995, Nucleic Acids Res., 23, 2259; Good et al., 1997, Gene Therapy, 4, 45. Transcripts from pol II or pol III promoters are expressed at high levels in all cells; the levels of a given pol II promoter in a given cell type depends on the nature of the gene regulatory sequences (enhancers, silencers, etc.) present nearby. Prokaryotic RNA polymerase promoters are also used, providing that the prokaryotic RNA polymerase enzyme is expressed in the appropriate cells (Elroy-Stein and Moss, 1990, Proc. Natl. Acad. Sci. USA, 87, 6743-7; Gao and Huang 1993, Nucleic Acids Res., 21, 2867-72; Lieber et al., 1993, Methods Enzymol., 217, 47-66; Zhou et al., 1990, Mol. Cell. Biol., 10, 4529-37). Several investigators have demonstrated that nucleic acid molecules expressed from such promoters can function in mammalian cells (e.g. Kashani-Sabet et al., 1992, Antisense Res. Dev., 2, 3-15; Ojwang et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 10802-6; Chen et al., 1992, Nucleic Acids Res., 20, 4581-9; Yu et al., 1993, Proc. Natl. Acad. Sci. USA, 90, 6340-4; L'Huillier et al., 1992, EMBO J., 11, 4411-8; Lisziewicz et al., 1993, Proc. Natl. Acad. Sci. U.S. A, 90, 8000-4; Thompson et al., 1995, Nucleic Acids Res., 23, 2259; Sullenger & Cech, 1993, Science, 262, 1566). More specifically, transcription units such as the ones derived from genes encoding U6 small nuclear (snRNA), transfer RNA (tRNA) and adenovirus VA RNA are useful in generating high concentrations of desired RNA molecules such as siNA in cells (Thompson et al., supra; Couture and Stinchcomb, 1996, supra; Noonberg et al., 1994, Nucleic Acid Res., 22, 2830; Noonberg et al., U.S. Pat. No. 5,624,803; Good et al., 1997, Gene Ther., 4, 45; Beigelman et al., International PCT Publication No. WO 96/18736. The above siNA transcription units can be incorporated into a variety of vectors for introduction into mammalian cells, including but not restricted to, plasmid DNA vectors, viral DNA vectors (such as adenovirus or adeno-associated virus vectors), or viral RNA vectors (such as retroviral or alphavirus vectors) (for a review see Couture and Stinchcomb, 1996, supra).
Vectors used to express the siNA molecules of the invention can encode one or both strands of an siNA duplex, or a single self-complementary strand that self hybridizes into an siNA duplex. The nucleic acid sequences encoding the siNA molecules of the instant invention can be operably linked in a manner that allows expression of the siNA molecule (see for example Paul et al., 2002, Nature Biotechnology, 19, 505; Miyagishi and Taira, 2002, Nature Biotechnology, 19, 497; Lee et al., 2002, Nature Biotechnology, 19, 500; and Novina et al., 2002, Nature Medicine, advance online publication doi:10.1038/nm725).
D. Carrier/Delivery Systems
The siNA molecules of the invention are added directly, or can be complexed with cationic lipids, packaged within liposomes, or as a recombinant plasmid or viral vectors which express the siNA molecules, or otherwise delivered to target cells or tissues. Methods for the delivery of nucleic acid molecules are described in Akhtar et al., 1992, Trends Cell Bio., 2, 139; Delivery Strategies for Antisense Oligonucleotide Therapeutics, ed. Akhtar, 1995, Maurer et al., 1999, Mol. Membr. Biol., 16, 129-140; Hofland and Huang, 1999, Handb. Exp. Pharmacol., 137, 165-192; and Lee et al., 2000, ACS Symp. Ser., 752, 184-192. Beigelman et al., U.S. Pat. No. 6,395,713 and Sullivan et al., PCT WO 94/02595 further describe the general methods for delivery of nucleic acid molecules. These protocols can be utilized for the delivery of virtually any nucleic acid molecule. Nucleic acid molecules can be administered to cells by a variety of methods known to those of skill in the art, including, but not restricted to, encapsulation in liposomes, by iontophoresis, or by incorporation into other vehicles, such as biodegradable polymers, hydrogels, cyclodextrins (see for example, Gonzalez et al., 1999, Bioconjugate Chem., 10, 1068-1074; Wang et al., International PCT Publication Nos. WO 03/47518 and WO 03/46185), poly(lactic-co-glycolic)acid (PLGA) and PLCA microspheres (see for example U.S. Pat. No. 6,447,796 and US Patent Application Publication No. US 2002130430), biodegradable nanocapsules, and bioadhesive microspheres, or by proteinaceous vectors (O'Hare and Normand, International PCT Publication No. WO 00/53722).
In one aspect, the present invention provides carrier systems containing the siNA molecules described herein. In some embodiments, the carrier system is a lipid-based carrier system, cationic lipid, or liposome nucleic acid complexes, a liposome, a micelle, a virosome, a lipid nanoparticle or a mixture thereof. In other embodiments, the carrier system is a polymer-based carrier system such as a cationic polymer-nucleic acid complex. In additional embodiments, the carrier system is a cyclodextrin-based carrier system such as a cyclodextrin polymer-nucleic acid complex. In further embodiments, the carrier system is a protein-based carrier system such as a cationic peptide-nucleic acid complex. Preferably, the carrier system is a lipid nanoparticle (“LNP”) formulation.
In certain embodiments, the siNA molecules of the invention are formulated with a lipid nanoparticle composition such as is described in U.S. patent application Ser. Nos. 11/353,630, 11/586,102, 61/189,295, 61/204,878, 61/235,476, 61/249,807, 61/298,022, 61/351,373, 61/347,640, 61/345,754, 61/322,054, 12/640,342, and 12/617,079, and PCT Applications Nos. PCT/US10/020,013 and PCT/US09/053,336. In certain preferred embodiments, the siNA molecules of the invention are formulated with a lipid nanoparticle composition comprising a cationic lipid/Cholesterol/PEG-C-DMA/DSPC in a 40/48/2/10 ratio or a cationic lipid/Cholesterol/PEG-DMG/DSPC in a 40/48/2/10 ratio. In more certain embodiments, the cationic lipid is DLinDMA (see Table 12), the PEG is PEG-DMG, and the N/P ratio of the formulation is 2.8. In more preferred embodiments, the cationic lipid is DLinDMA (see Tables 11 & 12).
In various embodiments, lipid nanoparticle formulations described in Table 11 are applied to any siNA molecule or combination of siNA molecules herein. In some embodiments, the invention features a composition comprising an siNA molecule of the invention formulated as any of formulation LNP-051; LNP-053; LNP-054; LNP-069; LNP-073; LNP-077; LNP-080; LNP-082; LNP-083; LNP-060; LNP-061; LNP-086; LNP-097; LNP-098; LNP-099; LNP-100; LNP-101; LNP-102; LNP-103; or LNP-104 (see Table 11).
In certain other embodiments, the invention features a composition comprising an siNA molecule of the invention formulated with any of the cationic lipid formulations described in U.S. Patent Application Nos. 61/189,295, 61/204,878, 61/235,476, 61/249,807, and 61/298,022.
In other embodiments, the invention features conjugates and/or complexes of siNA molecules of the invention. Such conjugates and/or complexes can be used to facilitate delivery of siNA molecules into a biological system, such as a cell. The conjugates and complexes provided by the instant invention can impart therapeutic activity by transferring therapeutic compounds across cellular membranes, altering the pharmacokinetics, and/or modulating the localization of nucleic acid molecules of the invention. Non-limiting, examples of such conjugates are described in U.S. Publication Nos. US2008/0152661 A1 and US 2004/0162260 A1 (e.g., CDM-LBA, CDM-Pip-LBA, CDM-PEG, CDM-NAG, etc.) and U.S. patent application Ser. Nos. 10/427,160 10/201,394, 61/322,422, and 61/315,223; and U.S. Pat. Nos. 6,528,631; 6,335,434; 6,235,886; 6,153,737; 5,214,136; and 5,138,045.
In various embodiments, polyethylene glycol (PEG) can be covalently attached to siNA compounds of the present invention. The attached PEG can be any molecular weight, preferably from about 100 to about 50,000 daltons (Da).
In yet other embodiments, the invention features compositions or formulations comprising surface-modified liposomes containing poly(ethylene glycol) lipids (PEG-modified, or long-circulating liposomes or stealth liposomes) and siNA molecules of the invention, such as is disclosed in for example, International PCT Publication No. WO 96/10391; Ansell et al., International PCT Publication No. WO 96/10390; Holland et al., International PCT Publication No. WO 96/10392.
In some embodiments, the siNA molecules of the invention can also be formulated or complexed with polyethyleneimine and derivatives thereof, such as polyethyleneimine-polyethyleneglycol-N-acetylgalactosamine (PEI-PEG-GAL) or polyethylene imine-polyethyleneglycol-tri-N-acetylgalactosamine (PEI-PEG-triGAL) derivatives. In one embodiment, the nucleic acid molecules of the invention are formulated as described in U.S. Patent Application Publication No. 20030077829.
In other embodiments, siNA molecules of the invention are complexed with membrane disruptive agents such as those described in U.S. Patent Application Publication No. 20010007666. In still other embodiments, the membrane disruptive agent or agents and the siNA molecule are also complexed with a cationic lipid or helper lipid molecule, such as those lipids described in U.S. Pat. No. 6,235,310.
In certain embodiments, siNA molecules of the invention are complexed with delivery systems as described in U.S. Patent Application Publication Nos. 2003077829; 20050287551; 20050164220; 20050191627; 20050118594; 20050153919; 20050085486; and 20030158133; and International PCT Publication Nos. WO 00/03683 and WO 02/087541.
In some embodiments, a liposomal formulation of the invention comprises an siNA molecule of the invention (e.g., siNA) formulated or complexed with compounds and compositions described in U.S. Pat. Nos. 6,858,224; 6,534,484; 6,287,591; 6,835,395; 6,586,410; 6,858,225; 6,815,432; 6,586,001; 6,120,798; 6,977,223; 6,998,115; 5,981,501; 5,976,567; 5,705,385; and U.S. Patent Application Publication Nos. 2006/0019912; 2006/0019258; 2006/0008909; 2005/0255153; 2005/0079212; 2005/0008689; 2003/0077829, 2005/0064595, 2005/0175682, 2005/0118253; 2004/0071654; 2005/0244504; 2005/0265961 and 2003/0077829.
Alternatively, recombinant plasmids and viral vectors, as discussed above, which express siNAs of the invention can be used to deliver the molecules of the invention. Delivery of siNA molecule expressing vectors can be systemic, such as by intravenous or intra-muscular administration, by administration to target cells ex-planted from a subject followed by reintroduction into the subject, or by any other means that would allow for introduction into the desired target cell (for a review see Couture et al., 1996, TIG., 12, 510). Such recombinant plasmids can also be administered directly or in conjunction with a suitable delivery reagents, including, for example, the Minis Transit LT1 lipophilic reagent; lipofectin; lipofectamine; cellfectin; polycations (e.g., polylysine) or liposomes lipid-based carrier system, cationic lipid, or liposome nucleic acid complexes, a micelle, a virosome, a lipid nanoparticle.
E. Kits
The present invention also provides nucleic acids in kit form. The kit may comprise a container. The kit typically contains a nucleic acid of the invention with instructions for its administration. In certain instances, the nucleic acids may have a targeting moiety attached. Methods of attaching targeting moieties (e.g. antibodies, proteins) are known to those of skill in the art. In certain instances, the nucleic acids are chemically modified. In other embodiments, the kit contains more than one siNA molecule of the invention. The kits may comprise an siNA molecule of the invention with a pharmaceutically acceptable carrier or diluent. The kits may further comprise excipients.
F. Therapeutic Uses/Pharmaceutical Compositions
The present body of knowledge in CTNNB1 research indicates the need for methods to assay CTNNB1 activity and for compounds that can regulate CTNNB1 expression for research, diagnostic, and therapeutic use. As described infra, the nucleic acid molecules of the present invention can be used in assays to diagnose disease state related of CTNNB1 levels. In addition, the nucleic acid molecules and pharmaceutical compositions can be used to treat disease states related to CTNNB1 RNA levels.
1. Disease States Associated with CTNNB1
Particular disease states that can be associated with CTNNB1 expression modulation include various cancers including solid tumors. Non-limiting examples of such cancers include: bilary tract cancer, bladder cancer, transitional cell carcinoma, urothelial carcinoma, osteosarcoma, brain cancer, gliomas, astrocytomas, breast carcinoma, metaplastic carcinoma, cervical cancer, cervical squamous cell carcinoma, rectal cancer, colorectal carcinoma, colon cancer, hereditary nonpolyposis colorectal cancer, colorectal adenocarcinomas, gastrointestinal stromal tumors (GISTs), endometrial carcinoma, endometrial stromal sarcomas, esophageal cancer, esophageal squamous cell carcinoma, esophageal adenocarcinoma, ocular melanoma, uveal melanoma, gallbladder carcinomas, gallbladder adenocarcinoma, renal cell carcinoma, clear cell renal cell carcinoma, transitional cell carcinoma, urothelial carcinomas, wilms tumor, leukemia, acute lymocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic (CLL), chronic myeloid (CML), chronic myelomonocytic (CMML), liver cancer, liver carcinoma, hepatoma, hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma, Lung cancer, non-small cell lung cancer (NSCLC), mesothelioma, B-cell lymphomas, non-Hodgkin lymphoma, diffuse large B-cell lymphoma, Mantle cell lymphoma, T-cell lymphomas, non-Hodgkin lymphoma, precursor T-lymphoblastic lymphoma/leukemia, peripheral T-cell lymphomas, multiple myeloma, nasopharyngeal carcinoma (NPC), neuroblastoma, oropharyngeal cancer, oral cavity squamous cell carcinomas, osteosarcoma, ovarian carcinoma, pancreatic cancer, pancreatic ductal adenocarcinoma, pseudopapillary neoplasms, acinar cell carcinomas, Prostate cancer, prostate adenocarcinoma, skin cancer, melanoma, malignant melanoma, cutaneous melanoma, small intestine carcinomas, stomach cancer, gastric carcinoma, gastrointestinal stromal tumor (GIST), uterine cancer, and uterine sarcoma.
It is understood that the siNA molecules of the invention can degrade the target CTNNB1 mRNA (and thus inhibit the diseases stated above). Inhibition of a disease can be evaluated by directly measuring the progress of the disease in a subject. It can also be inferred through observing a change or reversal in a condition associated with the disease. Additionally, the siNA molecules of the invention can be used as a prophylaxis. Thus, the use of the nucleic acid molecules and pharmaceutical compositions of the invention can be used to ameliorate, treat, prevent, and/or cure these diseases and others associated with regulation of CTNNB1 gene expression.
2. Pharmaceutical Compositions
The siNA molecules of the instant invention provide useful reagents and methods for a variety of therapeutic, prophylactic, cosmetic, veterinary, diagnostic, target validation, genomic discovery, genetic engineering, and pharmacogenomic applications.
a. Formulations
Thus, the present invention, in one aspect, also provides for pharmaceutical compositions of the siNA molecules described, i.e., compositions in a pharmaceutically acceptable carrier or diluent. These pharmaceutical compositions include salts, esters, or salts of such esters, of the above compounds, e.g., acid addition salts, for example, salts of hydrochloric, hydrobromic, hydroiodic, acetic acid, and benzene sulfonic acid. Other salts include for example, sodium, potassium, manganese, ammonium, and calcium salts. These formulations or compositions can comprise a pharmaceutically acceptable carrier or diluent as is generally known in the art.
In one embodiment, the invention features a pharmaceutical composition comprising an siNA molecule comprising at least a 15 nucleotide sequence of SEQ ID NO: 5. In another embodiment, the invention features a pharmaceutical composition comprising an siNA molecule comprising at least a 15 nucleotide sequence of SEQ ID NO: 4918. In yet another embodiment, the invention features a pharmaceutical composition comprising an siNA molecule comprising at least a 15 nucleotide sequence of SEQ ID NO: 194. In still another embodiment, the invention features a pharmaceutical composition comprising an siNA molecule comprising at least a 15 nucleotide sequence of SEQ ID NO: 5107. In another embodiment, the invention features a pharmaceutical composition comprising an siNA molecule comprising at least a 15 nucleotide sequence of SEQ ID NO: 196. In another embodiment, the invention features a pharmaceutical composition comprising an siNA molecule comprising at least a 15 nucleotide sequence of SEQ ID NO: 5109. In another embodiment, the invention features a pharmaceutical composition comprising an siNA molecule comprising at least a 15 nucleotide sequence of SEQ ID NO: 151. In yet another embodiment, the invention features a pharmaceutical composition comprising an siNA molecule comprising at least a 15 nucleotide sequence of SEQ ID NO: 5064. In still another embodiment, the invention features a pharmaceutical composition comprising an siNA molecule comprising formula (A).
The siNA molecules of the invention are preferably formulated as pharmaceutical compositions prior to administering to a subject, according to techniques known in the art. Pharmaceutical compositions of the present invention are characterized as being at least sterile and pyrogen-free. Methods for preparing pharmaceutical compositions of the invention are within the skill in the art for example as described in Remington's Pharmaceutical Science, 17th ed., Mack Publishing Company, Easton, Pa. (1985).
In some embodiments, pharmaceutical compositions of the invention (e.g. siNA and/or LNP formulations thereof) further comprise conventional pharmaceutical excipients and/or additives. Suitable pharmaceutical excipients include preservatives, flavoring agents, stabilizers, antioxidants, osmolality adjusting agents, buffers, and pH adjusting agents. Suitable additives include physiologically biocompatible buffers (e.g., trimethylamine hydrochloride), addition of chelants (such as, for example, DTPA or DTPA-bisamide) or calcium chelate complexes (as for example calcium DTPA, CaNaDTPA-bisamide), or, optionally, additions of calcium or sodium salts (for example, calcium chloride, calcium ascorbate, calcium gluconate or calcium lactate). In addition, antioxidants and suspending agents can be used.
Non-limiting examples of various types of formulations for local administration include ointments, lotions, creams, gels, foams, preparations for delivery by transdermal patches, powders, sprays, aerosols, capsules or cartridges for use in an inhaler or insufflator or drops (for example eye or nose drops), solutions/suspensions for nebulization, suppositories, pessaries, retention enemas and chewable or suckable tablets or pellets (for example for the treatment of aphthous ulcers) or liposome or microencapsulation preparations.
Ointments, creams and gels, can, for example, can be formulated with an aqueous or oily base with the addition of suitable thickening and/or gelling agent and/or solvents. Non limiting examples of such bases can thus, for example, include water and/or an oil such as liquid paraffin or a vegetable oil such as arachis oil or castor oil, or a solvent such as polyethylene glycol. Various thickening agents and gelling agents can be used depending on the nature of the base. Non-limiting examples of such agents include soft paraffin, aluminum stearate, cetostearyl alcohol, polyethylene glycols, woolfat, beeswax, carboxypolymethylene and cellulose derivatives, and/or glyceryl monostearate and/or non-ionic emulsifying agents.
In one embodiment lotions can be formulated with an aqueous or oily base and will in general also contain one or more emulsifying agents, stabilizing agents, dispersing agents, suspending agents or thickening agents.
In one embodiment powders for external application can be formed with the aid of any suitable powder base, for example, talc, lactose or starch. Drops can be formulated with an aqueous or non-aqueous base also comprising one or more dispersing agents, solubilizing agents, suspending agents or preservatives.
Compositions intended for oral use can be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions can contain one or more such sweetening agents, flavoring agents, coloring agents or preservative agents in order to provide pharmaceutically elegant and palatable preparations. Tablets contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients that are suitable for the manufacture of tablets. These excipients can be, for example, inert diluents; such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example starch, gelatin or acacia; and lubricating agents, for example magnesium stearate, stearic acid or talc. The tablets can be uncoated or they can be coated by known techniques. In some cases such coatings can be prepared by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monosterate or glyceryl distearate can be employed.
Formulations for oral use can also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin or olive oil.
Aqueous suspensions contain the active materials in a mixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients are suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydropropyl-methylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents can be a naturally-occurring phosphatide, for example, lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate; or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate. The aqueous suspensions can also contain one or more preservatives, for example ethyl, or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents, such as sucrose or saccharin.
Oily suspensions can be formulated by suspending the active ingredients in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. The oily suspensions can contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents and flavoring agents can be added to provide palatable oral preparations. These compositions can be preserved by the addition of an anti-oxidant such as ascorbic acid
Pharmaceutical compositions of the invention can also be in the form of oil-in-water emulsions. The oily phase can be a vegetable oil or a mineral oil or mixtures of these. Suitable emulsifying agents can be naturally-occurring gums, for example gum acacia or gum tragacanth, naturally-occurring phosphatides, for example soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol, anhydrides, for example sorbitan monooleate, and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsions can also contain sweetening and flavoring agents.
Syrups and elixirs can be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol, glucose or sucrose. Such formulations can also contain a demulcent, a preservative and flavoring and coloring agents. The pharmaceutical compositions can be in the form of a sterile injectable aqueous or oleaginous suspension. This suspension can be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents that have been mentioned above. The sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic parentally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.
The nucleic acid molecules of the invention can also be administered in the form of suppositories, e.g., for rectal administration of the drug. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient that is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug. Such materials include cocoa butter and polyethylene glycols.
Nucleic acid molecules of the invention can be administered parenterally in a sterile medium. The drug, depending on the vehicle and concentration used, can either be suspended or dissolved in the vehicle. Advantageously, adjuvants such as local anesthetics, preservatives and buffering agents can be dissolved in the vehicle.
In other embodiments, the siNA and LNP compositions and formulations provided herein for use in pulmonary delivery further comprise one or more surfactants. Suitable surfactants or surfactant components for enhancing the uptake of the compositions of the invention include synthetic and natural as well as full and truncated forms of surfactant protein A, surfactant protein B, surfactant protein C, surfactant protein D and surfactant Protein E, di-saturated phosphatidylcholine (other than dipalmitoyl), dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine; phosphatidic acid, ubiquinones, lysophosphatidylethanolamine, lysophosphatidylcholine, palmitoyl-lysophosphatidylcholine, dehydroepiandrosterone, dolichols, sulfatidic acid, glycerol-3-phosphate, dihydroxyacetone phosphate, glycerol, glycero-3-phosphocholine, dihydroxyacetone, palmitate, cytidine diphosphate (CDP) diacylglycerol, CDP choline, choline, choline phosphate; as well as natural and artificial lamellar bodies which are the natural carrier vehicles for the components of surfactant, omega-3 fatty acids, polyenic acid, polyenoic acid, lecithin, palmitinic acid, non-ionic block copolymers of ethylene or propylene oxides, polyoxypropylene, monomeric and polymeric, polyoxyethylene, monomeric and polymeric, poly(vinyl amine) with dextran and/or alkanoyl side chains, Brij 35, Triton X-100 and synthetic surfactants ALEC, Exosurf, Survan and Atovaquone, among others. These surfactants can be used either as single or part of a multiple component surfactant in a formulation, or as covalently bound additions to the 5′ and/or 3′ ends of the nucleic acid component of a pharmaceutical composition herein.
b. Combinations
The siNAs and pharmaceutical formulations according to the invention can be administered to a subject alone or used in combination with or include one or more other therapeutic agents, for example, anticancer agents. Thus, combinations of the presently disclosed compounds with other anti-cancer or chemotherapeutic agents are within the scope of the invention. Examples of such agents can be found in Cancer Principles and Practice of Oncology by V. T. Devita and S. Hellman (editors), 6th edition (Feb. 15, 2001), Lippincott Williams & Wilkins Publishers. A person of ordinary skill in the art would be able to discern which combinations of agents would be useful based on the particular characteristics of the drugs and the cancer involved. Such anti-cancer agents include, but are not limited to, the following: estrogen receptor modulators, androgen receptor modulators, retinoid receptor modulators, cytotoxic/cytostatic agents, antiproliferative agents, prenyl-protein transferase inhibitors, HMG-CoA reductase inhibitors and other angiogenesis inhibitors, inhibitors of cell proliferation and survival signaling, apoptosis inducing agents and agents that interfere with cell cycle checkpoints. The siNAs of the invention are also useful in combination with any therapeutic agent used in the treatment of HCC, for example, but not limitation sorafenib. The instant compounds are particularly useful when co-administered with radiation therapy.
In a further embodiment, therefore, the invention provides a combination comprising an siNA molecule of the invention, such as for example, but not limitation, an siNA molecule comprising at least a 15 nucleotide sequence of SEQ ID NO: 5, SEQ ID NO: 4918, SEQ ID NO: 194, SEQ ID NO: 5107, SEQ ID NO: 196, SEQ ID NO: 5109, SEQ ID NO: 151, or SEQ ID NO: 5064; or formula (A) or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof together with one or more anti-cancer or chemotherapeutic agents.
In certain embodiments, the instant siNA molecules of the invention are useful in combination with known anti-cancer agents including the following: estrogen receptor modulators, androgen receptor modulators, retinoid receptor modulators, cytotoxic agents, antiproliferative agents, prenyl-protein transferase inhibitors, HMG-CoA reductase inhibitors, HIV protease inhibitors, reverse transcriptase inhibitors, and other angiogenesis inhibitors.
Examples of estrogen receptor modulators that can be used in combination with the compounds of the invention include, but are not limited to, tamoxifen, raloxifene, idoxifene, LY353381, LY117081, toremifene, fulvestrant, 4-[7-(2,2-dimethyl-1-oxopropoxy-4-methyl-2-[4-[2-(1-piperidinyl)ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl-2,2-dimethylpropanoate, 4,4′-dihydroxybenzophenone-2,4-dinitrophenyl-hydrazone, and SH646.
Examples of androgen receptor modulators that can be used in combination with the compounds of the invention include, but are not limited to, finasteride and other 5α-reductase inhibitors, nilutamide, flutamide, bicalutamide, liarozole, and abiraterone acetate.
Examples of such retinoid receptor modulators that can be used in combination with the compounds of the invention include, but are not limited to, bexarotene, tretinoin, 13-cis-retinoic acid, 9-cis-retinoic acid, α-difluoromethylornithine, ILX23-7553, trans-N-(4′-hydroxyphenyl)retinamide, and N-4-carboxyphenyl retinamide.
Examples of cytotoxic agents that can be used in combination with the compounds of the invention include, but are not limited to, sertenef, cachectin, ifosfamide, tasonermin, lonidamine, carboplatin, altretamine, prednimustine, dibromodulcitol, ranimustine, fotemustine, nedaplatin, oxaliplatin, temozolomide, heptaplatin, estramustine, improsulfan tosilate, trofosfamide, nimustine, dibrospidium chloride, pumitepa, lobaplatin, satraplatin, profiromycin, cisplatin, irofulven, dexifosfamide, cis-aminedichloro(2-methyl-pyridine)platinum, benzylguanine, glufosfamide, GPX100, (trans, trans, trans)-bis-mu-(hexane-1,6-diamine)-mu-[diamine-platinum(II)]bis[diamine(chloro)platinum (II)]tetrachloride, diarizidinylspermine, arsenic trioxide, 1-(11-dodecylamino-10-hydroxyundecyl)-3,7-dimethylxanthine, zorubicin, idarubicin, daunorubicin, bisantrene, mitoxantrone, pirarubicin, pinafide, valrubicin, amrubicin, antineoplaston, 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycaminomycin, annamycin, galarubicin, elinafide, MEN10755, and 4-demethoxy-3-deamino-3-aziridinyl-4-methylsulphonyl-daunorubicin (see WO 00/50032).
An example of a hypoxia activatable compound that can be used in combination with the compounds of the invention is tirapazamine.
Examples of proteasome inhibitors that can be used in combination with the compounds of the invention include, but are not limited to, lactacystin and bortezomib.
Examples of microtubule inhibitors/microtubule-stabilising agents that can be used in combination with the compounds of the invention include, but are not limited to, paclitaxel, vindesine sulfate, 3′,4′-didehydro-4′-deoxy-8′-norvincaleukoblastine, docetaxol, rhizoxin, dolastatin, mivobulin isethionate, auristatin, cemadotin, RPR109881, BMS184476, vinflunine, cryptophycin, 2,3,4,5,6-pentafluoro-N-(3-fluoro-4-methoxyphenyl)benzene sulfonamide, anhydrovinblastine, N,N-dimethyl-L-valyl-L-valyl-N-methyl-L-valyl-L-prolyl-L-proline-t-butylamide, TDX258, the epothilones (see for example U.S. Pat. Nos. 6,284,781 and 6,288,237) and BMS188797.
Some examples of topoisomerase inhibitors that can be used in combination with the compounds of the invention include, but are not limited to, are topotecan, hycaptamine, irinotecan, rubitecan, 6-ethoxypropionyl-3′,4′-O-exo-benzylidene-chartreusin, 9-methoxy-N,N-dimethyl-5-nitropyrazolo[3,4,5-kl]acridine-2-(6H) propanamine, 1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3′,4′:b,7]-indolizino[1,2b]quinoline-10,13 (9H,15H)dione, lurtotecan, 7-[2-(N-isopropylamino)ethyl]-(20S)camptothecin, BNP1350, BNPI1100, BN80915, BN80942, etoposide phosphate, teniposide, sobuzoxane, 2′-dimethylamino-2′-deoxy-etoposide, GL331, N-[2-(dimethylamino)ethyl]-9-hydroxy-5,6-dimethyl-6H-pyrido[4,3-b]carbazole-1-carboxamide, asulacrine, (5a, 5 aB, 8aa,9b)-9-[2-[N-[2-(dimethylamino)ethyl]-N-methylamino]ethyl]-5-[4-hydro0xy-3,5-dimethoxyphenyl]-5,5a,6,8,8a,9-hexohydrofuro(3′,4′:6,7)naphtho(2,3-d)-1,3-dioxol-6-one, 2,3-(methylenedioxy)-5-methyl-7-hydroxy-8-methoxybenzo[c]-phenanthridinium, 6,9-bis[(2-aminoethyl)amino]benzo[g] isoguinoline-5,10-dione, 5-(3-aminopropylamino)-7,10-dihydroxy-2-(2-hydroxyethylaminomethyl)-6H-pyrazolo[4,5,1-de]acridin-6-one, N-[1-[2(diethylamino)ethylamino]-7-methoxy-9-oxo-9H-thioxanthen-4-ylmethyl]formamide, N-(2-(dimethylamino)ethyl)acridine-4-carboxamide, 6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-indeno[2,1-c]quinolin-7-one, and dimesna.
Examples of inhibitors of mitotic kinesins, and in particular the human mitotic kinesin KSP, that can be used in combination with the compounds of the invention include, but are not limited to, inhibitors described in PCT Publications WO 01/30768, WO 01/98278, WO 03/050,064, WO 03/050,122, WO 03/049,527, WO 03/049,679, WO 03/049,678, WO04/039774, WO03/079973, WO03/099211, WO03/105855, WO03/106417, WO04/037171, WO04/058148, WO04/058700, WO04/126699, WO05/018638, WO05/019206, WO05/019205, WO05/018547, WO05/017190, US2005/0176776. In an embodiment inhibitors of mitotic kinesins include, but are not limited to inhibitors of KSP, inhibitors of MKLP1, inhibitors of CENP-E, inhibitors of MCAK, inhibitors of Kif14, inhibitors of Mphosphl and inhibitors of Rab6-KIFL.
Examples of “histone deacetylase inhibitors” that can be used in combination with the compounds of the invention include, but are not limited to, TSA, oxamflatin, PXD101, MG98, valproic acid and scriptaid. Further reference to other histone deacetylase inhibitors may be found in the following manuscript; Miller, T. A. et al. J. Med. Chem. 46(24):5097-5116 (2003).
Inhibitors of kinases involved in mitotic progression that can be used in combination with the compounds of the invention include, but are not limited to, inhibitors of aurora kinase, inhibitors of Polo-like kinases (PLK) (in particular inhibitors of PLK-1), inhibitors of bub-1 and inhibitors of bub-R1.
Antiproliferative agents that can be used in combination with the compounds of the invention include, but are not limited to, antisense RNA and DNA oligonucleotides such as G3139, ODN698, RVASKRAS, GEM231, and INX3001, and antimetabolites such as enocitabine, carmofur, tegafur, pentostatin, doxifluridine, trimetrexate, fludarabine, capecitabine, galocitabine, cytarabine ocfosfate, fosteabine sodium hydrate, raltitrexed, paltitrexid, emitefur, tiazofurin, decitabine, nolatrexed, pemetrexed, nelzarabine, 2′-deoxy-2′-methylidenecytidine, 2′-fluoromethylene-2′-deoxycytidine, N-[5-(2,3-dihydro-benzofuryl)sulfonyl]-N′-(3,4-dichlorophenyl)urea, N6-[4-deoxy-4-[N2-[2(E),4(E)-tetradecadienoyl]glycylamino]-L-glycero-B-L-manno-heptopyranosyl]adenine, aplidine, ecteinascidin, troxacitabine, 4-[2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimidino[5,4-b][1,4]thiazin-6-yl-(S)-ethyl]-2,5-thienoyl-L-glutamic acid, aminopterin, 5-fluorouracil, alanosine, 11-acetyl-8-(carbamoyloxymethyl)-4-formyl-6-methoxy-14-oxa-1,11-diazatetracyclo(7.4.1.0.0)-tetradeca-2,4,6-trien-9-yl acetic acid ester, swainsonine, lometrexol, dexrazoxane, methioninase, 2′-cyano-2′-deoxy-N4-palmitoyl-1-B-D-arabino furanosyl cytosine and 3-aminopyridine-2-carboxaldehyde thiosemicarbazone.
Examples of monoclonal antibody targeted therapeutic agents that can be used in combination with the compounds of the invention include those therapeutic agents which have cytotoxic agents or radioisotopes attached to a cancer cell specific or target cell specific monoclonal antibody, such as, for example, Bexxar.
Examples of HMG-CoA reductase inhibitors that may be used that can be used in combination with the compounds of the invention include, but are not limited to, lovastatin (MEVACOR®; see U.S. Pat. Nos. 4,231,938, 4,294,926 and 4,319,039), simvastatin (ZOCOR®; see U.S. Pat. Nos. 4,444,784, 4,820,850 and 4,916,239), pravastatin (PRAVACHOL®; see U.S. Pat. Nos. 4,346,227, 4,537,859, 4,410,629, 5,030,447 and 5,180,589), fluvastatin (LESCOL®; see U.S. Pat. Nos. 5,354,772, 4,911,165, 4,929,437, 5,189,164, 5,118,853, 5,290,946 and 5,356,896) and atorvastatin (LIPITOR®; see U.S. Pat. Nos. 5,273,995, 4,681,893, 5,489,691 and 5,342,952). The structural formulas of these and additional HMG-CoA reductase inhibitors that may be used in the instant methods are described at page 87 of M. Yalpani, “Cholesterol Lowering Drugs”, Chemistry & Industry, pp. 85-89 (5 Feb. 1996) and U.S. Pat. Nos. 4,782,084 and 4,885,314.
Examples of prenyl-protein transferase inhibitors that can be used in combination with the compounds of the invention include, but are not limited to, can be found in the following publications and patents: WO 96/30343, WO 97/18813, WO 97/21701, WO 97/23478, WO 97/38665, WO 98/28980, WO 98/29119, WO 95/32987, U.S. Pat. No. 5,420,245, U.S. Pat. No. 5,523,430, U.S. Pat. No. 5,532,359, U.S. Pat. No. 5,510,510, U.S. Pat. No. 5,589,485, U.S. Pat. No. 5,602,098, European Patent Publ. 0 618 221, European Patent Publ. 0 675 112, European Patent Publ. 0 604 181, European Patent Publ. 0 696 593, WO 94/19357, WO 95/08542, WO 95/11917, WO 95/12612, WO 95/12572, WO 95/10514, U.S. Pat. No. 5,661,152, WO 95/10515, WO 95/10516, WO 95/24612, WO 95/34535, WO 95/25086, WO 96/05529, WO 96/06138, WO 96/06193, WO 96/16443, WO 96/21701, WO 96/21456, WO 96/22278, WO 96/24611, WO 96/24612, WO 96/05168, WO 96/05169, WO 96/00736, U.S. Pat. No. 5,571,792, WO 96/17861, WO 96/33159, WO 96/34850, WO 96/34851, WO 96/30017, WO 96/30018, WO 96/30362, WO 96/30363, WO 96/31111, WO 96/31477, WO 96/31478, WO 96/31501, WO 97/00252, WO 97/03047, WO 97/03050, WO 97/04785, WO 97/02920, WO 97/17070, WO 97/23478, WO 97/26246, WO 97/30053, WO 97/44350, WO 98/02436, and U.S. Pat. No. 5,532,359. For an example of the role of a prenyl-protein transferase inhibitor on angiogenesis see European J. of Cancer, Vol. 35, No. 9, pp. 1394-1401 (1999).
Examples of angiogenesis inhibitors that can be used in combination with the compounds of the invention include, but are not limited to, tyrosine kinase inhibitors, such as inhibitors of the tyrosine kinase receptors Flt-1 (VEGFR1) and Flk-1/KDR (VEGFR2), inhibitors of epidermal-derived, fibroblast-derived, or platelet derived growth factors, MMP (matrix metalloprotease) inhibitors, integrin blockers, interferon-α, interleukin-12, pentosan polysulfate, cyclooxygenase inhibitors, including nonsteroidal anti-inflammatories (NSAIDs) like aspirin and ibuprofen as well as selective cyclooxy-genase-2 inhibitors like celecoxib and rofecoxib (PNAS, Vol. 89, p. 7384 (1992); JNCI, Vol. 69, p. 475 (1982); Arch. Opthalmol., Vol. 108, p. 573 (1990); Anat. Rec., Vol. 238, p. 68 (1994); FEBS Letters, Vol. 372, p. 83 (1995); Clin, Orthop. Vol. 313, p. 76 (1995); J. Mol. Endocrinol., Vol. 16, p. 107 (1996); Jpn. J. Pharmacol., Vol. 75, p. 105 (1997); Cancer Res., Vol. 57, p. 1625 (1997); Cell, Vol. 93, p. 705 (1998); Intl. J. Mol. Med., Vol. 2, p. 715 (1998); J. Biol. Chem., Vol. 274, p. 9116 (1999)), steroidal anti-inflammatories (such as corticosteroids, mineralocorticoids, dexamethasone, prednisone, prednisolone, methylpred, betamethasone), carboxyamidotriazole, combretastatin A-4, squalamine, 6-O-chloroacetyl-carbonyl)-fumagillol, thalidomide, angiostatin, troponin-1, angiotensin II antagonists (see Fernandez et al., J. Lab. Clin. Med. 105:141-145 (1985)), and antibodies to VEGF (see, Nature Biotechnology, Vol. 17, pp. 963-968 (October 1999); Kim et al., Nature, 362, 841-844 (1993); WO 00/44777; and WO 00/61186).
Other therapeutic agents that modulate or inhibit angiogenesis may also be used in combination with the compounds of the instant invention and include agents that modulate or inhibit the coagulation and fibrinolysis systems (see review in Clin. Chem. La. Med. 38:679-692 (2000)). Examples of such agents that modulate or inhibit the coagulation and fibrinolysis pathways that can be used in combination with the compounds of the invention include, but are not limited to, heparin (see Thromb. Haemost. 80:10-23 (1998)), low molecular weight heparins and carboxypeptidase U inhibitors (also known as inhibitors of active thrombin activatable fibrinolysis inhibitor [TAFIa]) (see Thrombosis Res. 101:329-354 (2001)). TAFIa inhibitors have been described in PCT Publication WO 03/013,526 and U.S. Ser. No. 60/349,925 (filed Jan. 18, 2002).
Agents that interfere with cell cycle checkpoints that can be used in combination with the compounds of the invention include, but are not limited to, inhibitors of ATR, ATM, the Chk1 and Chk2 kinases and cdkuz and cdc kinase inhibitors and are specifically exemplified by 7-hydroxystaurosporin, flavopiridol, CYC202 (Cyclacel) and BMS-387032.
Agents that interfere with receptor tyrosine kinases (RTKs) that can be used in combination with the compounds of the invention include, but are not limited to, inhibitors of c-Kit, Eph, PDGF, Flt3 and CTNNB1. Further agents include inhibitors of RTKs as described by Bume-Jensen and Hunter, Nature, 411:355-365, 2001.
Inhibitors of cell proliferation and survival signaling pathway that can be used in combination with the compounds of the invention include, but are not limited to, inhibitors of EGFR (for example gefitinib and erlotinib), inhibitors of ERB-2 (for example trastuzumab), inhibitors of IGFR, inhibitors of cytokine receptors, inhibitors of CTNNB1, inhibitors of PI3K (for example LY294002), serine/threonine kinases (including but not limited to inhibitors of Akt such as described in WO 02/083064, WO 02/083139, WO 02/083140, US 2004-0116432, WO 02/083138, US 2004-0102360, WO 03/086404, WO 03/086279, WO 03/086394, WO 03/084473, WO 03/086403, WO 2004/041162, WO 2004/096131, WO 2004/096129, WO 2004/096135, WO 2004/096130, WO 2005/100356, WO 2005/100344), inhibitors of Raf kinase (for example BAY-43-9006), inhibitors of MEK (for example CI-1040 and PD-098059) and inhibitors of mTOR (for example Wyeth CCI-779). Such agents include small molecule inhibitor compounds and antibody antagonists.
Apoptosis inducing agents that can be used in combination with the compounds of the invention include, but are not limited to, activators of TNF receptor family members (including the TRAIL receptors).
NSAIDs that are selective COX-2 inhibitors that can be used in combination with the compounds of the invention include, but are not limited to, those NSAIDs disclosed in U.S. Pat. No. 5,474,995, U.S. Pat. No. 5,861,419, U.S. Pat. No. 6,001,843, U.S. Pat. No. 6,020,343, U.S. Pat. No. 5,409,944, U.S. Pat. No. 5,436,265, U.S. Pat. No. 5,536,752, U.S. Pat. No. 5,550,142, U.S. Pat. No. 5,604,260, U.S. Pat. No. 5,698,584, U.S. Pat. No. 5,710,140, WO 94/15932, U.S. Pat. No. 5,344,991, U.S. Pat. No. 5,134,142, U.S. Pat. No. 5,380,738, U.S. Pat. No. 5,393,790, U.S. Pat. No. 5,466,823, U.S. Pat. No. 5,633,272, and U.S. Pat. No. 5,932,598, all of which are hereby incorporated by reference.
Inhibitors of COX-2 that are particularly useful in combination with the compounds of the invention include: 3-phenyl-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone; and 5-chloro-3-(4-methylsulfonyl)-phenyl-2-(2-methyl-5-pyridinyl)pyridine; or a pharmaceutically acceptable salt thereof.
Compounds that have been described as specific inhibitors of COX-2 and are therefore useful in the present invention include, but are not limited to: parecoxib, CELEBREX® and BEXTRA® or a pharmaceutically acceptable salt thereof.
Angiogenesis inhibitors that can be used in combination with the compounds of the invention include, but are not limited to, endostatin, ukrain, ranpirnase, IM862, 5-methoxy-4-[2-methyl-3-(3-methyl-2-butenyl)oxiranyl]-1-oxaspiro[2,5]oct-6-yl(chloroacetyl)carbamate, acetyldinanaline, 5-amino-1-[[3,5-dichloro-4-(4-chlorobenzoyl)-phenyl]methyl]-1H-1,2,3-triazole-4-carboxamide, CM101, squalamine, combretastatin, RPI4610, NX31838, sulfated mannopentaose phosphate, 7,7-(carbonyl-bis[imino-N-methyl-4,2-pyrrolocarbonylimino[N-methyl-4,2-pyrrole]-carbonylimino]-bis-(1,3-naphthalene disulfonate), and 3-[(2,4-dimethylpyrrol-5-yl)methylene]-2-indolinone (SU5416).
Tyrosine kinase inhibitors that can be used in combination with the compounds of the invention include, but are not limited to, N-(trifluoromethylphenyl)-5-methylisoxazol-4-carboxamide, 3-[(2,4-dimethylpyrrol-5-yl)methylidenyl)indolin-2-one, 17-(allylamino)-17-demethoxygeldanamycin, 4-(3-chloro-4-fluorophenylamino)-7-methoxy-6-[3-(4-morpholinyl)propoxyl]quinazoline, N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine, BIBX1382, 2,3,9,10,11,12-hexahydro-10-(hydroxymethyl)-10-hydroxy-9-methyl-9,12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i][1,6]benzodiazocin-1-one, SH268, genistein, imatinib (STI571), CEP2563, 4-(3-chlorophenylamino)-5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidinemethane sulfonate, 4-(3-bromo-4-hydroxyphenyl)amino-6,7-dimethoxyquinazoline, 4-(4′-hydroxyphenyl)amino-6,7-dimethoxyquinazoline, SU6668, STI571A, N-4-chlorophenyl-4-(4-pyridylmethyl)-1-phthalazinamine, and EMD121974.
Combinations with compounds other than anti-cancer compounds are also encompassed in the instant compositions and methods. For example, combinations of the instantly claimed compounds with PPAR-γ (i.e., PPAR-gamma) agonists and PPAR-δ (i.e., PPAR-delta) agonists are useful in the treatment of certain malignancies. PPAR-γ and PPAR-δ are the nuclear peroxisome proliferator-activated receptors γ and δ. The expression of PPAR-γ on endothelial cells and its involvement in angiogenesis has been reported in the literature (see J. Cardiovasc. Pharmacol. 31:909-913 (1998); J. Biol. Chem. 274:9116-9121 (1999); Invest. Ophthalmol Vis. Sci. 41:2309-2317 (2000)). More recently, PPAR-γ agonists have been shown to inhibit the angiogenic response to VEGF in vitro; both troglitazone and rosiglitazone maleate inhibit the development of retinal neovascularization in mice. (Arch. Ophthamol. 119:709-717 (2001)). Examples of PPAR-γ agonists and PPAR-γ/α agonists that can be used in combination with the compounds of the invention include, but are not limited to, thiazolidinediones (such as DRF2725, CS-011, troglitazone, rosiglitazone, and pioglitazone), fenofibrate, gemfibrozil, clofibrate, GW2570, SB219994, AR-H039242, JTT-501, MCC-555, GW2331, GW409544, NN2344, KRP297, NP0110, DRF4158, NN622, G1262570, PNU182716, DRF552926, 2-[(5,7-dipropyl-3-trifluoromethyl-1,2-benzisoxazol-6-yl)oxy]-2-methylpropionic acid (disclosed in U.S. Ser. No. 09/782,856), and 2(R)-7-(3-(2-chloro-4-(4-fluorophenoxy)phenoxy)propoxy)-2-ethylchromane-2-carboxylic acid (disclosed in U.S. Ser. No. 60/235,708 and 60/244,697).
Another embodiment of the instant invention is the use of the presently disclosed compounds in combination with gene therapy for the treatment of cancer. For an overview of genetic strategies to treating cancer see Hall et al. (Am J Hum Genet 61:785-789 (1997)) and Kufe et al. (Cancer Medicine, 5th Ed, pp 876-889, BC Decker, Hamilton, 2000). Gene therapy can be used to deliver any tumor suppressing gene. Examples of such genes include, but are not limited to, p53, which can be delivered via recombinant virus-mediated gene transfer (see U.S. Pat. No. 6,069,134, for example), a uPA/uPAR antagonist (“Adenovirus-Mediated Delivery of a uPA/uPAR Antagonist Suppresses Angiogenesis-Dependent Tumor Growth and Dissemination in Mice,” Gene Therapy, August 5(8):1105-13 (1998)), and interferon gamma (J Immunol 164:217-222 (2000)).
The compounds of the instant invention may also be administered in combination with an inhibitor of inherent multidrug resistance (MDR), in particular MDR associated with high levels of expression of transporter proteins. Such MDR inhibitors include inhibitors of p-glycoprotein (P-gp), such as LY335979, XR9576, OC144-093, R101922, VX853 and PSC833 (valspodar).
A compound of the present invention may be employed in conjunction with anti-emetic agents to treat nausea or emesis, including acute, delayed, late-phase, and anticipatory emesis, which may result from the use of a compound of the present invention, alone or with radiation therapy. For the prevention or treatment of emesis, a compound of the present invention may be used in conjunction with other anti-emetic agents, especially neurokinin-1 receptor antagonists, 5HT3 receptor antagonists, such as ondansetron, granisetron, tropisetron, and zatisetron, GABAB receptor agonists, such as baclofen, a corticosteroid such as Decadron (dexamethasone), Kenalog, Aristocort, Nasalide, Preferid, Benecorten or others such as disclosed in U.S. Pat. Nos. 2,789,118, 2,990,401, 3,048,581, 3,126,375, 3,929,768, 3,996,359, 3,928,326 and 3,749,712, an antidopaminergic, such as the phenothiazines (for example prochlorperazine, fluphenazine, thioridazine and mesoridazine), metoclopramide or dronabinol. In an embodiment, an anti-emesis agent selected from a neurokinin-1 receptor antagonist, a 5HT3 receptor antagonist and a corticosteroid is administered as an adjuvant for the treatment or prevention of emesis that may result upon administration of the instant compounds.
Neurokinin-1 receptor antagonists of use in conjunction with the compounds of the present invention are fully described, for example, in U.S. Pat. Nos. 5,162,339, 5,232,929, 5,242,930, 5,373,003, 5,387,595, 5,459,270, 5,494,926, 5,496,833, 5,637,699, 5,719,147; European Patent Publication Nos. EP 0 360 390, 0 394 989, 0 428 434, 0 429 366, 0 430 771, 0 436 334, 0 443 132, 0 482 539, 0 498 069, 0 499 313, 0 512 901, 0 512 902, 0 514 273, 0 514 274, 0 514 275, 0 514 276, 0 515 681, 0 517 589, 0 520 555, 0 522 808, 0 528 495, 0 532 456, 0 533 280, 0 536 817, 0 545 478, 0 558 156, 0 577 394, 0 585 913, 0 590 152, 0 599 538, 0 610 793, 0 634 402, 0 686 629, 0 693 489, 0 694 535, 0 699 655, 0 699 674, 0 707 006, 0 708 101, 0 709 375, 0 709 376, 0 714 891, 0 723 959, 0 733 632 and 0 776 893; PCT International Patent Publication Nos. WO 90/05525, 90/05729, 91/09844, 91/18899, 92/01688, 92/06079, 92/12151, 92/15585, 92/17449, 92/20661, 92/20676, 92/21677, 92/22569, 93/00330, 93/00331, 93/01159, 93/01165, 93/01169, 93/01170, 93/06099, 93/09116, 93/10073, 93/14084, 93/14113, 93/18023, 93/19064, 93/21155, 93/21181, 93/23380, 93/24465, 94/00440, 94/01402, 94/02461, 94/02595, 94/03429, 94/03445, 94/04494, 94/04496, 94/05625, 94/07843, 94/08997, 94/10165, 94/10167, 94/10168, 94/10170, 94/11368, 94/13639, 94/13663, 94/14767, 94/15903, 94/19320, 94/19323, 94/20500, 94/26735, 94/26740, 94/29309, 95/02595, 95/04040, 95/04042, 95/06645, 95/07886, 95/07908, 95/08549, 95/11880, 95/14017, 95/15311, 95/16679, 95/17382, 95/18124, 95/18129, 95/19344, 95/20575, 95/21819, 95/22525, 95/23798, 95/26338, 95/28418, 95/30674, 95/30687, 95/33744, 96/05181, 96/05193, 96/05203, 96/06094, 96/07649, 96/10562, 96/16939, 96/18643, 96/20197, 96/21661, 96/29304, 96/29317, 96/29326, 96/29328, 96/31214, 96/32385, 96/37489, 97/01553, 97/01554, 97/03066, 97/08144, 97/14671, 97/17362, 97/18206, 97/19084, 97/19942 and 97/21702; and in British Patent Publication Nos. 2 266 529, 2 268 931, 2 269 170, 2 269 590, 2 271 774, 2 292 144, 2 293 168, 2 293 169, and 2 302 689. The preparation of such compounds is fully described in the aforementioned patents and publications, which are incorporated herein by reference.
In an embodiment, the neurokinin-1 receptor antagonist for use in conjunction with the compounds of the present invention is selected from: 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)ethoxy)-3-(S)-(4-fluorophenyl)-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)morpholine, or a pharmaceutically acceptable salt thereof, which is described in U.S. Pat. No. 5,719,147.
A compound of the instant invention may also be useful for treating or preventing cancer, including bone cancer, in combination with bisphosphonates (understood to include bisphosphonates, diphosphonates, bisphosphonic acids and diphosphonic acids). Examples of bisphosphonates include but are not limited to: etidronate (Didronel), pamidronate (Aredia), alendronate (Fosamax), risedronate (Actonel), zoledronate (Zometa), ibandronate (Boniva), incadronate or cimadronate, clodronate, EB-1053, minodronate, neridronate, piridronate and tiludronate including any and all pharmaceutically acceptable salts, derivatives, hydrates and mixtures thereof.
A compound of the instant invention may also be administered with an agent useful in the treatment of anemia. Such an anemia treatment agent is, for example, a continuous eythropoiesis receptor activator (such as epoetin alfa).
A compound of the instant invention may also be administered with an agent useful in the treatment of neutropenia. Such a neutropenia treatment agent is, for example, a hematopoietic growth factor which regulates the production and function of neutrophils such as a human granulocyte colony stimulating factor, (G-CSF). Examples of a G-CSF include filgrastim and PEG-filgrastim.
A compound of the instant invention may also be administered with an immunologic-enhancing drug, such as levamisole, isoprinosine and Zadaxin.
A compound of the instant invention may also be useful for treating or preventing breast cancer in combination with aromatase inhibitors. Examples of aromatase inhibitors include but are not limited to: anastrozole, letrozole and exemestane.
A compound of the instant invention may also be useful for treating or preventing cancer in combination with other siNA therapeutics.
The compounds of the instant invention may also be administered in combination with γ-secretase inhibitors and/or inhibitors of NOTCH signaling. Such inhibitors include compounds described in WO 01/90084, WO 02/30912, WO 01/70677, WO 03/013506, WO 02/36555, WO 03/093252, WO 03/093264, WO 03/093251, WO 03/093253, WO 2004/039800, WO 2004/039370, WO 2005/030731, WO 2005/014553, U.S. Ser. No. 10/957,251, WO 2004/089911, WO 02/081435, WO 02/081433, WO 03/018543, WO 2004/031137, WO 2004/031139, WO 2004/031138, WO 2004/101538, WO 2004/101539 and WO 02/47671 (including LY-450139).
A compound of the instant invention may also be useful for treating or preventing cancer in combination with PARP inhibitors.
A compound of the instant invention may also be useful for treating cancer in combination with the following therapeutic agents: abarelix (Plenaxis Depot®); aldesleukin (Prokine®); Aldesleukin (Proleukin®); Alemtuzumabb (Campath®); alitretinoin (Panretin); allopurinol (Zyloprim®); altretamine (Hexylen®); amifostine (Ethyol®); anastrozole (Arimidex®); arsenic trioxide (Trisenox®); asparaginase (Elspar®); azacitidine (Vidaza®); bendamustine hydrochloride (Treanda®); bevacuzimab (Avastin®); bexarotene capsules (Targretin®); bexarotene gel (Targretin®); bleomycin (Blenoxane®); bortezomib (Velcade®); brefeldin A; busulfan intravenous (Busulfex®); busulfan oral (Myleran®); calusterone (Methosarb®); capecitabine (Xeloda®); carboplatin (Paraplatin®); carmustine (BCNU®, BiCNU®); carmustine (Gliadel®); carmustine with Polifeprosan 20 Implant (Gliadel Wafer®); celecoxib (Celebrex); cetuximab (Erbitux®); chlorambucil (Leukeran®); cisplatin (Platinol®); cladribine (Leustatin 2-CdA®); clofarabine (Clolar®); cyclophosphamide (Cytoxan®, Neosar®); cyclophosphamide (Cytoxan Injection®); cyclophosphamide (Cytoxan Tablet®); cytarabine (Cytosar-U®); cytarabine liposomal (DepoCyt); dacarbazine (DTIC-Dome®); dactinomycin, actinomycin D (Cosmegen®); dalteparin sodium injection (Fragmin®); Darbepoetin alfa (Aranesp®); dasatinib (Sprycel®); daunorubicin liposomal (DanuoXome®); daunorubicin, daunomycin (Daunorubicin®); daunorubicin, daunomycin (Cerubidine®); degarelix (Firmagon®); Denileukin diftitox (Ontak®); dexrazoxane (Zinecard®); dexrazoxane hydrochloride (Totect®); didemnin B; 17-DMAG; docetaxel (Taxotere®); doxorubicin (Adriamycin PFS®); doxorubicin (Adriamycin®, Rubex®); doxorubicin (Adriamycin PFS Injection®); doxorubicin liposomal (Doxil®); dromostanolone propionate (Dromostanolone®); dromostanolone propionate (Masterone Injection®); eculizumab injection (Soliris®); Elliott's B Solution (Elliott's B Solution®); eltrombopag (Promacta®); epirubicin (Ellence®); Epoetin alfa (Epogen®); erlotinib (Tarceva®); estramustine (Emcyt®); ethinyl estradiol; etoposide phosphate (Etopophos®); etoposide, VP-16 (Vepesid®); everolimus tablets (Afinitor®); exemestane (Aromasin®); ferumoxytol (Feraheme Injection®); Filgrastim (Neupogen®); floxuridine (intraarterial) (FUDR®); fludarabine (Fludara®); fluorouracil, 5-FU (Adrucil®); fulvestrant (Faslodex®); gefitinib (Iressa®); geldanamycin; gemcitabine (Gemzar®); gemtuzumab ozogamicin (Mylotarg®); goserelin acetate (Zoladex Implant®); goserelin acetate (Zoladex®); histrelin acetate (Histrelin Implant®); hydroxyurea (Hydrea®); Ibritumomab Tiuxetan (Zevalin®); idarubicin (Idamycin®); ifosfamide (IFEX®); imatinib mesylate (Gleevec®); interferon alfa 2a (Roferon A®); Interferon alfa-2b (Intron A®); iobenguane 1123 injection (AdreView®); irinotecan (Camptosar®); ixabepilone (Ixempra®); lapatinib tablets (Tykerb®); lenalidomide (Revlimid®); letrozole (Femara®); leucovorin (Wellcovorin®, Leucovorin®); Leuprolide Acetate (Eligard®); levamisole (Ergamisol®); lomustine, CCNU (CeeBU); meclorethamine, nitrogen mustard (Mustargen®); megestrol acetate (Megace®); melphalan, L-PAM (Alkeran®); mercaptopurine, 6-MP (Purinethol®); mesna (Mesnex®); mesna (Mesnex Tabs®); methotrexate (Methotrexate®); methoxsalen (Uvadex®); 8-methoxypsoralen; mitomycin C (Mutamycin®); mitotane (Lysodren®); mitoxantrone (Novantrone®); mitramycin; nandrolone phenpropionate (Durabolin-50); nelarabine (Arranon®); nilotinib (Tasigna®); Nofetumomab (Verluma®); ofatumumab (Arzerra®); Oprelvekin (Neumega®); oxaliplatin (Eloxatin®); paclitaxel (Paxene®); paclitaxel (Taxol®); paclitaxel protein-bound particles (Abraxane®); palifermin (Kepivance®); pamidronate (Aredia®); panitumumab (Vectibix®); pazopanib tablets (Votrienttm®); pegademase (Adagen (Pegademase Bovine)®); pegaspargase (Oncaspar®); Pegfilgrastim (Neulasta®); pemetrexed disodium (Alimta®); pentostatin (Nipent®); pipobroman (Vercyte®); plerixafor (Mozobil®); plicamycin, mithramycin (Mithracin®); porfimer sodium (Photofrin®); pralatrexate injection (Folotyn®); procarbazine (Matulane®); quinacrine (Atabrine®); rapamycin; Rasburicase (Elitek®); raloxifene hydrochloride (Evista®); Rituximab (Rituxan®); romidepsin (Istodax®); romiplostim (Nplate®); sargramostim (Leukine®); Sargramostim (Prokine); sorafenib (Nexavar); streptozocin (Zanosar®); sunitinib maleate (Sutent); talc (Sclerosol); tamoxifen (Nolvadex); temozolomide (Temodar); temsirolimus (Torisel); teniposide, VM-26 (Vumon®); testolactone (Teslac®); thioguanine, 6-TG (Thioguanine®); thiopurine; thiotepa (Thioplex®); topotecan (Hycamtin®); toremifene (Fareston); Tositumomab (Bexxar); Tositumomab/I-131 tositumomab (Bexxar®); trans-retinoic acid; Trastuzumab (Herceptin®); tretinoin, ATRA (Vesanoid®); triethylenemelamine; Uracil Mustard (Uracil Mustard Capsules®); valrubicin (Valstar®); vinblastine (Velban®); vincristine (Oncovin®); vinorelbine (Navelbine®); vorinostat (Zolinza®); wortmannin; and zoledronate (Zometa®).
The invention also provides a combination comprising an siNA molecule of the invention comprising at least a 15 nucleotide sequence of SEQ ID NO: 5, SEQ ID NO: 4918, SEQ ID NO: 194, SEQ ID NO: 5107, SEQ ID NO: 196, SEQ ID NO: 5109, SEQ ID NO: 151, or SEQ ID NO: 5064; or formula (A) and/or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof together with another CTNNB1 inhibitor.
The combinations referred to above can conveniently be presented for use in the form of a pharmaceutical formulation and thus pharmaceutical compositions comprising a combination as defined above together with a pharmaceutically acceptable diluent or carrier represent a further aspect of the invention.
The individual compounds of such combinations can be administered either sequentially or simultaneously in separate or combined pharmaceutical formulations. In one embodiment, the individual compounds will be administered simultaneously in a combined pharmaceutical formulation.
Thus, the described molecules could be used in combination with one or more known compounds, treatments, or procedures to prevent or treat diseases, disorders, conditions, and traits described herein in a subject or organism as are known in the art, such as other CTNNB1 inhibitors.
3. Therapeutic Applications
The present body of knowledge in CTNNB1 research indicates the need for methods that can regulate CTNNB1 expression for therapeutic use.
Thus, one aspect of the invention comprises a method of treating a subject including, but not limited to, a human suffering from a condition which is mediated by the action, or by loss of action, of CTNNB1 gene expression, which method comprises administering to said subject an effective amount of a double-stranded siNA molecule of the invention. In one embodiment of this aspect, the siNA molecules comprises at least a 15 nucleotide sequence of SEQ ID NO: 5, SEQ ID NO: 4918, SEQ ID NO: 194, SEQ ID NO: 5107, SEQ ID NO: 196, SEQ ID NO: 5109, SEQ ID NO: 151, or SEQ ID NO: 5064; or formula (A). In another embodiment of this aspect, the condition is or is caused by cancer. Thus, in certain embodiments the molecules and compositions of the instant invention are useful in a method for treating cancer. Cancers treatable according to this aspect of the invention include bilary tract cancer, bladder cancer, transitional cell carcinoma, urothelial carcinoma, osteosarcoma, brain cancer, gliomas, astrocytomas, breast carcinoma, metaplastic carcinoma, cervical cancer, cervical squamous cell carcinoma, rectal cancer, colorectal carcinoma, colon cancer, hereditary nonpolyposis colorectal cancer, colorectal adenocarcinomas, gastrointestinal stromal tumors (GISTs), endometrial carcinoma, endometrial stromal sarcomas, esophageal cancer, esophageal squamous cell carcinoma, esophageal adenocarcinoma, ocular melanoma, uveal melanoma, gallbladder carcinomas, gallbladder adenocarcinoma, renal cell carcinoma, clear cell renal cell carcinoma, transitional cell carcinoma, urothelial carcinomas, wilms tumor, leukemia, acute lymocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic (CLL), chronic myeloid (CML), chronic myelomonocytic (CMML), liver cancer, liver carcinoma, hepatoma, hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma, lung cancer, non-small cell lung cancer (NSCLC), mesothelioma, B-cell lymphomas, non-Hodgkin lymphoma, diffuse large B-cell lymphoma, Mantle cell lymphoma, T-cell lymphomas, non-Hodgkin lymphoma, precursor T-lymphoblastic lymphoma/leukemia, peripheral T-cell lymphomas, multiple myeloma, nasopharyngeal carcinoma (NPC), neuroblastoma, oropharyngeal cancer, oral cavity squamous cell carcinomas, osteosarcoma, ovarian carcinoma, pancreatic cancer, pancreatic ductal adenocarcinoma, pseudopapillary neoplasms, acinar cell carcinomas, prostate cancer, prostate adenocarcinoma, skin cancer, melanoma, malignant melanoma, cutaneous melanoma, small intestine carcinomas, stomach cancer, gastric carcinoma, gastrointestinal stromal tumor (GIST), uterine cancer, uterine sarcoma
In one embodiment, the siNA molecules of the instant invention are useful in a method for treating or preventing cancer selected from: brain cancer, breast carcinoma, cervical cancer, colorectal carcinoma, renal cell carcinoma, leukemia, hepatocellular carcinoma, lung cancer, B-cell lymphomas, multiple myeloma, ovarian carcinoma, pancreatic cancer, prostate cancer, melanoma, and gastric carcinoma. In certain embodiments, the compounds of the instant invention are useful for treating breast carcinoma, colorectal carcinoma, hepatocellular carcinoma, lung cancer; and prostate cancer. In a particular embodiment, the compounds of the instant invention are useful for treating hepatocellular carcinoma.
In another embodiment, the siNA molecules of the instant invention are useful in a method for the prevention or modulation of the metastases of cancer cells and cancer. In particular, the siNA molecules of the instant invention are useful in a method to prevent or modulate the metastases of brain cancer, breast carcinoma, cervical cancer, colorectal carcinoma, renal cell carcinoma, leukemia, hepatocellular carcinoma, lung cancer, B-cell lymphomas, multiple myeloma, ovarian carcinoma, pancreatic cancer, prostate cancer, melanoma, and gastric carcinoma.
In certain embodiments, the administration of the siNA molecule is via local administration or systemic administration. In other embodiments, the invention features contacting the subject or organism with an siNA molecule of the invention via local administration to relevant tissues or cells, such as lung cells and tissues, such as via pulmonary delivery. In yet other embodiments, the invention features contacting the subject or organism with an siNA molecule of the invention via systemic administration (such as via intravenous or subcutaneous administration of siNA) to relevant tissues or cells, such as cancerous tissues or cells in a subject or organism.
siNA molecules of the invention are also used as reagents in ex vivo applications. For example, siNA reagents are introduced into tissue or cells that are transplanted into a subject for therapeutic effect. The cells and/or tissue can be derived from an organism or subject that later receives the explant, or can be derived from another organism or subject prior to transplantation. The siNA molecules can be used to modulate the expression of one or more genes in the cells or tissue, such that the cells or tissue obtain a desired phenotype or are able to perform a function when transplanted in vivo. In one embodiment, certain CTNNB1 target cells from a patient are extracted. These extracted cells are contacted with CTNNB1 siNAs targeting a specific nucleotide sequence within the cells under conditions suitable for uptake of the siNAs by these cells (e.g., using delivery reagents such as cationic lipids, liposomes and the like or using techniques such as electroporation to facilitate the delivery of siNAs into cells). The cells are then reintroduced back into the same patient or other patients.
For therapeutic applications, a pharmaceutically effective dose of the siNA molecules or pharmaceutical compositions of the invention is administered to the subject. A pharmaceutically effective dose is that dose required to prevent, inhibit the occurrence, or treat (alleviate a symptom to some extent, preferably all of the symptoms) a disease state. One skilled in the art can readily determine a therapeutically effective dose of the siNA of the invention to be administered to a given subject, by taking into account factors, such as the size and weight of the subject, the extent of the disease progression or penetration, the age, health, and sex of the subject, the route of administration, and whether the administration is regional or systemic. Generally, an amount between 0.1 μg/kg and 100 mg/kg body weight/day of active ingredients is administered dependent upon potency of the negatively charged polymer. Optimal dosing schedules can be calculated from measurements of drug accumulation in the body of the patient. The siNA molecules of the invention can be administered in a single dose or in multiple doses.
siNA molecules of the instant invention can be administered once monthly, once weekly, once daily (QD), or divided into multiple monthly, weekly, or daily doses, such as, for example, but not limitation, twice daily (BID), three times daily (TID), once every two weeks. Persons of ordinary skill in the art can easily estimate repetition rates for dosing based on measured residence times and concentrations of the drug in bodily fluids or tissues.
In addition, the administration can be continuous, i.e., every day, or intermittently. For example, intermittent administration of a compound of the instant invention may be administration one to six days per week or it may mean administration in cycles (e.g. daily administration for two to eight consecutive weeks, then a rest period with no administration for up to one week) or it may mean administration on alternate days.
G. Administration
Compositions or formulations can be administered in a variety of ways. Non-limiting examples of administration methods of the invention include oral, buccal, sublingual, parenteral (i.e., intraarticularly, intravenously, intraperitoneally, subcutaneously, or intramuscularly), local rectal administration or other local administration. In one embodiment, the composition of the invention can be administered by insufflation and inhalation. Administration can be accomplished via single or divided doses. In some embodiments, the pharmaceutical compositions are administered intravenously or intraperitoneally by a bolus injection (see, e.g., U.S. Pat. No. 5,286,634). Lipid nucleic acid particles can be administered by direct injection at the site of disease or by injection at a site distal from the site of disease (see, e.g., Culver, HUMAN GENE THERAPY, MaryAnn Liebert, Inc., Publishers, New York. pp. 70-71 (1994)). In one embodiment, the siNA molecules of the invention and formulations or compositions thereof are administered to a cell, subject, or organism as is described herein and as is generally known in the art.
1. In Vivo Administration
In any of the methods of treatment of the invention, the siNA can be administered to the subject systemically as described herein or otherwise known in the art, either alone as a monotherapy or in combination with additional therapies described herein or as are known in the art. Systemic administration can include, for example, pulmonary (inhalation, nebulization etc.) intravenous, subcutaneous, intramuscular, catheterization, nasopharangeal, transdermal, or oral/gastrointestinal administration as is generally known in the art.
In any of the methods of treatment or prevention of the invention, the siNA can be administered to the subject locally or to local tissues as described herein or otherwise known in the art, either alone as a monotherapy or in combination with additional therapies as are known in the art. Local administration can include, for example, inhalation, nebulization, catheterization, implantation, direct injection, dermal/transdermal application, patches, stenting, ear/eye drops, or portal vein administration to relevant tissues, or any other local administration technique, method or procedure, as is generally known in the art.
In one embodiment, the siNA molecules of the invention and formulations or compositions thereof are administered to the liver as is generally known in the art (see for example Wen et al., 2004, World J Gastroenterol., 10, 244-9; Murao et al., 2002, Pharm Res., 19, 1808-14; Liu et al., 2003, gene Ther., 10, 180-7; Hong et al., 2003, J Pharm Pharmacol., 54, 51-8; Herrmann et al., 2004, Arch Virol., 149, 1611-7; and Matsuno et al., 2003, gene Ther., 10, 1559-66).
In one embodiment, the invention features the use of methods to deliver the siNA molecules of the instant invention to hematopoietic cells, including monocytes and lymphocytes. These methods are described in detail by Hartmann et al., 1998, J. Phamacol. Exp. Ther., 285(2), 920-928; Kronenwett et al., 1998, Blood, 91(3), 852-862; Filion and Phillips, 1997, Biochim. Biophys. Acta., 1329(2), 345-356; Ma and Wei, 1996, Leuk. Res., 20(11/12), 925-930; and Bongartz et al., 1994, Nucleic Acids Research, 22(22), 4681-8.
In one embodiment, the siNA molecules of the invention and formulations or compositions thereof are administered directly or topically (e.g., locally) to the dermis or follicles as is generally known in the art (see for example Brand, 2001, Curr. Opin. Mol. Ther., 3, 244-8; Regnier et al., 1998, J. Drug Target, 5, 275-89; Kanikkannan, 2002, BioDrugs, 16, 339-47; Wraight et al., 2001, Pharmacol. Ther., 90, 89-104; and Preat and Dujardin, 2001, STP PharmaSciences, 11, 57-68). In one embodiment, the siNA molecules of the invention and formulations or compositions thereof are administered directly or topically using a hydroalcoholic gel formulation comprising an alcohol (e.g., ethanol or isopropanol), water, and optionally including additional agents such isopropyl myristate and carbomer 980. In other embodiments, the siNA are formulated to be administered topically to the nasal cavity. Topical preparations can be administered by one or more applications per day to the affected area; over skin areas occlusive dressings can advantageously be used. Continuous or prolonged delivery can be achieved by an adhesive reservoir system.
In one embodiment, an siNA molecule of the invention is administered iontophoretically, for example to a particular organ or compartment (e.g., the eye, back of the eye, heart, liver, kidney, bladder, prostate, tumor, CNS etc.). Non-limiting examples of iontophoretic delivery are described in, for example, WO 03/043689 and WO 03/030989, which are incorporated by reference in their entireties herein.
In one embodiment, the siNA molecules of the invention and formulations or compositions thereof are administered to the lung as is described herein and as is generally known in the art. In another embodiment, the siNA molecules of the invention and formulations or compositions thereof are administered to lung tissues and cells as is described in U.S. Patent Publication Nos. 2006/0062758; 2006/0014289; and 2004/0077540.
2. Aerosols and Delivery Devices
a. Aerosol Formulations
The compositions of the present invention, either alone or in combination with other suitable components, can be made into aerosol formulations (i.e., they can be “nebulized”) to be administered via inhalation (e.g., intranasally or intratracheally) (see, Brigham et al., Am. J. Sci., 298:278 (1989)). Aerosol formulations can be placed into pressurized acceptable propellants, such as dichlorodifluoromethane, propane, nitrogen, and the like.
In one embodiment, the siNA molecules of the invention and formulations thereof are administered via pulmonary delivery, such as by inhalation of an aerosol or spray dried formulation administered by an inhalation device or nebulizer, providing rapid local uptake of the nucleic acid molecules into relevant pulmonary tissues. Solid particulate compositions containing respirable dry particles of micronized nucleic acid compositions can be prepared by grinding dried or lyophilized nucleic acid compositions, and then passing the micronized composition through, for example, a 400 mesh screen to break up or separate out large agglomerates. A solid particulate composition comprising the siNA compositions of the invention can optionally contain a dispersant which serves to facilitate the formation of an aerosol as well as other therapeutic compounds. A suitable dispersant is lactose, which can be blended with the nucleic acid compound in any suitable ratio, such as a 1 to 1 ratio by weight.
Spray compositions comprising siNA molecules or compositions of the invention can, for example, be formulated as aqueous solutions or suspensions or as aerosols delivered from pressurized packs, such as a metered dose inhaler, with the use of a suitable liquefied propellant. In one embodiment, aerosol compositions of the invention suitable for inhalation can be either a suspension or a solution and generally contain an siNA molecule comprising at least a 15 nucleotide sequence of SEQ ID NO: 5, SEQ ID NO: 4918, SEQ ID NO: 194, SEQ ID NO: 5107, SEQ ID NO: 196, SEQ ID NO: 5109, SEQ ID NO: 151, or SEQ ID NO: 5064; or formula (A), and a suitable propellant such as a fluorocarbon or hydrogen-containing chlorofluorocarbon or mixtures thereof, particularly hydrofluoroalkanes, especially 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane or a mixture thereof. The aerosol composition can optionally contain additional formulation excipients well known in the art such as surfactants. Non-limiting examples include oleic acid, lecithin or an oligolactic acid or derivative such as those described in WO94/21229 and WO98/34596 and co-solvents for example ethanol. In one embodiment a pharmaceutical aerosol formulation of the invention comprising a compound of the invention and a fluorocarbon or hydrogen-containing chlorofluorocarbon or mixtures thereof as propellant, optionally in combination with a surfactant and/or a co-solvent.
The aerosol formulations of the invention can be buffered by the addition of suitable buffering agents.
Aerosol formulations can include optional additives including preservatives if the formulation is not prepared sterile. Non-limiting examples include, methyl hydroxybenzoate, anti-oxidants, flavorings, volatile oils, buffering agents and emulsifiers and other formulation surfactants. In one embodiment, fluorocarbon or perfluorocarbon carriers are used to reduce degradation and provide safer biocompatible non-liquid particulate suspension compositions of the invention (e.g., siNA and/or LNP formulations thereof). In another embodiment, a device comprising a nebulizer delivers a composition of the invention (e.g., siNA and/or LNP formulations thereof) comprising fluorochemicals that are bacteriostatic thereby decreasing the potential for microbial growth in compatible devices.
Capsules and cartridges comprising the composition of the invention for use in an inhaler or insufflator, of for example gelatine, can be formulated containing a powder mix for inhalation of a compound of the invention and a suitable powder base such as lactose or starch. In one embodiment, each capsule or cartridge contains an siNA molecule comprising at least a 15 nucleotide sequence of SEQ ID NO: 5, SEQ ID NO: 4918, SEQ ID NO: 194, SEQ ID NO: 5107, SEQ ID NO: 196, SEQ ID NO: 5109, SEQ ID NO: 151, or SEQ ID NO: 5064; or formula (A), and one or more excipients. In another embodiment, the compound of the invention can be presented without excipients such as lactose
The aerosol compositions of the present invention can be administered into the respiratory system as a formulation including particles of respirable size, e.g. particles of a size sufficiently small to pass through the nose, mouth and larynx upon inhalation and through the bronchi and alveoli of the lungs. In general, respirable particles range from about 0.5 to 10 microns in size. In one embodiment, the particulate range can be from 1 to 5 microns. In another embodiment, the particulate range can be from 2 to 3 microns. Particles of non-respirable size which are included in the aerosol tend to deposit in the throat and be swallowed, and the quantity of non-respirable particles in the aerosol is thus minimized. For nasal administration, a particle size in the range of 10-500 um is preferred to ensure retention in the nasal cavity.
In some embodiments, an siNA composition of the invention is administered topically to the nose for example, for the treatment of rhinitis, via pressurized aerosol formulations, aqueous formulations administered to the nose by pressurized pump or by nebulization. Suitable formulations contain water as the diluent or carrier for this purpose. In certain embodiments, the aqueous formulations for administration of the composition of the invention to the lung or nose can be provided with conventional excipients such as buffering agents, tonicity modifying agents and the like.
b. Devices
The siNA molecules of the invention can be formulated and delivered as particles and/or aerosols as discussed above and dispensed from various aerosolization devices known by those of skill in the art.
Aerosols of liquid or non-liquid particles comprising an siNA molecule or formulation of the invention can be produced by any suitable means, such as with a device comprising a nebulizer (see for example U.S. Pat. No. 4,501,729) such as ultrasonic or air jet nebulizers.
Solid particle aerosols comprising an siNA molecule or formulation of the invention and surfactant can be produced with any solid particulate aerosol generator. One type of solid particle aerosol generator used with the siNA molecules of the invention is an insufflator. A second type of illustrative aerosol generator comprises a metered dose inhaler (“MDI”). MDIs containing siNA molecules or formulations taught herein can be prepared by methods of the art (for example, see Byron, above and WO96/32099).
The siNA molecules can also be formulated as a fluid formulation for delivery from a fluid dispenser, such as those described and illustrated in WO05/044354.
In certain embodiments of the invention, nebulizer devices are used in applications for conscious, spontaneously breathing subjects, and for controlled ventilated subjects of all ages. The nebulizer devices can be used for targeted topical and systemic drug delivery to the lung. In one embodiment, a device comprising a nebulizer is used to deliver an siNA molecule or formulation of the invention locally to lung or pulmonary tissues. In another embodiment, a device comprising a nebulizer is used to deliver a an siNA molecule or formulation of the invention systemically.
H. Other Applications/Uses of siNA Molecules of the Invention
The siNA molecules of the invention can also be used for diagnostic applications, research applications, and/or manufacture of medicants.
In one aspect, the invention features a method for diagnosing a disease, trait, or condition in a subject comprising administering to the subject a composition of the invention under conditions suitable for the diagnosis of the disease, trait, or condition in the subject.
In one embodiment, siNA molecules of the invention are used to down regulate or inhibit the expression of CTNNB1 proteins arising from haplotype polymorphisms that are associated with a trait, disease or condition in a subject or organism. Analysis of CTNNB1 genes, or CTNNB1 protein or RNA levels can be used to identify subjects with such polymorphisms or those subjects who are at risk of developing traits, conditions, or diseases described herein. These subjects are amenable to treatment, for example, treatment with siNA molecules of the invention and any other composition useful in treating diseases related to target gene expression. As such, analysis of CTNNB1 protein or RNA levels can be used to determine treatment type and the course of therapy in treating a subject. Monitoring of CTNNB1 protein or RNA levels can be used to predict treatment outcome and to determine the efficacy of compounds and compositions that modulate the level and/or activity of certain CTNNB1 proteins associated with a trait, disorder, condition, or disease.
In another embodiment, the invention comprises use of a double-stranded nucleic acid according to the invention for use in the manufacture of a medicament. In an embodiment, the medicament is for use in treating a condition that is mediated by the action, or by loss of action, of CTNNB1. In one embodiment, the medicament is for use for the treatment of cancer. In an embodiment, the medicament is for use for the treatment of brain cancer, breast carcinoma, cervical cancer, colorectal carcinoma, renal cell carcinoma, leukemia, hepatocellular carcinoma, lung cancer, B-cell lymphomas, multiple myeloma, ovarian carcinoma, pancreatic cancer, prostate cancer, melanoma, and gastric carcinoma. In a particular embodiment, the compounds of the instant invention are useful for treating hepatocellular carcinoma.
In certain embodiments, siNAs wherein at least one strand comprises at least a 15 nucleotide sequence of SEQ ID NO: 5, SEQ ID NO: 4918, SEQ ID NO: 194, SEQ ID NO: 5107, SEQ ID NO: 196, SEQ ID NO: 5109, SEQ ID NO: 151, or SEQ ID NO: 5064; or formula (A), are for use in a method for treating a cancer, such as, for example but not limitation, brain cancer, breast carcinoma, cervical cancer, colorectal carcinoma, renal cell carcinoma, leukemia, hepatocellular carcinoma, lung cancer, B-cell lymphomas, multiple myeloma, ovarian carcinoma, pancreatic cancer, prostate cancer, melanoma, and gastric carcinoma.
I. Examples
The invention will now be illustrated with the following non-limiting examples. Those of skill in the art will readily recognize a variety of non-critical parameters which can be changed or modified to yield essentially the same results.
Example 1
Design, Synthesis, and Identification of siNAs Active Against CTNNB1
CTNNB1 siNA Synthesis
A series of siNA molecules were designed, synthesized and evaluated for efficacy against CTNNB1 gene expression. Certain CTNNB1 sequences were designed and selected by methods set forth in U.S. Application No. 60/182,604. Other sequences were designed and selected using a proprietary algorithm. The primary criteria for design of certain of the CTNNB1 sequences for human siNAs were (i) homology between two species (human and rhesus monkey) and (ii) high efficacy scores as determined by a proprietary algorithm. The effects of the siNAs on CTNNB1 RNA levels. The target sequences of the siNAs that were selected are set forth in Table 1a (target sequences). The sense and antisense strands of the siNA sequences corresponding to the target sequences in Table 1a are set forth in Table 1b. Various chemically modified siNAs that were synthesized are set forth in Table 1c.







TABLE 1a







CTNNB1 Target Sequences, noting human target sites.










Target Site
SEQ ID


Target Sequence
(human)
NO: 1





UCGAGCUCAGAGGGUACGA
 535
  1


 


GAGGCUCUUGUGCGUACUG
1601
  2


 


GCCCAGAAUGCAGUUCGCC
1709
  3


 


CGAGCUCAGAGGGUACGAG
 536
  4


 


CUGUUGGAUUGAUUCGAAA
1797
  5


 


GUCUGCUAUUGUACGUACC
 853
  6


 


AAUUCUUGGCUAUUACGAC
1143
  7


 


GGAUGUUCACAACCGAAUU
2014
  8


 


ACAGUAUGCAAUGACUCGA
 520
  9


 


AGCUUCCAGACACGCUAUC
 814
 10


 


UGUCUGCUAUUGUACGUAC
 852
 11


 


ACUGUUGGAUUGAUUCGAA
1796
 12


 


CAGGAUACCCAGCGCCGUA
1901
 13


 


GACACGCUAUCAUGCGUUC
 822
 14


 


UACUGUUGGAUUGAUUCGA
1795
 15


 


UUCUUGGCUAUUACGACAG
1145
 16


 


ACACGCUAUCAUGCGUUCU
 823
 17


 


CAGACACGCUAUCAUGCGU
 820
 18


 


UGUUGGAUUGAUUCGAAAU
1798
 19


 


CAGAUCCAAGUCAACGUCU
1380
 20


 


AGGCUCUUGUGCGUACUGU
1602
 21


 


GCGUACUGUCCUUCGGGCU
1612
 22


 


ACUAAUGUCCAGCGUUUGG
 626
 23


 


CACAUCCUAGCUCGGGAUG
2000
 24


 


GUUGCUGAGAGGGCUCGAG
2665
 25


 


CAUCUGACCAGCCGACACC
1676
 26


 


UGCGUACUGUCCUUCGGGC
1611
 27


 


ACAAGAUUACAAGAAACGG
2269
 28


 


GUUGUAAACUUGAUUAACU
 674
 29


 


UAAACUUGAUUAACUAUCA
 678
 30


 


AUAUAAUGAGGACCUAUAC
1245
 31


 


AAACUUGAUUAACUAUCAA
 679
 32


 


GAAAUAGUUGAAGGUUGUA
1970
 33


 


AUAAUGAGGACCUAUACUU
1247
 34


 


UUAAAUUCUUGGCUAUUAC
1140
 35


 


UGUAAACUUGAUUAACUAU
 676
 36


 


GUAAACUUGAUUAACUAUC
 677
 37


 


UUGUAAACUUGAUUAACUA
 675
 38


 


GCUUUAGUAAAUAUAAUGA
1235
 39


 


UGGCCACCACCCUGGUGCU
2488
 40


 


CUUUAGUAAAUAUAAUGAG
1236
 41


 


UUUAGUAAAUAUAAUGAGG
1237
 42


 


GUAAAUCGUCCUUUAGGUA
2555
 43


 


ACCUCACUUGCAAUAAUUA
1545
 44


 


UACCAUUCCAUUGUUUGUG
2050
 45


 


UCCAAAGAGUAGCUGCAGG
2097
 46


 


UAUCCAGUUGAUGGGCUGC
2510
 47


 


CAUGCAGAAUACAAAUGAU
 871
 48


 


CCAAAGAGUAGCUGCAGGG
2098
 49


 


CACCAUCCCACUGGCCUCU
1767
 50


 


ACCAUGCAGAAUACAAAUG
 869
 51


 


AAGACAUCACUGAGCCUGC
1641
 52


 


AAUCAGCUGGCCUGGUUUG
2582
 53


 


AACCUCACUUGCAAUAAUU
1544
 54


 


ACCUCAUGGAUGGGCUGCC
2550
 55


 


ACCAUUCCAUUGUUUGUGC
2051
 56


 


CCAUGCAGAAUACAAAUGA
 870
 57


 


CUUCGUCAUCUGACCAGCC
1670
 58


 


CUGUGAACUUGCUCAGGAC
2122
 59


 


AGACAUCACUGAGCCUGCC
1642
 60


 


GAGCCAAUGGCUUGGAAUG
2324
 61


 


ACUGAGCCUGCCAUCUGUG
1649
 62


 


AUUGAAGCUGAGGGAGCCA
2159
 63


 


GUUAUGGUCCAUCAGCUUU
 785
 64


 


AAUGUGGUCACCUGUGCAG
1511
 65


 


AGCUGGCCUGGUUUGAUAC
2586
 66


 


UGGCUGAACCAUCACAGAU
 642
 67


 


CACCCACCAUCCCACUGGC
1763
 68


 


CAAUGGCUUGGAAUGAGAC
2328
 69


 


UGGACCACAAGCAGAGUGC
1280
 70


 


CCAUUCCAUUGUUUGUGCA
2052
 71


 


CAGGACCUCAUGGAUGGGC
2546
 72


 


GUGAACUUGCUCAGGACAA
2124
 73


 


CCAGGACCUCAUGGAUGGG
2545
 74


 


GGCUGAACCAUCACAGAUG
 643
 75


 


GGUGCUGACUAUCCAGUUG
2501
 76


 


AUGGCUUGGAAUGAGACUG
2330
 77


 


GGGAAGACAUCACUGAGCC
1638
 78


 


UGGUGACAGGGAAGACAUC
1630
 79


 


UGCUCAUCCCACUAAUGUC
 616
 80


 


CUAUCCAGUUGAUGGGCUG
2509
 81


 


GGACCUCAUGGAUGGGCUG
2548
 82


 


CCCACUGGCCUCUGAUAAA
1773
 83


 


UCCGAAUGUCUGAGGACAA
2247
 84


 


UGGCUUGGAAUGAGACUGC
2331
 85


 


UUCAGAUGAUAUAAAUGUG
1498
 86


 


CCACAAGAUUACAAGAAAC
2267
 87


 


CUCACUUGCAAUAAUUAUA
1547
 88


 


CACUUGCAAUAAUUAUAAG
1549
 89


 


GUACCAUGCAGAAUACAAA
 867
 90


 


UCAACGUCUUGUUCAGAAC
1390
 91


 


AUCCCAUCUACACAGUUUG
 593
 92


 


UACUCAAGCUGAUUUGAUG
 274
 93


 


ACCAGGUGGUGGUUAAUAA
 759
 94


 


GCUGCAACUAAACAGGAAG
1439
 95


 


UGGAUUGAUUCGAAAUCUU
1801
 96


 


CAGAUGAUAUAAAUGUGGU
1500
 97


 


AUGGUGUCUGCUAUUGUAC
 848
 98


 


CACAAGAUUACAAGAAACG
2268
 99


 


CAAAUGAUGUAGAAACAGC
 882
100


 


GCCACAAGAUUACAAGAAA
2266
101


 


UACAAAUGAUGUAGAAACA
 880
102


 


UCGAAAUCUUGCCCUUUGU
1810
103


 


GAUUAACUAUCAAGAUGAU
 685
104


 


CCAGUGGAUUCUGUGUUGU
1007
105


 


AAAGGCUACUGUUGGAUUG
1789
106


 


ACAAGUAGCUGAUAUUGAU
 499
107


 


GAUGGAACAUGAGAUGGGU
2470
108


 


UCAAGAUGAUGCAGAACUU
 694
109


 


CAAGCUGAUUUGAUGGAGU
 278
110


 


UGGACUCUCAGGAAUCUUU
1415
111


 


UAAAUACCAUUCCAUUGUU
2046
112


 


AUUACAUCAAGAAGGAGCU
1057
113


 


UCAGGAAUCUUUCAGAUGC
1422
114


 


UGAUUAACUAUCAAGAUGA
 684
115


 


ACUUCACUCUAGGAAUGAA
2197
116


 


AACAUGCAGUUGUAAACUU
 666
117


 


AAGCUGAUUUGAUGGAGUU
 279
118


 


UCUGGGUUCAGAUGAUAUA
1492
119


 


UUACUUCACUCUAGGAAUG
2195
120


 


AGGAAUCUUUCAGAUGCUG
1424
121


 


GCUGAAACAUGCAGUUGUA
 661
122


 


GUUGCUUGUUCGUGCACAU
1882
123


 


GGAAGAAAUAGUUGAAGGU
1966
124


 


AGGACAAGCCACAAGAUUA
2259
125


 


CAUGCGUUCUCCUCAGAUG
 832
126


 


GAUGAUCCCAGCUACCGUU
2346
127


 


AGCCUGCCAUCUGUGCUCU
1653
128


 


UGGAUAUCGCCAGGAUGAU
2389
129


 


UCUUCGUCAUCUGACCAGC
1669
130


 


UGUGAACUUGCUCAGGACA
2123
131


 


CCUGUGCAGCUGGAAUUCU
1521
132


 


UGAACUUGCUCAGGACAAG
2125
133


 


UGCUGACUAUCCAGUUGAU
2503
134


 


GAUGAUAUAAAUGUGGUCA
1502
135


 


GUGCUGACUAUCCAGUUGA
2502
136


 


UGACUAUCCAGUUGAUGGG
2506
137


 


AACUUGCUCAGGACAAGGA
2127
138


 


CUGACUAUCCAGUUGAUGG
2505
139


 


GCUCAUCCCACUAAUGUCC
 617
140


 


GCUGACUAUCCAGUUGAUG
2504
141


 


AUGAUAUAAAUGUGGUCAC
1503
142


 


CUCAUCCCACUAAUGUCCA
 618
143


 


GCUUUAUUCUCCCAUUGAA
2074
144


 


CUGGUGCUGACUAUCCAGU
2499
145


 


AACUGUCUUUGGACUCUCA
1406
146


 


AGGGCAUGCAGAUCCCAUC
 582
147


 


GAUAUAAAUGUGGUCACCU
1505
148


 


UUCAGAUGCUGCAACUAAA
1432
149


 


AAGAAAUAGUUGAAGGUUG
1968
150


 


CCAGGAUGAUCCUAGCUAU
2398
151


 


UGGCCAUCUUUAAGUCUGG
 954
152


 


AGCUGAUAUUGAUGGACAG
 505
153


 


UCGGGAUGUUCACAACCGA
2011
154


 


UGUAGAAGCUGGUGGAAUG
1339
155


 


UAAAUAUAAUGAGGACCUA
1242
156


 


CUGAGACAUUAGAUGAGGG
 567
157


 


AGUAAAUAUAAUGAGGACC
1240
158


 


UGGAUACCUCCCAAGUCCU
 438
159


 


AGGAUGCCUUGGGUAUGGA
2445
160


 


AUUGUACGUACCAUGCAGA
 860
161


 


UUUGGACUCUCAGGAAUCU
1413
162


 


UUGGAUUGAUUCGAAAUCU
1800
163


 


UCAGAGGACUAAAUACCAU
2037
164


 


CCAGGAUGCCUUGGGUAUG
2443
165


 


AUGGAACAUGAGAUGGGUG
2471
166


 


GGCUACUGUUGGAUUGAUU
1792
167


 


AGGACCUCAUGGAUGGGCU
2547
168


 


UCUGUGCUCUUCGUCAUCU
1662
169


 


UGAUGGAGUUGGACAUGGC
 288
170


 


AUGAGGGCAUGCAGAUCCC
 579
171


 


ACUAUCCAGUUGAUGGGCU
2508
172


 


UGAGGGCAUGCAGAUCCCA
 580
173


 


UUGGAUAUCGCCAGGAUGA
2388
174


 


GCCCAGGACCUCAUGGAUG
2543
175


 


AACUUGCCACACGUGCAAU
 708
176


 


CCCAAGUCCUGUAUGAGUG
 447
177


 


CACAGAUGCUGAAACAUGC
 654
178


 


CUGGGACCUUGCAUAACCU
 912
179


 


AGUGGAUUCUGUGUUGUUU
1009
180


 


AAUGCAAGCUUUAGGACUU
1354
181


 


AGAAAUAGUUGAAGGUUGU
1969
182


 


UCCGCAUGGAAGAAAUAGU
1959
183


 


GCUAUGUUCCCUGAGACAU
 557
184


 


UCUGAGUGGUAAAGGCAAU
 403
185


 


UGCAAGCUUUAGGACUUCA
1356
186


 


UGGACAGUAUGCAAUGACU
 517
187


 


UUAGUAAAUAUAAUGAGGA
1238
188


 


CUCAGAUGGUGUCUGCUAU
 843
189


 


AGAACAAGUAGCUGAUAUU
 496
190


 


CUUGGAUAUCGCCAGGAUG
2387
191


 


CAUCUGUGCUCUUCGUCAU
1660
192


 


CCCUGGUGCUGACUAUCCA
2497
193


 


ACGACUAGUUCAGUUGCUU
1870
194


 


UCUUGGACUUGAUAUUGGU
2353
195


 


GGAUGAUCCUAGCUAUCGU
2401
196


 


AAUACAAAUGAUGUAGAAA
 878
197


 


GAACCAUCACAGAUGCUGA
 647
198


 


UUCACAUCCUAGCUCGGGA
1998
199


 


UGCAGAUCCCAUCUACACA
 588
200


 


GGACUAAAUACCAUUCCAU
2042
201


 


CUGCUAUUGUACGUACCAU
 855
202


 


CAGAGGACUAAAUACCAUU
2038
203


 


GAUAAAGGCUACUGUUGGA
1786
204


 


AGAUGAUAUAAAUGUGGUC
1501
205


 


AAAUCAUGCACCUUUGCGU
1834
206


 


ACGACAGACUGCCUUCAAA
1157
207


 


UAGUAAAUAUAAUGAGGAC
1239
208


 


UAAUGAGGACCUAUACUUA
1248
209


 


UGCUGAAACAUGCAGUUGU
 660
210


 


AUUUGAUGGAGUUGGACAU
 285
211


 


CUGCCAAGUGGGUGGUAUA
1582
212


 


UGGACUACCAGUUGUGGUU
1735
213


 


UUAAUAAGGCUGCAGUUAU
 771
214


 


ACAUCAAGAAGGAGCUAAA
1060
215


 


GGAUAUCGCCAGGAUGAUC
2390
216


 


CUGACAGAGUUACUUCACU
2186
217


 


GUGACAGGGAAGACAUCAC
1632
218


 


UCAUCCCACUAAUGUCCAG
 619
219


 


CUGCCAUCUGUGCUCUUCG
1656
220


 


AUAUAAAUGUGGUCACCUG
1506
221


 


CCACCCUGGUGCUGACUAU
2494
222


 


UGCUCUUCGUCAUCUGACC
1666
223


 


ACAGGGAAGACAUCACUGA
1635
224


 


AGUUGGACAUGGCCAUGGA
 294
225


 


UUGGCUGAACCAUCACAGA
 641
226


 


UAGAUGAGGGCAUGCAGAU
 576
227


 


AGAUGAGGGCAUGCAGAUC
 577
228


 


AUCUGUGCUCUUCGUCAUC
1661
229


 


GAACUUGCCACACGUGCAA
 707
230


 


CCAUCUGUGCUCUUCGUCA
1659
231


 


AUGGCAACCAAGAAAGCAA
1185
232


 


GAAACAUGCAGUUGUAAAC
 664
233


 


UGGUUAAGCUCUUACACCC
1749
234


 


AGCUUUAGUAAAUAUAAUG
1234
235


 


CUAUCAAGAUGAUGCAGAA
 691
236


 


AAGUCAACGUCUUGUUCAG
1387
237


 


GAUCCAAGUCAACGUCUUG
1382
238


 


CUAUCAUGCGUUCUCCUCA
 828
239


 


AAUAUAAUGAGGACCUAUA
1244
240


 


GUGCUAUCUGUCUGCUCUA
1304
241


 


GAAGCUUCCAGACACGCUA
 812
242


 


UAAUUAUAAGAACAAGAUG
1558
243


 


AUACAAAUGAUGUAGAAAC
 879
244


 


CUGUCUGCUCUAGUAAUAA
1311
245


 


UGCUAUUGUACGUACCAUG
 856
246


 


UGCUGAAGGUGCUAUCUGU
1296
247


 


UCUUUAAGUCUGGAGGCAU
 960
248


 


AUACCAUUCCAUUGUUUGU
2049
249


 


AGGCUACUGUUGGAUUGAU
1791
250


 


CAGUUAUGGUCCAUCAGCU
 783
251


 


ACAAGAUGAUGGUCUGCCA
1569
252


 


GACAUAUGCAGCUGCUGUU
2224
253


 


CCAUCAUCGUGAGGGCUUA
 934
254


 


GACAGAUCCAAGUCAACGU
1378
255


 


GAGACAUUAGAUGAGGGCA
 569
256


 


UUCGCCUUCACUAUGGACU
1722
257


 


UGUUCAGCUUCUGGGUUCA
1483
258


 


AUCUUGGACUUGAUAUUGG
2352
259


 


CGUGCAAUCCCUGAACUGA
 719
260


 


AGGUGGUGGUUAAUAAGGC
 762
261


 


UCUACACAGUUUGAUGCUG
 599
262


 


AGAUGGCCCAGAAUGCAGU
1704
263


 


CAAGAUUACAAGAAACGGC
2270
264


 


CUGAAACAUGCAGUUGUAA
 662
265


 


CUCCUUCUCUGAGUGGUAA
 396
266


 


AGCAAGCUCAUCAUACUGG
1199
267


 


AUUAUAAGAACAAGAUGAU
1560
268


 


UCUGUCUGCUCUAGUAAUA
1310
269


 


AAGCUUUAGUAAAUAUAAU
1233
270


 


GCCGGCUAUUGUAGAAGCU
1330
271


 


UGUCUGCUCUAGUAAUAAG
1312
272


 


AAUAAUUAUAAGAACAAGA
1556
273


 


UAUGGCCAGGAUGCCUUGG
2438
274


 


UGUCCCGCAAAUCAUGCAC
1826
275


 


CUUGUUCAGAACUGUCUUU
1397
276


 


GCUGUGAUACGAUGCUUCA
3181
277


 


GCGCCGUACGUCCAUGGGU
1912
278


 


AGAUGGUGUCUGCUAUUGU
 846
279


 


AGAACUGUCUUUGGACUCU
1404
280


 


CAUGCAGAUCCCAUCUACA
 586
281


 


CUCCUUGGGACUCUUGUUC
1469
282


 


GGUGCCACUACCACAGCUC
 380
283


 


AGCUGGUGGAAUGCAAGCU
1345
284


 


CCAUUCCACGACUAGUUCA
1863
285


 


CAGCGUUUGGCUGAACCAU
 635
286


 


AUCUUUAAGUCUGGAGGCA
 959
287


 


UGGCCAGGAUGCCUUGGGU
2440
288


 


GAAUACAAAUGAUGUAGAA
 877
289


 


UGGAUGGGCUGCCUCCAGG
2556
290


 


CGUACGUCCAUGGGUGGGA
1916
291


 


GGUGUCUGCUAUUGUACGU
 850
292


 


GGUGCUAUCUGUCUGCUCU
1303
293


 


CCUUCACUAUGGACUACCA
1726
294


 


GACUCUUGUUCAGCUUCUG
1477
295


 


AUCUACACAGUUUGAUGCU
 598
296


 


GUUUGUGCAGCUGCUUUAU
2062
297


 


CAAGAAACGGCUUUCAGUU
2278
298


 


GUUCAGUUGCUUGUUCGUG
1877
299


 


UCAGAUGAUAUAAAUGUGG
1499
300


 


AAUGUUAAAUUCUUGGCUA
1136
301


 


UGGGUUCAGAUGAUAUAAA
1494
302


 


AAUAGUUGAAGGUUGUACC
1972
303


 


CAUGCAGUUGUAAACUUGA
 668
304


 


AAUCUGAAUAAAGUGUAAC
2945
305


 


CACCACCCUGGUGCUGACU
2492
306


 


GAGUUGGACAUGGCCAUGG
 293
307


 


AUACCCAGCGCCGUACGUC
1905
308


 


GAGGGCUUACUGGCCAUCU
 944
309


 


GAGGGCAUGCAGAUCCCAU
 581
310


 


GAAGGGAUGGAAGGUCUCC
1454
311


 


GUCUGAGGACAAGCCACAA
2254
312


 


UCAUGCACCUUUGCGUGAG
1837
313


 


GGAAUCUUUCAGAUGCUGC
1425
314


 


UCACCUGACAGAUCCAAGU
1372
315


 


CUGAAGGUGCUAUCUGUCU
1298
316


 


GUCAUCUGACCAGCCGACA
1674
317


 


CAUUCCACGACUAGUUCAG
1864
318


 


UGAUCCUAGCUAUCGUUCU
2404
319


 


GAGCCCUUCACAUCCUAGC
1992
320


 


GAUGAGGGCAUGCAGAUCC
 578
321


 


AUGGGUAGGGUAAAUCAGU
3091
322


 


GUGCAAUCCCUGAACUGAC
 720
323


 


AUUCCAUUGUUUGUGCAGC
2054
324


 


CAUUCUGGUGCCACUACCA
 374
325


 


UACCAUGCAGAAUACAAAU
 868
326


 


AUGCAGUUCGCCUUCACUA
1716
327


 


UUACUGGCCAUCUUUAAGU
 950
328


 


GCUUCUGGGUUCAGAUGAU
1489
329


 


CAGGAAGGGAUGGAAGGUC
1451
330


 


GCUUAUGGCAACCAAGAAA
1181
331


 


UGACAGGGAAGACAUCACU
1633
332


 


AUCGCCAGGAUGAUCCUAG
2394
333


 


AGUAAUAAGCCGGCUAUUG
1322
334


 


AAUGAUGUAGAAACAGCUC
 884
335


 


UCUGAGGACAAGCCACAAG
2255
336


 


GGUCUCCUUGGGACUCUUG
1466
337


 


UGUUCAGAACUGUCUUUGG
1399
338


 


CUGGUGCCACUACCACAGC
 378
339


 


GUCCAUGGGUGGGACACAG
1921
340


 


GUGCGUUUAGCUGGUGGGC
1085
341


 


ACGUACCAUGCAGAAUACA
 865
342


 


GAUGUUCACAACCGAAUUG
2015
343


 


AGAAAGCAAGCUCAUCAUA
1195
344


 


GUUCAGCUUCUGGGUUCAG
1484
345


 


GCAGGGUGCCAUUCCACGA
1855
346


 


UAGAAGCUGGUGGAAUGCA
1341
347


 


CAUGGAAGAAAUAGUUGAA
1963
348


 


UGAUAUUGGUGCCCAGGGA
2362
349


 


GGCAUGCAGAUCCCAUCUA
 584
350


 


CGUACUGUCCUUCGGGCUG
1613
351


 


UUACGACAGACUGCCUUCA
1155
352


 


UAGUCACUGGCAGCAACAG
 334
353


 


GCCAUUACAACUCUCCACA
1031
354


 


GCCUUCACUAUGGACUACC
1725
355


 


GUUCACAACCGAAUUGUUA
2018
356


 


GGGACCUUGCAUAACCUUU
 914
357


 


AAGCCACAAGAUUACAAGA
2264
358


 


GCAGCAACAGUCUUACCUG
 343
359


 


UAUUACAUCAAGAAGGAGC
1056
360


 


UAAUAAGGCUGCAGUUAUG
 772
361


 


GGUGGUGGUUAAUAAGGCU
 763
362


 


UAAUGUCCAGCGUUUGGCU
 628
363


 


CUUCUCUGAGUGGUAAAGG
 399
364


 


ACCAGCCGACACCAAGAAG
1682
365


 


AUACCUCCCAAGUCCUGUA
 441
366


 


UCACUAUGGACUACCAGUU
1729
367


 


AGGAUACCCAGCGCCGUAC
1902
368


 


AGGGAAGACAUCACUGAGC
1637
369


 


GAUAUCGCCAGGAUGAUCC
2391
370


 


AAGUAGCUGAUAUUGAUGG
 501
371


 


CAAGCUUUAGGACUUCACC
1358
372


 


CCCUUUGUCCCGCAAAUCA
1821
373


 


UUAGAUGAGGGCAUGCAGA
 575
374


 


CAAUGACUCGAGCUCAGAG
 528
375


 


GUGGAUAUGGCCAGGAUGC
2433
376


 


GUUCAGAUGAUAUAAAUGU
1497
377


 


UCAGGACAAGGAAGCUGCA
2134
378


 


UUGAAGCUGAGGGAGCCAC
2160
379


 


UGGAGUUGGACAUGGCCAU
 291
380


 


AGAUGCUGAAACAUGCAGU
 657
381


 


UGAUGGUCUGCCAAGUGGG
1575
382


 


ACAUGCAGUUGUAAACUUG
 667
383


 


CAGAGUUACUUCACUCUAG
2190
384


 


GACUCGAGCUCAGAGGGUA
 532
385


 


CUGGCCAUCUUUAAGUCUG
 953
386


 


UACGAUGCUUCAAGAGAAA
3188
387


 


UGACCAGCUCUCUCUUCAG
2301
388


 


CUCUCUUCAGAACAGAGCC
2310
389


 


GCUUUCAGUUGAGCUGACC
2287
390


 


GGGUGGGACACAGCAGCAA
1927
391


 


UGCCACACGUGCAAUCCCU
 712
392


 


UCUGUGAACUUGCUCAGGA
2121
393


 


UGAGUAAUGGUGUAGAACA
2898
394


 


GUUGGAUUGAUUCGAAAUC
1799
395


 


UACAACUCUCCACAACCUU
1036
396


 


CAAGUCCUGUAUGAGUGGG
 449
397


 


AGGAAGGGAUGGAAGGUCU
1452
398


 


AGCUCAUCAUACUGGCUAG
1203
399


 


GCAAGCUUUAGGACUUCAC
1357
400


 


AUGUGGUCACCUGUGCAGC
1512
401


 


ACUCAAGCUGAUUUGAUGG
 275
402


 


GACAUGGCCAUGGAACCAG
 299
403


 


GUAAAUAUAAUGAGGACCU
1241
404


 


CGCAUGGAAGAAAUAGUUG
1961
405


 


GAUGCUGCAACUAAACAGG
1436
406


 


UGAUGGAACAUGAGAUGGG
2469
407


 


CCAGGUGGUGGUUAAUAAG
 760
408


 


UGAGGACAAGCCACAAGAU
2257
409


 


ACUGGCCAUCUUUAAGUCU
 952
410


 


AACGGCUUUCAGUUGAGCU
2283
411


 


CUACUGUUGGAUUGAUUCG
1794
412


 


GUUGUGGUUAAGCUCUUAC
1745
413


 


AUACUGGCUAGUGGUGGAC
1211
414


 


GACCUCAUGGAUGGGCUGC
2549
415


 


UAGCUCGGGAUGUUCACAA
2007
416


 


GAACAUGAGAUGGGUGGCC
2474
417


 


CAGAAUGCAGUUCGCCUUC
1712
418


 


ACGUCCAUGGGUGGGACAC
1919
419


 


UGGUUCACCAGUGGAUUCU
1000
420


 


AUAUCGCCAGGAUGAUCCU
2392
421


 


AACAGGAAGGGAUGGAAGG
1449
422


 


GUUGAGCUGACCAGCUCUC
2294
423


 


AAAUGUUAAAUUCUUGGCU
1135
424


 


GGCUAUUGUAGAAGCUGGU
1333
425


 


CAGUUGUGGUUAAGCUCUU
1743
426


 


CUACACAGUUUGAUGCUGC
 600
427


 


UGGAGGCAUUCCUGCCCUG
 970
428


 


GGACAGUUUACCAGUUGCC
3137
429


 


UCCAUUCUGGUGCCACUAC
 372
430


 


UACACCCACCAUCCCACUG
1761
431


 


CUGAGCCUGCCAUCUGUGC
1650
432


 


GAGGCAUUCCUGCCCUGGU
 972
433


 


CUUGGCUAUUACGACAGAC
1147
434


 


CCCUGAGACAUUAGAUGAG
 565
435


 


AUGCAAUGACUCGAGCUCA
 525
436


 


UAGAGGCUCUUGUGCGUAC
1599
437


 


UUCACUCUAGGAAUGAAGG
2199
438


 


GACAAGCCACAAGAUUACA
2261
439


 


CAGAACUUGCCACACGUGC
 705
440


 


GACCUUGCAUAACCUUUCC
 916
441


 


CACUACCACAGCUCCUUCU
 385
442


 


CUAUUUGGGAUAUGUAUGG
3076
443


 


UCUUGUUCAGAACUGUCUU
1396
444


 


GAUGCCUUGGGUAUGGACC
2447
445


 


UUGUAGAAGCUGGUGGAAU
1338
446


 


AGGUGUGGCGACAUAUGCA
2215
447


 


GCAAUCCCUGAACUGACAA
 722
448


 


UGCUCUAGUAAUAAGCCGG
1316
449


 


CCGACACCAAGAAGCAGAG
1687
450


 


AGAUGAUGCAGAACUUGCC
 697
451


 


UUGAUGGGCUGCCAGAUCU
2517
452


 


AGCCGACACCAAGAAGCAG
1685
453


 


UAUGGGUAGGGUAAAUCAG
3090
454


 


CUCAUCAUACUGGCUAGUG
1205
455


 


UAUUACGACAGACUGCCUU
1153
456


 


CAAUCCCUGAACUGACAAA
 723
457


 


UCUCCUUGGGACUCUUGUU
1468
458


 


GAGAUGGGUGGCCACCACC
2480
459


 


CAGGGUGCCAUUCCACGAC
1856
460


 


AGUUACUUCACUCUAGGAA
2193
461


 


UUGGACUUGAUAUUGGUGC
2355
462


 


CCCUUCACAUCCUAGCUCG
1995
463


 


AGACACGCUAUCAUGCGUU
 821
464


 


AAUGCAGUUCGCCUUCACU
1715
465


 


CUUAUGGCAACCAAGAAAG
1182
466


 


CUCCCAAGUCCUGUAUGAG
 445
467


 


CUUACACCCACCAUCCCAC
1759
468


 


UGGAAGGUCUCCUUGGGAC
1461
469


 


AGCCCUUCACAUCCUAGCU
1993
470


 


GAUGGGCUGCCUCCAGGUG
2558
471


 


AGCUUCUGGGUUCAGAUGA
1488
472


 


GAGCCUGCCAUCUGUGCUC
1652
473


 


UUAAGUCUGGAGGCAUUCC
 963
474


 


ACCUGUGCAGCUGGAAUUC
1520
475


 


UCCCGCAAAUCAUGCACCU
1828
476


 


AAGGUGUGGCGACAUAUGC
2214
477


 


AGCUAUUGAAGCUGAGGGA
2155
478


 


GUUAGUCACUGGCAGCAAC
 332
479


 


UUCAGUUGCUUGUUCGUGC
1878
480


 


GAUGAUGGUCUGCCAAGUG
1573
481


 


CUAAACAGGAAGGGAUGGA
1446
482


 


CCACGACUAGUUCAGUUGC
1868
483


 


ACUAGUUCAGUUGCUUGUU
1873
484


 


GUUCACCAGUGGAUUCUGU
1002
485


 


GUGGUAAAGGCAAUCCUGA
 408
486


 


UUGAUGGAGUUGGACAUGG
 287
487


 


ACUUGCUCAGGACAAGGAA
2128
488


 


CCAGUUGAUGGGCUGCCAG
2513
489


 


GAAAGCAAGCUCAUCAUAC
1196
490


 


ACAUUAGAUGAGGGCAUGC
 572
491


 


UCCCACUAAUGUCCAGCGU
 622
492


 


GGCAACCAAGAAAGCAAGC
1187
493


 


AAAUAGUUGAAGGUUGUAC
1971
494


 


GGAUAUGUAUGGGUAGGGU
3083
495


 


UAAUCUGAAUAAAGUGUAA
2944
496


 


UGCACAUCAGGAUACCCAG
1894
497


 


GUAAUAAGCCGGCUAUUGU
1323
498


 


AAGCUCAUCAUACUGGCUA
1202
499


 


ACGUGCAAUCCCUGAACUG
 718
500


 


AGUUGUGGUUAAGCUCUUA
1744
501


 


AGGACCAGGUGGUGGUUAA
 756
502


 


GCUCUAGUAAUAAGCCGGC
1317
503


 


GAUUUGAUGGAGUUGGACA
 284
504


 


UGAUGUAGAAACAGCUCGU
 886
505


 


CUGGUGGAUAUGGCCAGGA
2430
506


 


CAUCAUACUGGCUAGUGGU
1207
507


 


GAUCCCAUCUACACAGUUU
 592
508


 


CACGCUAUCAUGCGUUCUC
 824
509


 


GACAGUAUGCAAUGACUCG
 519
510


 


AAGUUGUUGUAACCUGCUG
3166
511


 


GCUAUUACGACAGACUGCC
1151
512


 


GCCUCCAGGUGACAGCAAU
2566
513


 


UCCUGUAUGAGUGGGAACA
 453
514


 


AUGCAGAUCCCAUCUACAC
 587
515


 


UUUCCCAUCAUCGUGAGGG
 930
516


 


CCAAGUGGGUGGUAUAGAG
1585
517


 


GGACCUUGCAUAACCUUUC
 915
518


 


UCCCAAGUCCUGUAUGAGU
 446
519


 


CACGACUAGUUCAGUUGCU
1869
520


 


CCGCAUGGAAGAAAUAGUU
1960
521


 


GGCCCAGAAUGCAGUUCGC
1708
522


 


CCAUGGAACCAGACAGAAA
 306
523


 


GAAACGGCUUUCAGUUGAG
2281
524


 


GGGAUAUGUAUGGGUAGGG
3082
525


 


UUGGGACUCUUGUUCAGCU
1473
526


 


UAUGUUCCCUGAGACAUUA
 559
527


 


GGACUCUCAGGAAUCUUUC
1416
528


 


AAGCUGCAGAAGCUAUUGA
2145
529


 


GCCCUUCACAUCCUAGCUC
1994
530


 


AGAGAUGGCCCAGAAUGCA
1702
531


 


GCAAUCCUGAGGAAGAGGA
 417
532


 


CAGGAUGCCUUGGGUAUGG
2444
533


 


CUGCUAUGUUCCCUGAGAC
 555
534


 


UUCACAACCGAAUUGUUAU
2019
535


 


AAAGCAAGCUCAUCAUACU
1197
536


 


AGGCAAUCCUGAGGAAGAG
 415
537


 


UGUUUGUGCAGCUGCUUUA
2061
538


 


GGAAUGCAAGCUUUAGGAC
1352
539


 


CCGGCUAUUGUAGAAGCUG
1331
540


 


AAUAAGCCGGCUAUUGUAG
1325
541


 


UCAGCUUCUGGGUUCAGAU
1486
542


 


CCUGUAUGAGUGGGAACAG
 454
543


 


CACUCAAGAACAAGUAGCU
 490
544


 


CCUUCACAUCCUAGCUCGG
1996
545


 


AUGCACCUUUGCGUGAGCA
1839
546


 


UGUUCGUGCACAUCAGGAU
1888
547


 


UCAGUUGCUUGUUCGUGCA
1879
548


 


CCCGCAAAUCAUGCACCUU
1829
549


 


GCUGAUUUGAUGGAGUUGG
 281
550


 


AUAGAGGCUCUUGUGCGUA
1598
551


 


CAGGACAAGGAAGCUGCAG
2135
552


 


AGCUCUUACACCCACCAUC
1755
553


 


CAUCACAGAUGCUGAAACA
 651
554


 


CUAUUGUAGAAGCUGGUGG
1335
555


 


AUGCCCAGGACCUCAUGGA
2541
556


 


UGACUCGAGCUCAGAGGGU
 531
557


 


AGUUUGAUGCUGCUCAUCC
 606
558


 


UCCUUCGGGCUGGUGACAG
1620
559


 


AUGAAGGUGUGGCGACAUA
2211
560


 


AGUUGAGCUGACCAGCUCU
2293
561


 


CUGUAUGAGUGGGAACAGG
 455
562


 


CUCAGAGGGUACGAGCUGC
 540
563


 


GGCAAUCCUGAGGAAGAGG
 416
564


 


CAUACUGGCUAGUGGUGGA
1210
565


 


ACAAGCCACAAGAUUACAA
2262
566


 


GCUCUUGUGCGUACUGUCC
1604
567


 


AUGUGGAUACCUCCCAAGU
 435
568


 


UUGUUUGUGCAGCUGCUUU
2060
569


 


ACAUAUGCAGCUGCUGUUU
2225
570


 


UCAGUCCUUCACUCAAGAA
 481
571


 


ACCUUGCAUAACCUUUCCC
 917
572


 


GGCGACAUAUGCAGCUGCU
2221
573


 


UGGUGUCUGCUAUUGUACG
 849
574


 


GUUCCCUGAGACAUUAGAU
 562
575


 


AUAAAGGCUACUGUUGGAU
1787
576


 


GUGCCAUUCCACGACUAGU
1860
577


 


UGGGUGGUAUAGAGGCUCU
1590
578


 


GGCCAUCUUUAAGUCUGGA
 955
579


 


UAUUGGUGCCCAGGGAGAA
2365
580


 


CUCGAGCUCAGAGGGUACG
 534
581


 


AGAACUUGCCACACGUGCA
 706
582


 


UACCAGUUGUGGUUAAGCU
1740
583


 


CGUUUGGCUGAACCAUCAC
 638
584


 


GCUAUUGUAGAAGCUGGUG
1334
585


 


GGAGGCAUUCCUGCCCUGG
 971
586


 


ACCACCCUGGUGCUGACUA
2493
587


 


AAUCUUGCCCUUUGUCCCG
1814
588


 


CGUUUAGCUGGUGGGCUGC
1088
589


 


CAGUUGAGCUGACCAGCUC
2292
590


 


UGAUAUAAAUGUGGUCACC
1504
591


 


CUGAGUGGUAAAGGCAAUC
 404
592


 


AAGGUGCUAUCUGUCUGCU
1301
593


 


UCCUAGCUCGGGAUGUUCA
2004
594


 


UCAAGCUGAUUUGAUGGAG
 277
595


 


CCAGCUCUCUCUUCAGAAC
2304
596


 


ACAUGGCCAUGGAACCAGA
 300
597


 


UACCCAGCGCCGUACGUCC
1906
598


 


AUAGUUGAAGGUUGUACCG
1973
599


 


AGCUUUAGGACUUCACCUG
1360
600


 


ACAUCCAAAGAGUAGCUGC
2094
601


 


UUGCAUAACCUUUCCCAUC
 920
602


 


UGGCCCAGAAUGCAGUUCG
1707
603


 


AUUCGAAAUCUUGCCCUUU
1808
604


 


AUAAGCCGGCUAUUGUAGA
1326
605


 


CGACAGACUGCCUUCAAAU
1158
606


 


UGCAGUUAUGGUCCAUCAG
 781
607


 


GUUUGAUGCUGCUCAUCCC
 607
608


 


CUAAUGUCCAGCGUUUGGC
 627
609


 


CAAGUAGCUGAUAUUGAUG
 500
610


 


UCUGACAGAGUUACUUCAC
2185
611


 


GGUGGUAUAGAGGCUCUUG
1592
612


 


GACCAGGUGGUGGUUAAUA
 758
613


 


CCUCAUGGAUGGGCUGCCU
2551
614


 


UGUCUUUGGACUCUCAGGA
1409
615


 


GAACAAGUAGCUGAUAUUG
 497
616


 


GUGCCACUACCACAGCUCC
 381
617


 


GCACCUUUGCGUGAGCAGG
1841
618


 


GACUUCACCUGACAGAUCC
1368
619


 


AAAUACCAUUCCAUUGUUU
2047
620


 


CUCAAGAACAAGUAGCUGA
 492
621


 


UCCUCUGUGAACUUGCUCA
2118
622


 


UCUGGAGGCAUUCCUGCCC
 968
623


 


AAGUCUGGAGGCAUUCCUG
 965
624


 


UUGAAGGUUGUACCGGAGC
1977
625


 


ACAUCCUAGCUCGGGAUGU
2001
626


 


ACCAAGAAAGCAAGCUCAU
1191
627


 


UUUGGCUGAACCAUCACAG
 640
628


 


CACACGUGCAAUCCCUGAA
 715
629


 


GCUCAUCAUACUGGCUAGU
1204
630


 


GGGUAGGGUAAAUCAGUAA
3093
631


 


UUCACCUGACAGAUCCAAG
1371
632


 


UGGUAAAGGCAAUCCUGAG
 409
633


 


GAUCCUAGCUAUCGUUCUU
2405
634


 


UUCGUCAUCUGACCAGCCG
1671
635


 


AAUCUUUCAGAUGCUGCAA
1427
636


 


UGCAGUUCGCCUUCACUAU
1717
637


 


AGGAUGAUCCUAGCUAUCG
2400
638


 


CAGCUCUCUCUUCAGAACA
2305
639


 


GGUGGGACACAGCAGCAAU
1928
640


 


CAGGAUGAUCCUAGCUAUC
2399
641


 


AGGAAGAGGAUGUGGAUAC
 426
642


 


AUCUGUCUGCUCUAGUAAU
1309
643


 


UAACCUUUCCCAUCAUCGU
 925
644


 


CUGCUUUAUUCUCCCAUUG
2072
645


 


AAUUGUAAUCUGAAUAAAG
2939
646


 


UCUUGUUCAGCUUCUGGGU
1480
647


 


GUUCGUGCACAUCAGGAUA
1889
648


 


AUGAUGCAGAACUUGCCAC
 699
649


 


GCUGAUAUUGAUGGACAGU
 506
650


 


GGUUAAGCUCUUACACCCA
1750
651


 


GCCCUUUGUCCCGCAAAUC
1820
652


 


UCAGAGGGUACGAGCUGCU
 541
653


 


AAACAUGCAGUUGUAAACU
 665
654


 


CUUGCCCUUUGUCCCGCAA
1817
655


 


UUACAAGAAACGGCUUUCA
2275
656


 


CACUCUGGUGGAUAUGGCC
2426
657


 


CAUCUUUAAGUCUGGAGGC
 958
658


 


UGCCAUCUGUGCUCUUCGU
1657
659


 


UCUUGGCUAUUACGACAGA
1146
660


 


AUUUGGGAUAUGUAUGGGU
3078
661


 


CAGUGGAUUCUGUGUUGUU
1008
662


 


CCUUCGGGCUGGUGACAGG
1621
663


 


GGACACAGCAGCAAUUUGU
1932
664


 


CCAGCGCCGUACGUCCAUG
1909
665


 


AAGAAACGGCUUUCAGUUG
2279
666


 


AUUAGAUGAGGGCAUGCAG
 574
667


 


ACCAGCUCUCUCUUCAGAA
2303
668


 


AGUUAUGGUCCAUCAGCUU
 784
669


 


GACUAUCCAGUUGAUGGGC
2507
670


 


AUGCUUGGUUCACCAGUGG
 995
671


 


CUAGCUCGGGAUGUUCACA
2006
672


 


CUCUUACACCCACCAUCCC
1757
673


 


CUUGCUCAGGACAAGGAAG
2129
674


 


AGAUUACAAGAAACGGCUU
2272
675


 


ACCACAGCUCCUUCUCUGA
 389
676


 


AGAUGCUGCAACUAAACAG
1435
677


 


UUAAGCUCUUACACCCACC
1752
678


 


AAUAAGGCUGCAGUUAUGG
 773
679


 


UUGGGAUAUGUAUGGGUAG
3080
680


 


GUAACCUGCUGUGAUACGA
3174
681


 


UGGUCUGCCAAGUGGGUGG
1578
682


 


CCUUCUCUGAGUGGUAAAG
 398
683


 


GAAGCUAUUGAAGCUGAGG
2153
684


 


AUGCAGAACUUGCCACACG
 702
685


 


GUAGCUGAUAUUGAUGGAC
 503
686


 


CUCAAGCUGAUUUGAUGGA
 276
687


 


GCAUGGAAGAAAUAGUUGA
1962
688


 


CUGGUGGAAUGCAAGCUUU
1347
689


 


CCCAGGACCUCAUGGAUGG
2544
690


 


UUUGGGAUAUGUAUGGGUA
3079
691


 


CAAAGUUGUUGUAACCUGC
3164
692


 


CCGAAUUGUUAUCAGAGGA
2026
693


 


UAAUUGUAAUCUGAAUAAA
2938
694


 


AUUGUAAUCUGAAUAAAGU
2940
695


 


CGAAUUGUUAUCAGAGGAC
2027
696


 


CCAAGUCCUGUAUGAGUGG
 448
697


 


AAGCCGGCUAUUGUAGAAG
1328
698


 


AUCCUAGCUAUCGUUCUUU
2406
699


 


AUAACCUUUCCCAUCAUCG
 924
700


 


GCCAAGUGGGUGGUAUAGA
1584
701


 


CGACUAGUUCAGUUGCUUG
1871
702


 


UUGGUUCACCAGUGGAUUC
 999
703


 


GUUCAGAACUGUCUUUGGA
1400
704


 


UGCUGUGAUACGAUGCUUC
3180
705


 


UCCAGGUGACAGCAAUCAG
2569
706


 


UAUGGUCCAUCAGCUUUCU
 787
707


 


UGCCAUUCCACGACUAGUU
1861
708


 


AACCAAGAAAGCAAGCUCA
1190
709


 


AUAAUUAUAAGAACAAGAU
1557
710


 


GUUAAGCUCUUACACCCAC
1751
711


 


UUGAGUAAUGGUGUAGAAC
2897
712


 


GUGUGGCGACAUAUGCAGC
2217
713


 


GACCAGCUCUCUCUUCAGA
2302
714


 


UUGUACCGGAGCCCUUCAC
1984
715


 


AUGGCCAUGGAACCAGACA
 302
716


 


UGGUGGAUAUGGCCAGGAU
2431
717


 


CCUCUGACAGAGUUACUUC
2183
718


 


AUGAUCCUAGCUAUCGUUC
2403
719


 


AUGGUCCAUCAGCUUUCUA
 788
720


 


GGACUCUUGUUCAGCUUCU
1476
721


 


GCUAUCAUGCGUUCUCCUC
 827
722


 


GCUGACCAGCUCUCUCUUC
2299
723


 


UCGUGCACAUCAGGAUACC
1891
724


 


UACUUCACUCUAGGAAUGA
2196
725


 


UGAAACAUGCAGUUGUAAA
 663
726


 


UAUGCCAUUACAACUCUCC
1028
727


 


UGUUAUCAGAGGACUAAAU
2032
728


 


GAUGGAAGGUCUCCUUGGG
1459
729


 


CAUCCAAAGAGUAGCUGCA
2095
730


 


GCCGACACCAAGAAGCAGA
1686
731


 


CUUUGGACUCUCAGGAAUC
1412
732


 


GGAACAUGAGAUGGGUGGC
2473
733


 


UGGCAGUGCGUUUAGCUGG
1080
734


 


GGAAGCUGCAGAAGCUAUU
2143
735


 


CUCUAGGAAUGAAGGUGUG
2203
736


 


GUACGAGCUGCUAUGUUCC
 548
737


 


UCCACGACUAGUUCAGUUG
1867
738


 


CCUCAGAUGGUGUCUGCUA
 842
739


 


CUCUGUGAACUUGCUCAGG
2120
740


 


GCAGUUAUGGUCCAUCAGC
 782
741


 


UCUUACACCCACCAUCCCA
1758
742


 


CGCCAGGAUGAUCCUAGCU
2396
743


 


CACCUGACAGAUCCAAGUC
1373
744


 


UCACCUGUGCAGCUGGAAU
1518
745


 


GGAUGGGCUGCCUCCAGGU
2557
746


 


UACCGGAGCCCUUCACAUC
1987
747


 


UGAGACAUUAGAUGAGGGC
 568
748


 


CACUCUAGGAAUGAAGGUG
2201
749


 


UUGAUGCUGCUCAUCCCAC
 609
750


 


UUCUCUGAGUGGUAAAGGC
 400
751


 


UGUUAGUCACUGGCAGCAA
 331
752


 


GAAGAAAUAGUUGAAGGUU
1967
753


 


CUUCACUCUAGGAAUGAAG
2198
754


 


CUGGGUUCAGAUGAUAUAA
1493
755


 


GGACAAGCCACAAGAUUAC
2260
756


 


ACCCUGGUGCUGACUAUCC
2496
757


 


UUGAUAUUGGUGCCCAGGG
2361
758


 


ACCUCCCAAGUCCUGUAUG
 443
759


 


GUAUGCAAUGACUCGAGCU
 523
760


 


CCAGUUGUGGUUAAGCUCU
1742
761


 


AUGACUCGAGCUCAGAGGG
 530
762


 


UUGUUGUAACCUGCUGUGA
3169
763


 


CCAAGUCAACGUCUUGUUC
1385
764


 


AUCAGAGGACUAAAUACCA
2036
765


 


UGUAUGGGUAGGGUAAAUC
3088
766


 


CGUGAGCAGGGUGCCAUUC
1850
767


 


UGAUGGGCUGCCAGAUCUG
2518
768


 


CUUGUUCGUGCACAUCAGG
1886
769


 


CCAUCACAGAUGCUGAAAC
 650
770


 


ACAGUUUACCAGUUGCCUU
3139
771


 


ACCGAAUUGUUAUCAGAGG
2025
772


 


GCAGUGCGUUUAGCUGGUG
1082
773


 


AACAUGAGAUGGGUGGCCA
2475
774


 


CCUGACAGAUCCAAGUCAA
1375
775


 


GGGAUGUUCACAACCGAAU
2013
776


 


GGAUUGAUUCGAAAUCUUG
1802
777


 


GAAGCUGCAGAAGCUAUUG
2144
778


 


AAUGACUCGAGCUCAGAGG
 529
779


 


UUGUUCAGCUUCUGGGUUC
1482
780


 


CCUCACUUGCAAUAAUUAU
1546
781


 


CAGAUGGUGUCUGCUAUUG
 845
782


 


CUUCACUCAAGAACAAGUA
 487
783


 


AUCACAGAUGCUGAAACAU
 652
784


 


AGUUCGCCUUCACUAUGGA
1720
785


 


UACUGGCCAUCUUUAAGUC
 951
786


 


CAAGCUUUAGUAAAUAUAA
1232
787


 


AGCCACAAGAUUACAAGAA
2265
788


 


AAGCAGAGAUGGCCCAGAA
1698
789


 


GAUGCAGAACUUGCCACAC
 701
790


 


AUCUUUCAGAUGCUGCAAC
1428
791


 


UGGGACACAGCAGCAAUUU
1930
792


 


ACAGAUCCAAGUCAACGUC
1379
793


 


ACAGCAGCAAUUUGUGGAG
1936
794


 


UGCAACUAAACAGGAAGGG
1441
795


 


GCUCAGGACAAGGAAGCUG
2132
796


 


GACUAAAUACCAUUCCAUU
2043
797


 


UUUGAUGCUGCUCAUCCCA
 608
798


 


UGGCAGCAACAGUCUUACC
 341
799


 


AAGAAAGCAAGCUCAUCAU
1194
800


 


UGAUCUUGGACUUGAUAUU
2350
801


 


CUGAAUAAAGUGUAACAAU
2948
802


 


ACUAAAUACCAUUCCAUUG
2044
803


 


AUCCCACUAAUGUCCAGCG
 621
804


 


CCACUACCACAGCUCCUUC
 384
805


 


CAUCAGGAUACCCAGCGCC
1898
806


 


UCACAGAUGCUGAAACAUG
 653
807


 


UUUGCGUGAGCAGGGUGCC
1846
808


 


GCUGAUCUUGGACUUGAUA
2348
809


 


GGCUAUUACGACAGACUGC
1150
810


 


GGACAUGGCCAUGGAACCA
 298
811


 


AACAAGAUGAUGGUCUGCC
1568
812


 


UUACAUCAAGAAGGAGCUA
1058
813


 


AAUCAUGCACCUUUGCGUG
1835
814


 


GCAAAUCAUGCACCUUUGC
1832
815


 


GAGUGGUAAAGGCAAUCCU
 406
816


 


UCGCCUUCACUAUGGACUA
1723
817


 


AUCCAUUCUGGUGCCACUA
 371
818


 


AUCAGGAUACCCAGCGCCG
1899
819


 


AGUAUGCAAUGACUCGAGC
 522
820


 


CGGCUUUCAGUUGAGCUGA
2285
821


 


GCUGCAGUUAUGGUCCAUC
 779
822


 


AUUGAGUAAUGGUGUAGAA
2896
823


 


GUAAUCUGAAUAAAGUGUA
2943
824


 


UUGAUGGACAGUAUGCAAU
 513
825


 


GAUAUGUAUGGGUAGGGUA
3084
826


 


GAACAAGAUGAUGGUCUGC
1567
827


 


UUAUCAGAGGACUAAAUAC
2034
828


 


UUCACCAGUGGAUUCUGUG
1003
829


 


AAGGUUGUACCGGAGCCCU
1980
830


 


GUAGAAGCUGGUGGAAUGC
1340
831


 


AUGCUGCAACUAAACAGGA
1437
832


 


UCACUCUGGUGGAUAUGGC
2425
833


 


CUGAUUUGAUGGAGUUGGA
 282
834


 


UCAUCAUACUGGCUAGUGG
1206
835


 


GCUUGUUCGUGCACAUCAG
1885
836


 


UCUGCUCUAGUAAUAAGCC
1314
837


 


UAUCUGUCUGCUCUAGUAA
1308
838


 


GCAAGCUCAUCAUACUGGC
1200
839


 


AGAGGGUACGAGCUGCUAU
 543
840


 


UGUGCGUACUGUCCUUCGG
1609
841


 


GGAAGGGAUGGAAGGUCUC
1453
842


 


AUGCGUUCUCCUCAGAUGG
 833
843


 


GACAGAGUUACUUCACUCU
2188
844


 


UUGGCUAUUACGACAGACU
1148
845


 


GGACUACCAGUUGUGGUUA
1736
846


 


UUCAGAACUGUCUUUGGAC
1401
847


 


AUCUGACCAGCCGACACCA
1677
848


 


ACACAGCAGCAAUUUGUGG
1934
849


 


UACCACAGCUCCUUCUCUG
 388
850


 


CGUCCAUGGGUGGGACACA
1920
851


 


UGUGGUUAAGCUCUUACAC
1747
852


 


UUGUACGUACCAUGCAGAA
 861
853


 


GAUACCCAGCGCCGUACGU
1904
854


 


UCAUGCGUUCUCCUCAGAU
 831
855


 


GCACAUCAGGAUACCCAGC
1895
856


 


GAUUACAAGAAACGGCUUU
2273
857


 


ACUACCAGUUGUGGUUAAG
1738
858


 


GUCUUGUUCAGAACUGUCU
1395
859


 


UCAUCUGACCAGCCGACAC
1675
860


 


CUUUGCGUGAGCAGGGUGC
1845
861


 


CUGUCUUUGGACUCUCAGG
1408
862


 


UACAUCAAGAAGGAGCUAA
1059
863


 


AGAUCCAAGUCAACGUCUU
1381
864


 


CAAGUCAACGUCUUGUUCA
1386
865


 


UCCUUGGGACUCUUGUUCA
1470
866


 


GGUGGAAUGCAAGCUUUAG
1349
867


 


CUGCAACUAAACAGGAAGG
1440
868


 


UUAGGACUUCACCUGACAG
1364
869


 


AGUAGCUGAUAUUGAUGGA
 502
870


 


UAUAAUGAGGACCUAUACU
1246
871


 


CCUGCUGUGAUACGAUGCU
3178
872


 


AUGGGUGGCCACCACCCUG
2483
873


 


GACUCUCAGGAAUCUUUCA
1417
874


 


GUGCACAUCAGGAUACCCA
1893
875


 


UUCCAGACACGCUAUCAUG
 817
876


 


UUGCCACACGUGCAAUCCC
 711
877


 


UCAGAUGCUGCAACUAAAC
1433
878


 


CUUUAGGACUUCACCUGAC
1362
879


 


CAUGCACCUUUGCGUGAGC
1838
880


 


ACAACUCUCCACAACCUUU
1037
881


 


UGGGACUCUUGUUCAGCUU
1474
882


 


GCUUGGUUCACCAGUGGAU
 997
883


 


UUCCCAUCAUCGUGAGGGC
 931
884


 


GUCUGCUCUAGUAAUAAGC
1313
885


 


CAGCUUCUGGGUUCAGAUG
1487
886


 


CGUCAUCUGACCAGCCGAC
1673
887


 


UGUUCCCUGAGACAUUAGA
 561
888


 


GCAACCAAGAAAGCAAGCU
1188
889


 


GGAGUUGGACAUGGCCAUG
 292
890


 


GUCCGCAUGGAAGAAAUAG
1958
891


 


CUGAUCUUGGACUUGAUAU
2349
892


 


AUGGAAGGUCUCCUUGGGA
1460
893


 


GAUGGUCUGCCAAGUGGGU
1576
894


 


ACUAUCAAGAUGAUGCAGA
 690
895


 


ACAGAUGCUGAAACAUGCA
 655
896


 


UUCAGUUGAGCUGACCAGC
2290
897


 


AGAGGCUCUUGUGCGUACU
1600
898


 


GGUGGAUAUGGCCAGGAUG
2432
899


 


CUUGCCACACGUGCAAUCC
 710
900


 


GAAUGCAGUUCGCCUUCAC
1714
901


 


CCUAGCUCGGGAUGUUCAC
2005
902


 


UUCACUAUGGACUACCAGU
1728
903


 


GAUGGGUGGCCACCACCCU
2482
904


 


UGGUUAAUAAGGCUGCAGU
 768
905


 


AUCAAGAUGAUGCAGAACU
 693
906


 


CUGCUGUGAUACGAUGCUU
3179
907


 


AUGCCUUGGGUAUGGACCC
2448
908


 


UGUGAUACGAUGCUUCAAG
3183
909


 


GAGUGCUGAAGGUGCUAUC
1293
910


 


GAGGGUACGAGCUGCUAUG
 544
911


 


UUAAUUGUAAUCUGAAUAA
2937
912


 


CACCAAGAAGCAGAGAUGG
1691
913


 


GAAUGCAAGCUUUAGGACU
1353
914


 


ACCUUUGCGUGAGCAGGGU
1843
915


 


AGGUGCUAUCUGUCUGCUC
1302
916


 


UUGCUCAGGACAAGGAAGC
2130
917


 


GCUGAGGGAGCCACAGCUC
2165
918


 


CUACCACAGCUCCUUCUCU
 387
919


 


UGGAACAUGAGAUGGGUGG
2472
920


 


GCUAUUGUACGUACCAUGC
 857
921


 


UCUUGCCCUUUGUCCCGCA
1816
922


 


UUAUAAGAACAAGAUGAUG
1561
923


 


GGAAGCUUCCAGACACGCU
 811
924


 


UAAGCCGGCUAUUGUAGAA
1327
925


 


GGACCAGGUGGUGGUUAAU
 757
926


 


CUGAUAUUGAUGGACAGUA
 507
927


 


UGGGUAGGGUAAAUCAGUA
3092
928


 


ACUUGAUAUUGGUGCCCAG
2359
929


 


UAAGCUCUUACACCCACCA
1753
930


 


CUACUCAAGCUGAUUUGAU
 273
931


 


GGUGCCAUUCCACGACUAG
1859
932


 


UUGGACAUGGCCAUGGAAC
 296
933


 


CUGCUCAUCCCACUAAUGU
 615
934


 


CAUGGCCAUGGAACCAGAC
 301
935


 


UAUGGCAACCAAGAAAGCA
1184
936


 


ACCAGUGGAUUCUGUGUUG
1006
937


 


ACAGAGUUACUUCACUCUA
2189
938


 


UAGGACUUCACCUGACAGA
1365
939


 


GCCAGGAUGCCUUGGGUAU
2442
940


 


AAUGAGGACCUAUACUUAC
1249
941


 


AUUCUUGGCUAUUACGACA
1144
942


 


CUUUAUUCUCCCAUUGAAA
2075
943


 


UAGCUGAUAUUGAUGGACA
 504
944


 


GAACUGUCUUUGGACUCUC
1405
945


 


UUAGUCACUGGCAGCAACA
 333
946


 


CCAUUACAACUCUCCACAA
1032
947


 


GUGGUUAAGCUCUUACACC
1748
948


 


UGAUUUGAUGGAGUUGGAC
 283
949


 


GCAGAGAUGGCCCAGAAUG
1700
950


 


ACUAAACAGGAAGGGAUGG
1445
951


 


ACAAAUGUUAAAUUCUUGG
1133
952


 


GCAAUGACUCGAGCUCAGA
 527
953


 


CUCGGGAUGUUCACAACCG
2010
954


 


GUGUCUGCUAUUGUACGUA
 851
955


 


UGUGGAUACCUCCCAAGUC
 436
956


 


GGAUGCCUUGGGUAUGGAC
2446
957


 


AAAUUCUUGGCUAUUACGA
1142
958


 


UACGAGCUGCUAUGUUCCC
 549
959


 


CAGUGCGUUUAGCUGGUGG
1083
960


 


CAAGAUGAUGCAGAACUUG
 695
961


 


AUGAUGUAGAAACAGCUCG
 885
962


 


UGCAGCUGCUUUAUUCUCC
2067
963


 


CCACAGCUCCUUCUCUGAG
 390
964


 


CAGUUCGCCUUCACUAUGG
1719
965


 


AAGCUUCCAGACACGCUAU
 813
966


 


UUUCAGUUGAGCUGACCAG
2289
967


 


UCUGGUGCCACUACCACAG
 377
968


 


CGCUAUCAUGCGUUCUCCU
 826
969


 


GACAGGGAAGACAUCACUG
1634
970


 


AUCAUACUGGCUAGUGGUG
1208
971


 


GCUGGUGACAGGGAAGACA
1628
972


 


AUCCUAGCUCGGGAUGUUC
2003
973


 


GUCCUGUAUGAGUGGGAAC
 452
974


 


UGGGAUAUGUAUGGGUAGG
3081
975


 


CUUGGACUUGAUAUUGGUG
2354
976


 


CCUUUGUCCCGCAAAUCAU
1822
977


 


UGAAGGUGCUAUCUGUCUG
1299
978


 


CCUUCACUCAAGAACAAGU
 486
979


 


GAAGGUCUCCUUGGGACUC
1463
980


 


AGAAACGGCUUUCAGUUGA
2280
981


 


ACCCAGCGCCGUACGUCCA
1907
982


 


CAUAACCUUUCCCAUCAUC
 923
983


 


GAAGGUUGUACCGGAGCCC
1979
984


 


GUCCCGCAAAUCAUGCACC
1827
985


 


CAAGCUCAUCAUACUGGCU
1201
986


 


CGCCGUACGUCCAUGGGUG
1913
987


 


AGAGUUACUUCACUCUAGG
2191
988


 


GUUGGACAUGGCCAUGGAA
 295
989


 


UGGCUAUUACGACAGACUG
1149
990


 


ACUCGAGCUCAGAGGGUAC
 533
991


 


ACAGUUUGAUGCUGCUCAU
 604
992


 


GGUGGUUAAUAAGGCUGCA
 766
993


 


CUUUGUCCCGCAAAUCAUG
1823
994


 


AAUACCAUUCCAUUGUUUG
2048
995


 


CCACACGUGCAAUCCCUGA
 714
996


 


AUGGCCAGGAUGCCUUGGG
2439
997


 


GGAUACCCAGCGCCGUACG
1903
998


 


UCGCCAGGAUGAUCCUAGC
2395
999


 


UGGUCCAUCAGCUUUCUAA
 789
1000 


 


AUAUGUAUGGGUAGGGUAA
3085
1001 


 


CCCAGAAUGCAGUUCGCCU
1710
1002 


 


UAUUGUAGAAGCUGGUGGA
1336
1003 


 


GUAUGGGUAGGGUAAAUCA
3089
1004 


 


GAUCUUGGACUUGAUAUUG
2351
1005 


 


ACACGUGCAAUCCCUGAAC
 716
1006 


 


AGCGCCGUACGUCCAUGGG
1911
1007 


 


UGUACCGGAGCCCUUCACA
1985
1008 


 


GUUGAUGGGCUGCCAGAUC
2516
1009 


 


ACACCCACCAUCCCACUGG
1762
1010 


 


UACGACAGACUGCCUUCAA
1156
1011 


 


UUGUUCGUGCACAUCAGGA
1887
1012 


 


CAAAUCAUGCACCUUUGCG
1833
1013 


 


GUCUGGAGGCAUUCCUGCC
 967
1014 


 


CACUAUGGACUACCAGUUG
1730
1015 


 


UAUCAUGCGUUCUCCUCAG
 829
1016 


 


GUAGAAACAGCUCGUUGUA
 890
1017 


 


CUCCUCUGACAGAGUUACU
2181
1018 


 


UGCUCAGGACAAGGAAGCU
2131
1019 


 


CAAGUGGGUGGUAUAGAGG
1586
1020 


 


UGGUGGUUAAUAAGGCUGC
 765
1021 


 


ACUUCACCUGACAGAUCCA
1369
1022 


 


CGCCUUCACUAUGGACUAC
1724
1023 


 


UGCGUUCUCCUCAGAUGGU
 834
1024 


 


GUUGUACCGGAGCCCUUCA
1983
1025 


 


CGACACCAAGAAGCAGAGA
1688
1026 


 


UCACCAGUGGAUUCUGUGU
1004
1027 


 


GGUGACAGGGAAGACAUCA
1631
1028 


 


UCUAGUAAUAAGCCGGCUA
1319
1029 


 


GUGGUUAAUAAGGCUGCAG
 767
1030 


 


UCCUCAGAUGGUGUCUGCU
 841
1031 


 


AUGGACAGUAUGCAAUGAC
 516
1032 


 


UGCGUGAGCAGGGUGCCAU
1848
1033 


 


ACUCUAGGAAUGAAGGUGU
2202
1034 


 


GACAUUAGAUGAGGGCAUG
 571
1035 


 


CUGGUGACAGGGAAGACAU
1629
1036 


 


UGAUUCGAAAUCUUGCCCU
1806
1037 


 


GCUCUUACACCCACCAUCC
1756
1038 


 


GUCCUUCGGGCUGGUGACA
1619
1039 


 


GUGCGUACUGUCCUUCGGG
1610
1040 


 


UGGUGCUGACUAUCCAGUU
2500
1041 


 


GCUAUUGAAGCUGAGGGAG
2156
1042 


 


CAACCAAGAAAGCAAGCUC
1189
1043 


 


GUGCAGCUGCUUUAUUCUC
2066
1044 


 


CUAUCUGUCUGCUCUAGUA
1307
1045 


 


AAACAGGAAGGGAUGGAAG
1448
1046 


 


ACUGGCUAGUGGUGGACCC
1213
1047 


 


CCUCUGUGAACUUGCUCAG
2119
1048 


 


UGUAGAAACAGCUCGUUGU
 889
1049 


 


CUGACAGAUCCAAGUCAAC
1376
1050 


 


GGAAGAGGAUGUGGAUACC
 427
1051 


 


ACCAUCACAGAUGCUGAAA
 649
1052 


 


CCGUACGUCCAUGGGUGGG
1915
1053 


 


CAUUCCAUUGUUUGUGCAG
2053
1054 


 


CUCCAGGUGACAGCAAUCA
2568
1055 


 


CUACCAGUUGUGGUUAAGC
1739
1056 


 


UUGUGGUUAAGCUCUUACA
1746
1057 


 


UAGUAAUAAGCCGGCUAUU
1321
1058 


 


CAGUCCUUCACUCAAGAAC
 482
1059 


 


AGCUGAUUUGAUGGAGUUG
 280
1060 


 


AGGUCUCCUUGGGACUCUU
1465
1061 


 


ACUAUGGACUACCAGUUGU
1731
1062 


 


CAGCAGCAAUUUGUGGAGG
1937
1063 


 


CGUGCACAUCAGGAUACCC
1892
1064 


 


CGUUCUCCUCAGAUGGUGU
 836
1065 


 


CAGUAUGCAAUGACUCGAG
 521
1066 


 


GGUAUAGAGGCUCUUGUGC
1595
1067 


 


AUCCAGUUGAUGGGCUGCC
2511
1068 


 


UGCCAAGUGGGUGGUAUAG
1583
1069 


 


ACAUCAGGAUACCCAGCGC
1897
1070 


 


GCCAUCUUUAAGUCUGGAG
 956
1071 


 


AACCUUUCCCAUCAUCGUG
 926
1072 


 


CUAGUUCAGUUGCUUGUUC
1874
1073 


 


UUCACUCAAGAACAAGUAG
 488
1074 


 


AAGAAGCAGAGAUGGCCCA
1695
1075 


 


UCCUCUGACAGAGUUACUU
2182
1076 


 


AAUUGUUAUCAGAGGACUA
2029
1077 


 


UCUCAGUCCUUCACUCAAG
 479
1078 


 


UCCAGACACGCUAUCAUGC
 818
1079 


 


CACUAAUGUCCAGCGUUUG
 625
1080 


 


UUGUAACCUGCUGUGAUAC
3172
1081 


 


CUUCUGGGUUCAGAUGAUA
1490
1082 


 


GCCGUACGUCCAUGGGUGG
1914
1083 


 


UAGUUGAAGGUUGUACCGG
1974
1084 


 


GAGGACAAGCCACAAGAUU
2258
1085 


 


GGGAGCCACAGCUCCUCUG
2170
1086 


 


CUUCACCUGACAGAUCCAA
1370
1087 


 


UCUUUCAGAUGCUGCAACU
1429
1088 


 


UGUAACCUGCUGUGAUACG
3173
1089 


 


CCUCCCAAGUCCUGUAUGA
 444
1090 


 


GGCAGUGCGUUUAGCUGGU
1081
1091 


 


CUCUAGUAAUAAGCCGGCU
1318
1092 


 


GCUGUUAGUCACUGGCAGC
 329
1093 


 


GUCAACGUCUUGUUCAGAA
1389
1094 


 


GAAGAGGAUGUGGAUACCU
 428
1095 


 


UAACCUGCUGUGAUACGAU
3175
1096 


 


GUUAUUUGGAACCUUGUUU
3117
1097 


 


UCACAACCGAAUUGUUAUC
2020
1098 


 


CGGGCUGGUGACAGGGAAG
1625
1099 


 


ACAACCGAAUUGUUAUCAG
2022
1100 


 


CCACUAAUGUCCAGCGUUU
 624
1101 


 


CACUGAGCCUGCCAUCUGU
1648
1102 


 


GGUCCAUCAGCUUUCUAAA
 790
1103 


 


AUCCCAAAGUUGUUGUAAC
3160
1104 


 


UGAGGACCUAUACUUACGA
1251
1105 


 


UGUCUGAGGACAAGCCACA
2253
1106 


 


AGUUGAUGGGCUGCCAGAU
2515
1107 


 


UGACCAGCCGACACCAAGA
1680
1108 


 


AGGGAGCCACAGCUCCUCU
2169
1109 


 


AAAGUUGUUGUAACCUGCU
3165
1110 


 


CUGCAGUUAUGGUCCAUCA
 780
1111 


 


UGAAGGUUGUACCGGAGCC
1978
1112 


 


UUCCCUGAGACAUUAGAUG
 563
1113 


 


CUUCGGGCUGGUGACAGGG
1622
1114 


 


UUGAGCUGACCAGCUCUCU
2295
1115 


 


GAACUUGCUCAGGACAAGG
2126
1116 


 


CCAGCCGACACCAAGAAGC
1683
1117 


 


AGGGUGCCAUUCCACGACU
1857
1118 


 


UUGUGCAGCUGCUUUAUUC
2064
1119 


 


UCACUCAAGAACAAGUAGC
 489
1120 


 


GCUGGUGGAAUGCAAGCUU
1346
1121 


 


GCAACUAAACAGGAAGGGA
1442
1122 


 


AGGUUGUACCGGAGCCCUU
1981
1123 


 


AGGCUGCAGUUAUGGUCCA
 777
1124 


 


GCAGAUCCCAUCUACACAG
 589
1125 


 


CUAGGAAUGAAGGUGUGGC
2205
1126 


 


AGCUCCUUCUCUGAGUGGU
 394
1127 


 


UUACAACUCUCCACAACCU
1035
1128 


 


GGUAAAGGCAAUCCUGAGG
 410
1129 


 


GUUCGCCUUCACUAUGGAC
1721
1130 


 


CAAAUGUUAAAUUCUUGGC
1134
1131 


 


CUGUGAUACGAUGCUUCAA
3182
1132 


 


ACAAAUGAUGUAGAAACAG
 881
1133 


 


GGUACGAGCUGCUAUGUUC
 547
1134 


 


GAAUUGUUAUCAGAGGACU
2028
1135 


 


CAACCGAAUUGUUAUCAGA
2023
1136 


 


GUGAUACGAUGCUUCAAGA
3184
1137 


 


AAAGGCAAUCCUGAGGAAG
 413
1138 


 


CAGCUCCUCUGACAGAGUU
2178
1139 


 


AUGGUCUGCCAAGUGGGUG
1577
1140 


 


GCUACUGUUGGAUUGAUUC
1793
1141 


 


UGCAAUGACUCGAGCUCAG
 526
1142 


 


GACUUGAUAUUGGUGCCCA
2358
1143 


 


CAGAACUGUCUUUGGACUC
1403
1144 


 


UAGUUCAGUUGCUUGUUCG
1875
1145 


 


ACAGACUGCCUUCAAAUUU
1160
1146 


 


GGGUGGUAUAGAGGCUCUU
1591
1147 


 


AUGGACUACCAGUUGUGGU
1734
1148 


 


AUUGUUAUCAGAGGACUAA
2030
1149 


 


UAAGGCUGCAGUUAUGGUC
 775
1150 


 


AAAUCUUGCCCUUUGUCCC
1813
1151 


 


AGCAGCAAUUUGUGGAGGG
1938
1152 


 


AGAGGACUAAAUACCAUUC
2039
1153 


 


GCUGAAGGUGCUAUCUGUC
1297
1154 


 


UGUAUGAGUGGGAACAGGG
 456
1155 


 


CAGAUCCCAUCUACACAGU
 590
1156 


 


GACACAGCAGCAAUUUGUG
1933
1157 


 


GGGCAUGCAGAUCCCAUCU
 583
1158 


 


CAUGCCCAGGACCUCAUGG
2540
1159 


 


GAAGCUGAGGGAGCCACAG
2162
1160 


 


CUGUUAGUCACUGGCAGCA
 330
1161 


 


CUUGUUCAGCUUCUGGGUU
1481
1162 


 


AAGCUGGUGGAAUGCAAGC
1344
1163 


 


GAGGAUGUGGAUACCUCCC
 431
1164 


 


AUAAAUGUGGUCACCUGUG
1508
1165 


 


UACGUCCAUGGGUGGGACA
1918
1166 


 


GAUGGAGUUGGACAUGGCC
 289
1167 


 


UGUCCAGCGUUUGGCUGAA
 631
1168 


 


GAGCAGGGUGCCAUUCCAC
1853
1169 


 


AAAUAUAAUGAGGACCUAU
1243
1170 


 


UACUGGCUAGUGGUGGACC
1212
1171 


 


UGCUUGGUUCACCAGUGGA
 996
1172 


 


CUGAGGACAAGCCACAAGA
2256
1173 


 


CUUGUGCGUACUGUCCUUC
1607
1174 


 


UGUUAUUUGGAACCUUGUU
3116
1175 


 


UAGCUUAUGGCAACCAAGA
1179
1176 


 


UGAUACGAUGCUUCAAGAG
3185
1177 


 


UGGUAUAGAGGCUCUUGUG
1594
1178 


 


GAUGUAGAAACAGCUCGUU
 887
1179 


 


CCUUUCCCAUCAUCGUGAG
 928
1180 


 


GCGUUCUCCUCAGAUGGUG
 835
1181 


 


UCAGGAUACCCAGCGCCGU
1900
1182 


 


ACGGCUUUCAGUUGAGCUG
2284
1183 


 


GUUGAAGGUUGUACCGGAG
1976
1184 


 


UAUCGCCAGGAUGAUCCUA
2393
1185 


 


GUGCUGAAGGUGCUAUCUG
1295
1186 


 


GUCUUUGGACUCUCAGGAA
1410
1187 


 


GGGAUGGAAGGUCUCCUUG
1457
1188 


 


UGAGCUGACCAGCUCUCUC
2296
1189 


 


CUUUCCCAUCAUCGUGAGG
 929
1190 


 


AAGCUUUAGGACUUCACCU
1359
1191 


 


UGGAAUGCAAGCUUUAGGA
1351
1192 


 


CUGGAGGCAUUCCUGCCCU
 969
1193 


 


AGUUCAGUUGCUUGUUCGU
1876
1194 


 


GAGCUGCUAUGUUCCCUGA
 552
1195 


 


GGCCAGGAUGCCUUGGGUA
2441
1196 


 


GAUGAUCCUAGCUAUCGUU
2402
1197 


 


GAUUGAUUCGAAAUCUUGC
1803
1198 


 


CAGAGAUGGCCCAGAAUGC
1701
1199 


 


CAGCGCCGUACGUCCAUGG
1910
1200 


 


AUGUAGAAACAGCUCGUUG
 888
1201 


 


AGUGCUGAAGGUGCUAUCU
1294
1202 


 


GACUACCAGUUGUGGUUAA
1737
1203 


 


ACAGGAAGGGAUGGAAGGU
1450
1204 


 


CAGGUGGUGGUUAAUAAGG
 761
1205 


 


AAGGCUGCAGUUAUGGUCC
 776
1206 


 


UAAAUGUGGUCACCUGUGC
1509
1207 


 


UAAAGGCUACUGUUGGAUU
1788
1208 


 


GAUGGACAGUAUGCAAUGA
 515
1209 


 


UUCUGGGUUCAGAUGAUAU
1491
1210 


 


GUACUGUCCUUCGGGCUGG
1614
1211 


 


CUUGGUUCACCAGUGGAUU
 998
1212 


 


UAUUGAAGCUGAGGGAGCC
2158
1213 


 


GUUGUUGUAACCUGCUGUG
3168
1214 


 


AGCAGGGUGCCAUUCCACG
1854
1215 


 


GUCCUCUGUGAACUUGCUC
2117
1216 


 


UCUGACCAGCCGACACCAA
1678
1217 


 


GCCAUGGAACCAGACAGAA
 305
1218 


 


AAGCUAUUGAAGCUGAGGG
2154
1219 


 


GAUUCGAAAUCUUGCCCUU
1807
1220 


 


AGUUGCUUGUUCGUGCACA
1881
1221 


 


AAGAACAAGAUGAUGGUCU
1565
1222 


 


AGUGGUAAAGGCAAUCCUG
 407
1223 


 


CAGAUGCUGCAACUAAACA
1434
1224 


 


CCUGAGACAUUAGAUGAGG
 566
1225 


 


UCCCAAAGUUGUUGUAACC
3161
1226 


 


CUGACCAGCCGACACCAAG
1679
1227 


 


AUCCAAAGAGUAGCUGCAG
2096
1228 


 


AUGUCCAGCGUUUGGCUGA
 630
1229 


 


UCUUGUGCGUACUGUCCUU
1606
1230 


 


AGGAUGUGGAUACCUCCCA
 432
1231 


 


GGCUGCAGUUAUGGUCCAU
 778
1232 


 


UCACAUCCUAGCUCGGGAU
1999
1233 


 


ACCAAGAAGCAGAGAUGGC
1692
1234 


 


GCCACCACCCUGGUGCUGA
2490
1235 


 


CCCACUAAUGUCCAGCGUU
 623
1236 


 


ACUGGCAGCAACAGUCUUA
 339
1237 


 


AUCUGAAUAAAGUGUAACA
2946
1238 


 


GCCUGCCAUCUGUGCUCUU
1654
1239 


 


CAUUACAACUCUCCACAAC
1033
1240 


 


CUCCUCAGAUGGUGUCUGC
 840
1241 


 


CAGUUGCUUGUUCGUGCAC
1880
1242 


 


AUCCUGAGGAAGAGGAUGU
 420
1243 


 


CACCAGUGGAUUCUGUGUU
1005
1244 


 


CAAGAAAGCAAGCUCAUCA
1193
1245 


 


CUUGCAUAACCUUUCCCAU
 919
1246 


 


CUUCACUAUGGACUACCAG
1727
1247 


 


UUGCUUGUUCGUGCACAUC
1883
1248 


 


UAUUGUACGUACCAUGCAG
 859
1249 


 


GAAAUCUUGCCCUUUGUCC
1812
1250 


 


CUCUUGUGCGUACUGUCCU
1605
1251 


 


CACAACCGAAUUGUUAUCA
2021
1252 


 


GCUCCUCUGACAGAGUUAC
2180
1253 


 


AGCGUUUGGCUGAACCAUC
 636
1254 


 


AAACGGCUUUCAGUUGAGC
2282
1255 


 


UUUGUCCCGCAAAUCAUGC
1824
1256 


 


UCUAGGAAUGAAGGUGUGG
2204
1257 


 


AAGUCCUGUAUGAGUGGGA
 450
1258 


 


GGUUCACCAGUGGAUUCUG
1001
1259 


 


GGUCUGCCAAGUGGGUGGU
1579
1260 


 


AGCUCCUCUGACAGAGUUA
2179
1261 


 


UUCUGGUGCCACUACCACA
 376
1262 


 


UGCUAUGUUCCCUGAGACA
 556
1263 


 


AUUGAUUCGAAAUCUUGCC
1804
1264 


 


CUCAUGGAUGGGCUGCCUC
2552
1265 


 


GCUGCUUUAUUCUCCCAUU
2071
1266 


 


AUCAUGCACCUUUGCGUGA
1836
1267 


 


GUCACUGGCAGCAACAGUC
 336
1268 


 


UGAGUGGGAACAGGGAUUU
 460
1269 


 


AAUUAUAAGAACAAGAUGA
1559
1270 


 


UGGACAGUUUACCAGUUGC
3136
1271 


 


AUGAGGACCUAUACUUACG
1250
1272 


 


GGAAGGUCUCCUUGGGACU
1462
1273 


 


UGGAAGAAAUAGUUGAAGG
1965
1274 


 


GGUGUUAUUUGGAACCUUG
3114
1275 


 


GUGCUCUUCGUCAUCUGAC
1665
1276 


 


GGCCAUGGAACCAGACAGA
 304
1277 


 


CGGCUGUUAGUCACUGGCA
 327
1278 


 


UUCCACGACUAGUUCAGUU
1866
1279 


 


AGCAGAGAUGGCCCAGAAU
1699
1280 


 


GCCAGGAUGAUCCUAGCUA
2397
1281 


 


GCCAUCUGUGCUCUUCGUC
1658
1282 


 


UAGAAACAGCUCGUUGUAC
 891
1283 


 


AGAUGAUGGUCUGCCAAGU
1572
1284 


 


ACCUUUCCCAUCAUCGUGA
 927
1285 


 


AUGGAGUUGGACAUGGCCA
 290
1286 


 


CUGUGCUCUUCGUCAUCUG
1663
1287 


 


UAUAAGAACAAGAUGAUGG
1562
1288 


 


UCUGAAUAAAGUGUAACAA
2947
1289 


 


CCAGAAUGCAGUUCGCCUU
1711
1290 


 


AGAACAAGAUGAUGGUCUG
1566
1291 


 


AUCUUGCCCUUUGUCCCGC
1815
1292 


 


GCGUUUAGCUGGUGGGCUG
1087
1293 


 


GGGUUCAGAUGAUAUAAAU
1495
1294 


 


UUUAGGACUUCACCUGACA
1363
1295 


 


CACAGCUCCUUCUCUGAGU
 391
1296 


 


AACGUCUUGUUCAGAACUG
1392
1297 


 


CACAGCAGCAAUUUGUGGA
1935
1298 


 


GACUAGUUCAGUUGCUUGU
1872
1299 


 


GACAGACUGCCUUCAAAUU
1159
1300 


 


CUCUCUCUUCAGAACAGAG
2308
1301 


 


GUCCAGCGUUUGGCUGAAC
 632
1302 


 


UAAGAACAAGAUGAUGGUC
1564
1303 


 


UCCAAGUCAACGUCUUGUU
1384
1304 


 


ACACCAAGAAGCAGAGAUG
1690
1305 


 


CUCAGGAAUCUUUCAGAUG
1421
1306 


 


UAAAUUCUUGGCUAUUACG
1141
1307 


 


CUAUGGACUACCAGUUGUG
1732
1308 


 


CCAGCGUUUGGCUGAACCA
 634
1309 


 


UCCCAUCAUCGUGAGGGCU
 932
1310 


 


AGGACUUCACCUGACAGAU
1366
1311 


 


UUGUGCGUACUGUCCUUCG
1608
1312 


 


CCAUGGGUGGGACACAGCA
1923
1313 


 


GGAUGGAAGGUCUCCUUGG
1458
1314 


 


CCCAGCGCCGUACGUCCAU
1908
1315 


 


GCUCAGAGGGUACGAGCUG
 539
1316 


 


AUGUUCACAACCGAAUUGU
2016
1317 


 


UGCUUGUUCGUGCACAUCA
1884
1318 


 


AUGUUCCCUGAGACAUUAG
 560
1319 


 


GUAAAGGCAAUCCUGAGGA
 411
1320 


 


CACUGGCAGCAACAGUCUU
 338
1321 


 


AUCAUGCGUUCUCCUCAGA
 830
1322 


 


UAUGUAUGGGUAGGGUAAA
3086
1323 


 


GUGUUAUUUGGAACCUUGU
3115
1324 


 


ACAGCUCCUCUGACAGAGU
2177
1325 


 


UAUGGACUACCAGUUGUGG
1733
1326 


 


AUUCUGGUGCCACUACCAC
 375
1327 


 


UGCCUCCAGGUGACAGCAA
2565
1328 


 


UACCUCCCAAGUCCUGUAU
 442
1329 


 


CCAGACACGCUAUCAUGCG
 819
1330 


 


UGAUGCAGAACUUGCCACA
 700
1331 


 


GUUUAGCUGGUGGGCUGCA
1089
1332 


 


GUCUGCCAAGUGGGUGGUA
1580
1333 


 


GGUUGUACCGGAGCCCUUC
1982
1334 


 


GUACCGGAGCCCUUCACAU
1986
1335 


 


CAAUCCUGAGGAAGAGGAU
 418
1336 


 


GCUAUCUGUCUGCUCUAGU
1306
1337 


 


UGACAGAUCCAAGUCAACG
1377
1338 


 


CAUGAUGGAACAUGAGAUG
2467
1339 


 


UUGGACUCUCAGGAAUCUU
1414
1340 


 


CUCUUCGUCAUCUGACCAG
1668
1341 


 


UUGCCCUUUGUCCCGCAAA
1818
1342 


 


GAAGCAGAGAUGGCCCAGA
1697
1343 


 


CCUUGCAUAACCUUUCCCA
 918
1344 


 


CAGUUUGAUGCUGCUCAUC
 605
1345 


 


ACCUGACAGAUCCAAGUCA
1374
1346 


 


CUUUCAGAUGCUGCAACUA
1430
1347 


 


GAUACGAUGCUUCAAGAGA
3186
1348 


 


AUGCAAGCUUUAGGACUUC
1355
1349 


 


GGAUGUGGAUACCUCCCAA
 433
1350 


 


AGAAUGCAGUUCGCCUUCA
1713
1351 


 


CGAAAUCUUGCCCUUUGUC
1811
1352 


 


ACUCAAGAACAAGUAGCUG
 491
1353 


 


GAAUGAAGGUGUGGCGACA
2209
1354 


 


UGCACCUUUGCGUGAGCAG
1840
1355 


 


ACGAGCUGCUAUGUUCCCU
 550
1356 


 


AAGAGGAUGUGGAUACCUC
 429
1357 


 


GAUAUGGCCAGGAUGCCUU
2436
1358 


 


UAUAGAGGCUCUUGUGCGU
1597
1359 


 


GGUUCAGAUGAUAUAAAUG
1496
1360 


 


AGGGAUGGAAGGUCUCCUU
1456
1361 


 


UAUCCCAAAGUUGUUGUAA
3159
1362 


 


UCUCUCUUCAGAACAGAGC
2309
1363 


 


CUGACCAGCUCUCUCUUCA
2300
1364 


 


ACCUGCUGUGAUACGAUGC
3177
1365 


 


AUGGCAGUGCGUUUAGCUG
1079
1366 


 


AUCCAAGUCAACGUCUUGU
1383
1367 


 


GCUGCCUCCAGGUGACAGC
2563
1368 


 


AGUGCGUUUAGCUGGUGGG
1084
1369 


 


AGCCGGCUAUUGUAGAAGC
1329
1370 


 


CAUUAGAUGAGGGCAUGCA
 573
1371 


 


GAAGGUGUGGCGACAUAUG
2213
1372 


 


AAGUGGGUGGUAUAGAGGC
1587
1373 


 


CUGAGGGAGCCACAGCUCC
2166
1374 


 


GCGUUUGGCUGAACCAUCA
 637
1375 


 


UCCUUCUCUGAGUGGUAAA
 397
1376 


 


GCAGUUCGCCUUCACUAUG
1718
1377 


 


GGACUUGAUAUUGGUGCCC
2357
1378 


 


GUUUGGCUGAACCAUCACA
 639
1379 


 


GCAUGCAGAUCCCAUCUAC
 585
1380 


 


GAUGGGCUGCCAGAUCUGG
2519
1381 


 


GGACUUCACCUGACAGAUC
1367
1382 


 


CAACGUCUUGUUCAGAACU
1391
1383 


 


GAUAUUGAUGGACAGUAUG
 509
1384 


 


UGGCCAUGGAACCAGACAG
 303
1385 


 


CAAGAACAAGUAGCUGAUA
 494
1386 


 


GGCUGUUAGUCACUGGCAG
 328
1387 


 


CAUUGUUUGUGCAGCUGCU
2058
1388 


 


UAAACAGGAAGGGAUGGAA
1447
1389 


 


AUAAGAACAAGAUGAUGGU
1563
1390 


 


GUGGAAUGCAAGCUUUAGG
1350
1391 


 


GGAAUGAAGGUGUGGCGAC
2208
1392 


 


GACACCAAGAAGCAGAGAU
1689
1393 


 


ACUGUCUUUGGACUCUCAG
1407
1394 


 


GGACAAGGAAGCUGCAGAA
2137
1395 


 


UCUGCUAUUGUACGUACCA
 854
1396 


 


AGCUGCUUUAUUCUCCCAU
2070
1397 


 


AGGGUACGAGCUGCUAUGU
 545
1398 


 


GAAGACAUCACUGAGCCUG
1640
1399 


 


CGGGAUGUUCACAACCGAA
2012
1400 


 


CAGCCGACACCAAGAAGCA
1684
1401 


 


UGUUCACAACCGAAUUGUU
2017
1402 


 


GCUCUCUCUUCAGAACAGA
2307
1403 


 


UCAGAUGGUGUCUGCUAUU
 844
1404 


 


UGAGUGGUAAAGGCAAUCC
 405
1405 


 


UGGUGCCACUACCACAGCU
 379
1406 


 


UUGUCCCGCAAAUCAUGCA
1825
1407 


 


CACCCUGGUGCUGACUAUC
2495
1408 


 


AAUGUCCAGCGUUUGGCUG
 629
1409 


 


GGGCUGCCUCCAGGUGACA
2561
1410 


 


GAGUUACUUCACUCUAGGA
2192
1411 


 


UUCGAAAUCUUGCCCUUUG
1809
1412 


 


GUAUAGAGGCUCUUGUGCG
1596
1413 


 


AGCUGACCAGCUCUCUCUU
2298
1414 


 


CUAUUGUACGUACCAUGCA
 858
1415 


 


UAUGCAAUGACUCGAGCUC
 524
1416 


 


UGCCCAGGACCUCAUGGAU
2542
1417 


 


AACAAGUAGCUGAUAUUGA
 498
1418 


 


AAGGCAAUCCUGAGGAAGA
 414
1419 


 


CAAGAUGAUGGUCUGCCAA
1570
1420 


 


UGCCAUUACAACUCUCCAC
1030
1421 


 


AUGUAUGGGUAGGGUAAAU
3087
1422 


 


UGUGCUCUUCGUCAUCUGA
1664
1423 


 


AAGGCUACUGUUGGAUUGA
1790
1424 


 


UACUGUCCUUCGGGCUGGU
1615
1425 


 


AUAAGGCUGCAGUUAUGGU
 774
1426 


 


UCGUCAUCUGACCAGCCGA
1672
1427 


 


GUUGUAACCUGCUGUGAUA
3171
1428 


 


AAGAUUACAAGAAACGGCU
2271
1429 


 


UUAUGGCAACCAAGAAAGC
1183
1430 


 


UCCAGUUGAUGGGCUGCCA
2512
1431 


 


GGGACACAGCAGCAAUUUG
1931
1432 


 


AUGAUGGAACAUGAGAUGG
2468
1433 


 


UAUUUGGGAUAUGUAUGGG
3077
1434 


 


CAGCUGCUUUAUUCUCCCA
2069
1435 


 


GCUACUCAAGCUGAUUUGA
 272
1436 


 


UCCCUGAGACAUUAGAUGA
 564
1437 


 


GUGGAUACCUCCCAAGUCC
 437
1438 


 


UAGGAAUGAAGGUGUGGCG
2206
1439 


 


UGACAGAGUUACUUCACUC
2187
1440 


 


AGCGGCUGUUAGUCACUGG
 325
1441 


 


AUGGUUCAGAAUUAAACUU
3222
1442 


 


AACCGAAUUGUUAUCAGAG
2024
1443 


 


GGGUGCCAUUCCACGACUA
1858
1444 


 


AUGAUGGUCUGCCAAGUGG
1574
1445 


 


CACAUCAGGAUACCCAGCG
1896
1446 


 


AGGAAUGAAGGUGUGGCGA
2207
1447 


 


GAAGGUGCUAUCUGUCUGC
1300
1448 


 


CCAAGAAAGCAAGCUCAUC
1192
1449 


 


CGAGCUGCUAUGUUCCCUG
 551
1450 


 


CCUGGUGCUGACUAUCCAG
2498
1451 


 


UGCUAUCUGUCUGCUCUAG
1305
1452 


 


AUUGUAGAAGCUGGUGGAA
1337
1453 
















TABLE 1b







Various c-CTNNB1 siNA sense and antisense sequences corresponding 


to the identified target sequences in Table 1a.












SEQ


SEQ


Target Site
ID


ID


(human)
NO:
Sense Sequence
Antisense Sequence
NO:





 535
  1
UCGAGCUCAGAGGGUACGA
UCGUACCCUCUGAGCUCGA
4914


 


1601
  2
GAGGCUCUUGUGCGUACUG
CAGUACGCACAAGAGCCUC
4915


 


1709
  3
GCCCAGAAUGCAGUUCGCC
GGCGAACUGCAUUCUGGGC
4916


 


 536
  4
CGAGCUCAGAGGGUACGAG
CUCGUACCCUCUGAGCUCG
4917


 


1797
  5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAG
4918


 


 853
  6
GUCUGCUAUUGUACGUACC
GGUACGUACAAUAGCAGAC
4919


 


1143
  7
AAUUCUUGGCUAUUACGAC
GUCGUAAUAGCCAAGAAUU
4920


 


2014
  8
GGAUGUUCACAACCGAAUU
AAUUCGGUUGUGAACAUCC
4921


 


 520
  9
ACAGUAUGCAAUGACUCGA
UCGAGUCAUUGCAUACUGU
4922


 


 814
 10
AGCUUCCAGACACGCUAUC
GAUAGCGUGUCUGGAAGCU
4923


 


 852
 11
UGUCUGCUAUUGUACGUAC
GUACGUACAAUAGCAGACA
4924


 


1796
 12
ACUGUUGGAUUGAUUCGAA
UUCGAAUCAAUCCAACAGU
4925


 


1901
 13
CAGGAUACCCAGCGCCGUA
UACGGCGCUGGGUAUCCUG
4926


 


 822
 14
GACACGCUAUCAUGCGUUC
GAACGCAUGAUAGCGUGUC
4927


 


1795
 15
UACUGUUGGAUUGAUUCGA
UCGAAUCAAUCCAACAGUA
4928


 


1145
 16
UUCUUGGCUAUUACGACAG
CUGUCGUAAUAGCCAAGAA
4929


 


 823
 17
ACACGCUAUCAUGCGUUCU
AGAACGCAUGAUAGCGUGU
4930


 


 820
 18
CAGACACGCUAUCAUGCGU
ACGCAUGAUAGCGUGUCUG
4931


 


1798
 19
UGUUGGAUUGAUUCGAAAU
AUUUCGAAUCAAUCCAACA
4932


 


1380
 20
CAGAUCCAAGUCAACGUCU
AGACGUUGACUUGGAUCUG
4933


 


1602
 21
AGGCUCUUGUGCGUACUGU
ACAGUACGCACAAGAGCCU
4934


 


1612
 22
GCGUACUGUCCUUCGGGCU
AGCCCGAAGGACAGUACGC
4935


 


 626
 23
ACUAAUGUCCAGCGUUUGG
CCAAACGCUGGACAUUAGU
4936


 


2000
 24
CACAUCCUAGCUCGGGAUG
CAUCCCGAGCUAGGAUGUG
4937


 


2665
 25
GUUGCUGAGAGGGCUCGAG
CUCGAGCCCUCUCAGCAAC
4938


 


1676
 26
CAUCUGACCAGCCGACACC
GGUGUCGGCUGGUCAGAUG
4939


 


1611
 27
UGCGUACUGUCCUUCGGGC
GCCCGAAGGACAGUACGCA
4940


 


2269
 28
ACAAGAUUACAAGAAACGG
CCGUUUCUUGUAAUCUUGU
4941


 


 674
 29
GUUGUAAACUUGAUUAACU
AGUUAAUCAAGUUUACAAC
4942


 


 678
 30
UAAACUUGAUUAACUAUCA
UGAUAGUUAAUCAAGUUUA
4943


 


1245
 31
AUAUAAUGAGGACCUAUAC
GUAUAGGUCCUCAUUAUAU
4944


 


 679
 32
AAACUUGAUUAACUAUCAA
UUGAUAGUUAAUCAAGUUU
4945


 


1970
 33
GAAAUAGUUGAAGGUUGUA
UACAACCUUCAACUAUUUC
4946


 


1247
 34
AUAAUGAGGACCUAUACUU
AAGUAUAGGUCCUCAUUAU
4947


 


1140
 35
UUAAAUUCUUGGCUAUUAC
GUAAUAGCCAAGAAUUUAA
4948


 


 676
 36
UGUAAACUUGAUUAACUAU
AUAGUUAAUCAAGUUUACA
4949


 


 677
 37
GUAAACUUGAUUAACUAUC
GAUAGUUAAUCAAGUUUAC
4950


 


 675
 38
UUGUAAACUUGAUUAACUA
UAGUUAAUCAAGUUUACAA
4951


 


1235
 39
GCUUUAGUAAAUAUAAUGA
UCAUUAUAUUUACUAAAGC
4952


 


2488
 40
UGGCCACCACCCUGGUGCU
AGCACCAGGGUGGUGGCCA
4953


 


1236
 41
CUUUAGUAAAUAUAAUGAG
CUCAUUAUAUUUACUAAAG
4954


 


1237
 42
UUUAGUAAAUAUAAUGAGG
CCUCAUUAUAUUUACUAAA
4955


 


2555
 43
GUAAAUCGUCCUUUAGGUA
UACCUAAAGGACGAUUUAC
4956


 


1545
 44
ACCUCACUUGCAAUAAUUA
UAAUUAUUGCAAGUGAGGU
4957


 


2050
 45
UACCAUUCCAUUGUUUGUG
CACAAACAAUGGAAUGGUA
4958


 


2097
 46
UCCAAAGAGUAGCUGCAGG
CCUGCAGCUACUCUUUGGA
4959


 


2510
 47
UAUCCAGUUGAUGGGCUGC
GCAGCCCAUCAACUGGAUA
4960


 


 871
 48
CAUGCAGAAUACAAAUGAU
AUCAUUUGUAUUCUGCAUG
4961


 


2098
 49
CCAAAGAGUAGCUGCAGGG
CCCUGCAGCUACUCUUUGG
4962


 


1767
 50
CACCAUCCCACUGGCCUCU
AGAGGCCAGUGGGAUGGUG
4963


 


 869
 51
ACCAUGCAGAAUACAAAUG
CAUUUGUAUUCUGCAUGGU
4964


 


1641
 52
AAGACAUCACUGAGCCUGC
GCAGGCUCAGUGAUGUCUU
4965


 


2582
 53
AAUCAGCUGGCCUGGUUUG
CAAACCAGGCCAGCUGAUU
4966


 


1544
 54
AACCUCACUUGCAAUAAUU
AAUUAUUGCAAGUGAGGUU
4967


 


2550
 55
ACCUCAUGGAUGGGCUGCC
GGCAGCCCAUCCAUGAGGU
4968


 


2051
 56
ACCAUUCCAUUGUUUGUGC
GCACAAACAAUGGAAUGGU
4969


 


 870
 57
CCAUGCAGAAUACAAAUGA
UCAUUUGUAUUCUGCAUGG
4970


 


1670
 58
CUUCGUCAUCUGACCAGCC
GGCUGGUCAGAUGACGAAG
4971


 


2122
 59
CUGUGAACUUGCUCAGGAC
GUCCUGAGCAAGUUCACAG
4972


 


1642
 60
AGACAUCACUGAGCCUGCC
GGCAGGCUCAGUGAUGUCU
4973


 


2324
 61
GAGCCAAUGGCUUGGAAUG
CAUUCCAAGCCAUUGGCUC
4974


 


1649
 62
ACUGAGCCUGCCAUCUGUG
CACAGAUGGCAGGCUCAGU
4975


 


2159
 63
AUUGAAGCUGAGGGAGCCA
UGGCUCCCUCAGCUUCAAU
4976


 


 785
 64
GUUAUGGUCCAUCAGCUUU
AAAGCUGAUGGACCAUAAC
4977


 


1511
 65
AAUGUGGUCACCUGUGCAG
CUGCACAGGUGACCACAUU
4978


 


2586
 66
AGCUGGCCUGGUUUGAUAC
GUAUCAAACCAGGCCAGCU
4979


 


 642
 67
UGGCUGAACCAUCACAGAU
AUCUGUGAUGGUUCAGCCA
4980


 


1763
 68
CACCCACCAUCCCACUGGC
GCCAGUGGGAUGGUGGGUG
4981


 


2328
 69
CAAUGGCUUGGAAUGAGAC
GUCUCAUUCCAAGCCAUUG
4982


 


1280
 70
UGGACCACAAGCAGAGUGC
GCACUCUGCUUGUGGUCCA
4983


 


2052
 71
CCAUUCCAUUGUUUGUGCA
UGCACAAACAAUGGAAUGG
4984


 


2546
 72
CAGGACCUCAUGGAUGGGC
GCCCAUCCAUGAGGUCCUG
4985


 


2124
 73
GUGAACUUGCUCAGGACAA
UUGUCCUGAGCAAGUUCAC
4986


 


2545
 74
CCAGGACCUCAUGGAUGGG
CCCAUCCAUGAGGUCCUGG
4987


 


 643
 75
GGCUGAACCAUCACAGAUG
CAUCUGUGAUGGUUCAGCC
4988


 


2501
 76
GGUGCUGACUAUCCAGUUG
CAACUGGAUAGUCAGCACC
4989


 


2330
 77
AUGGCUUGGAAUGAGACUG
CAGUCUCAUUCCAAGCCAU
4990


 


1638
 78
GGGAAGACAUCACUGAGCC
GGCUCAGUGAUGUCUUCCC
4991


 


1630
 79
UGGUGACAGGGAAGACAUC
GAUGUCUUCCCUGUCACCA
4992


 


 616
 80
UGCUCAUCCCACUAAUGUC
GACAUUAGUGGGAUGAGCA
4993


 


2509
 81
CUAUCCAGUUGAUGGGCUG
CAGCCCAUCAACUGGAUAG
4994


 


2548
 82
GGACCUCAUGGAUGGGCUG
CAGCCCAUCCAUGAGGUCC
4995


 


1773
 83
CCCACUGGCCUCUGAUAAA
UUUAUCAGAGGCCAGUGGG
4996


 


2247
 84
UCCGAAUGUCUGAGGACAA
UUGUCCUCAGACAUUCGGA
4997


 


2331
 85
UGGCUUGGAAUGAGACUGC
GCAGUCUCAUUCCAAGCCA
4998


 


1498
 86
UUCAGAUGAUAUAAAUGUG
CACAUUUAUAUCAUCUGAA
4999


 


2267
 87
CCACAAGAUUACAAGAAAC
GUUUCUUGUAAUCUUGUGG
5000


 


1547
 88
CUCACUUGCAAUAAUUAUA
UAUAAUUAUUGCAAGUGAG
5001


 


1549
 89
CACUUGCAAUAAUUAUAAG
CUUAUAAUUAUUGCAAGUG
5002


 


 867
 90
GUACCAUGCAGAAUACAAA
UUUGUAUUCUGCAUGGUAC
5003


 


1390
 91
UCAACGUCUUGUUCAGAAC
GUUCUGAACAAGACGUUGA
5004


 


 593
 92
AUCCCAUCUACACAGUUUG
CAAACUGUGUAGAUGGGAU
5005


 


 274
 93
UACUCAAGCUGAUUUGAUG
CAUCAAAUCAGCUUGAGUA
5006


 


 759
 94
ACCAGGUGGUGGUUAAUAA
UUAUUAACCACCACCUGGU
5007


 


1439
 95
GCUGCAACUAAACAGGAAG
CUUCCUGUUUAGUUGCAGC
5008


 


1801
 96
UGGAUUGAUUCGAAAUCUU
AAGAUUUCGAAUCAAUCCA
5009


 


1500
 97
CAGAUGAUAUAAAUGUGGU
ACCACAUUUAUAUCAUCUG
5010


 


 848
 98
AUGGUGUCUGCUAUUGUAC
GUACAAUAGCAGACACCAU
5011


 


2268
 99
CACAAGAUUACAAGAAACG
CGUUUCUUGUAAUCUUGUG
5012


 


 882
100
CAAAUGAUGUAGAAACAGC
GCUGUUUCUACAUCAUUUG
5013


 


2266
101
GCCACAAGAUUACAAGAAA
UUUCUUGUAAUCUUGUGGC
5014


 


 880
102
UACAAAUGAUGUAGAAACA
UGUUUCUACAUCAUUUGUA
5015


 


1810
103
UCGAAAUCUUGCCCUUUGU
ACAAAGGGCAAGAUUUCGA
5016


 


 685
104
GAUUAACUAUCAAGAUGAU
AUCAUCUUGAUAGUUAAUC
5017


 


1007
105
CCAGUGGAUUCUGUGUUGU
ACAACACAGAAUCCACUGG
5018


 


1789
106
AAAGGCUACUGUUGGAUUG
CAAUCCAACAGUAGCCUUU
5019


 


 499
107
ACAAGUAGCUGAUAUUGAU
AUCAAUAUCAGCUACUUGU
5020


 


2470
108
GAUGGAACAUGAGAUGGGU
ACCCAUCUCAUGUUCCAUC
5021


 


 694
109
UCAAGAUGAUGCAGAACUU
AAGUUCUGCAUCAUCUUGA
5022


 


 278
110
CAAGCUGAUUUGAUGGAGU
ACUCCAUCAAAUCAGCUUG
5023


 


1415
111
UGGACUCUCAGGAAUCUUU
AAAGAUUCCUGAGAGUCCA
5024


 


2046
112
UAAAUACCAUUCCAUUGUU
AACAAUGGAAUGGUAUUUA
5025


 


1057
113
AUUACAUCAAGAAGGAGCU
AGCUCCUUCUUGAUGUAAU
5026


 


1422
114
UCAGGAAUCUUUCAGAUGC
GCAUCUGAAAGAUUCCUGA
5027


 


 684
115
UGAUUAACUAUCAAGAUGA
UCAUCUUGAUAGUUAAUCA
5028


 


2197
116
ACUUCACUCUAGGAAUGAA
UUCAUUCCUAGAGUGAAGU
5029


 


 666
117
AACAUGCAGUUGUAAACUU
AAGUUUACAACUGCAUGUU
5030


 


 279
118
AAGCUGAUUUGAUGGAGUU
AACUCCAUCAAAUCAGCUU
5031


 


1492
119
UCUGGGUUCAGAUGAUAUA
UAUAUCAUCUGAACCCAGA
5032


 


2195
120
UUACUUCACUCUAGGAAUG
CAUUCCUAGAGUGAAGUAA
5033


 


1424
121
AGGAAUCUUUCAGAUGCUG
CAGCAUCUGAAAGAUUCCU
5034


 


 661
122
GCUGAAACAUGCAGUUGUA
UACAACUGCAUGUUUCAGC
5035


 


1882
123
GUUGCUUGUUCGUGCACAU
AUGUGCACGAACAAGCAAC
5036


 


1966
124
GGAAGAAAUAGUUGAAGGU
ACCUUCAACUAUUUCUUCC
5037


 


2259
125
AGGACAAGCCACAAGAUUA
UAAUCUUGUGGCUUGUCCU
5038


 


 832
126
CAUGCGUUCUCCUCAGAUG
CAUCUGAGGAGAACGCAUG
5039


 


2346
127
GAUGAUCCCAGCUACCGUU
AACGGUAGCUGGGAUCAUC
5040


 


1653
128
AGCCUGCCAUCUGUGCUCU
AGAGCACAGAUGGCAGGCU
5041


 


2389
129
UGGAUAUCGCCAGGAUGAU
AUCAUCCUGGCGAUAUCCA
5042


 


1669
130
UCUUCGUCAUCUGACCAGC
GCUGGUCAGAUGACGAAGA
5043


 


2123
131
UGUGAACUUGCUCAGGACA
UGUCCUGAGCAAGUUCACA
5044


 


1521
132
CCUGUGCAGCUGGAAUUCU
AGAAUUCCAGCUGCACAGG
5045


 


2125
133
UGAACUUGCUCAGGACAAG
CUUGUCCUGAGCAAGUUCA
5046


 


2503
134
UGCUGACUAUCCAGUUGAU
AUCAACUGGAUAGUCAGCA
5047


 


1502
135
GAUGAUAUAAAUGUGGUCA
UGACCACAUUUAUAUCAUC
5048


 


2502
136
GUGCUGACUAUCCAGUUGA
UCAACUGGAUAGUCAGCAC
5049


 


2506
137
UGACUAUCCAGUUGAUGGG
CCCAUCAACUGGAUAGUCA
5050


 


2127
138
AACUUGCUCAGGACAAGGA
UCCUUGUCCUGAGCAAGUU
5051


 


2505
139
CUGACUAUCCAGUUGAUGG
CCAUCAACUGGAUAGUCAG
5052


 


 617
140
GCUCAUCCCACUAAUGUCC
GGACAUUAGUGGGAUGAGC
5053


 


2504
141
GCUGACUAUCCAGUUGAUG
CAUCAACUGGAUAGUCAGC
5054


 


1503
142
AUGAUAUAAAUGUGGUCAC
GUGACCACAUUUAUAUCAU
5055


 


 618
143
CUCAUCCCACUAAUGUCCA
UGGACAUUAGUGGGAUGAG
5056


 


2074
144
GCUUUAUUCUCCCAUUGAA
UUCAAUGGGAGAAUAAAGC
5057


 


2499
145
CUGGUGCUGACUAUCCAGU
ACUGGAUAGUCAGCACCAG
5058


 


1406
146
AACUGUCUUUGGACUCUCA
UGAGAGUCCAAAGACAGUU
5059


 


 582
147
AGGGCAUGCAGAUCCCAUC
GAUGGGAUCUGCAUGCCCU
5060


 


1505
148
GAUAUAAAUGUGGUCACCU
AGGUGACCACAUUUAUAUC
5061


 


1432
149
UUCAGAUGCUGCAACUAAA
UUUAGUUGCAGCAUCUGAA
5062


 


1968
150
AAGAAAUAGUUGAAGGUUG
CAACCUUCAACUAUUUCUU
5063


 


2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGG
5064


 


 954
152
UGGCCAUCUUUAAGUCUGG
CCAGACUUAAAGAUGGCCA
5065


 


 505
153
AGCUGAUAUUGAUGGACAG
CUGUCCAUCAAUAUCAGCU
5066


 


2011
154
UCGGGAUGUUCACAACCGA
UCGGUUGUGAACAUCCCGA
5067


 


1339
155
UGUAGAAGCUGGUGGAAUG
CAUUCCACCAGCUUCUACA
5068


 


1242
156
UAAAUAUAAUGAGGACCUA
UAGGUCCUCAUUAUAUUUA
5069


 


 567
157
CUGAGACAUUAGAUGAGGG
CCCUCAUCUAAUGUCUCAG
5070


 


1240
158
AGUAAAUAUAAUGAGGACC
GGUCCUCAUUAUAUUUACU
5071


 


 438
159
UGGAUACCUCCCAAGUCCU
AGGACUUGGGAGGUAUCCA
5072


 


2445
160
AGGAUGCCUUGGGUAUGGA
UCCAUACCCAAGGCAUCCU
5073


 


 860
161
AUUGUACGUACCAUGCAGA
UCUGCAUGGUACGUACAAU
5074


 


1413
162
UUUGGACUCUCAGGAAUCU
AGAUUCCUGAGAGUCCAAA
5075


 


1800
163
UUGGAUUGAUUCGAAAUCU
AGAUUUCGAAUCAAUCCAA
5076


 


2037
164
UCAGAGGACUAAAUACCAU
AUGGUAUUUAGUCCUCUGA
5077


 


2443
165
CCAGGAUGCCUUGGGUAUG
CAUACCCAAGGCAUCCUGG
5078


 


2471
166
AUGGAACAUGAGAUGGGUG
CACCCAUCUCAUGUUCCAU
5079


 


1792
167
GGCUACUGUUGGAUUGAUU
AAUCAAUCCAACAGUAGCC
5080


 


2547
168
AGGACCUCAUGGAUGGGCU
AGCCCAUCCAUGAGGUCCU
5081


 


1662
169
UCUGUGCUCUUCGUCAUCU
AGAUGACGAAGAGCACAGA
5082


 


 288
170
UGAUGGAGUUGGACAUGGC
GCCAUGUCCAACUCCAUCA
5083


 


 579
171
AUGAGGGCAUGCAGAUCCC
GGGAUCUGCAUGCCCUCAU
5084


 


2508
172
ACUAUCCAGUUGAUGGGCU
AGCCCAUCAACUGGAUAGU
5085


 


 580
173
UGAGGGCAUGCAGAUCCCA
UGGGAUCUGCAUGCCCUCA
5086


 


2388
174
UUGGAUAUCGCCAGGAUGA
UCAUCCUGGCGAUAUCCAA
5087


 


2543
175
GCCCAGGACCUCAUGGAUG
CAUCCAUGAGGUCCUGGGC
5088


 


 708
176
AACUUGCCACACGUGCAAU
AUUGCACGUGUGGCAAGUU
5089


 


 447
177
CCCAAGUCCUGUAUGAGUG
CACUCAUACAGGACUUGGG
5090


 


 654
178
CACAGAUGCUGAAACAUGC
GCAUGUUUCAGCAUCUGUG
5091


 


 912
179
CUGGGACCUUGCAUAACCU
AGGUUAUGCAAGGUCCCAG
5092


 


1009
180
AGUGGAUUCUGUGUUGUUU
AAACAACACAGAAUCCACU
5093


 


1354
181
AAUGCAAGCUUUAGGACUU
AAGUCCUAAAGCUUGCAUU
5094


 


1969
182
AGAAAUAGUUGAAGGUUGU
ACAACCUUCAACUAUUUCU
5095


 


1959
183
UCCGCAUGGAAGAAAUAGU
ACUAUUUCUUCCAUGCGGA
5096


 


 557
184
GCUAUGUUCCCUGAGACAU
AUGUCUCAGGGAACAUAGC
5097


 


 403
185
UCUGAGUGGUAAAGGCAAU
AUUGCCUUUACCACUCAGA
5098


 


1356
186
UGCAAGCUUUAGGACUUCA
UGAAGUCCUAAAGCUUGCA
5099


 


 517
187
UGGACAGUAUGCAAUGACU
AGUCAUUGCAUACUGUCCA
5100


 


1238
188
UUAGUAAAUAUAAUGAGGA
UCCUCAUUAUAUUUACUAA
5101


 


 843
189
CUCAGAUGGUGUCUGCUAU
AUAGCAGACACCAUCUGAG
5102


 


 496
190
AGAACAAGUAGCUGAUAUU
AAUAUCAGCUACUUGUUCU
5103


 


2387
191
CUUGGAUAUCGCCAGGAUG
CAUCCUGGCGAUAUCCAAG
5104


 


1660
192
CAUCUGUGCUCUUCGUCAU
AUGACGAAGAGCACAGAUG
5105


 


2497
193
CCCUGGUGCUGACUAUCCA
UGGAUAGUCAGCACCAGGG
5106


 


1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGU
5107


 


2353
195
UCUUGGACUUGAUAUUGGU
ACCAAUAUCAAGUCCAAGA
5108


 


2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCC
5109


 


 878
197
AAUACAAAUGAUGUAGAAA
UUUCUACAUCAUUUGUAUU
5110


 


 647
198
GAACCAUCACAGAUGCUGA
UCAGCAUCUGUGAUGGUUC
5111


 


1998
199
UUCACAUCCUAGCUCGGGA
UCCCGAGCUAGGAUGUGAA
5112


 


 588
200
UGCAGAUCCCAUCUACACA
UGUGUAGAUGGGAUCUGCA
5113


 


2042
201
GGACUAAAUACCAUUCCAU
AUGGAAUGGUAUUUAGUCC
5114


 


 855
202
CUGCUAUUGUACGUACCAU
AUGGUACGUACAAUAGCAG
5115


 


2038
203
CAGAGGACUAAAUACCAUU
AAUGGUAUUUAGUCCUCUG
5116


 


1786
204
GAUAAAGGCUACUGUUGGA
UCCAACAGUAGCCUUUAUC
5117


 


1501
205
AGAUGAUAUAAAUGUGGUC
GACCACAUUUAUAUCAUCU
5118


 


1834
206
AAAUCAUGCACCUUUGCGU
ACGCAAAGGUGCAUGAUUU
5119


 


1157
207
ACGACAGACUGCCUUCAAA
UUUGAAGGCAGUCUGUCGU
5120


 


1239
208
UAGUAAAUAUAAUGAGGAC
GUCCUCAUUAUAUUUACUA
5121


 


1248
209
UAAUGAGGACCUAUACUUA
UAAGUAUAGGUCCUCAUUA
5122


 


 660
210
UGCUGAAACAUGCAGUUGU
ACAACUGCAUGUUUCAGCA
5123


 


 285
211
AUUUGAUGGAGUUGGACAU
AUGUCCAACUCCAUCAAAU
5124


 


1582
212
CUGCCAAGUGGGUGGUAUA
UAUACCACCCACUUGGCAG
5125


 


1735
213
UGGACUACCAGUUGUGGUU
AACCACAACUGGUAGUCCA
5126


 


 771
214
UUAAUAAGGCUGCAGUUAU
AUAACUGCAGCCUUAUUAA
5127


 


1060
215
ACAUCAAGAAGGAGCUAAA
UUUAGCUCCUUCUUGAUGU
5128


 


2390
216
GGAUAUCGCCAGGAUGAUC
GAUCAUCCUGGCGAUAUCC
5129


 


2186
217
CUGACAGAGUUACUUCACU
AGUGAAGUAACUCUGUCAG
5130


 


1632
218
GUGACAGGGAAGACAUCAC
GUGAUGUCUUCCCUGUCAC
5131


 


 619
219
UCAUCCCACUAAUGUCCAG
CUGGACAUUAGUGGGAUGA
5132


 


1656
220
CUGCCAUCUGUGCUCUUCG
CGAAGAGCACAGAUGGCAG
5133


 


1506
221
AUAUAAAUGUGGUCACCUG
CAGGUGACCACAUUUAUAU
5134


 


2494
222
CCACCCUGGUGCUGACUAU
AUAGUCAGCACCAGGGUGG
5135


 


1666
223
UGCUCUUCGUCAUCUGACC
GGUCAGAUGACGAAGAGCA
5136


 


1635
224
ACAGGGAAGACAUCACUGA
UCAGUGAUGUCUUCCCUGU
5137


 


 294
225
AGUUGGACAUGGCCAUGGA
UCCAUGGCCAUGUCCAACU
5138


 


 641
226
UUGGCUGAACCAUCACAGA
UCUGUGAUGGUUCAGCCAA
5139


 


 576
227
UAGAUGAGGGCAUGCAGAU
AUCUGCAUGCCCUCAUCUA
5140


 


 577
228
AGAUGAGGGCAUGCAGAUC
GAUCUGCAUGCCCUCAUCU
5141


 


1661
229
AUCUGUGCUCUUCGUCAUC
GAUGACGAAGAGCACAGAU
5142


 


 707
230
GAACUUGCCACACGUGCAA
UUGCACGUGUGGCAAGUUC
5143


 


1659
231
CCAUCUGUGCUCUUCGUCA
UGACGAAGAGCACAGAUGG
5144


 


1185
232
AUGGCAACCAAGAAAGCAA
UUGCUUUCUUGGUUGCCAU
5145


 


 664
233
GAAACAUGCAGUUGUAAAC
GUUUACAACUGCAUGUUUC
5146


 


1749
234
UGGUUAAGCUCUUACACCC
GGGUGUAAGAGCUUAACCA
5147


 


1234
235
AGCUUUAGUAAAUAUAAUG
CAUUAUAUUUACUAAAGCU
5148


 


 691
236
CUAUCAAGAUGAUGCAGAA
UUCUGCAUCAUCUUGAUAG
5149


 


1387
237
AAGUCAACGUCUUGUUCAG
CUGAACAAGACGUUGACUU
5150


 


1382
238
GAUCCAAGUCAACGUCUUG
CAAGACGUUGACUUGGAUC
5151


 


 828
239
CUAUCAUGCGUUCUCCUCA
UGAGGAGAACGCAUGAUAG
5152


 


1244
240
AAUAUAAUGAGGACCUAUA
UAUAGGUCCUCAUUAUAUU
5153


 


1304
241
GUGCUAUCUGUCUGCUCUA
UAGAGCAGACAGAUAGCAC
5154


 


 812
242
GAAGCUUCCAGACACGCUA
UAGCGUGUCUGGAAGCUUC
5155


 


1558
243
UAAUUAUAAGAACAAGAUG
CAUCUUGUUCUUAUAAUUA
5156


 


 879
244
AUACAAAUGAUGUAGAAAC
GUUUCUACAUCAUUUGUAU
5157


 


1311
245
CUGUCUGCUCUAGUAAUAA
UUAUUACUAGAGCAGACAG
5158


 


 856
246
UGCUAUUGUACGUACCAUG
CAUGGUACGUACAAUAGCA
5159


 


1296
247
UGCUGAAGGUGCUAUCUGU
ACAGAUAGCACCUUCAGCA
5160


 


 960
248
UCUUUAAGUCUGGAGGCAU
AUGCCUCCAGACUUAAAGA
5161


 


2049
249
AUACCAUUCCAUUGUUUGU
ACAAACAAUGGAAUGGUAU
5162


 


1791
250
AGGCUACUGUUGGAUUGAU
AUCAAUCCAACAGUAGCCU
5163


 


 783
251
CAGUUAUGGUCCAUCAGCU
AGCUGAUGGACCAUAACUG
5164


 


1569
252
ACAAGAUGAUGGUCUGCCA
UGGCAGACCAUCAUCUUGU
5165


 


2224
253
GACAUAUGCAGCUGCUGUU
AACAGCAGCUGCAUAUGUC
5166


 


 934
254
CCAUCAUCGUGAGGGCUUA
UAAGCCCUCACGAUGAUGG
5167


 


1378
255
GACAGAUCCAAGUCAACGU
ACGUUGACUUGGAUCUGUC
5168


 


 569
256
GAGACAUUAGAUGAGGGCA
UGCCCUCAUCUAAUGUCUC
5169


 


1722
257
UUCGCCUUCACUAUGGACU
AGUCCAUAGUGAAGGCGAA
5170


 


1483
258
UGUUCAGCUUCUGGGUUCA
UGAACCCAGAAGCUGAACA
5171


 


2352
259
AUCUUGGACUUGAUAUUGG
CCAAUAUCAAGUCCAAGAU
5172


 


 719
260
CGUGCAAUCCCUGAACUGA
UCAGUUCAGGGAUUGCACG
5173


 


 762
261
AGGUGGUGGUUAAUAAGGC
GCCUUAUUAACCACCACCU
5174


 


 599
262
UCUACACAGUUUGAUGCUG
CAGCAUCAAACUGUGUAGA
5175


 


1704
263
AGAUGGCCCAGAAUGCAGU
ACUGCAUUCUGGGCCAUCU
5176


 


2270
264
CAAGAUUACAAGAAACGGC
GCCGUUUCUUGUAAUCUUG
5177


 


 662
265
CUGAAACAUGCAGUUGUAA
UUACAACUGCAUGUUUCAG
5178


 


 396
266
CUCCUUCUCUGAGUGGUAA
UUACCACUCAGAGAAGGAG
5179


 


1199
267
AGCAAGCUCAUCAUACUGG
CCAGUAUGAUGAGCUUGCU
5180


 


1560
268
AUUAUAAGAACAAGAUGAU
AUCAUCUUGUUCUUAUAAU
5181


 


1310
269
UCUGUCUGCUCUAGUAAUA
UAUUACUAGAGCAGACAGA
5182


 


1233
270
AAGCUUUAGUAAAUAUAAU
AUUAUAUUUACUAAAGCUU
5183


 


1330
271
GCCGGCUAUUGUAGAAGCU
AGCUUCUACAAUAGCCGGC
5184


 


1312
272
UGUCUGCUCUAGUAAUAAG
CUUAUUACUAGAGCAGACA
5185


 


1556
273
AAUAAUUAUAAGAACAAGA
UCUUGUUCUUAUAAUUAUU
5186


 


2438
274
UAUGGCCAGGAUGCCUUGG
CCAAGGCAUCCUGGCCAUA
5187


 


1826
275
UGUCCCGCAAAUCAUGCAC
GUGCAUGAUUUGCGGGACA
5188


 


1397
276
CUUGUUCAGAACUGUCUUU
AAAGACAGUUCUGAACAAG
5189


 


3181
277
GCUGUGAUACGAUGCUUCA
UGAAGCAUCGUAUCACAGC
5190


 


1912
278
GCGCCGUACGUCCAUGGGU
ACCCAUGGACGUACGGCGC
5191


 


 846
279
AGAUGGUGUCUGCUAUUGU
ACAAUAGCAGACACCAUCU
5192


 


1404
280
AGAACUGUCUUUGGACUCU
AGAGUCCAAAGACAGUUCU
5193


 


 586
281
CAUGCAGAUCCCAUCUACA
UGUAGAUGGGAUCUGCAUG
5194


 


1469
282
CUCCUUGGGACUCUUGUUC
GAACAAGAGUCCCAAGGAG
5195


 


 380
283
GGUGCCACUACCACAGCUC
GAGCUGUGGUAGUGGCACC
5196


 


1345
284
AGCUGGUGGAAUGCAAGCU
AGCUUGCAUUCCACCAGCU
5197


 


1863
285
CCAUUCCACGACUAGUUCA
UGAACUAGUCGUGGAAUGG
5198


 


 635
286
CAGCGUUUGGCUGAACCAU
AUGGUUCAGCCAAACGCUG
5199


 


 959
287
AUCUUUAAGUCUGGAGGCA
UGCCUCCAGACUUAAAGAU
5200


 


2440
288
UGGCCAGGAUGCCUUGGGU
ACCCAAGGCAUCCUGGCCA
5201


 


 877
289
GAAUACAAAUGAUGUAGAA
UUCUACAUCAUUUGUAUUC
5202


 


2556
290
UGGAUGGGCUGCCUCCAGG
CCUGGAGGCAGCCCAUCCA
5203


 


1916
291
CGUACGUCCAUGGGUGGGA
UCCCACCCAUGGACGUACG
5204


 


 850
292
GGUGUCUGCUAUUGUACGU
ACGUACAAUAGCAGACACC
5205


 


1303
293
GGUGCUAUCUGUCUGCUCU
AGAGCAGACAGAUAGCACC
5206


 


1726
294
CCUUCACUAUGGACUACCA
UGGUAGUCCAUAGUGAAGG
5207


 


1477
295
GACUCUUGUUCAGCUUCUG
CAGAAGCUGAACAAGAGUC
5208


 


 598
296
AUCUACACAGUUUGAUGCU
AGCAUCAAACUGUGUAGAU
5209


 


2062
297
GUUUGUGCAGCUGCUUUAU
AUAAAGCAGCUGCACAAAC
5210


 


2278
298
CAAGAAACGGCUUUCAGUU
AACUGAAAGCCGUUUCUUG
5211


 


1877
299
GUUCAGUUGCUUGUUCGUG
CACGAACAAGCAACUGAAC
5212


 


1499
300
UCAGAUGAUAUAAAUGUGG
CCACAUUUAUAUCAUCUGA
5213


 


1136
301
AAUGUUAAAUUCUUGGCUA
UAGCCAAGAAUUUAACAUU
5214


 


1494
302
UGGGUUCAGAUGAUAUAAA
UUUAUAUCAUCUGAACCCA
5215


 


1972
303
AAUAGUUGAAGGUUGUACC
GGUACAACCUUCAACUAUU
5216


 


 668
304
CAUGCAGUUGUAAACUUGA
UCAAGUUUACAACUGCAUG
5217


 


2945
305
AAUCUGAAUAAAGUGUAAC
GUUACACUUUAUUCAGAUU
5218


 


2492
306
CACCACCCUGGUGCUGACU
AGUCAGCACCAGGGUGGUG
5219


 


 293
307
GAGUUGGACAUGGCCAUGG
CCAUGGCCAUGUCCAACUC
5220


 


1905
308
AUACCCAGCGCCGUACGUC
GACGUACGGCGCUGGGUAU
5221


 


 944
309
GAGGGCUUACUGGCCAUCU
AGAUGGCCAGUAAGCCCUC
5222


 


 581
310
GAGGGCAUGCAGAUCCCAU
AUGGGAUCUGCAUGCCCUC
5223


 


1454
311
GAAGGGAUGGAAGGUCUCC
GGAGACCUUCCAUCCCUUC
5224


 


2254
312
GUCUGAGGACAAGCCACAA
UUGUGGCUUGUCCUCAGAC
5225


 


1837
313
UCAUGCACCUUUGCGUGAG
CUCACGCAAAGGUGCAUGA
5226


 


1425
314
GGAAUCUUUCAGAUGCUGC
GCAGCAUCUGAAAGAUUCC
5227


 


1372
315
UCACCUGACAGAUCCAAGU
ACUUGGAUCUGUCAGGUGA
5228


 


1298
316
CUGAAGGUGCUAUCUGUCU
AGACAGAUAGCACCUUCAG
5229


 


1674
317
GUCAUCUGACCAGCCGACA
UGUCGGCUGGUCAGAUGAC
5230


 


1864
318
CAUUCCACGACUAGUUCAG
CUGAACUAGUCGUGGAAUG
5231


 


2404
319
UGAUCCUAGCUAUCGUUCU
AGAACGAUAGCUAGGAUCA
5232


 


1992
320
GAGCCCUUCACAUCCUAGC
GCUAGGAUGUGAAGGGCUC
5233


 


 578
321
GAUGAGGGCAUGCAGAUCC
GGAUCUGCAUGCCCUCAUC
5234


 


3091
322
AUGGGUAGGGUAAAUCAGU
ACUGAUUUACCCUACCCAU
5235


 


 720
323
GUGCAAUCCCUGAACUGAC
GUCAGUUCAGGGAUUGCAC
5236


 


2054
324
AUUCCAUUGUUUGUGCAGC
GCUGCACAAACAAUGGAAU
5237


 


 374
325
CAUUCUGGUGCCACUACCA
UGGUAGUGGCACCAGAAUG
5238


 


 868
326
UACCAUGCAGAAUACAAAU
AUUUGUAUUCUGCAUGGUA
5239


 


1716
327
AUGCAGUUCGCCUUCACUA
UAGUGAAGGCGAACUGCAU
5240


 


 950
328
UUACUGGCCAUCUUUAAGU
ACUUAAAGAUGGCCAGUAA
5241


 


1489
329
GCUUCUGGGUUCAGAUGAU
AUCAUCUGAACCCAGAAGC
5242


 


1451
330
CAGGAAGGGAUGGAAGGUC
GACCUUCCAUCCCUUCCUG
5243


 


1181
331
GCUUAUGGCAACCAAGAAA
UUUCUUGGUUGCCAUAAGC
5244


 


1633
332
UGACAGGGAAGACAUCACU
AGUGAUGUCUUCCCUGUCA
5245


 


2394
333
AUCGCCAGGAUGAUCCUAG
CUAGGAUCAUCCUGGCGAU
5246


 


1322
334
AGUAAUAAGCCGGCUAUUG
CAAUAGCCGGCUUAUUACU
5247


 


 884
335
AAUGAUGUAGAAACAGCUC
GAGCUGUUUCUACAUCAUU
5248


 


2255
336
UCUGAGGACAAGCCACAAG
CUUGUGGCUUGUCCUCAGA
5249


 


1466
337
GGUCUCCUUGGGACUCUUG
CAAGAGUCCCAAGGAGACC
5250


 


1399
338
UGUUCAGAACUGUCUUUGG
CCAAAGACAGUUCUGAACA
5251


 


 378
339
CUGGUGCCACUACCACAGC
GCUGUGGUAGUGGCACCAG
5252


 


1921
340
GUCCAUGGGUGGGACACAG
CUGUGUCCCACCCAUGGAC
5253


 


1085
341
GUGCGUUUAGCUGGUGGGC
GCCCACCAGCUAAACGCAC
5254


 


 865
342
ACGUACCAUGCAGAAUACA
UGUAUUCUGCAUGGUACGU
5255


 


2015
343
GAUGUUCACAACCGAAUUG
CAAUUCGGUUGUGAACAUC
5256


 


1195
344
AGAAAGCAAGCUCAUCAUA
UAUGAUGAGCUUGCUUUCU
5257


 


1484
345
GUUCAGCUUCUGGGUUCAG
CUGAACCCAGAAGCUGAAC
5258


 


1855
346
GCAGGGUGCCAUUCCACGA
UCGUGGAAUGGCACCCUGC
5259


 


1341
347
UAGAAGCUGGUGGAAUGCA
UGCAUUCCACCAGCUUCUA
5260


 


1963
348
CAUGGAAGAAAUAGUUGAA
UUCAACUAUUUCUUCCAUG
5261


 


2362
349
UGAUAUUGGUGCCCAGGGA
UCCCUGGGCACCAAUAUCA
5262


 


 584
350
GGCAUGCAGAUCCCAUCUA
UAGAUGGGAUCUGCAUGCC
5263


 


1613
351
CGUACUGUCCUUCGGGCUG
CAGCCCGAAGGACAGUACG
5264


 


1155
352
UUACGACAGACUGCCUUCA
UGAAGGCAGUCUGUCGUAA
5265


 


 334
353
UAGUCACUGGCAGCAACAG
CUGUUGCUGCCAGUGACUA
5266


 


1031
354
GCCAUUACAACUCUCCACA
UGUGGAGAGUUGUAAUGGC
5267


 


1725
355
GCCUUCACUAUGGACUACC
GGUAGUCCAUAGUGAAGGC
5268


 


2018
356
GUUCACAACCGAAUUGUUA
UAACAAUUCGGUUGUGAAC
5269


 


 914
357
GGGACCUUGCAUAACCUUU
AAAGGUUAUGCAAGGUCCC
5270


 


2264
358
AAGCCACAAGAUUACAAGA
UCUUGUAAUCUUGUGGCUU
5271


 


 343
359
GCAGCAACAGUCUUACCUG
CAGGUAAGACUGUUGCUGC
5272


 


1056
360
UAUUACAUCAAGAAGGAGC
GCUCCUUCUUGAUGUAAUA
5273


 


 772
361
UAAUAAGGCUGCAGUUAUG
CAUAACUGCAGCCUUAUUA
5274


 


 763
362
GGUGGUGGUUAAUAAGGCU
AGCCUUAUUAACCACCACC
5275


 


 628
363
UAAUGUCCAGCGUUUGGCU
AGCCAAACGCUGGACAUUA
5276


 


 399
364
CUUCUCUGAGUGGUAAAGG
CCUUUACCACUCAGAGAAG
5277


 


1682
365
ACCAGCCGACACCAAGAAG
CUUCUUGGUGUCGGCUGGU
5278


 


 441
366
AUACCUCCCAAGUCCUGUA
UACAGGACUUGGGAGGUAU
5279


 


1729
367
UCACUAUGGACUACCAGUU
AACUGGUAGUCCAUAGUGA
5280


 


1902
368
AGGAUACCCAGCGCCGUAC
GUACGGCGCUGGGUAUCCU
5281


 


1637
369
AGGGAAGACAUCACUGAGC
GCUCAGUGAUGUCUUCCCU
5282


 


2391
370
GAUAUCGCCAGGAUGAUCC
GGAUCAUCCUGGCGAUAUC
5283


 


 501
371
AAGUAGCUGAUAUUGAUGG
CCAUCAAUAUCAGCUACUU
5284


 


1358
372
CAAGCUUUAGGACUUCACC
GGUGAAGUCCUAAAGCUUG
5285


 


1821
373
CCCUUUGUCCCGCAAAUCA
UGAUUUGCGGGACAAAGGG
5286


 


 575
374
UUAGAUGAGGGCAUGCAGA
UCUGCAUGCCCUCAUCUAA
5287


 


 528
375
CAAUGACUCGAGCUCAGAG
CUCUGAGCUCGAGUCAUUG
5288


 


2433
376
GUGGAUAUGGCCAGGAUGC
GCAUCCUGGCCAUAUCCAC
5289


 


1497
377
GUUCAGAUGAUAUAAAUGU
ACAUUUAUAUCAUCUGAAC
5290


 


2134
378
UCAGGACAAGGAAGCUGCA
UGCAGCUUCCUUGUCCUGA
5291


 


2160
379
UUGAAGCUGAGGGAGCCAC
GUGGCUCCCUCAGCUUCAA
5292


 


 291
380
UGGAGUUGGACAUGGCCAU
AUGGCCAUGUCCAACUCCA
5293


 


 657
381
AGAUGCUGAAACAUGCAGU
ACUGCAUGUUUCAGCAUCU
5294


 


1575
382
UGAUGGUCUGCCAAGUGGG
CCCACUUGGCAGACCAUCA
5295


 


 667
383
ACAUGCAGUUGUAAACUUG
CAAGUUUACAACUGCAUGU
5296


 


2190
384
CAGAGUUACUUCACUCUAG
CUAGAGUGAAGUAACUCUG
5297


 


 532
385
GACUCGAGCUCAGAGGGUA
UACCCUCUGAGCUCGAGUC
5298


 


 953
386
CUGGCCAUCUUUAAGUCUG
CAGACUUAAAGAUGGCCAG
5299


 


3188
387
UACGAUGCUUCAAGAGAAA
UUUCUCUUGAAGCAUCGUA
5300


 


2301
388
UGACCAGCUCUCUCUUCAG
CUGAAGAGAGAGCUGGUCA
5301


 


2310
389
CUCUCUUCAGAACAGAGCC
GGCUCUGUUCUGAAGAGAG
5302


 


2287
390
GCUUUCAGUUGAGCUGACC
GGUCAGCUCAACUGAAAGC
5303


 


1927
391
GGGUGGGACACAGCAGCAA
UUGCUGCUGUGUCCCACCC
5304


 


 712
392
UGCCACACGUGCAAUCCCU
AGGGAUUGCACGUGUGGCA
5305


 


2121
393
UCUGUGAACUUGCUCAGGA
UCCUGAGCAAGUUCACAGA
5306


 


2898
394
UGAGUAAUGGUGUAGAACA
UGUUCUACACCAUUACUCA
5307


 


1799
395
GUUGGAUUGAUUCGAAAUC
GAUUUCGAAUCAAUCCAAC
5308


 


1036
396
UACAACUCUCCACAACCUU
AAGGUUGUGGAGAGUUGUA
5309


 


 449
397
CAAGUCCUGUAUGAGUGGG
CCCACUCAUACAGGACUUG
5310


 


1452
398
AGGAAGGGAUGGAAGGUCU
AGACCUUCCAUCCCUUCCU
5311


 


1203
399
AGCUCAUCAUACUGGCUAG
CUAGCCAGUAUGAUGAGCU
5312


 


1357
400
GCAAGCUUUAGGACUUCAC
GUGAAGUCCUAAAGCUUGC
5313


 


1512
401
AUGUGGUCACCUGUGCAGC
GCUGCACAGGUGACCACAU
5314


 


 275
402
ACUCAAGCUGAUUUGAUGG
CCAUCAAAUCAGCUUGAGU
5315


 


 299
403
GACAUGGCCAUGGAACCAG
CUGGUUCCAUGGCCAUGUC
5316


 


1241
404
GUAAAUAUAAUGAGGACCU
AGGUCCUCAUUAUAUUUAC
5317


 


1961
405
CGCAUGGAAGAAAUAGUUG
CAACUAUUUCUUCCAUGCG
5318


 


1436
406
GAUGCUGCAACUAAACAGG
CCUGUUUAGUUGCAGCAUC
5319


 


2469
407
UGAUGGAACAUGAGAUGGG
CCCAUCUCAUGUUCCAUCA
5320


 


 760
408
CCAGGUGGUGGUUAAUAAG
CUUAUUAACCACCACCUGG
5321


 


2257
409
UGAGGACAAGCCACAAGAU
AUCUUGUGGCUUGUCCUCA
5322


 


 952
410
ACUGGCCAUCUUUAAGUCU
AGACUUAAAGAUGGCCAGU
5323


 


2283
411
AACGGCUUUCAGUUGAGCU
AGCUCAACUGAAAGCCGUU
5324


 


1794
412
CUACUGUUGGAUUGAUUCG
CGAAUCAAUCCAACAGUAG
5325


 


1745
413
GUUGUGGUUAAGCUCUUAC
GUAAGAGCUUAACCACAAC
5326


 


1211
414
AUACUGGCUAGUGGUGGAC
GUCCACCACUAGCCAGUAU
5327


 


2549
415
GACCUCAUGGAUGGGCUGC
GCAGCCCAUCCAUGAGGUC
5328


 


2007
416
UAGCUCGGGAUGUUCACAA
UUGUGAACAUCCCGAGCUA
5329


 


2474
417
GAACAUGAGAUGGGUGGCC
GGCCACCCAUCUCAUGUUC
5330


 


1712
418
CAGAAUGCAGUUCGCCUUC
GAAGGCGAACUGCAUUCUG
5331


 


1919
419
ACGUCCAUGGGUGGGACAC
GUGUCCCACCCAUGGACGU
5332


 


1000
420
UGGUUCACCAGUGGAUUCU
AGAAUCCACUGGUGAACCA
5333


 


2392
421
AUAUCGCCAGGAUGAUCCU
AGGAUCAUCCUGGCGAUAU
5334


 


1449
422
AACAGGAAGGGAUGGAAGG
CCUUCCAUCCCUUCCUGUU
5335


 


2294
423
GUUGAGCUGACCAGCUCUC
GAGAGCUGGUCAGCUCAAC
5336


 


1135
424
AAAUGUUAAAUUCUUGGCU
AGCCAAGAAUUUAACAUUU
5337


 


1333
425
GGCUAUUGUAGAAGCUGGU
ACCAGCUUCUACAAUAGCC
5338


 


1743
426
CAGUUGUGGUUAAGCUCUU
AAGAGCUUAACCACAACUG
5339


 


 600
427
CUACACAGUUUGAUGCUGC
GCAGCAUCAAACUGUGUAG
5340


 


 970
428
UGGAGGCAUUCCUGCCCUG
CAGGGCAGGAAUGCCUCCA
5341


 


3137
429
GGACAGUUUACCAGUUGCC
GGCAACUGGUAAACUGUCC
5342


 


 372
430
UCCAUUCUGGUGCCACUAC
GUAGUGGCACCAGAAUGGA
5343


 


1761
431
UACACCCACCAUCCCACUG
CAGUGGGAUGGUGGGUGUA
5344


 


1650
432
CUGAGCCUGCCAUCUGUGC
GCACAGAUGGCAGGCUCAG
5345


 


 972
433
GAGGCAUUCCUGCCCUGGU
ACCAGGGCAGGAAUGCCUC
5346


 


1147
434
CUUGGCUAUUACGACAGAC
GUCUGUCGUAAUAGCCAAG
5347


 


 565
435
CCCUGAGACAUUAGAUGAG
CUCAUCUAAUGUCUCAGGG
5348


 


 525
436
AUGCAAUGACUCGAGCUCA
UGAGCUCGAGUCAUUGCAU
5349


 


1599
437
UAGAGGCUCUUGUGCGUAC
GUACGCACAAGAGCCUCUA
5350


 


2199
438
UUCACUCUAGGAAUGAAGG
CCUUCAUUCCUAGAGUGAA
5351


 


2261
439
GACAAGCCACAAGAUUACA
UGUAAUCUUGUGGCUUGUC
5352


 


 705
440
CAGAACUUGCCACACGUGC
GCACGUGUGGCAAGUUCUG
5353


 


 916
441
GACCUUGCAUAACCUUUCC
GGAAAGGUUAUGCAAGGUC
5354


 


 385
442
CACUACCACAGCUCCUUCU
AGAAGGAGCUGUGGUAGUG
5355


 


3076
443
CUAUUUGGGAUAUGUAUGG
CCAUACAUAUCCCAAAUAG
5356


 


1396
444
UCUUGUUCAGAACUGUCUU
AAGACAGUUCUGAACAAGA
5357


 


2447
445
GAUGCCUUGGGUAUGGACC
GGUCCAUACCCAAGGCAUC
5358


 


1338
446
UUGUAGAAGCUGGUGGAAU
AUUCCACCAGCUUCUACAA
5359


 


2215
447
AGGUGUGGCGACAUAUGCA
UGCAUAUGUCGCCACACCU
5360


 


 722
448
GCAAUCCCUGAACUGACAA
UUGUCAGUUCAGGGAUUGC
5361


 


1316
449
UGCUCUAGUAAUAAGCCGG
CCGGCUUAUUACUAGAGCA
5362


 


1687
450
CCGACACCAAGAAGCAGAG
CUCUGCUUCUUGGUGUCGG
5363


 


 697
451
AGAUGAUGCAGAACUUGCC
GGCAAGUUCUGCAUCAUCU
5364


 


2517
452
UUGAUGGGCUGCCAGAUCU
AGAUCUGGCAGCCCAUCAA
5365


 


1685
453
AGCCGACACCAAGAAGCAG
CUGCUUCUUGGUGUCGGCU
5366


 


3090
454
UAUGGGUAGGGUAAAUCAG
CUGAUUUACCCUACCCAUA
5367


 


1205
455
CUCAUCAUACUGGCUAGUG
CACUAGCCAGUAUGAUGAG
5368


 


1153
456
UAUUACGACAGACUGCCUU
AAGGCAGUCUGUCGUAAUA
5369


 


 723
457
CAAUCCCUGAACUGACAAA
UUUGUCAGUUCAGGGAUUG
5370


 


1468
458
UCUCCUUGGGACUCUUGUU
AACAAGAGUCCCAAGGAGA
5371


 


2480
459
GAGAUGGGUGGCCACCACC
GGUGGUGGCCACCCAUCUC
5372


 


1856
460
CAGGGUGCCAUUCCACGAC
GUCGUGGAAUGGCACCCUG
5373


 


2193
461
AGUUACUUCACUCUAGGAA
UUCCUAGAGUGAAGUAACU
5374


 


2355
462
UUGGACUUGAUAUUGGUGC
GCACCAAUAUCAAGUCCAA
5375


 


1995
463
CCCUUCACAUCCUAGCUCG
CGAGCUAGGAUGUGAAGGG
5376


 


 821
464
AGACACGCUAUCAUGCGUU
AACGCAUGAUAGCGUGUCU
5377


 


1715
465
AAUGCAGUUCGCCUUCACU
AGUGAAGGCGAACUGCAUU
5378


 


1182
466
CUUAUGGCAACCAAGAAAG
CUUUCUUGGUUGCCAUAAG
5379


 


 445
467
CUCCCAAGUCCUGUAUGAG
CUCAUACAGGACUUGGGAG
5380


 


1759
468
CUUACACCCACCAUCCCAC
GUGGGAUGGUGGGUGUAAG
5381


 


1461
469
UGGAAGGUCUCCUUGGGAC
GUCCCAAGGAGACCUUCCA
5382


 


1993
470
AGCCCUUCACAUCCUAGCU
AGCUAGGAUGUGAAGGGCU
5383


 


2558
471
GAUGGGCUGCCUCCAGGUG
CACCUGGAGGCAGCCCAUC
5384


 


1488
472
AGCUUCUGGGUUCAGAUGA
UCAUCUGAACCCAGAAGCU
5385


 


1652
473
GAGCCUGCCAUCUGUGCUC
GAGCACAGAUGGCAGGCUC
5386


 


 963
474
UUAAGUCUGGAGGCAUUCC
GGAAUGCCUCCAGACUUAA
5387


 


1520
475
ACCUGUGCAGCUGGAAUUC
GAAUUCCAGCUGCACAGGU
5388


 


1828
476
UCCCGCAAAUCAUGCACCU
AGGUGCAUGAUUUGCGGGA
5389


 


2214
477
AAGGUGUGGCGACAUAUGC
GCAUAUGUCGCCACACCUU
5390


 


2155
478
AGCUAUUGAAGCUGAGGGA
UCCCUCAGCUUCAAUAGCU
5391


 


 332
479
GUUAGUCACUGGCAGCAAC
GUUGCUGCCAGUGACUAAC
5392


 


1878
480
UUCAGUUGCUUGUUCGUGC
GCACGAACAAGCAACUGAA
5393


 


1573
481
GAUGAUGGUCUGCCAAGUG
CACUUGGCAGACCAUCAUC
5394


 


1446
482
CUAAACAGGAAGGGAUGGA
UCCAUCCCUUCCUGUUUAG
5395


 


1868
483
CCACGACUAGUUCAGUUGC
GCAACUGAACUAGUCGUGG
5396


 


1873
484
ACUAGUUCAGUUGCUUGUU
AACAAGCAACUGAACUAGU
5397


 


1002
485
GUUCACCAGUGGAUUCUGU
ACAGAAUCCACUGGUGAAC
5398


 


 408
486
GUGGUAAAGGCAAUCCUGA
UCAGGAUUGCCUUUACCAC
5399


 


 287
487
UUGAUGGAGUUGGACAUGG
CCAUGUCCAACUCCAUCAA
5400


 


2128
488
ACUUGCUCAGGACAAGGAA
UUCCUUGUCCUGAGCAAGU
5401


 


2513
489
CCAGUUGAUGGGCUGCCAG
CUGGCAGCCCAUCAACUGG
5402


 


1196
490
GAAAGCAAGCUCAUCAUAC
GUAUGAUGAGCUUGCUUUC
5403


 


 572
491
ACAUUAGAUGAGGGCAUGC
GCAUGCCCUCAUCUAAUGU
5404


 


 622
492
UCCCACUAAUGUCCAGCGU
ACGCUGGACAUUAGUGGGA
5405


 


1187
493
GGCAACCAAGAAAGCAAGC
GCUUGCUUUCUUGGUUGCC
5406


 


1971
494
AAAUAGUUGAAGGUUGUAC
GUACAACCUUCAACUAUUU
5407


 


3083
495
GGAUAUGUAUGGGUAGGGU
ACCCUACCCAUACAUAUCC
5408


 


2944
496
UAAUCUGAAUAAAGUGUAA
UUACACUUUAUUCAGAUUA
5409


 


1894
497
UGCACAUCAGGAUACCCAG
CUGGGUAUCCUGAUGUGCA
5410


 


1323
498
GUAAUAAGCCGGCUAUUGU
ACAAUAGCCGGCUUAUUAC
5411


 


1202
499
AAGCUCAUCAUACUGGCUA
UAGCCAGUAUGAUGAGCUU
5412


 


 718
500
ACGUGCAAUCCCUGAACUG
CAGUUCAGGGAUUGCACGU
5413


 


1744
501
AGUUGUGGUUAAGCUCUUA
UAAGAGCUUAACCACAACU
5414


 


 756
502
AGGACCAGGUGGUGGUUAA
UUAACCACCACCUGGUCCU
5415


 


1317
503
GCUCUAGUAAUAAGCCGGC
GCCGGCUUAUUACUAGAGC
5416


 


 284
504
GAUUUGAUGGAGUUGGACA
UGUCCAACUCCAUCAAAUC
5417


 


 886
505
UGAUGUAGAAACAGCUCGU
ACGAGCUGUUUCUACAUCA
5418


 


2430
506
CUGGUGGAUAUGGCCAGGA
UCCUGGCCAUAUCCACCAG
5419


 


1207
507
CAUCAUACUGGCUAGUGGU
ACCACUAGCCAGUAUGAUG
5420


 


 592
508
GAUCCCAUCUACACAGUUU
AAACUGUGUAGAUGGGAUC
5421


 


 824
509
CACGCUAUCAUGCGUUCUC
GAGAACGCAUGAUAGCGUG
5422


 


 519
510
GACAGUAUGCAAUGACUCG
CGAGUCAUUGCAUACUGUC
5423


 


3166
511
AAGUUGUUGUAACCUGCUG
CAGCAGGUUACAACAACUU
5424


 


1151
512
GCUAUUACGACAGACUGCC
GGCAGUCUGUCGUAAUAGC
5425


 


2566
513
GCCUCCAGGUGACAGCAAU
AUUGCUGUCACCUGGAGGC
5426


 


 453
514
UCCUGUAUGAGUGGGAACA
UGUUCCCACUCAUACAGGA
5427


 


 587
515
AUGCAGAUCCCAUCUACAC
GUGUAGAUGGGAUCUGCAU
5428


 


 930
516
UUUCCCAUCAUCGUGAGGG
CCCUCACGAUGAUGGGAAA
5429


 


1585
517
CCAAGUGGGUGGUAUAGAG
CUCUAUACCACCCACUUGG
5430


 


 915
518
GGACCUUGCAUAACCUUUC
GAAAGGUUAUGCAAGGUCC
5431


 


 446
519
UCCCAAGUCCUGUAUGAGU
ACUCAUACAGGACUUGGGA
5432


 


1869
520
CACGACUAGUUCAGUUGCU
AGCAACUGAACUAGUCGUG
5433


 


1960
521
CCGCAUGGAAGAAAUAGUU
AACUAUUUCUUCCAUGCGG
5434


 


1708
522
GGCCCAGAAUGCAGUUCGC
GCGAACUGCAUUCUGGGCC
5435


 


 306
523
CCAUGGAACCAGACAGAAA
UUUCUGUCUGGUUCCAUGG
5436


 


2281
524
GAAACGGCUUUCAGUUGAG
CUCAACUGAAAGCCGUUUC
5437


 


3082
525
GGGAUAUGUAUGGGUAGGG
CCCUACCCAUACAUAUCCC
5438


 


1473
526
UUGGGACUCUUGUUCAGCU
AGCUGAACAAGAGUCCCAA
5439


 


 559
527
UAUGUUCCCUGAGACAUUA
UAAUGUCUCAGGGAACAUA
5440


 


1416
528
GGACUCUCAGGAAUCUUUC
GAAAGAUUCCUGAGAGUCC
5441


 


2145
529
AAGCUGCAGAAGCUAUUGA
UCAAUAGCUUCUGCAGCUU
5442


 


1994
530
GCCCUUCACAUCCUAGCUC
GAGCUAGGAUGUGAAGGGC
5443


 


1702
531
AGAGAUGGCCCAGAAUGCA
UGCAUUCUGGGCCAUCUCU
5444


 


 417
532
GCAAUCCUGAGGAAGAGGA
UCCUCUUCCUCAGGAUUGC
5445


 


2444
533
CAGGAUGCCUUGGGUAUGG
CCAUACCCAAGGCAUCCUG
5446


 


 555
534
CUGCUAUGUUCCCUGAGAC
GUCUCAGGGAACAUAGCAG
5447


 


2019
535
UUCACAACCGAAUUGUUAU
AUAACAAUUCGGUUGUGAA
5448


 


1197
536
AAAGCAAGCUCAUCAUACU
AGUAUGAUGAGCUUGCUUU
5449


 


 415
537
AGGCAAUCCUGAGGAAGAG
CUCUUCCUCAGGAUUGCCU
5450


 


2061
538
UGUUUGUGCAGCUGCUUUA
UAAAGCAGCUGCACAAACA
5451


 


1352
539
GGAAUGCAAGCUUUAGGAC
GUCCUAAAGCUUGCAUUCC
5452


 


1331
540
CCGGCUAUUGUAGAAGCUG
CAGCUUCUACAAUAGCCGG
5453


 


1325
541
AAUAAGCCGGCUAUUGUAG
CUACAAUAGCCGGCUUAUU
5454


 


1486
542
UCAGCUUCUGGGUUCAGAU
AUCUGAACCCAGAAGCUGA
5455


 


 454
543
CCUGUAUGAGUGGGAACAG
CUGUUCCCACUCAUACAGG
5456


 


 490
544
CACUCAAGAACAAGUAGCU
AGCUACUUGUUCUUGAGUG
5457


 


1996
545
CCUUCACAUCCUAGCUCGG
CCGAGCUAGGAUGUGAAGG
5458


 


1839
546
AUGCACCUUUGCGUGAGCA
UGCUCACGCAAAGGUGCAU
5459


 


1888
547
UGUUCGUGCACAUCAGGAU
AUCCUGAUGUGCACGAACA
5460


 


1879
548
UCAGUUGCUUGUUCGUGCA
UGCACGAACAAGCAACUGA
5461


 


1829
549
CCCGCAAAUCAUGCACCUU
AAGGUGCAUGAUUUGCGGG
5462


 


 281
550
GCUGAUUUGAUGGAGUUGG
CCAACUCCAUCAAAUCAGC
5463


 


1598
551
AUAGAGGCUCUUGUGCGUA
UACGCACAAGAGCCUCUAU
5464


 


2135
552
CAGGACAAGGAAGCUGCAG
CUGCAGCUUCCUUGUCCUG
5465


 


1755
553
AGCUCUUACACCCACCAUC
GAUGGUGGGUGUAAGAGCU
5466


 


 651
554
CAUCACAGAUGCUGAAACA
UGUUUCAGCAUCUGUGAUG
5467


 


1335
555
CUAUUGUAGAAGCUGGUGG
CCACCAGCUUCUACAAUAG
5468


 


2541
556
AUGCCCAGGACCUCAUGGA
UCCAUGAGGUCCUGGGCAU
5469


 


 531
557
UGACUCGAGCUCAGAGGGU
ACCCUCUGAGCUCGAGUCA
5470


 


 606
558
AGUUUGAUGCUGCUCAUCC
GGAUGAGCAGCAUCAAACU
5471


 


1620
559
UCCUUCGGGCUGGUGACAG
CUGUCACCAGCCCGAAGGA
5472


 


2211
560
AUGAAGGUGUGGCGACAUA
UAUGUCGCCACACCUUCAU
5473


 


2293
561
AGUUGAGCUGACCAGCUCU
AGAGCUGGUCAGCUCAACU
5474


 


 455
562
CUGUAUGAGUGGGAACAGG
CCUGUUCCCACUCAUACAG
5475


 


 540
563
CUCAGAGGGUACGAGCUGC
GCAGCUCGUACCCUCUGAG
5476


 


 416
564
GGCAAUCCUGAGGAAGAGG
CCUCUUCCUCAGGAUUGCC
5477


 


1210
565
CAUACUGGCUAGUGGUGGA
UCCACCACUAGCCAGUAUG
5478


 


2262
566
ACAAGCCACAAGAUUACAA
UUGUAAUCUUGUGGCUUGU
5479


 


1604
567
GCUCUUGUGCGUACUGUCC
GGACAGUACGCACAAGAGC
5480


 


 435
568
AUGUGGAUACCUCCCAAGU
ACUUGGGAGGUAUCCACAU
5481


 


2060
569
UUGUUUGUGCAGCUGCUUU
AAAGCAGCUGCACAAACAA
5482


 


2225
570
ACAUAUGCAGCUGCUGUUU
AAACAGCAGCUGCAUAUGU
5483


 


 481
571
UCAGUCCUUCACUCAAGAA
UUCUUGAGUGAAGGACUGA
5484


 


 917
572
ACCUUGCAUAACCUUUCCC
GGGAAAGGUUAUGCAAGGU
5485


 


2221
573
GGCGACAUAUGCAGCUGCU
AGCAGCUGCAUAUGUCGCC
5486


 


 849
574
UGGUGUCUGCUAUUGUACG
CGUACAAUAGCAGACACCA
5487


 


 562
575
GUUCCCUGAGACAUUAGAU
AUCUAAUGUCUCAGGGAAC
5488


 


1787
576
AUAAAGGCUACUGUUGGAU
AUCCAACAGUAGCCUUUAU
5489


 


1860
577
GUGCCAUUCCACGACUAGU
ACUAGUCGUGGAAUGGCAC
5490


 


1590
578
UGGGUGGUAUAGAGGCUCU
AGAGCCUCUAUACCACCCA
5491


 


 955
579
GGCCAUCUUUAAGUCUGGA
UCCAGACUUAAAGAUGGCC
5492


 


2365
580
UAUUGGUGCCCAGGGAGAA
UUCUCCCUGGGCACCAAUA
5493


 


 534
581
CUCGAGCUCAGAGGGUACG
CGUACCCUCUGAGCUCGAG
5494


 


 706
582
AGAACUUGCCACACGUGCA
UGCACGUGUGGCAAGUUCU
5495


 


1740
583
UACCAGUUGUGGUUAAGCU
AGCUUAACCACAACUGGUA
5496


 


 638
584
CGUUUGGCUGAACCAUCAC
GUGAUGGUUCAGCCAAACG
5497


 


1334
585
GCUAUUGUAGAAGCUGGUG
CACCAGCUUCUACAAUAGC
5498


 


 971
586
GGAGGCAUUCCUGCCCUGG
CCAGGGCAGGAAUGCCUCC
5499


 


2493
587
ACCACCCUGGUGCUGACUA
UAGUCAGCACCAGGGUGGU
5500


 


1814
588
AAUCUUGCCCUUUGUCCCG
CGGGACAAAGGGCAAGAUU
5501


 


1088
589
CGUUUAGCUGGUGGGCUGC
GCAGCCCACCAGCUAAACG
5502


 


2292
590
CAGUUGAGCUGACCAGCUC
GAGCUGGUCAGCUCAACUG
5503


 


1504
591
UGAUAUAAAUGUGGUCACC
GGUGACCACAUUUAUAUCA
5504


 


 404
592
CUGAGUGGUAAAGGCAAUC
GAUUGCCUUUACCACUCAG
5505


 


1301
593
AAGGUGCUAUCUGUCUGCU
AGCAGACAGAUAGCACCUU
5506


 


2004
594
UCCUAGCUCGGGAUGUUCA
UGAACAUCCCGAGCUAGGA
5507


 


 277
595
UCAAGCUGAUUUGAUGGAG
CUCCAUCAAAUCAGCUUGA
5508


 


2304
596
CCAGCUCUCUCUUCAGAAC
GUUCUGAAGAGAGAGCUGG
5509


 


 300
597
ACAUGGCCAUGGAACCAGA
UCUGGUUCCAUGGCCAUGU
5510


 


1906
598
UACCCAGCGCCGUACGUCC
GGACGUACGGCGCUGGGUA
5511


 


1973
599
AUAGUUGAAGGUUGUACCG
CGGUACAACCUUCAACUAU
5512


 


1360
600
AGCUUUAGGACUUCACCUG
CAGGUGAAGUCCUAAAGCU
5513


 


2094
601
ACAUCCAAAGAGUAGCUGC
GCAGCUACUCUUUGGAUGU
5514


 


 920
602
UUGCAUAACCUUUCCCAUC
GAUGGGAAAGGUUAUGCAA
5515


 


1707
603
UGGCCCAGAAUGCAGUUCG
CGAACUGCAUUCUGGGCCA
5516


 


1808
604
AUUCGAAAUCUUGCCCUUU
AAAGGGCAAGAUUUCGAAU
5517


 


1326
605
AUAAGCCGGCUAUUGUAGA
UCUACAAUAGCCGGCUUAU
5518


 


1158
606
CGACAGACUGCCUUCAAAU
AUUUGAAGGCAGUCUGUCG
5519


 


 781
607
UGCAGUUAUGGUCCAUCAG
CUGAUGGACCAUAACUGCA
5520


 


 607
608
GUUUGAUGCUGCUCAUCCC
GGGAUGAGCAGCAUCAAAC
5521


 


 627
609
CUAAUGUCCAGCGUUUGGC
GCCAAACGCUGGACAUUAG
5522


 


 500
610
CAAGUAGCUGAUAUUGAUG
CAUCAAUAUCAGCUACUUG
5523


 


2185
611
UCUGACAGAGUUACUUCAC
GUGAAGUAACUCUGUCAGA
5524


 


1592
612
GGUGGUAUAGAGGCUCUUG
CAAGAGCCUCUAUACCACC
5525


 


 758
613
GACCAGGUGGUGGUUAAUA
UAUUAACCACCACCUGGUC
5526


 


2551
614
CCUCAUGGAUGGGCUGCCU
AGGCAGCCCAUCCAUGAGG
5527


 


1409
615
UGUCUUUGGACUCUCAGGA
UCCUGAGAGUCCAAAGACA
5528


 


 497
616
GAACAAGUAGCUGAUAUUG
CAAUAUCAGCUACUUGUUC
5529


 


 381
617
GUGCCACUACCACAGCUCC
GGAGCUGUGGUAGUGGCAC
5530


 


1841
618
GCACCUUUGCGUGAGCAGG
CCUGCUCACGCAAAGGUGC
5531


 


1368
619
GACUUCACCUGACAGAUCC
GGAUCUGUCAGGUGAAGUC
5532


 


2047
620
AAAUACCAUUCCAUUGUUU
AAACAAUGGAAUGGUAUUU
5533


 


 492
621
CUCAAGAACAAGUAGCUGA
UCAGCUACUUGUUCUUGAG
5534


 


2118
622
UCCUCUGUGAACUUGCUCA
UGAGCAAGUUCACAGAGGA
5535


 


 968
623
UCUGGAGGCAUUCCUGCCC
GGGCAGGAAUGCCUCCAGA
5536


 


 965
624
AAGUCUGGAGGCAUUCCUG
CAGGAAUGCCUCCAGACUU
5537


 


1977
625
UUGAAGGUUGUACCGGAGC
GCUCCGGUACAACCUUCAA
5538


 


2001
626
ACAUCCUAGCUCGGGAUGU
ACAUCCCGAGCUAGGAUGU
5539


 


1191
627
ACCAAGAAAGCAAGCUCAU
AUGAGCUUGCUUUCUUGGU
5540


 


 640
628
UUUGGCUGAACCAUCACAG
CUGUGAUGGUUCAGCCAAA
5541


 


 715
629
CACACGUGCAAUCCCUGAA
UUCAGGGAUUGCACGUGUG
5542


 


1204
630
GCUCAUCAUACUGGCUAGU
ACUAGCCAGUAUGAUGAGC
5543


 


3093
631
GGGUAGGGUAAAUCAGUAA
UUACUGAUUUACCCUACCC
5544


 


1371
632
UUCACCUGACAGAUCCAAG
CUUGGAUCUGUCAGGUGAA
5545


 


 409
633
UGGUAAAGGCAAUCCUGAG
CUCAGGAUUGCCUUUACCA
5546


 


2405
634
GAUCCUAGCUAUCGUUCUU
AAGAACGAUAGCUAGGAUC
5547


 


1671
635
UUCGUCAUCUGACCAGCCG
CGGCUGGUCAGAUGACGAA
5548


 


1427
636
AAUCUUUCAGAUGCUGCAA
UUGCAGCAUCUGAAAGAUU
5549


 


1717
637
UGCAGUUCGCCUUCACUAU
AUAGUGAAGGCGAACUGCA
5550


 


2400
638
AGGAUGAUCCUAGCUAUCG
CGAUAGCUAGGAUCAUCCU
5551


 


2305
639
CAGCUCUCUCUUCAGAACA
UGUUCUGAAGAGAGAGCUG
5552


 


1928
640
GGUGGGACACAGCAGCAAU
AUUGCUGCUGUGUCCCACC
5553


 


2399
641
CAGGAUGAUCCUAGCUAUC
GAUAGCUAGGAUCAUCCUG
5554


 


 426
642
AGGAAGAGGAUGUGGAUAC
GUAUCCACAUCCUCUUCCU
5555


 


1309
643
AUCUGUCUGCUCUAGUAAU
AUUACUAGAGCAGACAGAU
5556


 


 925
644
UAACCUUUCCCAUCAUCGU
ACGAUGAUGGGAAAGGUUA
5557


 


2072
645
CUGCUUUAUUCUCCCAUUG
CAAUGGGAGAAUAAAGCAG
5558


 


2939
646
AAUUGUAAUCUGAAUAAAG
CUUUAUUCAGAUUACAAUU
5559


 


1480
647
UCUUGUUCAGCUUCUGGGU
ACCCAGAAGCUGAACAAGA
5560


 


1889
648
GUUCGUGCACAUCAGGAUA
UAUCCUGAUGUGCACGAAC
5561


 


 699
649
AUGAUGCAGAACUUGCCAC
GUGGCAAGUUCUGCAUCAU
5562


 


 506
650
GCUGAUAUUGAUGGACAGU
ACUGUCCAUCAAUAUCAGC
5563


 


1750
651
GGUUAAGCUCUUACACCCA
UGGGUGUAAGAGCUUAACC
5564


 


1820
652
GCCCUUUGUCCCGCAAAUC
GAUUUGCGGGACAAAGGGC
5565


 


 541
653
UCAGAGGGUACGAGCUGCU
AGCAGCUCGUACCCUCUGA
5566


 


 665
654
AAACAUGCAGUUGUAAACU
AGUUUACAACUGCAUGUUU
5567


 


1817
655
CUUGCCCUUUGUCCCGCAA
UUGCGGGACAAAGGGCAAG
5568


 


2275
656
UUACAAGAAACGGCUUUCA
UGAAAGCCGUUUCUUGUAA
5569


 


2426
657
CACUCUGGUGGAUAUGGCC
GGCCAUAUCCACCAGAGUG
5570


 


 958
658
CAUCUUUAAGUCUGGAGGC
GCCUCCAGACUUAAAGAUG
5571


 


1657
659
UGCCAUCUGUGCUCUUCGU
ACGAAGAGCACAGAUGGCA
5572


 


1146
660
UCUUGGCUAUUACGACAGA
UCUGUCGUAAUAGCCAAGA
5573


 


3078
661
AUUUGGGAUAUGUAUGGGU
ACCCAUACAUAUCCCAAAU
5574


 


1008
662
CAGUGGAUUCUGUGUUGUU
AACAACACAGAAUCCACUG
5575


 


1621
663
CCUUCGGGCUGGUGACAGG
CCUGUCACCAGCCCGAAGG
5576


 


1932
664
GGACACAGCAGCAAUUUGU
ACAAAUUGCUGCUGUGUCC
5577


 


1909
665
CCAGCGCCGUACGUCCAUG
CAUGGACGUACGGCGCUGG
5578


 


2279
666
AAGAAACGGCUUUCAGUUG
CAACUGAAAGCCGUUUCUU
5579


 


 574
667
AUUAGAUGAGGGCAUGCAG
CUGCAUGCCCUCAUCUAAU
5580


 


2303
668
ACCAGCUCUCUCUUCAGAA
UUCUGAAGAGAGAGCUGGU
5581


 


 784
669
AGUUAUGGUCCAUCAGCUU
AAGCUGAUGGACCAUAACU
5582


 


2507
670
GACUAUCCAGUUGAUGGGC
GCCCAUCAACUGGAUAGUC
5583


 


 995
671
AUGCUUGGUUCACCAGUGG
CCACUGGUGAACCAAGCAU
5584


 


2006
672
CUAGCUCGGGAUGUUCACA
UGUGAACAUCCCGAGCUAG
5585


 


1757
673
CUCUUACACCCACCAUCCC
GGGAUGGUGGGUGUAAGAG
5586


 


2129
674
CUUGCUCAGGACAAGGAAG
CUUCCUUGUCCUGAGCAAG
5587


 


2272
675
AGAUUACAAGAAACGGCUU
AAGCCGUUUCUUGUAAUCU
5588


 


 389
676
ACCACAGCUCCUUCUCUGA
UCAGAGAAGGAGCUGUGGU
5589


 


1435
677
AGAUGCUGCAACUAAACAG
CUGUUUAGUUGCAGCAUCU
5590


 


1752
678
UUAAGCUCUUACACCCACC
GGUGGGUGUAAGAGCUUAA
5591


 


 773
679
AAUAAGGCUGCAGUUAUGG
CCAUAACUGCAGCCUUAUU
5592


 


3080
680
UUGGGAUAUGUAUGGGUAG
CUACCCAUACAUAUCCCAA
5593


 


3174
681
GUAACCUGCUGUGAUACGA
UCGUAUCACAGCAGGUUAC
5594


 


1578
682
UGGUCUGCCAAGUGGGUGG
CCACCCACUUGGCAGACCA
5595


 


 398
683
CCUUCUCUGAGUGGUAAAG
CUUUACCACUCAGAGAAGG
5596


 


2153
684
GAAGCUAUUGAAGCUGAGG
CCUCAGCUUCAAUAGCUUC
5597


 


 702
685
AUGCAGAACUUGCCACACG
CGUGUGGCAAGUUCUGCAU
5598


 


 503
686
GUAGCUGAUAUUGAUGGAC
GUCCAUCAAUAUCAGCUAC
5599


 


 276
687
CUCAAGCUGAUUUGAUGGA
UCCAUCAAAUCAGCUUGAG
5600


 


1962
688
GCAUGGAAGAAAUAGUUGA
UCAACUAUUUCUUCCAUGC
5601


 


1347
689
CUGGUGGAAUGCAAGCUUU
AAAGCUUGCAUUCCACCAG
5602


 


2544
690
CCCAGGACCUCAUGGAUGG
CCAUCCAUGAGGUCCUGGG
5603


 


3079
691
UUUGGGAUAUGUAUGGGUA
UACCCAUACAUAUCCCAAA
5604


 


3164
692
CAAAGUUGUUGUAACCUGC
GCAGGUUACAACAACUUUG
5605


 


2026
693
CCGAAUUGUUAUCAGAGGA
UCCUCUGAUAACAAUUCGG
5606


 


2938
694
UAAUUGUAAUCUGAAUAAA
UUUAUUCAGAUUACAAUUA
5607


 


2940
695
AUUGUAAUCUGAAUAAAGU
ACUUUAUUCAGAUUACAAU
5608


 


2027
696
CGAAUUGUUAUCAGAGGAC
GUCCUCUGAUAACAAUUCG
5609


 


 448
697
CCAAGUCCUGUAUGAGUGG
CCACUCAUACAGGACUUGG
5610


 


1328
698
AAGCCGGCUAUUGUAGAAG
CUUCUACAAUAGCCGGCUU
5611


 


2406
699
AUCCUAGCUAUCGUUCUUU
AAAGAACGAUAGCUAGGAU
5612


 


 924
700
AUAACCUUUCCCAUCAUCG
CGAUGAUGGGAAAGGUUAU
5613


 


1584
701
GCCAAGUGGGUGGUAUAGA
UCUAUACCACCCACUUGGC
5614


 


1871
702
CGACUAGUUCAGUUGCUUG
CAAGCAACUGAACUAGUCG
5615


 


 999
703
UUGGUUCACCAGUGGAUUC
GAAUCCACUGGUGAACCAA
5616


 


1400
704
GUUCAGAACUGUCUUUGGA
UCCAAAGACAGUUCUGAAC
5617


 


3180
705
UGCUGUGAUACGAUGCUUC
GAAGCAUCGUAUCACAGCA
5618


 


2569
706
UCCAGGUGACAGCAAUCAG
CUGAUUGCUGUCACCUGGA
5619


 


 787
707
UAUGGUCCAUCAGCUUUCU
AGAAAGCUGAUGGACCAUA
5620


 


1861
708
UGCCAUUCCACGACUAGUU
AACUAGUCGUGGAAUGGCA
5621


 


1190
709
AACCAAGAAAGCAAGCUCA
UGAGCUUGCUUUCUUGGUU
5622


 


1557
710
AUAAUUAUAAGAACAAGAU
AUCUUGUUCUUAUAAUUAU
5623


 


1751
711
GUUAAGCUCUUACACCCAC
GUGGGUGUAAGAGCUUAAC
5624


 


2897
712
UUGAGUAAUGGUGUAGAAC
GUUCUACACCAUUACUCAA
5625


 


2217
713
GUGUGGCGACAUAUGCAGC
GCUGCAUAUGUCGCCACAC
5626


 


2302
714
GACCAGCUCUCUCUUCAGA
UCUGAAGAGAGAGCUGGUC
5627


 


1984
715
UUGUACCGGAGCCCUUCAC
GUGAAGGGCUCCGGUACAA
5628


 


 302
716
AUGGCCAUGGAACCAGACA
UGUCUGGUUCCAUGGCCAU
5629


 


2431
717
UGGUGGAUAUGGCCAGGAU
AUCCUGGCCAUAUCCACCA
5630


 


2183
718
CCUCUGACAGAGUUACUUC
GAAGUAACUCUGUCAGAGG
5631


 


2403
719
AUGAUCCUAGCUAUCGUUC
GAACGAUAGCUAGGAUCAU
5632


 


 788
720
AUGGUCCAUCAGCUUUCUA
UAGAAAGCUGAUGGACCAU
5633


 


1476
721
GGACUCUUGUUCAGCUUCU
AGAAGCUGAACAAGAGUCC
5634


 


 827
722
GCUAUCAUGCGUUCUCCUC
GAGGAGAACGCAUGAUAGC
5635


 


2299
723
GCUGACCAGCUCUCUCUUC
GAAGAGAGAGCUGGUCAGC
5636


 


1891
724
UCGUGCACAUCAGGAUACC
GGUAUCCUGAUGUGCACGA
5637


 


2196
725
UACUUCACUCUAGGAAUGA
UCAUUCCUAGAGUGAAGUA
5638


 


 663
726
UGAAACAUGCAGUUGUAAA
UUUACAACUGCAUGUUUCA
5639


 


1028
727
UAUGCCAUUACAACUCUCC
GGAGAGUUGUAAUGGCAUA
5640


 


2032
728
UGUUAUCAGAGGACUAAAU
AUUUAGUCCUCUGAUAACA
5641


 


1459
729
GAUGGAAGGUCUCCUUGGG
CCCAAGGAGACCUUCCAUC
5642


 


2095
730
CAUCCAAAGAGUAGCUGCA
UGCAGCUACUCUUUGGAUG
5643


 


1686
731
GCCGACACCAAGAAGCAGA
UCUGCUUCUUGGUGUCGGC
5644


 


1412
732
CUUUGGACUCUCAGGAAUC
GAUUCCUGAGAGUCCAAAG
5645


 


2473
733
GGAACAUGAGAUGGGUGGC
GCCACCCAUCUCAUGUUCC
5646


 


1080
734
UGGCAGUGCGUUUAGCUGG
CCAGCUAAACGCACUGCCA
5647


 


2143
735
GGAAGCUGCAGAAGCUAUU
AAUAGCUUCUGCAGCUUCC
5648


 


2203
736
CUCUAGGAAUGAAGGUGUG
CACACCUUCAUUCCUAGAG
5649


 


 548
737
GUACGAGCUGCUAUGUUCC
GGAACAUAGCAGCUCGUAC
5650


 


1867
738
UCCACGACUAGUUCAGUUG
CAACUGAACUAGUCGUGGA
5651


 


 842
739
CCUCAGAUGGUGUCUGCUA
UAGCAGACACCAUCUGAGG
5652


 


2120
740
CUCUGUGAACUUGCUCAGG
CCUGAGCAAGUUCACAGAG
5653


 


 782
741
GCAGUUAUGGUCCAUCAGC
GCUGAUGGACCAUAACUGC
5654


 


1758
742
UCUUACACCCACCAUCCCA
UGGGAUGGUGGGUGUAAGA
5655


 


2396
743
CGCCAGGAUGAUCCUAGCU
AGCUAGGAUCAUCCUGGCG
5656


 


1373
744
CACCUGACAGAUCCAAGUC
GACUUGGAUCUGUCAGGUG
5657


 


1518
745
UCACCUGUGCAGCUGGAAU
AUUCCAGCUGCACAGGUGA
5658


 


2557
746
GGAUGGGCUGCCUCCAGGU
ACCUGGAGGCAGCCCAUCC
5659


 


1987
747
UACCGGAGCCCUUCACAUC
GAUGUGAAGGGCUCCGGUA
5660


 


 568
748
UGAGACAUUAGAUGAGGGC
GCCCUCAUCUAAUGUCUCA
5661


 


2201
749
CACUCUAGGAAUGAAGGUG
CACCUUCAUUCCUAGAGUG
5662


 


 609
750
UUGAUGCUGCUCAUCCCAC
GUGGGAUGAGCAGCAUCAA
5663


 


 400
751
UUCUCUGAGUGGUAAAGGC
GCCUUUACCACUCAGAGAA
5664


 


 331
752
UGUUAGUCACUGGCAGCAA
UUGCUGCCAGUGACUAACA
5665


 


1967
753
GAAGAAAUAGUUGAAGGUU
AACCUUCAACUAUUUCUUC
5666


 


2198
754
CUUCACUCUAGGAAUGAAG
CUUCAUUCCUAGAGUGAAG
5667


 


1493
755
CUGGGUUCAGAUGAUAUAA
UUAUAUCAUCUGAACCCAG
5668


 


2260
756
GGACAAGCCACAAGAUUAC
GUAAUCUUGUGGCUUGUCC
5669


 


2496
757
ACCCUGGUGCUGACUAUCC
GGAUAGUCAGCACCAGGGU
5670


 


2361
758
UUGAUAUUGGUGCCCAGGG
CCCUGGGCACCAAUAUCAA
5671


 


 443
759
ACCUCCCAAGUCCUGUAUG
CAUACAGGACUUGGGAGGU
5672


 


 523
760
GUAUGCAAUGACUCGAGCU
AGCUCGAGUCAUUGCAUAC
5673


 


1742
761
CCAGUUGUGGUUAAGCUCU
AGAGCUUAACCACAACUGG
5674


 


 530
762
AUGACUCGAGCUCAGAGGG
CCCUCUGAGCUCGAGUCAU
5675


 


3169
763
UUGUUGUAACCUGCUGUGA
UCACAGCAGGUUACAACAA
5676


 


1385
764
CCAAGUCAACGUCUUGUUC
GAACAAGACGUUGACUUGG
5677


 


2036
765
AUCAGAGGACUAAAUACCA
UGGUAUUUAGUCCUCUGAU
5678


 


3088
766
UGUAUGGGUAGGGUAAAUC
GAUUUACCCUACCCAUACA
5679


 


1850
767
CGUGAGCAGGGUGCCAUUC
GAAUGGCACCCUGCUCACG
5680


 


2518
768
UGAUGGGCUGCCAGAUCUG
CAGAUCUGGCAGCCCAUCA
5681


 


1886
769
CUUGUUCGUGCACAUCAGG
CCUGAUGUGCACGAACAAG
5682


 


 650
770
CCAUCACAGAUGCUGAAAC
GUUUCAGCAUCUGUGAUGG
5683


 


3139
771
ACAGUUUACCAGUUGCCUU
AAGGCAACUGGUAAACUGU
5684


 


2025
772
ACCGAAUUGUUAUCAGAGG
CCUCUGAUAACAAUUCGGU
5685


 


1082
773
GCAGUGCGUUUAGCUGGUG
CACCAGCUAAACGCACUGC
5686


 


2475
774
AACAUGAGAUGGGUGGCCA
UGGCCACCCAUCUCAUGUU
5687


 


1375
775
CCUGACAGAUCCAAGUCAA
UUGACUUGGAUCUGUCAGG
5688


 


2013
776
GGGAUGUUCACAACCGAAU
AUUCGGUUGUGAACAUCCC
5689


 


1802
777
GGAUUGAUUCGAAAUCUUG
CAAGAUUUCGAAUCAAUCC
5690


 


2144
778
GAAGCUGCAGAAGCUAUUG
CAAUAGCUUCUGCAGCUUC
5691


 


 529
779
AAUGACUCGAGCUCAGAGG
CCUCUGAGCUCGAGUCAUU
5692


 


1482
780
UUGUUCAGCUUCUGGGUUC
GAACCCAGAAGCUGAACAA
5693


 


1546
781
CCUCACUUGCAAUAAUUAU
AUAAUUAUUGCAAGUGAGG
5694


 


 845
782
CAGAUGGUGUCUGCUAUUG
CAAUAGCAGACACCAUCUG
5695


 


 487
783
CUUCACUCAAGAACAAGUA
UACUUGUUCUUGAGUGAAG
5696


 


 652
784
AUCACAGAUGCUGAAACAU
AUGUUUCAGCAUCUGUGAU
5697


 


1720
785
AGUUCGCCUUCACUAUGGA
UCCAUAGUGAAGGCGAACU
5698


 


 951
786
UACUGGCCAUCUUUAAGUC
GACUUAAAGAUGGCCAGUA
5699


 


1232
787
CAAGCUUUAGUAAAUAUAA
UUAUAUUUACUAAAGCUUG
5700


 


2265
788
AGCCACAAGAUUACAAGAA
UUCUUGUAAUCUUGUGGCU
5701


 


1698
789
AAGCAGAGAUGGCCCAGAA
UUCUGGGCCAUCUCUGCUU
5702


 


 701
790
GAUGCAGAACUUGCCACAC
GUGUGGCAAGUUCUGCAUC
5703


 


1428
791
AUCUUUCAGAUGCUGCAAC
GUUGCAGCAUCUGAAAGAU
5704


 


1930
792
UGGGACACAGCAGCAAUUU
AAAUUGCUGCUGUGUCCCA
5705


 


1379
793
ACAGAUCCAAGUCAACGUC
GACGUUGACUUGGAUCUGU
5706


 


1936
794
ACAGCAGCAAUUUGUGGAG
CUCCACAAAUUGCUGCUGU
5707


 


1441
795
UGCAACUAAACAGGAAGGG
CCCUUCCUGUUUAGUUGCA
5708


 


2132
796
GCUCAGGACAAGGAAGCUG
CAGCUUCCUUGUCCUGAGC
5709


 


2043
797
GACUAAAUACCAUUCCAUU
AAUGGAAUGGUAUUUAGUC
5710


 


 608
798
UUUGAUGCUGCUCAUCCCA
UGGGAUGAGCAGCAUCAAA
5711


 


 341
799
UGGCAGCAACAGUCUUACC
GGUAAGACUGUUGCUGCCA
5712


 


1194
800
AAGAAAGCAAGCUCAUCAU
AUGAUGAGCUUGCUUUCUU
5713


 


2350
801
UGAUCUUGGACUUGAUAUU
AAUAUCAAGUCCAAGAUCA
5714


 


2948
802
CUGAAUAAAGUGUAACAAU
AUUGUUACACUUUAUUCAG
5715


 


2044
803
ACUAAAUACCAUUCCAUUG
CAAUGGAAUGGUAUUUAGU
5716


 


 621
804
AUCCCACUAAUGUCCAGCG
CGCUGGACAUUAGUGGGAU
5717


 


 384
805
CCACUACCACAGCUCCUUC
GAAGGAGCUGUGGUAGUGG
5718


 


1898
806
CAUCAGGAUACCCAGCGCC
GGCGCUGGGUAUCCUGAUG
5719


 


 653
807
UCACAGAUGCUGAAACAUG
CAUGUUUCAGCAUCUGUGA
5720


 


1846
808
UUUGCGUGAGCAGGGUGCC
GGCACCCUGCUCACGCAAA
5721


 


2348
809
GCUGAUCUUGGACUUGAUA
UAUCAAGUCCAAGAUCAGC
5722


 


1150
810
GGCUAUUACGACAGACUGC
GCAGUCUGUCGUAAUAGCC
5723


 


 298
811
GGACAUGGCCAUGGAACCA
UGGUUCCAUGGCCAUGUCC
5724


 


1568
812
AACAAGAUGAUGGUCUGCC
GGCAGACCAUCAUCUUGUU
5725


 


1058
813
UUACAUCAAGAAGGAGCUA
UAGCUCCUUCUUGAUGUAA
5726


 


1835
814
AAUCAUGCACCUUUGCGUG
CACGCAAAGGUGCAUGAUU
5727


 


1832
815
GCAAAUCAUGCACCUUUGC
GCAAAGGUGCAUGAUUUGC
5728


 


 406
816
GAGUGGUAAAGGCAAUCCU
AGGAUUGCCUUUACCACUC
5729


 


1723
817
UCGCCUUCACUAUGGACUA
UAGUCCAUAGUGAAGGCGA
5730


 


 371
818
AUCCAUUCUGGUGCCACUA
UAGUGGCACCAGAAUGGAU
5731


 


1899
819
AUCAGGAUACCCAGCGCCG
CGGCGCUGGGUAUCCUGAU
5732


 


 522
820
AGUAUGCAAUGACUCGAGC
GCUCGAGUCAUUGCAUACU
5733


 


2285
821
CGGCUUUCAGUUGAGCUGA
UCAGCUCAACUGAAAGCCG
5734


 


 779
822
GCUGCAGUUAUGGUCCAUC
GAUGGACCAUAACUGCAGC
5735


 


2896
823
AUUGAGUAAUGGUGUAGAA
UUCUACACCAUUACUCAAU
5736


 


2943
824
GUAAUCUGAAUAAAGUGUA
UACACUUUAUUCAGAUUAC
5737


 


 513
825
UUGAUGGACAGUAUGCAAU
AUUGCAUACUGUCCAUCAA
5738


 


3084
826
GAUAUGUAUGGGUAGGGUA
UACCCUACCCAUACAUAUC
5739


 


1567
827
GAACAAGAUGAUGGUCUGC
GCAGACCAUCAUCUUGUUC
5740


 


2034
828
UUAUCAGAGGACUAAAUAC
GUAUUUAGUCCUCUGAUAA
5741


 


1003
829
UUCACCAGUGGAUUCUGUG
CACAGAAUCCACUGGUGAA
5742


 


1980
830
AAGGUUGUACCGGAGCCCU
AGGGCUCCGGUACAACCUU
5743


 


1340
831
GUAGAAGCUGGUGGAAUGC
GCAUUCCACCAGCUUCUAC
5744


 


1437
832
AUGCUGCAACUAAACAGGA
UCCUGUUUAGUUGCAGCAU
5745


 


2425
833
UCACUCUGGUGGAUAUGGC
GCCAUAUCCACCAGAGUGA
5746


 


 282
834
CUGAUUUGAUGGAGUUGGA
UCCAACUCCAUCAAAUCAG
5747


 


1206
835
UCAUCAUACUGGCUAGUGG
CCACUAGCCAGUAUGAUGA
5748


 


1885
836
GCUUGUUCGUGCACAUCAG
CUGAUGUGCACGAACAAGC
5749


 


1314
837
UCUGCUCUAGUAAUAAGCC
GGCUUAUUACUAGAGCAGA
5750


 


1308
838
UAUCUGUCUGCUCUAGUAA
UUACUAGAGCAGACAGAUA
5751


 


1200
839
GCAAGCUCAUCAUACUGGC
GCCAGUAUGAUGAGCUUGC
5752


 


 543
840
AGAGGGUACGAGCUGCUAU
AUAGCAGCUCGUACCCUCU
5753


 


1609
841
UGUGCGUACUGUCCUUCGG
CCGAAGGACAGUACGCACA
5754


 


1453
842
GGAAGGGAUGGAAGGUCUC
GAGACCUUCCAUCCCUUCC
5755


 


 833
843
AUGCGUUCUCCUCAGAUGG
CCAUCUGAGGAGAACGCAU
5756


 


2188
844
GACAGAGUUACUUCACUCU
AGAGUGAAGUAACUCUGUC
5757


 


1148
845
UUGGCUAUUACGACAGACU
AGUCUGUCGUAAUAGCCAA
5758


 


1736
846
GGACUACCAGUUGUGGUUA
UAACCACAACUGGUAGUCC
5759


 


1401
847
UUCAGAACUGUCUUUGGAC
GUCCAAAGACAGUUCUGAA
5760


 


1677
848
AUCUGACCAGCCGACACCA
UGGUGUCGGCUGGUCAGAU
5761


 


1934
849
ACACAGCAGCAAUUUGUGG
CCACAAAUUGCUGCUGUGU
5762


 


 388
850
UACCACAGCUCCUUCUCUG
CAGAGAAGGAGCUGUGGUA
5763


 


1920
851
CGUCCAUGGGUGGGACACA
UGUGUCCCACCCAUGGACG
5764


 


1747
852
UGUGGUUAAGCUCUUACAC
GUGUAAGAGCUUAACCACA
5765


 


 861
853
UUGUACGUACCAUGCAGAA
UUCUGCAUGGUACGUACAA
5766


 


1904
854
GAUACCCAGCGCCGUACGU
ACGUACGGCGCUGGGUAUC
5767


 


 831
855
UCAUGCGUUCUCCUCAGAU
AUCUGAGGAGAACGCAUGA
5768


 


1895
856
GCACAUCAGGAUACCCAGC
GCUGGGUAUCCUGAUGUGC
5769


 


2273
857
GAUUACAAGAAACGGCUUU
AAAGCCGUUUCUUGUAAUC
5770


 


1738
858
ACUACCAGUUGUGGUUAAG
CUUAACCACAACUGGUAGU
5771


 


1395
859
GUCUUGUUCAGAACUGUCU
AGACAGUUCUGAACAAGAC
5772


 


1675
860
UCAUCUGACCAGCCGACAC
GUGUCGGCUGGUCAGAUGA
5773


 


1845
861
CUUUGCGUGAGCAGGGUGC
GCACCCUGCUCACGCAAAG
5774


 


1408
862
CUGUCUUUGGACUCUCAGG
CCUGAGAGUCCAAAGACAG
5775


 


1059
863
UACAUCAAGAAGGAGCUAA
UUAGCUCCUUCUUGAUGUA
5776


 


1381
864
AGAUCCAAGUCAACGUCUU
AAGACGUUGACUUGGAUCU
5777


 


1386
865
CAAGUCAACGUCUUGUUCA
UGAACAAGACGUUGACUUG
5778


 


1470
866
UCCUUGGGACUCUUGUUCA
UGAACAAGAGUCCCAAGGA
5779


 


1349
867
GGUGGAAUGCAAGCUUUAG
CUAAAGCUUGCAUUCCACC
5780


 


1440
868
CUGCAACUAAACAGGAAGG
CCUUCCUGUUUAGUUGCAG
5781


 


1364
869
UUAGGACUUCACCUGACAG
CUGUCAGGUGAAGUCCUAA
5782


 


 502
870
AGUAGCUGAUAUUGAUGGA
UCCAUCAAUAUCAGCUACU
5783


 


1246
871
UAUAAUGAGGACCUAUACU
AGUAUAGGUCCUCAUUAUA
5784


 


3178
872
CCUGCUGUGAUACGAUGCU
AGCAUCGUAUCACAGCAGG
5785


 


2483
873
AUGGGUGGCCACCACCCUG
CAGGGUGGUGGCCACCCAU
5786


 


1417
874
GACUCUCAGGAAUCUUUCA
UGAAAGAUUCCUGAGAGUC
5787


 


1893
875
GUGCACAUCAGGAUACCCA
UGGGUAUCCUGAUGUGCAC
5788


 


 817
876
UUCCAGACACGCUAUCAUG
CAUGAUAGCGUGUCUGGAA
5789


 


 711
877
UUGCCACACGUGCAAUCCC
GGGAUUGCACGUGUGGCAA
5790


 


1433
878
UCAGAUGCUGCAACUAAAC
GUUUAGUUGCAGCAUCUGA
5791


 


1362
879
CUUUAGGACUUCACCUGAC
GUCAGGUGAAGUCCUAAAG
5792


 


1838
880
CAUGCACCUUUGCGUGAGC
GCUCACGCAAAGGUGCAUG
5793


 


1037
881
ACAACUCUCCACAACCUUU
AAAGGUUGUGGAGAGUUGU
5794


 


1474
882
UGGGACUCUUGUUCAGCUU
AAGCUGAACAAGAGUCCCA
5795


 


 997
883
GCUUGGUUCACCAGUGGAU
AUCCACUGGUGAACCAAGC
5796


 


 931
884
UUCCCAUCAUCGUGAGGGC
GCCCUCACGAUGAUGGGAA
5797


 


1313
885
GUCUGCUCUAGUAAUAAGC
GCUUAUUACUAGAGCAGAC
5798


 


1487
886
CAGCUUCUGGGUUCAGAUG
CAUCUGAACCCAGAAGCUG
5799


 


1673
887
CGUCAUCUGACCAGCCGAC
GUCGGCUGGUCAGAUGACG
5800


 


 561
888
UGUUCCCUGAGACAUUAGA
UCUAAUGUCUCAGGGAACA
5801


 


1188
889
GCAACCAAGAAAGCAAGCU
AGCUUGCUUUCUUGGUUGC
5802


 


 292
890
GGAGUUGGACAUGGCCAUG
CAUGGCCAUGUCCAACUCC
5803


 


1958
891
GUCCGCAUGGAAGAAAUAG
CUAUUUCUUCCAUGCGGAC
5804


 


2349
892
CUGAUCUUGGACUUGAUAU
AUAUCAAGUCCAAGAUCAG
5805


 


1460
893
AUGGAAGGUCUCCUUGGGA
UCCCAAGGAGACCUUCCAU
5806


 


1576
894
GAUGGUCUGCCAAGUGGGU
ACCCACUUGGCAGACCAUC
5807


 


 690
895
ACUAUCAAGAUGAUGCAGA
UCUGCAUCAUCUUGAUAGU
5808


 


 655
896
ACAGAUGCUGAAACAUGCA
UGCAUGUUUCAGCAUCUGU
5809


 


2290
897
UUCAGUUGAGCUGACCAGC
GCUGGUCAGCUCAACUGAA
5810


 


1600
898
AGAGGCUCUUGUGCGUACU
AGUACGCACAAGAGCCUCU
5811


 


2432
899
GGUGGAUAUGGCCAGGAUG
CAUCCUGGCCAUAUCCACC
5812


 


 710
900
CUUGCCACACGUGCAAUCC
GGAUUGCACGUGUGGCAAG
5813


 


1714
901
GAAUGCAGUUCGCCUUCAC
GUGAAGGCGAACUGCAUUC
5814


 


2005
902
CCUAGCUCGGGAUGUUCAC
GUGAACAUCCCGAGCUAGG
5815


 


1728
903
UUCACUAUGGACUACCAGU
ACUGGUAGUCCAUAGUGAA
5816


 


2482
904
GAUGGGUGGCCACCACCCU
AGGGUGGUGGCCACCCAUC
5817


 


 768
905
UGGUUAAUAAGGCUGCAGU
ACUGCAGCCUUAUUAACCA
5818


 


 693
906
AUCAAGAUGAUGCAGAACU
AGUUCUGCAUCAUCUUGAU
5819


 


3179
907
CUGCUGUGAUACGAUGCUU
AAGCAUCGUAUCACAGCAG
5820


 


2448
908
AUGCCUUGGGUAUGGACCC
GGGUCCAUACCCAAGGCAU
5821


 


3183
909
UGUGAUACGAUGCUUCAAG
CUUGAAGCAUCGUAUCACA
5822


 


1293
910
GAGUGCUGAAGGUGCUAUC
GAUAGCACCUUCAGCACUC
5823


 


 544
911
GAGGGUACGAGCUGCUAUG
CAUAGCAGCUCGUACCCUC
5824


 


2937
912
UUAAUUGUAAUCUGAAUAA
UUAUUCAGAUUACAAUUAA
5825


 


1691
913
CACCAAGAAGCAGAGAUGG
CCAUCUCUGCUUCUUGGUG
5826


 


1353
914
GAAUGCAAGCUUUAGGACU
AGUCCUAAAGCUUGCAUUC
5827


 


1843
915
ACCUUUGCGUGAGCAGGGU
ACCCUGCUCACGCAAAGGU
5828


 


1302
916
AGGUGCUAUCUGUCUGCUC
GAGCAGACAGAUAGCACCU
5829


 


2130
917
UUGCUCAGGACAAGGAAGC
GCUUCCUUGUCCUGAGCAA
5830


 


2165
918
GCUGAGGGAGCCACAGCUC
GAGCUGUGGCUCCCUCAGC
5831


 


 387
919
CUACCACAGCUCCUUCUCU
AGAGAAGGAGCUGUGGUAG
5832


 


2472
920
UGGAACAUGAGAUGGGUGG
CCACCCAUCUCAUGUUCCA
5833


 


 857
921
GCUAUUGUACGUACCAUGC
GCAUGGUACGUACAAUAGC
5834


 


1816
922
UCUUGCCCUUUGUCCCGCA
UGCGGGACAAAGGGCAAGA
5835


 


1561
923
UUAUAAGAACAAGAUGAUG
CAUCAUCUUGUUCUUAUAA
5836


 


 811
924
GGAAGCUUCCAGACACGCU
AGCGUGUCUGGAAGCUUCC
5837


 


1327
925
UAAGCCGGCUAUUGUAGAA
UUCUACAAUAGCCGGCUUA
5838


 


 757
926
GGACCAGGUGGUGGUUAAU
AUUAACCACCACCUGGUCC
5839


 


 507
927
CUGAUAUUGAUGGACAGUA
UACUGUCCAUCAAUAUCAG
5840


 


3092
928
UGGGUAGGGUAAAUCAGUA
UACUGAUUUACCCUACCCA
5841


 


2359
929
ACUUGAUAUUGGUGCCCAG
CUGGGCACCAAUAUCAAGU
5842


 


1753
930
UAAGCUCUUACACCCACCA
UGGUGGGUGUAAGAGCUUA
5843


 


 273
931
CUACUCAAGCUGAUUUGAU
AUCAAAUCAGCUUGAGUAG
5844


 


1859
932
GGUGCCAUUCCACGACUAG
CUAGUCGUGGAAUGGCACC
5845


 


 296
933
UUGGACAUGGCCAUGGAAC
GUUCCAUGGCCAUGUCCAA
5846


 


 615
934
CUGCUCAUCCCACUAAUGU
ACAUUAGUGGGAUGAGCAG
5847


 


 301
935
CAUGGCCAUGGAACCAGAC
GUCUGGUUCCAUGGCCAUG
5848


 


1184
936
UAUGGCAACCAAGAAAGCA
UGCUUUCUUGGUUGCCAUA
5849


 


1006
937
ACCAGUGGAUUCUGUGUUG
CAACACAGAAUCCACUGGU
5850


 


2189
938
ACAGAGUUACUUCACUCUA
UAGAGUGAAGUAACUCUGU
5851


 


1365
939
UAGGACUUCACCUGACAGA
UCUGUCAGGUGAAGUCCUA
5852


 


2442
940
GCCAGGAUGCCUUGGGUAU
AUACCCAAGGCAUCCUGGC
5853


 


1249
941
AAUGAGGACCUAUACUUAC
GUAAGUAUAGGUCCUCAUU
5854


 


1144
942
AUUCUUGGCUAUUACGACA
UGUCGUAAUAGCCAAGAAU
5855


 


2075
943
CUUUAUUCUCCCAUUGAAA
UUUCAAUGGGAGAAUAAAG
5856


 


 504
944
UAGCUGAUAUUGAUGGACA
UGUCCAUCAAUAUCAGCUA
5857


 


1405
945
GAACUGUCUUUGGACUCUC
GAGAGUCCAAAGACAGUUC
5858


 


 333
946
UUAGUCACUGGCAGCAACA
UGUUGCUGCCAGUGACUAA
5859


 


1032
947
CCAUUACAACUCUCCACAA
UUGUGGAGAGUUGUAAUGG
5860


 


1748
948
GUGGUUAAGCUCUUACACC
GGUGUAAGAGCUUAACCAC
5861


 


 283
949
UGAUUUGAUGGAGUUGGAC
GUCCAACUCCAUCAAAUCA
5862


 


1700
950
GCAGAGAUGGCCCAGAAUG
CAUUCUGGGCCAUCUCUGC
5863


 


1445
951
ACUAAACAGGAAGGGAUGG
CCAUCCCUUCCUGUUUAGU
5864


 


1133
952
ACAAAUGUUAAAUUCUUGG
CCAAGAAUUUAACAUUUGU
5865


 


 527
953
GCAAUGACUCGAGCUCAGA
UCUGAGCUCGAGUCAUUGC
5866


 


2010
954
CUCGGGAUGUUCACAACCG
CGGUUGUGAACAUCCCGAG
5867


 


 851
955
GUGUCUGCUAUUGUACGUA
UACGUACAAUAGCAGACAC
5868


 


 436
956
UGUGGAUACCUCCCAAGUC
GACUUGGGAGGUAUCCACA
5869


 


2446
957
GGAUGCCUUGGGUAUGGAC
GUCCAUACCCAAGGCAUCC
5870


 


1142
958
AAAUUCUUGGCUAUUACGA
UCGUAAUAGCCAAGAAUUU
5871


 


 549
959
UACGAGCUGCUAUGUUCCC
GGGAACAUAGCAGCUCGUA
5872


 


1083
960
CAGUGCGUUUAGCUGGUGG
CCACCAGCUAAACGCACUG
5873


 


 695
961
CAAGAUGAUGCAGAACUUG
CAAGUUCUGCAUCAUCUUG
5874


 


 885
962
AUGAUGUAGAAACAGCUCG
CGAGCUGUUUCUACAUCAU
5875


 


2067
963
UGCAGCUGCUUUAUUCUCC
GGAGAAUAAAGCAGCUGCA
5876


 


 390
964
CCACAGCUCCUUCUCUGAG
CUCAGAGAAGGAGCUGUGG
5877


 


1719
965
CAGUUCGCCUUCACUAUGG
CCAUAGUGAAGGCGAACUG
5878


 


 813
966
AAGCUUCCAGACACGCUAU
AUAGCGUGUCUGGAAGCUU
5879


 


2289
967
UUUCAGUUGAGCUGACCAG
CUGGUCAGCUCAACUGAAA
5880


 


 377
968
UCUGGUGCCACUACCACAG
CUGUGGUAGUGGCACCAGA
5881


 


 826
969
CGCUAUCAUGCGUUCUCCU
AGGAGAACGCAUGAUAGCG
5882


 


1634
970
GACAGGGAAGACAUCACUG
CAGUGAUGUCUUCCCUGUC
5883


 


1208
971
AUCAUACUGGCUAGUGGUG
CACCACUAGCCAGUAUGAU
5884


 


1628
972
GCUGGUGACAGGGAAGACA
UGUCUUCCCUGUCACCAGC
5885


 


2003
973
AUCCUAGCUCGGGAUGUUC
GAACAUCCCGAGCUAGGAU
5886


 


 452
974
GUCCUGUAUGAGUGGGAAC
GUUCCCACUCAUACAGGAC
5887


 


3081
975
UGGGAUAUGUAUGGGUAGG
CCUACCCAUACAUAUCCCA
5888


 


2354
976
CUUGGACUUGAUAUUGGUG
CACCAAUAUCAAGUCCAAG
5889


 


1822
977
CCUUUGUCCCGCAAAUCAU
AUGAUUUGCGGGACAAAGG
5890


 


1299
978
UGAAGGUGCUAUCUGUCUG
CAGACAGAUAGCACCUUCA
5891


 


 486
979
CCUUCACUCAAGAACAAGU
ACUUGUUCUUGAGUGAAGG
5892


 


1463
980
GAAGGUCUCCUUGGGACUC
GAGUCCCAAGGAGACCUUC
5893


 


2280
981
AGAAACGGCUUUCAGUUGA
UCAACUGAAAGCCGUUUCU
5894


 


1907
982
ACCCAGCGCCGUACGUCCA
UGGACGUACGGCGCUGGGU
5895


 


 923
983
CAUAACCUUUCCCAUCAUC
GAUGAUGGGAAAGGUUAUG
5896


 


1979
984
GAAGGUUGUACCGGAGCCC
GGGCUCCGGUACAACCUUC
5897


 


1827
985
GUCCCGCAAAUCAUGCACC
GGUGCAUGAUUUGCGGGAC
5898


 


1201
986
CAAGCUCAUCAUACUGGCU
AGCCAGUAUGAUGAGCUUG
5899


 


1913
987
CGCCGUACGUCCAUGGGUG
CACCCAUGGACGUACGGCG
5900


 


2191
988
AGAGUUACUUCACUCUAGG
CCUAGAGUGAAGUAACUCU
5901


 


 295
989
GUUGGACAUGGCCAUGGAA
UUCCAUGGCCAUGUCCAAC
5902


 


1149
990
UGGCUAUUACGACAGACUG
CAGUCUGUCGUAAUAGCCA
5903


 


 533
991
ACUCGAGCUCAGAGGGUAC
GUACCCUCUGAGCUCGAGU
5904


 


 604
992
ACAGUUUGAUGCUGCUCAU
AUGAGCAGCAUCAAACUGU
5905


 


 766
993
GGUGGUUAAUAAGGCUGCA
UGCAGCCUUAUUAACCACC
5906


 


1823
994
CUUUGUCCCGCAAAUCAUG
CAUGAUUUGCGGGACAAAG
5907


 


2048
995
AAUACCAUUCCAUUGUUUG
CAAACAAUGGAAUGGUAUU
5908


 


 714
996
CCACACGUGCAAUCCCUGA
UCAGGGAUUGCACGUGUGG
5909


 


2439
997
AUGGCCAGGAUGCCUUGGG
CCCAAGGCAUCCUGGCCAU
5910


 


1903
998
GGAUACCCAGCGCCGUACG
CGUACGGCGCUGGGUAUCC
5911


 


2395
999
UCGCCAGGAUGAUCCUAGC
GCUAGGAUCAUCCUGGCGA
5912


 


 789
1000 
UGGUCCAUCAGCUUUCUAA
UUAGAAAGCUGAUGGACCA
5913


 


3085
1001 
AUAUGUAUGGGUAGGGUAA
UUACCCUACCCAUACAUAU
5914


 


1710
1002 
CCCAGAAUGCAGUUCGCCU
AGGCGAACUGCAUUCUGGG
5915


 


1336
1003 
UAUUGUAGAAGCUGGUGGA
UCCACCAGCUUCUACAAUA
5916


 


3089
1004 
GUAUGGGUAGGGUAAAUCA
UGAUUUACCCUACCCAUAC
5917


 


2351
1005 
GAUCUUGGACUUGAUAUUG
CAAUAUCAAGUCCAAGUAC
5918


 


 716
1006 
ACACGUGCAAUCCCUGAAC
GUUCAGGGAUUGCACGUGU
5919


 


1911
1007 
AGCGCCGUACGUCCAUGGG
CCCAUGGACGUACGGCGCU
5920


 


1985
1008 
UGUACCGGAGCCCUUCACA
UGUGAAGGGCUCCGGUACA
5921


 


2516
1009 
GUUGAUGGGCUGCCAGAUC
GAUCUGGCAGCCCAUCAAC
5922


 


1762
1010 
ACACCCACCAUCCCACUGG
CCAGUGGGAUGGUGGGUGU
5923


 


1156
1011 
UACGACAGACUGCCUUCAA
UUGAAGGCAGUCUGUCGUA
5924


 


1887
1012 
UUGUUCGUGCACAUCAGGA
UCCUGAUGUGCACGAACAA
5925


 


1833
1013 
CAAAUCAUGCACCUUUGCG
CGCAAAGGUGCAUGAUUUG
5926


 


 967
1014 
GUCUGGAGGCAUUCCUGCC
GGCAGGAAUGCCUCCAGAC
5927


 


1730
1015 
CACUAUGGACUACCAGUUG
CAACUGGUAGUCCAUAGUG
5928


 


 829
1016 
UAUCAUGCGUUCUCCUCAG
CUGAGGAGAACGCAUGAUA
5929


 


 890
1017 
GUAGAAACAGCUCGUUGUA
UACAACGAGCUGUUUCUAC
5930


 


2181
1018 
CUCCUCUGACAGAGUUACU
AGUAACUCUGUCAGAGGAG
5931


 


2131
1019 
UGCUCAGGACAAGGAAGCU
AGCUUCCUUGUCCUGAGCA
5932


 


1586
1020 
CAAGUGGGUGGUAUAGAGG
CCUCUAUACCACCCACUUG
5933


 


 765
1021 
UGGUGGUUAAUAAGGCUGC
GCAGCCUUAUUAACCACCA
5934


 


1369
1022 
ACUUCACCUGACAGAUCCA
UGGAUCUGUCAGGUGAAGU
5935


 


1724
1023 
CGCCUUCACUAUGGACUAC
GUAGUCCAUAGUGAAGGCG
5936


 


 834
1024 
UGCGUUCUCCUCAGAUGGU
ACCAUCUGAGGAGAACGCA
5937


 


1983
1025 
GUUGUACCGGAGCCCUUCA
UGAAGGGCUCCGGUACAAC
5938


 


1688
1026 
CGACACCAAGAAGCAGAGA
UCUCUGCUUCUUGGUGUCG
5939


 


1004
1027 
UCACCAGUGGAUUCUGUGU
ACACAGAAUCCACUGGUGA
5940


 


1631
1028 
GGUGACAGGGAAGACAUCA
UGAUGUCUUCCCUGUCACC
5941


 


1319
1029 
UCUAGUAAUAAGCCGGCUA
UAGCCGGCUUAUUACUAGA
5942


 


 767
1030 
GUGGUUAAUAAGGCUGCAG
CUGCAGCCUUAUUAACCAC
5943


 


 841
1031 
UCCUCAGAUGGUGUCUGCU
AGCAGACACCAUCUGAGGA
5944


 


 516
1032 
AUGGACAGUAUGCAAUGAC
GUCAUUGCAUACUGUCCAU
5945


 


1848
1033 
UGCGUGAGCAGGGUGCCAU
AUGGCACCCUGCUCACGCA
5946


 


2202
1034 
ACUCUAGGAAUGAAGGUGU
ACACCUUCAUUCCUAGAGU
5947


 


 571
1035 
GACAUUAGAUGAGGGCAUG
CAUGCCCUCAUCUAAUGUC
5948


 


1629
1036 
CUGGUGACAGGGAAGACAU
AUGUCUUCCCUGUCACCAG
5949


 


1806
1037 
UGAUUCGAAAUCUUGCCCU
AGGGCAAGAUUUCGAAUCA
5950


 


1756
1038 
GCUCUUACACCCACCAUCC
GGAUGGUGGGUGUAAGAGC
5951


 


1619
1039 
GUCCUUCGGGCUGGUGACA
UGUCACCAGCCCGAAGGAC
5952


 


1610
1040 
GUGCGUACUGUCCUUCGGG
CCCGAAGGACAGUACGCAC
5953


 


2500
1041 
UGGUGCUGACUAUCCAGUU
AACUGGAUAGUCAGCACCA
5954


 


2156
1042 
GCUAUUGAAGCUGAGGGAG
CUCCCUCAGCUUCAAUAGC
5955


 


1189
1043 
CAACCAAGAAAGCAAGCUC
GAGCUUGCUUUCUUGGUUG
5956


 


2066
1044 
GUGCAGCUGCUUUAUUCUC
GAGAAUAAAGCAGCUGCAC
5957


 


1307
1045 
CUAUCUGUCUGCUCUAGUA
UACUAGAGCAGACAGAUAG
5958


 


1448
1046 
AAACAGGAAGGGAUGGAAG
CUUCCAUCCCUUCCUGUUU
5959


 


1213
1047 
ACUGGCUAGUGGUGGACCC
GGGUCCACCACUAGCCAGU
5960


 


2119
1048 
CCUCUGUGAACUUGCUCAG
CUGAGCAAGUUCACAGAGG
5961


 


 889
1049 
UGUAGAAACAGCUCGUUGU
ACAACGAGCUGUUUCUACA
5962


 


1376
1050 
CUGACAGAUCCAAGUCAAC
GUUGACUUGGAUCUGUCAG
5963


 


 427
1051 
GGAAGAGGAUGUGGAUACC
GGUAUCCACAUCCUCUUCC
5964


 


 649
1052 
ACCAUCACAGAUGCUGAAA
UUUCAGCAUCUGUGAUGGU
5965


 


1915
1053 
CCGUACGUCCAUGGGUGGG
CCCACCCAUGGACGUACGG
5966


 


2053
1054 
CAUUCCAUUGUUUGUGCAG
CUGCACAAACAAUGGAAUG
5967


 


2568
1055 
CUCCAGGUGACAGCAAUCA
UGAUUGCUGUCACCUGGAG
5968


 


1739
1056 
CUACCAGUUGUGGUUAAGC
GCUUAACCACAACUGGUAG
5969


 


1746
1057 
UUGUGGUUAAGCUCUUACA
UGUAAGAGCUUAACCACAA
5970


 


1321
1058 
UAGUAAUAAGCCGGCUAUU
AAUAGCCGGCUUAUUACUA
5971


 


 482
1059 
CAGUCCUUCACUCAAGAAC
GUUCUUGAGUGAAGGACUG
5972


 


 280
1060 
AGCUGAUUUGAUGGAGUUG
CAACUCCAUCAAAUCAGCU
5973


 


1465
1061 
AGGUCUCCUUGGGACUCUU
AAGAGUCCCAAGGAGACCU
5974


 


1731
1062 
ACUAUGGACUACCAGUUGU
ACAACUGGUAGUCCAUAGU
5975


 


1937
1063 
CAGCAGCAAUUUGUGGAGG
CCUCCACAAAUUGCUGCUG
5976


 


1892
1064 
CGUGCACAUCAGGAUACCC
GGGUAUCCUGAUGUGCACG
5977


 


 836
1065 
CGUUCUCCUCAGAUGGUGU
ACACCAUCUGAGGAGAACG
5978


 


 521
1066 
CAGUAUGCAAUGACUCGAG
CUCGAGUCAUUGCAUACUG
5979


 


1595
1067 
GGUAUAGAGGCUCUUGUGC
GCACAAGAGCCUCUAUACC
5980


 


2511
1068 
AUCCAGUUGAUGGGCUGCC
GGCAGCCCAUCAACUGGAU
5981


 


1583
1069 
UGCCAAGUGGGUGGUAUAG
CUAUACCACCCACUUGGCA
5982


 


1897
1070 
ACAUCAGGAUACCCAGCGC
GCGCUGGGUAUCCUGAUGU
5983


 


 956
1071 
GCCAUCUUUAAGUCUGGAG
CUCCAGACUUAAAGAUGGC
5984


 


 926
1072 
AACCUUUCCCAUCAUCGUG
CACGAUGAUGGGAAAGGUU
5985


 


1874
1073 
CUAGUUCAGUUGCUUGUUC
GAACAAGCAACUGAACUAG
5986


 


 488
1074 
UUCACUCAAGAACAAGUAG
CUACUUGUUCUUGAGUGAA
5987


 


1695
1075 
AAGAAGCAGAGAUGGCCCA
UGGGCCAUCUCUGCUUCUU
5988


 


2182
1076 
UCCUCUGACAGAGUUACUU
AAGUAACUCUGUCAGAGGA
5989


 


2029
1077 
AAUUGUUAUCAGAGGACUA
UAGUCCUCUGAUAACAAUU
5990


 


 479
1078 
UCUCAGUCCUUCACUCAAG
CUUGAGUGAAGGACUGAGA
5991


 


 818
1079 
UCCAGACACGCUAUCAUGC
GCAUGAUAGCGUGUCUGGA
5992


 


 625
1080 
CACUAAUGUCCAGCGUUUG
CAAACGCUGGACAUUAGUG
5993


 


3172
1081 
UUGUAACCUGCUGUGAUAC
GUAUCACAGCAGGUUACAA
5994


 


1490
1082 
CUUCUGGGUUCAGAUGAUA
UAUCAUCUGAACCCAGAAG
5995


 


1914
1083 
GCCGUACGUCCAUGGGUGG
CCACCCAUGGACGUACGGC
5996


 


1974
1084 
UAGUUGAAGGUUGUACCGG
CCGGUACAACCUUCAACUA
5997


 


2258
1085 
GAGGACAAGCCACAAGAUU
AAUCUUGUGGCUUGUCCUC
5998


 


2170
1086 
GGGAGCCACAGCUCCUCUG
CAGAGGAGCUGUGGCUCCC
5999


 


1370
1087 
CUUCACCUGACAGAUCCAA
UUGGAUCUGUCAGGUGAAG
6000


 


1429
1088 
UCUUUCAGAUGCUGCAACU
AGUUGCAGCAUCUGAAAGA
6001


 


3173
1089 
UGUAACCUGCUGUGAUACG
CGUAUCACAGCAGGUUACA
6002


 


 444
1090 
CCUCCCAAGUCCUGUAUGA
UCAUACAGGACUUGGGAGG
6003


 


1081
1091 
GGCAGUGCGUUUAGCUGGU
ACCAGCUAAACGCACUGCC
6004


 


1318
1092 
CUCUAGUAAUAAGCCGGCU
AGCCGGCUUAUUACUAGAG
6005


 


 329
1093 
GCUGUUAGUCACUGGCAGC
GCUGCCAGUGACUAACAGC
6006


 


1389
1094 
GUCAACGUCUUGUUCAGAA
UUCUGAACAAGACGUUGAC
6007


 


 428
1095 
GAAGAGGAUGUGGAUACCU
AGGUAUCCACAUCCUCUUC
6008


 


3175
1096 
UAACCUGCUGUGAUACGAU
AUCGUAUCACAGCAGGUUA
6009


 


3117
1097 
GUUAUUUGGAACCUUGUUU
AAACAAGGUUCCAAAUAAC
6010


 


2020
1098 
UCACAACCGAAUUGUUAUC
GAUAACAAUUCGGUUGUGA
6011


 


1625
1099 
CGGGCUGGUGACAGGGAAG
CUUCCCUGUCACCAGCCCG
6012


 


2022
1100 
ACAACCGAAUUGUUAUCAG
CUGAUAACAAUUCGGUUGU
6013


 


 624
1101 
CCACUAAUGUCCAGCGUUU
AAACGCUGGACAUUAGUGG
6014


 


1648
1102 
CACUGAGCCUGCCAUCUGU
ACAGAUGGCAGGCUCAGUG
6015


 


 790
1103 
GGUCCAUCAGCUUUCUAAA
UUUAGAAAGCUGAUGGACC
6016


 


3160
1104 
AUCCCAAAGUUGUUGUAAC
GUUACAACAACUUUGGGAU
6017


 


1251
1105 
UGAGGACCUAUACUUACGA
UCGUAAGUAUAGGUCCUCA
6018


 


2253
1106 
UGUCUGAGGACAAGCCACA
UGUGGCUUGUCCUCAGACA
6019


 


2515
1107 
AGUUGAUGGGCUGCCAGAU
AUCUGGCAGCCCAUCAACU
6020


 


1680
1108 
UGACCAGCCGACACCAAGA
UCUUGGUGUCGGCUGGUCA
6021


 


2169
1109 
AGGGAGCCACAGCUCCUCU
AGAGGAGCUGUGGCUCCCU
6022


 


3165
1110 
AAAGUUGUUGUAACCUGCU
AGCAGGUUACAACAACUUU
6023


 


 780
1111 
CUGCAGUUAUGGUCCAUCA
UGAUGGACCAUAACUGCAG
6024


 


1978
1112 
UGAAGGUUGUACCGGAGCC
GGCUCCGGUACAACCUUCA
6025


 


 563
1113 
UUCCCUGAGACAUUAGAUG
CAUCUAAUGUCUCAGGGAA
6026


 


1622
1114 
CUUCGGGCUGGUGACAGGG
CCCUGUCACCAGCCCGAAG
6027


 


2295
1115 
UUGAGCUGACCAGCUCUCU
AGAGAGCUGGUCAGCUCAA
6028


 


2126
1116 
GAACUUGCUCAGGACAAGG
CCUUGUCCUGAGCAAGUUC
6029


 


1683
1117 
CCAGCCGACACCAAGAAGC
GCUUCUUGGUGUCGGCUGG
6030


 


1857
1118 
AGGGUGCCAUUCCACGACU
AGUCGUGGAAUGGCACCCU
6031


 


2064
1119 
UUGUGCAGCUGCUUUAUUC
GAAUAAAGCAGCUGCACAA
6032


 


 489
1120 
UCACUCAAGAACAAGUAGC
GCUACUUGUUCUUGAGUGA
6033


 


1346
1121 
GCUGGUGGAAUGCAAGCUU
AAGCUUGCAUUCCACCAGC
6034


 


1442
1122 
GCAACUAAACAGGAAGGGA
UCCCUUCCUGUUUAGUUGC
6035


 


1981
1123 
AGGUUGUACCGGAGCCCUU
AAGGGCUCCGGUACAACCU
6036


 


 777
1124 
AGGCUGCAGUUAUGGUCCA
UGGACCAUAACUGCAGCCU
6037


 


 589
1125 
GCAGAUCCCAUCUACACAG
CUGUGUAGAUGGGAUCUGC
6038


 


2205
1126 
CUAGGAAUGAAGGUGUGGC
GCCACACCUUCAUUCCUAG
6039


 


 394
1127 
AGCUCCUUCUCUGAGUGGU
ACCACUCAGAGAAGGAGCU
6040


 


1035
1128 
UUACAACUCUCCACAACCU
AGGUUGUGGAGAGUUGUAA
6041


 


 410
1129 
GGUAAAGGCAAUCCUGAGG
CCUCAGGAUUGCCUUUACC
6042


 


1721
1130 
GUUCGCCUUCACUAUGGAC
GUCCAUAGUGAAGGCGAAC
6043


 


1134
1131 
CAAAUGUUAAAUUCUUGGC
GCCAAGAAUUUAACAUUUG
6044


 


3182
1132 
CUGUGAUACGAUGCUUCAA
UUGAAGCAUCGUAUCACAG
6045


 


 881
1133 
ACAAAUGAUGUAGAAACAG
CUGUUUCUACAUCAUUUGU
6046


 


 547
1134 
GGUACGAGCUGCUAUGUUC
GAACAUAGCAGCUCGUACC
6047


 


2028
1135 
GAAUUGUUAUCAGAGGACU
AGUCCUCUGAUAACAAUUC
6048


 


2023
1136 
CAACCGAAUUGUUAUCAGA
UCUGAUAACAAUUCGGUUG
6049


 


3184
1137 
GUGAUACGAUGCUUCAAGA
UCUUGAAGCAUCGUAUCAC
6050


 


 413
1138 
AAAGGCAAUCCUGAGGAAG
CUUCCUCAGGAUUGCCUUU
6051


 


2178
1139 
CAGCUCCUCUGACAGAGUU
AACUCUGUCAGAGGAGCUG
6052


 


1577
1140 
AUGGUCUGCCAAGUGGGUG
CACCCACUUGGCAGACCAU
6053


 


1793
1141 
GCUACUGUUGGAUUGAUUC
GAAUCAAUCCAACAGUAGC
6054


 


 526
1142 
UGCAAUGACUCGAGCUCAG
CUGAGCUCGAGUCAUUGCA
6055


 


2358
1143 
GACUUGAUAUUGGUGCCCA
UGGGCACCAAUAUCAAGUC
6056


 


1403
1144 
CAGAACUGUCUUUGGACUC
GAGUCCAAAGACAGUUCUG
6057


 


1875
1145 
UAGUUCAGUUGCUUGUUCG
CGAACAAGCAACUGAACUA
6058


 


1160
1146 
ACAGACUGCCUUCAAAUUU
AAAUUUGAAGGCAGUCUGU
6059


 


1591
1147 
GGGUGGUAUAGAGGCUCUU
AAGAGCCUCUAUACCACCC
6060


 


1734
1148 
AUGGACUACCAGUUGUGGU
ACCACAACUGGUAGUCCAU
6061


 


2030
1149 
AUUGUUAUCAGAGGACUAA
UUAGUCCUCUGAUAACAAU
6062


 


 775
1150 
UAAGGCUGCAGUUAUGGUC
GACCAUAACUGCAGCCUUA
6063


 


1813
1151 
AAAUCUUGCCCUUUGUCCC
GGGACAAAGGGCAAGAUUU
6064


 


1938
1152 
AGCAGCAAUUUGUGGAGGG
CCCUCCACAAAUUGCUGCU
6065


 


2039
1153 
AGAGGACUAAAUACCAUUC
GAAUGGUAUUUAGUCCUCU
6066


 


1297
1154 
GCUGAAGGUGCUAUCUGUC
GACAGAUAGCACCUUCAGC
6067


 


 456
1155 
UGUAUGAGUGGGAACAGGG
CCCUGUUCCCACUCAUACA
6068


 


 590
1156 
CAGAUCCCAUCUACACAGU
ACUGUGUAGAUGGGAUCUG
6069


 


1933
1157 
GACACAGCAGCAAUUUGUG
CACAAAUUGCUGCUGUGUC
6070


 


 583
1158 
GGGCAUGCAGAUCCCAUCU
AGAUGGGAUCUGCAUGCCC
6071


 


2540
1159 
CAUGCCCAGGACCUCAUGG
CCAUGAGGUCCUGGGCAUG
6072


 


2162
1160 
GAAGCUGAGGGAGCCACAG
CUGUGGCUCCCUCAGCUUC
6073


 


 330
1161 
CUGUUAGUCACUGGCAGCA
UGCUGCCAGUGACUAACAG
6074


 


1481
1162 
CUUGUUCAGCUUCUGGGUU
AACCCAGAAGCUGAACAAG
6075


 


1344
1163 
AAGCUGGUGGAAUGCAAGC
GCUUGCAUUCCACCAGCUU
6076


 


 431
1164 
GAGGAUGUGGAUACCUCCC
GGGAGGUAUCCACAUCCUC
6077


 


1508
1165 
AUAAAUGUGGUCACCUGUG
CACAGGUGACCACAUUUAU
6078


 


1918
1166 
UACGUCCAUGGGUGGGACA
UGUCCCACCCAUGGACGUA
6079


 


 289
1167 
GAUGGAGUUGGACAUGGCC
GGCCAUGUCCAACUCCAUC
6080


 


 631
1168 
UGUCCAGCGUUUGGCUGAA
UUCAGCCAAACGCUGGACA
6081


 


1853
1169 
GAGCAGGGUGCCAUUCCAC
GUGGAAUGGCACCCUGCUC
6082


 


1243
1170 
AAAUAUAAUGAGGACCUAU
AUAGGUCCUCAUUAUAUUU
6083


 


1212
1171 
UACUGGCUAGUGGUGGACC
GGUCCACCACUAGCCAGUA
6084


 


 996
1172 
UGCUUGGUUCACCAGUGGA
UCCACUGGUGAACCAAGCA
6085


 


2256
1173 
CUGAGGACAAGCCACAAGA
UCUUGUGGCUUGUCCUCAG
6086


 


1607
1174 
CUUGUGCGUACUGUCCUUC
GAAGGACAGUACGCACAAG
6087


 


3116
1175 
UGUUAUUUGGAACCUUGUU
AACAAGGUUCCAAAUAACA
6088


 


1179
1176 
UAGCUUAUGGCAACCAAGA
UCUUGGUUGCCAUAAGCUA
6089


 


3185
1177 
UGAUACGAUGCUUCAAGAG
CUCUUGAAGCAUCGUAUCA
6090


 


1594
1178 
UGGUAUAGAGGCUCUUGUG
CACAAGAGCCUCUAUACCA
6091


 


 887
1179 
GAUGUAGAAACAGCUCGUU
AACGAGCUGUUUCUACAUC
6092


 


 928
1180 
CCUUUCCCAUCAUCGUGAG
CUCACGAUGAUGGGAAAGG
6093


 


 835
1181 
GCGUUCUCCUCAGAUGGUG
CACCAUCUGAGGAGAACGC
6094


 


1900
1182 
UCAGGAUACCCAGCGCCGU
ACGGCGCUGGGUAUCCUGA
6095


 


2284
1183 
ACGGCUUUCAGUUGAGCUG
CAGCUCAACUGAAAGCCGU
6096


 


1976
1184 
GUUGAAGGUUGUACCGGAG
CUCCGGUACAACCUUCAAC
6097


 


2393
1185 
UAUCGCCAGGAUGAUCCUA
UAGGAUCAUCCUGGCGAUA
6098


 


1295
1186 
GUGCUGAAGGUGCUAUCUG
CAGAUAGCACCUUCAGCAC
6099


 


1410
1187 
GUCUUUGGACUCUCAGGAA
UUCCUGAGAGUCCAAAGAC
6100


 


1457
1188 
GGGAUGGAAGGUCUCCUUG
CAAGGAGACCUUCCAUCCC
6101


 


2296
1189 
UGAGCUGACCAGCUCUCUC
GAGAGAGCUGGUCAGCUCA
6102


 


 929
1190 
CUUUCCCAUCAUCGUGAGG
CCUCACGAUGAUGGGAAAG
6103


 


1359
1191 
AAGCUUUAGGACUUCACCU
AGGUGAAGUCCUAAAGCUU
6104


 


1351
1192 
UGGAAUGCAAGCUUUAGGA
UCCUAAAGCUUGCAUUCCA
6105


 


 969
1193 
CUGGAGGCAUUCCUGCCCU
AGGGCAGGAAUGCCUCCAG
6106


 


1876
1194 
AGUUCAGUUGCUUGUUCGU
ACGAACAAGCAACUGAACU
6107


 


 552
1195 
GAGCUGCUAUGUUCCCUGA
UCAGGGAACAUAGCAGCUC
6108


 


2441
1196 
GGCCAGGAUGCCUUGGGUA
UACCCAAGGCAUCCUGGCC
6109


 


2402
1197 
GAUGAUCCUAGCUAUCGUU
AACGAUAGCUAGGAUCAUC
6110


 


1803
1198 
GAUUGAUUCGAAAUCUUGC
GCAAGAUUUCGAAUCAAUC
6111


 


1701
1199 
CAGAGAUGGCCCAGAAUGC
GCAUUCUGGGCCAUCUCUG
6112


 


1910
1200 
CAGCGCCGUACGUCCAUGG
CCAUGGACGUACGGCGCUG
6113


 


 888
1201 
AUGUAGAAACAGCUCGUUG
CAACGAGCUGUUUCUACAU
6114


 


1294
1202 
AGUGCUGAAGGUGCUAUCU
AGAUAGCACCUUCAGCACU
6115


 


1737
1203 
GACUACCAGUUGUGGUUAA
UUAACCACAACUGGUAGUC
6116


 


1450
1204 
ACAGGAAGGGAUGGAAGGU
ACCUUCCAUCCCUUCCUGU
6117


 


 761
1205 
CAGGUGGUGGUUAAUAAGG
CCUUAUUAACCACCACCUG
6118


 


 776
1206 
AAGGCUGCAGUUAUGGUCC
GGACCAUAACUGCAGCCUU
6119


 


1509
1207 
UAAAUGUGGUCACCUGUGC
GCACAGGUGACCACAUUUA
6120


 


1788
1208 
UAAAGGCUACUGUUGGAUU
AAUCCAACAGUAGCCUUUA
6121


 


 515
1209 
GAUGGACAGUAUGCAAUGA
UCAUUGCAUACUGUCCAUC
6122


 


1491
1210 
UUCUGGGUUCAGAUGAUAU
AUAUCAUCUGAACCCAGAA
6123


 


1614
1211 
GUACUGUCCUUCGGGCUGG
CCAGCCCGAAGGACAGUAC
6124


 


 998
1212 
CUUGGUUCACCAGUGGAUU
AAUCCACUGGUGAACCAAG
6125


 


2158
1213 
UAUUGAAGCUGAGGGAGCC
GGCUCCCUCAGCUUCAAUA
6126


 


3168
1214 
GUUGUUGUAACCUGCUGUG
CACAGCAGGUUACAACAAC
6127


 


1854
1215 
AGCAGGGUGCCAUUCCACG
CGUGGAAUGGCACCCUGCU
6128


 


2117
1216 
GUCCUCUGUGAACUUGCUC
GAGCAAGUUCACAGAGGAC
6129


 


1678
1217 
UCUGACCAGCCGACACCAA
UUGGUGUCGGCUGGUCAGA
6130


 


 305
1218 
GCCAUGGAACCAGACAGAA
UUCUGUCUGGUUCCAUGGC
6131


 


2154
1219 
AAGCUAUUGAAGCUGAGGG
CCCUCAGCUUCAAUAGCUU
6132


 


1807
1220 
GAUUCGAAAUCUUGCCCUU
AAGGGCAAGAUUUCGAAUC
6133


 


1881
1221 
AGUUGCUUGUUCGUGCACA
UGUGCACGAACAAGCAACU
6134


 


1565
1222 
AAGAACAAGAUGAUGGUCU
AGACCAUCAUCUUGUUCUU
6135


 


 407
1223 
AGUGGUAAAGGCAAUCCUG
CAGGAUUGCCUUUACCACU
6136


 


1434
1224 
CAGAUGCUGCAACUAAACA
UGUUUAGUUGCAGCAUCUG
6137


 


 566
1225 
CCUGAGACAUUAGAUGAGG
CCUCAUCUAAUGUCUCAGG
6138


 


3161
1226 
UCCCAAAGUUGUUGUAACC
GGUUACAACAACUUUGGGA
6139


 


1679
1227 
CUGACCAGCCGACACCAAG
CUUGGUGUCGGCUGGUCAG
6140


 


2096
1228 
AUCCAAAGAGUAGCUGCAG
CUGCAGCUACUCUUUGGAU
6141


 


 630
1229 
AUGUCCAGCGUUUGGCUGA
UCAGCCAAACGCUGGACAU
6142


 


1606
1230 
UCUUGUGCGUACUGUCCUU
AAGGACAGUACGCACAAGA
6143


 


 432
1231 
AGGAUGUGGAUACCUCCCA
UGGGAGGUAUCCACAUCCU
6144


 


 778
1232 
GGCUGCAGUUAUGGUCCAU
AUGGACCAUAACUGCAGCC
6145


 


1999
1233 
UCACAUCCUAGCUCGGGAU
AUCCCGAGCUAGGAUGUGA
6146


 


1692
1234 
ACCAAGAAGCAGAGAUGGC
GCCAUCUCUGCUUCUUGGU
6147


 


2490
1235 
GCCACCACCCUGGUGCUGA
UCAGCACCAGGGUGGUGGC
6148


 


 623
1236 
CCCACUAAUGUCCAGCGUU
AACGCUGGACAUUAGUGGG
6149


 


 339
1237 
ACUGGCAGCAACAGUCUUA
UAAGACUGUUGCUGCCAGU
6150


 


2946
1238 
AUCUGAAUAAAGUGUAACA
UGUUACACUUUAUUCAGAU
6151


 


1654
1239 
GCCUGCCAUCUGUGCUCUU
AAGAGCACAGAUGGCAGGC
6152


 


1033
1240 
CAUUACAACUCUCCACAAC
GUUGUGGAGAGUUGUAAUG
6153


 


 840
1241 
CUCCUCAGAUGGUGUCUGC
GCAGACACCAUCUGAGGAG
6154


 


1880
1242 
CAGUUGCUUGUUCGUGCAC
GUGCACGAACAAGCAACUG
6155


 


 420
1243 
AUCCUGAGGAAGAGGAUGU
ACAUCCUCUUCCUCAGGAU
6156


 


1005
1244 
CACCAGUGGAUUCUGUGUU
AACACAGAAUCCACUGGUG
6157


 


1193
1245 
CAAGAAAGCAAGCUCAUCA
UGAUGAGCUUGCUUUCUUG
6158


 


 919
1246 
CUUGCAUAACCUUUCCCAU
AUGGGAAAGGUUAUGCAAG
6159


 


1727
1247 
CUUCACUAUGGACUACCAG
CUGGUAGUCCAUAGUGAAG
6160


 


1883
1248 
UUGCUUGUUCGUGCACAUC
GAUGUGCACGAACAAGCAA
6161


 


 859
1249 
UAUUGUACGUACCAUGCAG
CUGCAUGGUACGUACAAUA
6162


 


1812
1250 
GAAAUCUUGCCCUUUGUCC
GGACAAAGGGCAAGAUUUC
6163


 


1605
1251 
CUCUUGUGCGUACUGUCCU
AGGACAGUACGCACAAGAG
6164


 


2021
1252 
CACAACCGAAUUGUUAUCA
UGAUAACAAUUCGGUUGUG
6165


 


2180
1253 
GCUCCUCUGACAGAGUUAC
GUAACUCUGUCAGAGGAGC
6166


 


 636
1254 
AGCGUUUGGCUGAACCAUC
GAUGGUUCAGCCAAACGCU
6167


 


2282
1255 
AAACGGCUUUCAGUUGAGC
GCUCAACUGAAAGCCGUUU
6168


 


1824
1256 
UUUGUCCCGCAAAUCAUGC
GCAUGAUUUGCGGGACAAA
6169


 


2204
1257 
UCUAGGAAUGAAGGUGUGG
CCACACCUUCAUUCCUAGA
6170


 


 450
1258 
AAGUCCUGUAUGAGUGGGA
UCCCACUCAUACAGGACUU
6171


 


1001
1259 
GGUUCACCAGUGGAUUCUG
CAGAAUCCACUGGUGAACC
6172


 


1579
1260 
GGUCUGCCAAGUGGGUGGU
ACCACCCACUUGGCAGACC
6173


 


2179
1261 
AGCUCCUCUGACAGAGUUA
UAACUCUGUCAGAGGAGCU
6174


 


 376
1262 
UUCUGGUGCCACUACCACA
UGUGGUAGUGGCACCAGAA
6175


 


 556
1263 
UGCUAUGUUCCCUGAGACA
UGUCUCAGGGAACAUAGCA
6176


 


1804
1264 
AUUGAUUCGAAAUCUUGCC
GGCAAGAUUUCGAAUCAAU
6177


 


2552
1265 
CUCAUGGAUGGGCUGCCUC
GAGGCAGCCCAUCCAUGAG
6178


 


2071
1266 
GCUGCUUUAUUCUCCCAUU
AAUGGGAGAAUAAAGCAGC
6179


 


1836
1267 
AUCAUGCACCUUUGCGUGA
UCACGCAAAGGUGCAUGAU
6180


 


 336
1268 
GUCACUGGCAGCAACAGUC
GACUGUUGCUGCCAGUGAC
6181


 


 460
1269 
UGAGUGGGAACAGGGAUUU
AAAUCCCUGUUCCCACUCA
6182


 


1559
1270 
AAUUAUAAGAACAAGAUGA
UCAUCUUGUUCUUAUAAUU
6183


 


3136
1271 
UGGACAGUUUACCAGUUGC
GCAACUGGUAAACUGUCCA
6184


 


1250
1272 
AUGAGGACCUAUACUUACG
CGUAAGUAUAGGUCCUCAU
6185


 


1462
1273 
GGAAGGUCUCCUUGGGACU
AGUCCCAAGGAGACCUUCC
6186


 


1965
1274 
UGGAAGAAAUAGUUGAAGG
CCUUCAACUAUUUCUUCCA
6187


 


3114
1275 
GGUGUUAUUUGGAACCUUG
CAAGGUUCCAAAUAACACC
6188


 


1665
1276 
GUGCUCUUCGUCAUCUGAC
GUCAGAUGACGAAGAGCAC
6189


 


 304
1277 
GGCCAUGGAACCAGACAGA
UCUGUCUGGUUCCAUGGCC
6190


 


 327
1278 
CGGCUGUUAGUCACUGGCA
UGCCAGUGACUAACAGCCG
6191


 


1866
1279 
UUCCACGACUAGUUCAGUU
AACUGAACUAGUCGUGGAA
6192


 


1699
1280 
AGCAGAGAUGGCCCAGAAU
AUUCUGGGCCAUCUCUGCU
6193


 


2397
1281 
GCCAGGAUGAUCCUAGCUA
UAGCUAGGAUCAUCCUGGC
6194


 


1658
1282 
GCCAUCUGUGCUCUUCGUC
GACGAAGAGCACAGAUGGC
6195


 


 891
1283 
UAGAAACAGCUCGUUGUAC
GUACAACGAGCUGUUUCUA
6196


 


1572
1284 
AGAUGAUGGUCUGCCAAGU
ACUUGGCAGACCAUCAUCU
6197


 


 927
1285 
ACCUUUCCCAUCAUCGUGA
UCACGAUGAUGGGAAAGGU
6198


 


 290
1286 
AUGGAGUUGGACAUGGCCA
UGGCCAUGUCCAACUCCAU
6199


 


1663
1287 
CUGUGCUCUUCGUCAUCUG
CAGAUGACGAAGAGCACAG
6200


 


1562
1288 
UAUAAGAACAAGAUGAUGG
CCAUCAUCUUGUUCUUAUA
6201


 


2947
1289 
UCUGAAUAAAGUGUAACAA
UUGUUACACUUUAUUCAGA
6202


 


1711
1290 
CCAGAAUGCAGUUCGCCUU
AAGGCGAACUGCAUUCUGG
6203


 


1566
1291 
AGAACAAGAUGAUGGUCUG
CAGACCAUCAUCUUGUUCU
6204


 


1815
1292 
AUCUUGCCCUUUGUCCCGC
GCGGGACAAAGGGCAAGAU
6205


 


1087
1293 
GCGUUUAGCUGGUGGGCUG
CAGCCCACCAGCUAAACGC
6206


 


1495
1294 
GGGUUCAGAUGAUAUAAAU
AUUUAUAUCAUCUGAACCC
6207


 


1363
1295 
UUUAGGACUUCACCUGACA
UGUCAGGUGAAGUCCUAAA
6208


 


 391
1296 
CACAGCUCCUUCUCUGAGU
ACUCAGAGAAGGAGCUGUG
6209


 


1392
1297 
AACGUCUUGUUCAGAACUG
CAGUUCUGAACAAGACGUU
6210


 


1935
1298 
CACAGCAGCAAUUUGUGGA
UCCACAAAUUGCUGCUGUG
6211


 


1872
1299 
GACUAGUUCAGUUGCUUGU
ACAAGCAACUGAACUAGUC
6212


 


1159
1300 
GACAGACUGCCUUCAAAUU
AAUUUGAAGGCAGUCUGUC
6213


 


2308
1301 
CUCUCUCUUCAGAACAGAG
CUCUGUUCUGAAGAGAGAG
6214


 


 632
1302 
GUCCAGCGUUUGGCUGAAC
GUUCAGCCAAACGCUGGAC
6215


 


1564
1303 
UAAGAACAAGAUGAUGGUC
GACCAUCAUCUUGUUCUUA
6216


 


1384
1304 
UCCAAGUCAACGUCUUGUU
AACAAGACGUUGACUUGGA
6217


 


1690
1305 
ACACCAAGAAGCAGAGAUG
CAUCUCUGCUUCUUGGUGU
6218


 


1421
1306 
CUCAGGAAUCUUUCAGAUG
CAUCUGAAAGAUUCCUGAG
6219


 


1141
1307 
UAAAUUCUUGGCUAUUACG
CGUAAUAGCCAAGAAUUUA
6220


 


1732
1308 
CUAUGGACUACCAGUUGUG
CACAACUGGUAGUCCAUAG
6221


 


 634
1309 
CCAGCGUUUGGCUGAACCA
UGGUUCAGCCAAACGCUGG
6222


 


 932
1310 
UCCCAUCAUCGUGAGGGCU
AGCCCUCACGAUGAUGGGA
6223


 


1366
1311 
AGGACUUCACCUGACAGAU
AUCUGUCAGGUGAAGUCCU
6224


 


1608
1312 
UUGUGCGUACUGUCCUUCG
CGAAGGACAGUACGCACAA
6225


 


1923
1313 
CCAUGGGUGGGACACAGCA
UGCUGUGUCCCACCCAUGG
6226


 


1458
1314 
GGAUGGAAGGUCUCCUUGG
CCAAGGAGACCUUCCAUCC
6227


 


1908
1315 
CCCAGCGCCGUACGUCCAU
AUGGACGUACGGCGCUGGG
6228


 


 539
1316 
GCUCAGAGGGUACGAGCUG
CAGCUCGUACCCUCUGAGC
6229


 


2016
1317 
AUGUUCACAACCGAAUUGU
ACAAUUCGGUUGUGAACAU
6230


 


1884
1318 
UGCUUGUUCGUGCACAUCA
UGAUGUGCACGAACAAGCA
6231


 


 560
1319 
AUGUUCCCUGAGACAUUAG
CUAAUGUCUCAGGGAACAU
6232


 


 411
1320 
GUAAAGGCAAUCCUGAGGA
UCCUCAGGAUUGCCUUUAC
6233


 


 338
1321 
CACUGGCAGCAACAGUCUU
AAGACUGUUGCUGCCAGUG
6234


 


 830
1322 
AUCAUGCGUUCUCCUCAGA
UCUGAGGAGAACGCAUGAU
6235


 


3086
1323 
UAUGUAUGGGUAGGGUAAA
UUUACCCUACCCAUACAUA
6236


 


3115
1324 
GUGUUAUUUGGAACCUUGU
ACAAGGUUCCAAAUAACAC
6237


 


2177
1325 
ACAGCUCCUCUGACAGAGU
ACUCUGUCAGAGGAGCUGU
6238


 


1733
1326 
UAUGGACUACCAGUUGUGG
CCACAACUGGUAGUCCAUA
6239


 


 375
1327 
AUUCUGGUGCCACUACCAC
GUGGUAGUGGCACCAGAAU
6240


 


2565
1328 
UGCCUCCAGGUGACAGCAA
UUGCUGUCACCUGGAGGCA
6241


 


 442
1329 
UACCUCCCAAGUCCUGUAU
AUACAGGACUUGGGAGGUA
6242


 


 819
1330 
CCAGACACGCUAUCAUGCG
CGCAUGAUAGCGUGUCUGG
6243


 


 700
1331 
UGAUGCAGAACUUGCCACA
UGUGGCAAGUUCUGCAUCA
6244


 


1089
1332 
GUUUAGCUGGUGGGCUGCA
UGCAGCCCACCAGCUAAAC
6245


 


1580
1333 
GUCUGCCAAGUGGGUGGUA
UACCACCCACUUGGCAGAC
6246


 


1982
1334 
GGUUGUACCGGAGCCCUUC
GAAGGGCUCCGGUACAACC
6247


 


1986
1335 
GUACCGGAGCCCUUCACAU
AUGUGAAGGGCUCCGGUAC
6248


 


 418
1336 
CAAUCCUGAGGAAGAGGAU
AUCCUCUUCCUCAGGAUUG
6249


 


1306
1337 
GCUAUCUGUCUGCUCUAGU
ACUAGAGCAGACAGAUAGC
6250


 


1377
1338 
UGACAGAUCCAAGUCAACG
CGUUGACUUGGAUCUGUCA
6251


 


2467
1339 
CAUGAUGGAACAUGAGAUG
CAUCUCAUGUUCCAUCAUG
6252


 


1414
1340 
UUGGACUCUCAGGAAUCUU
AAGAUUCCUGAGAGUCCAA
6253


 


1668
1341 
CUCUUCGUCAUCUGACCAG
CUGGUCAGAUGACGAAGAG
6254


 


1818
1342 
UUGCCCUUUGUCCCGCAAA
UUUGCGGGACAAAGGGCAA
6255


 


1697
1343 
GAAGCAGAGAUGGCCCAGA
UCUGGGCCAUCUCUGCUUC
6256


 


 918
1344 
CCUUGCAUAACCUUUCCCA
UGGGAAAGGUUAUGCAAGG
6257


 


 605
1345 
CAGUUUGAUGCUGCUCAUC
GAUGAGCAGCAUCAAACUG
6258


 


1374
1346 
ACCUGACAGAUCCAAGUCA
UGACUUGGAUCUGUCAGGU
6259


 


1430
1347 
CUUUCAGAUGCUGCAACUA
UAGUUGCAGCAUCUGAAAG
6260


 


3186
1348 
GAUACGAUGCUUCAAGAGA
UCUCUUGAAGCAUCGUAUC
6261


 


1355
1349 
AUGCAAGCUUUAGGACUUC
GAAGUCCUAAAGCUUGCAU
6262


 


 433
1350 
GGAUGUGGAUACCUCCCAA
UUGGGAGGUAUCCACAUCC
6263


 


1713
1351 
AGAAUGCAGUUCGCCUUCA
UGAAGGCGAACUGCAUUCU
6264


 


1811
1352 
CGAAAUCUUGCCCUUUGUC
GACAAAGGGCAAGAUUUCG
6265


 


 491
1353 
ACUCAAGAACAAGUAGCUG
CAGCUACUUGUUCUUGAGU
6266


 


2209
1354 
GAAUGAAGGUGUGGCGACA
UGUCGCCACACCUUCAUUC
6267


 


1840
1355 
UGCACCUUUGCGUGAGCAG
CUGCUCACGCAAAGGUGCA
6268


 


 550
1356 
ACGAGCUGCUAUGUUCCCU
AGGGAACAUAGCAGCUCGU
6269


 


 429
1357 
AAGAGGAUGUGGAUACCUC
GAGGUAUCCACAUCCUCUU
6270


 


2436
1358 
GAUAUGGCCAGGAUGCCUU
AAGGCAUCCUGGCCAUAUC
6271


 


1597
1359 
UAUAGAGGCUCUUGUGCGU
ACGCACAAGAGCCUCUAUA
6272


 


1496
1360 
GGUUCAGAUGAUAUAAAUG
CAUUUAUAUCAUCUGAACC
6273


 


1456
1361 
AGGGAUGGAAGGUCUCCUU
AAGGAGACCUUCCAUCCCU
6274


 


3159
1362 
UAUCCCAAAGUUGUUGUAA
UUACAACAACUUUGGGAUA
6275


 


2309
1363 
UCUCUCUUCAGAACAGAGC
GCUCUGUUCUGAAGAGAGA
6276


 


2300
1364 
CUGACCAGCUCUCUCUUCA
UGAAGAGAGAGCUGGUCAG
6277


 


3177
1365 
ACCUGCUGUGAUACGAUGC
GCAUCGUAUCACAGCAGGU
6278


 


1079
1366 
AUGGCAGUGCGUUUAGCUG
CAGCUAAACGCACUGCCAU
6279


 


1383
1367 
AUCCAAGUCAACGUCUUGU
ACAAGACGUUGACUUGGAU
6280


 


2563
1368 
GCUGCCUCCAGGUGACAGC
GCUGUCACCUGGAGGCAGC
6281


 


1084
1369 
AGUGCGUUUAGCUGGUGGG
CCCACCAGCUAAACGCACU
6282


 


1329
1370 
AGCCGGCUAUUGUAGAAGC
GCUUCUACAAUAGCCGGCU
6283


 


 573
1371 
CAUUAGAUGAGGGCAUGCA
UGCAUGCCCUCAUCUAAUG
6284


 


2213
1372 
GAAGGUGUGGCGACAUAUG
CAUAUGUCGCCACACCUUC
6285


 


1587
1373 
AAGUGGGUGGUAUAGAGGC
GCCUCUAUACCACCCACUU
6286


 


2166
1374 
CUGAGGGAGCCACAGCUCC
GGAGCUGUGGCUCCCUCAG
6287


 


 637
1375 
GCGUUUGGCUGAACCAUCA
UGAUGGUUCAGCCAAACGC
6288


 


 397
1376 
UCCUUCUCUGAGUGGUAAA
UUUACCACUCAGAGAAGGA
6289


 


1718
1377 
GCAGUUCGCCUUCACUAUG
CAUAGUGAAGGCGAACUGC
6290


 


2357
1378 
GGACUUGAUAUUGGUGCCC
GGGCACCAAUAUCAAGUCC
6291


 


 639
1379 
GUUUGGCUGAACCAUCACA
UGUGAUGGUUCAGCCAAAC
6292


 


 585
1380 
GCAUGCAGAUCCCAUCUAC
GUAGAUGGGAUCUGCAUGC
6293


 


2519
1381 
GAUGGGCUGCCAGAUCUGG
CCAGAUCUGGCAGCCCAUC
6294


 


1367
1382 
GGACUUCACCUGACAGAUC
GAUCUGUCAGGUGAAGUCC
6295


 


1391
1383 
CAACGUCUUGUUCAGAACU
AGUUCUGAACAAGACGUUG
6296


 


 509
1384 
GAUAUUGAUGGACAGUAUG
CAUACUGUCCAUCAAUAUC
6297


 


 303
1385 
UGGCCAUGGAACCAGACAG
CUGUCUGGUUCCAUGGCCA
6298


 


 494
1386 
CAAGAACAAGUAGCUGAUA
UAUCAGCUACUUGUUCUUG
6299


 


 328
1387 
GGCUGUUAGUCACUGGCAG
CUGCCAGUGACUAACAGCC
6300


 


2058
1388 
CAUUGUUUGUGCAGCUGCU
AGCAGCUGCACAAACAAUG
6301


 


1447
1389 
UAAACAGGAAGGGAUGGAA
UUCCAUCCCUUCCUGUUUA
6302


 


1563
1390 
AUAAGAACAAGAUGAUGGU
ACCAUCAUCUUGUUCUUAU
6303


 


1350
1391 
GUGGAAUGCAAGCUUUAGG
CCUAAAGCUUGCAUUCCAC
6304


 


2208
1392 
GGAAUGAAGGUGUGGCGAC
GUCGCCACACCUUCAUUCC
6305


 


1689
1393 
GACACCAAGAAGCAGAGAU
AUCUCUGCUUCUUGGUGUC
6306


 


1407
1394 
ACUGUCUUUGGACUCUCAG
CUGAGAGUCCAAAGACAGU
6307


 


2137
1395 
GGACAAGGAAGCUGCAGAA
UUCUGCAGCUUCCUUGUCC
6308


 


 854
1396 
UCUGCUAUUGUACGUACCA
UGGUACGUACAAUAGCAGA
6309


 


2070
1397 
AGCUGCUUUAUUCUCCCAU
AUGGGAGAAUAAAGCAGCU
6310


 


 545
1398 
AGGGUACGAGCUGCUAUGU
ACAUAGCAGCUCGUACCCU
6311


 


1640
1399 
GAAGACAUCACUGAGCCUG
CAGGCUCAGUGAUGUCUUC
6312


 


2012
1400 
CGGGAUGUUCACAACCGAA
UUCGGUUGUGAACAUCCCG
6313


 


1684
1401 
CAGCCGACACCAAGAAGCA
UGCUUCUUGGUGUCGGCUG
6314


 


2017
1402 
UGUUCACAACCGAAUUGUU
AACAAUUCGGUUGUGAACA
6315


 


2307
1403 
GCUCUCUCUUCAGAACAGA
UCUGUUCUGAAGAGAGAGC
6316


 


 844
1404 
UCAGAUGGUGUCUGCUAUU
AAUAGCAGACACCAUCUGA
6317


 


 405
1405 
UGAGUGGUAAAGGCAAUCC
GGAUUGCCUUUACCACUCA
6318


 


 379
1406 
UGGUGCCACUACCACAGCU
AGCUGUGGUAGUGGCACCA
6319


 


1825
1407 
UUGUCCCGCAAAUCAUGCA
UGCAUGAUUUGCGGGACAA
6320


 


2495
1408 
CACC CUGGUGCUGACUAUC
GAUAGUCAGCACCAGGGUG
6321


 


 629
1409 
AAUGUCCAGCGUUUGGCUG
CAGCCAAACGCUGGACAUU
6322


 


2561
1410 
GGGCUGCCUCCAGGUGACA
UGUCACCUGGAGGCAGCCC
6323


 


2192
1411 
GAGUUACUUCACUCUAGGA
UCCUAGAGUGAAGUAACUC
6324


 


1809
1412 
UUCGAAAUCUUGCCCUUUG
CAAAGGGCAAGAUUUCGAA
6325


 


1596
1413 
GUAUAGAGGCUCUUGUGCG
CGCACAAGAGCCUCUAUAC
6326


 


2298
1414 
AGCUGACCAGCUCUCUCUU
AAGAGAGAGCUGGUCAGCU
6327


 


 858
1415 
CUAUUGUACGUACCAUGCA
UGCAUGGUACGUACAAUAG
6328


 


 524
1416 
UAUGCAAUGACUCGAGCUC
GAGCUCGAGUCAUUGCAUA
6329


 


2542
1417 
UGCCCAGGACCUCAUGGAU
AUCCAUGAGGUCCUGGGCA
6330


 


 498
1418 
AACAAGUAGCUGAUAUUGA
UCAAUAUCAGCUACUUGUU
6331


 


 414
1419 
AAGGCAAUCCUGAGGAAGA
UCUUCCUCAGGAUUGCCUU
6332


 


1570
1420 
CAAGAUGAUGGUCUGCCAA
UUGGCAGACCAUCAUCUUG
6333


 


1030
1421 
UGCCAUUACAACUCUCCAC
GUGGAGAGUUGUAAUGGCA
6334


 


3087
1422 
AUGUAUGGGUAGGGUAAAU
AUUUACCCUACCCAUACAU
6335


 


1664
1423 
UGUGCUCUUCGUCAUCUGA
UCAGAUGACGAAGAGCACA
6336


 


1790
1424 
AAGGCUACUGUUGGAUUGA
UCAAUCCAACAGUAGCCUU
6337


 


1615
1425 
UACUGUCCUUCGGGCUGGU
ACCAGCCCGAAGGACAGUA
6338


 


 774
1426 
AUAAGGCUGCAGUUAUGGU
ACCAUAACUGCAGCCUUAU
6339


 


1672
1427 
UCGUCAUCUGACCAGCCGA
UCGGCUGGUCAGAUGACGA
6340


 


3171
1428 
GUUGUAACCUGCUGUGAUA
UAUCACAGCAGGUUACAAC
6341


 


2271
1429 
AAGAUUACAAGAAACGGCU
AGCCGUUUCUUGUAAUCUU
6342


 


1183
1430 
UUAUGGCAACCAAGAAAGC
GCUUUCUUGGUUGCCAUAA
6343


 


2512
1431 
UCCAGUUGAUGGGCUGCCA
UGGCAGCCCAUCAACUGGA
6344


 


1931
1432 
GGGACACAGCAGCAAUUUG
CAAAUUGCUGCUGUGUCCC
6345


 


2468
1433 
AUGAUGGAACAUGAGAUGG
CCAUCUCAUGUUCCAUCAU
6346


 


3077
1434 
UAUUUGGGAUAUGUAUGGG
CCCAUACAUAUCCCAAAUA
6347


 


2069
1435 
CAGCUGCUUUAUUCUCCCA
UGGGAGAAUAAAGCAGCUG
6348


 


 272
1436 
GCUACUCAAGCUGAUUUGA
UCAAAUCAGCUUGAGUAGC
6349


 


 564
1437 
UCCCUGAGACAUUAGAUGA
UCAUCUAAUGUCUCAGGGA
6350


 


 437
1438 
GUGGAUACCUCCCAAGUCC
GGACUUGGGAGGUAUCCAC
6351


 


2206
1439 
UAGGAAUGAAGGUGUGGCG
CGCCACACCUUCAUUCCUA
6352


 


2187
1440 
UGACAGAGUUACUUCACUC
GAGUGAAGUAACUCUGUCA
6353


 


 325
1441 
AGCGGCUGUUAGUCACUGG
CCAGUGACUAACAGCCGCU
6354


 


3222
1442 
AUGGUUCAGAAUUAAACUU
AAGUUUAAUUCUGAACCAU
6355


 


2024
1443 
AACCGAAUUGUUAUCAGAG
CUCUGAUAACAAUUCGGUU
6356


 


1858
1444 
GGGUGCCAUUCCACGACUA
UAGUCGUGGAAUGGCACCC
6357


 


1574
1445 
AUGAUGGUCUGCCAAGUGG
CCACUUGGCAGACCAUCAU
6358


 


1896
1446 
CACAUCAGGAUACCCAGCG
CGCUGGGUAUCCUGAUGUG
6359


 


2207
1447 
AGGAAUGAAGGUGUGGCGA
UCGCCACACCUUCAUUCCU
6360


 


1300
1448 
GAAGGUGCUAUCUGUCUGC
GCAGACAGAUAGCACCUUC
6361


 


1192
1449 
CCAAGAAAGCAAGCUCAUC
GAUGAGCUUGCUUUCUUGG
6362


 


 551
1450 
CGAGCUGCUAUGUUCCCUG
CAGGGAACAUAGCAGCUCG
6363


 


2498
1451 
CCUGGUGCUGACUAUCCAG
CUGGAUAGUCAGCACCAGG
6364


 


1305
1452 
UGCUAUCUGUCUGCUCUAG
CUAGAGCAGACAGAUAGCA
6365


 


1337
1453 
AUUGUAGAAGCUGGUGGAA
UUCCACCAGCUUCUACAAU
6366









For each oligonucleotide of a target sequence, the two individual, complementary strands of the siNA were synthesized separately using solid phase synthesis, then purified separately by reversed phase solid phase extraction (SPE). The complementary strands were annealed to form the double strand (duplex) and delivered in the desired concentration and buffer of choice.
Briefly, the single strand oligonucleotides were synthesized using phosphoramidite chemistry on an automated solid-phase synthesizer, using procedures as are generally known in the art (see for example U.S. application Ser. No. 12/064,014). A synthesis column was packed with solid support derivatized with the first nucleoside residue (natural or chemically modified). Synthesis was initiated by detritylation of the acid labile 5′-O-dimethoxytrityl group to release the 5′-hydroxyl. A suitably protected phosphoramidite and a suitable activator in acetonitrile were delivered simultaneously to the synthesis column resulting in coupling of the amidite to the 5′-hydroxyl. The column was then washed with a solvent, such as acetonitrile. An oxidizing solution, such as an iodine solution was pumped through the column to oxidize the phosphite triester linkage P(III) to its phosphotriester P(V) analog. Unreacted 5′-hydroxyl groups were capped using reagents such as acetic anhydride in the presence of 2,6-lutidine and N-methylimidazole. The elongation cycle was resumed with the detritylation step for the next phosphoramidite incorporation. This process was repeated until the desired sequence was synthesized. The synthesis concluded with the final 5′-terminus protecting group (trityl or 5′-O-dimethoxytrityl).
Upon completion of the synthesis, the solid-support and associated oligonucleotide were dried under argon pressure or vacuum. Aqueous base was added and the mixture was heated to effect cleavage of the succinyl linkage, removal of the cyanoethyl phosphate protecting group, and deprotection of the exocyclic amine protection.
The following process was performed on single strands that do not contain ribonucleotides. After treating the solid support with the aqueous base, the mixture was filtered to separate the solid support from the deprotected crude synthesis material. The solid support was then rinsed with water, which is combined with the filtrate. The resultant basic solution allows for retention of the 5′-O-dimethoxytrityl group to remain on the 5′ terminal position (trityl-on).
For single strands that contain ribonucleotides, the following process was performed. After treating the solid support with the aqueous base, the mixture was filtered to separate the solid support from the deprotected crude synthesis material. The solid support was then rinsed with dimethylsulfoxide (DMSO), which was combined with the filtrate. Fluoride reagent, such as triethylamine trihydrofluoride, was added to the mixture, and the solution was heated. The reaction was quenched with suitable buffer to provide a solution of crude single strand with the 5′-O-dimethoxytrityl group on the final 5′ terminal position.
The trityl-on solution of each crude single strand was purified using chromatographic purification, such as SPE RPC purification. The hydrophobic nature of the trityl group permits stronger retention of the desired full-length oligo than the non-tritylated truncated failure sequences. The failure sequences were selectively washed from the resin with a suitable solvent, such as low percent acetonitrile. Retained oligonucleotides were then detritylated on-column with trifluoroacetic acid to remove the acid-labile trityl group. Residual acid was washed from the column, a salt exchange was performed, and a final desalting of the material commenced. The full-length oligo was recovered in a purified form with an aqueous-organic solvent. The final product was then analyzed for purity (HPLC), identity (Maldi-TOF MS), and yield (UV A260). The oligos were dried via lyophilization or vacuum condensation.
Annealing:
Based on the analysis of the product, the dried oligos were dissolved in appropriate buffers followed by mixing equal molar amounts (calculated using the theoretical extinction coefficient) of the sense and antisense oligonucleotide strands. The solution was then analyzed for purity of duplex by chromatographic methods and desired final concentration. If the analysis indicated an excess of either strand, then the additional non-excess strand was titrated until duplexing was complete. When analysis indicated that the target product purity has been achieved the material was delivered and ready for use.
Below is a table showing various modified siNAs synthesized using this protocol or that can be synthesized using this protocol or using methods known in the art.







TABLE lc







CTNNB1 siNA Strands Synthesized (Antisense    


sequences are readily identified as being complementary to the target sequence shown).













Target
SEQ


SEQ



Site
ID


ID


R Number
(human)
NO: 1
Target Sequence
Modified Sequence
NO: 2















R-008247452-000C
535
1
UCGAGCUCAGAGGGUACGA
B ucGAGcucAGAGGGuAcGATT B 
1454


R-008247452-000C
535
1
UCGAGCUCAGAGGGUACGA
UCGuAcccucuGAGcucGAUU
1455


R-008247449-000W
1601
2
GAGGCUCUUGUGCGUACUG
B GAGGcucuuGuGcGuAcuGTT B
1456


R-008247449-000W
1601
2
GAGGCUCUUGUGCGUACUG
CAGuAcGcAcAAGAGccucUU
1457


R-008247575-000Y
1709
3
GCCCAGAAUGCAGUUCGCC
B GcccAGAAuGcAGuucGccTT B
1458


R-008247575-000Y
1709
3
GCCCAGAAUGCAGUUCGCC
GGCGAAcuGcAuucuGGGcUU
1459


R-008247572-000X
536
4
CGAGCUCAGAGGGUACGAG
B cGAGcucAGAGGGuAcGAGTT B
1460


R-008247572-000X
536
4
CGAGCUCAGAGGGUACGAG
CUCGuAcccucuGAGcucGUU
1461


R-008247569-000R
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAAucAAuccAAcAGUU
1463


R-008247569-000R
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAATT B
1462


R-008247446-000V
853
6
GUCUGCUAUUGUACGUACC
B GucuGcuAuuGuAcGuAccTT B
1464


R-008247446-000V
853
6
GUCUGCUAUUGUACGUACC
GGUAcGuAcAAuAGcAGAcUU
1465


R-008247566-000P
1143
7
AAUUCUUGGCUAUUACGAC
GUCGuAAuAGccAAGAAuuUU
1467


R-008247566-000P
1143
7
AAUUCUUGGCUAUUACGAC
B AAuucuuGGcuAuuAcGAcTT B
1466


R-008247563-000N
2014
8
GGAUGUUCACAACCGAAUU
B GGAuGuucAcAAccGAAuuTT B
1468


R-008247563-000N
2014
8
GGAUGUUCACAACCGAAUU
AAUucGGuuGuGAAcAuccUU
1469


R-008247560-000M
520
9
ACAGUAUGCAAUGACUCGA
B AcAGuAuGcAAuGAcucGATT B
1470


R-008247560-000M
520
9
ACAGUAUGCAAUGACUCGA
UCGAGucAuuGcAuAcuGuUU
1471


R-008247443-000U
814
10
AGCUUCCAGACACGCUAUC
B AGcuuccAGAcAcGcuAucTT B 
1472


R-008247443-000U
814
10
AGCUUCCAGACACGCUAUC
GAUAGcGuGucuGGAAGcuUU
1473


R-008247440-000T
852
11
UGUCUGCUAUUGUACGUAC
GUAcGuAcAAuAGcAGAcAUU
1475


R-008247440-000T
852
11
UGUCUGCUAUUGUACGUAC
B uGucuGcuAuuGuAcGuAcTT B
1474


R-008247557-000F
1796
12
ACUGUUGGAUUGAUUCGAA
UUCGAAucAAuccAAcAGuUU
1477


R-008247557-000F
1796
12
ACUGUUGGAUUGAUUCGAA
B AcuGuuGGAuuGAuucGAATT B
1476


R-008247437-000L
1901
13
CAGGAUACCCAGCGCCGUA
UACGGcGcuGGGuAuccuGUU
1479


R-008247437-000L
1901
13
CAGGAUACCCAGCGCCGUA
B cAGGAuAcccAGcGccGuATT B
1478


R-008247554-000E
822
14
GACACGCUAUCAUGCGUUC
B GAcAcGcuAucAuGcGuucTT B
1480


R-008247554-000E
822
14
GACACGCUAUCAUGCGUUC
GAAcGcAuGAuAGcGuGucUU      
1481


R-008247551-000D
1795
15
UACUGUUGGAUUGAUUCGA
UCGAAucAAuccAAcAGuAUU       
1483


R-008247551-000D
1795
15
UACUGUUGGAUUGAUUCGA
B uAcuGuuGGAuuGAuucGATT B
1482


R-008247548-000X
1145
16
UUCUUGGCUAUUACGACAG
B uucuuGGcuAuuAcGAcAGTT B
1484


R-008247548-000X
1145
16
UUCUUGGCUAUUACGACAG
CUGucGuAAuAGccAAGAAUU
1485


R-008247545-000W
823
17
ACACGCUAUCAUGCGUUCU
B AcAcGcuAucAuGcGuucuTT B 
1486


R-008247545-000W
823
17
ACACGCUAUCAUGCGUUCU
AGAAcGcAuGAuAGcGuGuUU
1487


R-008247434-000K
820
18
CAGACACGCUAUCAUGCGU
B cAGAcAcGcuAucAuGcGuTT B
1488


R-008247434-000K
820
18
CAGACACGCUAUCAUGCGU
ACGcAuGAuAGcGuGucuGUU
1489


R-008247431-000J
1798
19
UGUUGGAUUGAUUCGAAAU
B uGuuGGAuuGAuucGAAAuTT B
1490


R-008247431-000J
1798
19
UGUUGGAUUGAUUCGAAAU
AUUucGAAucAAuccAAcAUU
1491


R-008247428-000C
1380
20
CAGAUCCAAGUCAACGUCU
B cAGAuccAAGucAAcGucuTT B
1492


R-008247428-000C
1380
20
CAGAUCCAAGUCAACGUCU
AGAcGuuGAcuuGGAucuGUU
1493


R-008247542-000V
1602
21
AGGCUCUUGUGCGUACUGU
B AGGcucuuGuGcGuAcuGuTT B
1494


R-008247542-000V
1602
21
AGGCUCUUGUGCGUACUGU
ACAGuAcGcAcAAGAGccuUU
1495


R-008247539-000N
1612
22
GCGUACUGUCCUUCGGGCU
B GcGuAcuGuccuucGGGcuTT B
1496


R-008247539-000N
1612
22
GCGUACUGUCCUUCGGGCU
AGCccGAAGGAcAGuAcGcUU
1497


R-008247425-000B
626
23
ACUAAUGUCCAGCGUUUGG
B AcuAAuGuccAGcGuuuGGTT B
1498


R-008247425-000B
626
23
ACUAAUGUCCAGCGUUUGG
CCAAAcGcuGGAcAuuAGuUU   
1499


R-008247536-000M
2000
24
CACAUCCUAGCUCGGGAUG
B cAcAuccuAGcucGGGAuGTT B
1500


R-008247536-000M
2000
24
CACAUCCUAGCUCGGGAUG
CAUcccGAGcuAGGAuGuGUU
1501


R-008247422-000A
2665
25
GUUGCUGAGAGGGCUCGAG
B GuuGcuGAGAGGGcucGAGTT B
1502


R-008247422-000A
2665
25
GUUGCUGAGAGGGCUCGAG
CUCGAGcccucucAGcAAcUU
1503


R-008247533-000L
1676
26
CAUCUGACCAGCCGACACC
GGUGucGGcuGGucAGAuGUU
1505


R-008247533-000L
1676
26
CAUCUGACCAGCCGACACC
B cAucuGAccAGccGAcAccTT B
1504


R-008247530-000K
1611
27
UGCGUACUGUCCUUCGGGC
B uGcGuAcuGuccuucGGGcTT B
1506


R-008247530-000K
1611
27
UGCGUACUGUCCUUCGGGC
GCCcGAAGGAcAGuAcGcAUU
1507


R-008247419-000U
2269
28
ACAAGAUUACAAGAAACGG
B AcAAGAuuAcAAGAAAcGGTT B
1508


R-008247419-000U
2269
28
ACAAGAUUACAAGAAACGG
CCGuuucuuGuAAucuuGuUU
1509


R-008247527-000D
674
29
GUUGUAAACUUGAUUAACU
B GuuGuAAAcuuGAuuAAcuTT B
1510


R-008247527-000D
674
29
GUUGUAAACUUGAUUAACU
AGUuAAucAAGuuuAcAAcUU
1511


R-008247602-000K
678
30
UAAACUUGAUUAACUAUCA
B uAAAcuuGAuuAAcuAucATT B
1512


R-008247602-000K
678
30
UAAACUUGAUUAACUAUCA
UGAuAGuuAAucAAGuuuAUU
1513


R-008247599-000T
1245
31
AUAUAAUGAGGACCUAUAC
B AuAuAAuGAGGAccuAuAcTT B
1514


R-008247599-000T
1245
31
AUAUAAUGAGGACCUAUAC
GUAuAGGuccucAuuAuAuUU
1515


R-008247596-000S
679
32
AAACUUGAUUAACUAUCAA
B AAAcuuGAuuAAcuAucAATT B  
1516


R-008247596-000S
679
32
AAACUUGAUUAACUAUCAA
UUGAuAGuuAAucAAGuuuUU      
1517


R-008247593-000R
1970
33
GAAAUAGUUGAAGGUUGUA
B GAAAuAGuuGAAGGuuGuATT B
1518


R-008247593-000R
1970
33
GAAAUAGUUGAAGGUUGUA
UACAAccuucAAcuAuuucUU
1519


R-008247590-000P
1247
34
AUAAUGAGGACCUAUACUU
AAGuAuAGGuccucAuuAuUU
1521


R-008247590-000P
1247
34
AUAAUGAGGACCUAUACUU
B AuAAuGAGGAccuAuAcuuTT B
1520


R-008247464-000M
1140
35
UUAAAUUCUUGGCUAUUAC
B uuAAAuucuuGGcuAuuAcTT B
1522


R-008247464-000M
1140
35
UUAAAUUCUUGGCUAUUAC
GUAAuAGccAAGAAuuuAAUU
1523


R-008247587-000H
676
36
UGUAAACUUGAUUAACUAU
B uGuAAAcuuGAuuAAcuAuTT B
1524


R-008247587-000H
676
36
UGUAAACUUGAUUAACUAU
AUAGuuAAucAAGuuuAcAUU
1525


R-008247461-000L
677
37
GUAAACUUGAUUAACUAUC
GAUAGuuAAucAAGuuuAcUU
1527


R-008247461-000L
677
37
GUAAACUUGAUUAACUAUC
B GuAAAcuuGAuuAAcuAucTT B
1526


R-008247458-000E
675
38
UUGUAAACUUGAUUAACUA
B uuGuAAAcuuGAuuAAcuATT B
1528


R-008247458-000E
675
38
UUGUAAACUUGAUUAACUA
UAGuuAAucAAGuuuAcAAUU
1529


R-008247584-000G
1235
39
GCUUUAGUAAAUAUAAUGA
B GcuuuAGuAAAuAuAAuGATT B
1530


R-008247584-000G
1235
39
GCUUUAGUAAAUAUAAUGA
UCAuuAuAuuuAcuAAAGcUU
1531


R-008247581-000F
2488
40
UGGCCACCACCCUGGUGCU
B uGGccAccAcccuGGuGcuTT B
1532


R-008247581-000F
2488
40
UGGCCACCACCCUGGUGCU
AGCAccAGGGuGGuGGccAUU
1533


R-008247578-000Z
1236
41
CUUUAGUAAAUAUAAUGAG
B cuuuAGuAAAuAuAAuGAGTT B
1534


R-008247578-000Z
1236
41
CUUUAGUAAAUAUAAUGAG
CUCAuuAuAuuuAcuAAAGUU
1535


R-008247455-000D
1237
42
UUUAGUAAAUAUAAUGAGG
CCUcAuuAuAuuuAcuAAAUU
1537


R-008247455-000D
1237
42
UUUAGUAAAUAUAAUGAGG
B uuuAGuAAAuAuAAuGAGGTT B
1536


R-008042883-001A
2555
43
GUAAAUCGUCCUUUAGGUA
B GuAAAucGuccuuuAGGuATT B
1538


R-008042883-001A
2555
43
GUAAAUCGUCCUUUAGGUA
UACcuAAAGGAcGAuuuAcUU
1539


R-008308583-000P
1545
44
ACCUCACUUGCAAUAAUUA
B AccucAcuuGcAAuAAuuATT B
1540


R-008308583-000P
1545
44
ACCUCACUUGCAAUAAUUA
UAAuuAuuGcAAGuGAGGuUU
1541


R-008308520-000J
2050
45
UACCAUUCCAUUGUUUGUG
B uAccAuuccAuuGuuuGuGTT B
1542


R-008308520-000J
2050
45
UACCAUUCCAUUGUUUGUG
CACAAAcAAuGGAAuGGuAUU
1543


R-008308622-000L
2097
46
UCCAAAGAGUAGCUGCAGG
CCUGcAGcuAcucuuuGGAUU
1545


R-008308622-000L
2097
46
UCCAAAGAGUAGCUGCAGG
B uccAAAGAGuAGcuGcAGGTT B
1544


R-008308652-000N
2510
47
UAUCCAGUUGAUGGGCUGC
B uAuccAGuuGAuGGGcuGcTT B
1546


R-008308652-000N
2510
47
UAUCCAGUUGAUGGGCUGC
GCAGcccAucAAcuGGAuAUU
1547


R-008308718-000F
871
48
CAUGCAGAAUACAAAUGAU
AUCAuuuGuAuucuGcAuGUU
1549


R-008308718-000F
871
48
CAUGCAGAAUACAAAUGAU
B cAuGcAGAAuAcAAAuGAuTT B
1548


R-008308694-000A
2098
49
CCAAAGAGUAGCUGCAGGG
CCCuGcAGcuAcucuuuGGUU
1551


R-008308694-000A
2098
49
CCAAAGAGUAGCUGCAGGG
B ccAAAGAGuAGcuGcAGGGTT B   
1550


R-008308517-000C
1767
50
CACCAUCCCACUGGCCUCU
B cAccAucccAcuGGccucuTT B   
1552


R-008308517-000C
1767
50
CACCAUCCCACUGGCCUCU
AGAGGccAGuGGGAuGGuGUU
1553


R-008308619-000E
869
51
ACCAUGCAGAAUACAAAUG
B AccAuGcAGAAuAcAAAuGTT B
1554


R-008308619-000E
869
51
ACCAUGCAGAAUACAAAUG
CAUuuGuAuucuGcAuGGuUU
1555


R-008308514-000B
1641
52
AAGACAUCACUGAGCCUGC
B AAGAcAucAcuGAGccuGcTT B
1556


R-008308514-000B
1641
52
AAGACAUCACUGAGCCUGC
GCAGGcucAGuGAuGucuuUU
1557


R-008308616-000D
2582
53
AAUCAGCUGGCCUGGUUUG
B AAucAGcuGGccuGGuuuGTT B
1558


R-008308616-000D
2582
53
AAUCAGCUGGCCUGGUUUG
CAAAccAGGccAGcuGAuuUU
1559


R-008308580-000N
1544
54
AACCUCACUUGCAAUAAUU
AAUuAuuGcAAGuGAGGuuUU
1561


R-008308580-000N
1544
54
AACCUCACUUGCAAUAAUU
B AAccucAcuuGcAAuAAuuTT B
1560


R-008308736-000Y
2550
55
ACCUCAUGGAUGGGCUGCC
B AccucAuGGAuGGGcuGccTT B
1562


R-008308736-000Y
2550
55
ACCUCAUGGAUGGGCUGCC
GGCAGcccAuccAuGAGGuUU
1563


R-008308613-000C
2051
56
ACCAUUCCAUUGUUUGUGC
GCAcAAAcAAuGGAAuGGuUU
1565


R-008308613-000C
2051
56
ACCAUUCCAUUGUUUGUGC
B AccAuuccAuuGuuuGuGcTT B
1564


R-008308577-000G
870
57
CCAUGCAGAAUACAAAUGA
UCAuuuGuAuucuGcAuGGUU
1567


R-008308577-000G
870
57
CCAUGCAGAAUACAAAUGA
B ccAuGcAGAAuAcAAAuGATT B
1566


R-008308691-000Z
1670
58
CUUCGUCAUCUGACCAGCC
B cuucGucAucuGAccAGccTT B
1568


R-008308691-000Z
1670
58
CUUCGUCAUCUGACCAGCC
GGCuGGucAGAuGAcGAAGUU
1569


R-008308649-000G
2122
59
CUGUGAACUUGCUCAGGAC
B cuGuGAAcuuGcucAGGAcTT B
1570


R-008308649-000G
2122
59
CUGUGAACUUGCUCAGGAC
GUCcuGAGcAAGuucAcAGUU
1571


R-008308553-000M
1642
60
AGACAUCACUGAGCCUGCC
B AGAcAucAcuGAGccuGccTT B
1572


R-008308553-000M
1642
60
AGACAUCACUGAGCCUGCC
GGCAGGcucAGuGAuGucuUU
1573


R-008308574-000F
2324
61
GAGCCAAUGGCUUGGAAUG
B GAGccAAuGGcuuGGAAuGTT B
1574


R-008308574-000F
2324
61
GAGCCAAUGGCUUGGAAUG
CAUuccAAGccAuuGGcucUU
1575


R-008308688-000T
1649
62
ACUGAGCCUGCCAUCUGUG
B AcuGAGccuGccAucuGuGTT B
1576


R-008308688-000T
1649
62
ACUGAGCCUGCCAUCUGUG
CACAGAuGGcAGGcucAGuUU
1577


R-008308550-000L
2159
63
AUUGAAGCUGAGGGAGCCA
B AuuGAAGcuGAGGGAGccATT B
1578


R-008308550-000L
2159
63
AUUGAAGCUGAGGGAGCCA
UGGcucccucAGcuucAAuUU
1579


R-008308511-000A
785
64
GUUAUGGUCCAUCAGCUUU
B GuuAuGGuccAucAGcuuuTT B
1580


R-008308511-000A
785
64
GUUAUGGUCCAUCAGCUUU
AAAGcuGAuGGAccAuAAcUU
1581


R-008308685-000S
1511
65
AAUGUGGUCACCUGUGCAG
B AAuGuGGucAccuGuGcAGTT B
1582


R-008308685-000S
1511
65
AAUGUGGUCACCUGUGCAG
CUGcAcAGGuGAccAcAuuUU
1583


R-008308610-000B
2586
66
AGCUGGCCUGGUUUGAUAC
B AGcuGGccuGGuuuGAuAcTT B
1584


R-008308610-000B
2586
66
AGCUGGCCUGGUUUGAUAC
GUAucAAAccAGGccAGcuUU
1585


R-008308571-000E
642
67
UGGCUGAACCAUCACAGAU
B uGGcuGAAccAucAcAGAuTT B  
1586


R-008308571-000E
642
67
UGGCUGAACCAUCACAGAU
AUCuGuGAuGGuucAGccAUU      
1587


R-008308715-000E
1763
68
CACCCACCAUCCCACUGGC
B cAcccAccAucccAcuGGcTT B
1588


R-008308715-000E
1763
68
CACCCACCAUCCCACUGGC
GCCAGuGGGAuGGuGGGuGUU
1589


R-008308682-000R
2328
69
CAAUGGCUUGGAAUGAGAC
GUCucAuuccAAGccAuuGUU
1591


R-008308682-000R
2328
69
CAAUGGCUUGGAAUGAGAC
B cAAuGGcuuGGAAuGAGAcTT B
1590


R-008308646-000F
1280
70
UGGACCACAAGCAGAGUGC
GCAcucuGcuuGuGGuccAUU
1593


R-008308646-000F
1280
70
UGGACCACAAGCAGAGUGC
B uGGAccAcAAGcAGAGuGcTT B
1592


R-008308508-000U
2052
71
CCAUUCCAUUGUUUGUGCA
B ccAuuccAuuGuuuGuGcATT B
1594


R-008308508-000U
2052
71
CCAUUCCAUUGUUUGUGCA
UGCAcAAAcAAuGGAAuGGUU
1595


R-008308547-000E
2546
72
CAGGACCUCAUGGAUGGGC
GCCcAuccAuGAGGuccuGUU
1597


R-008308547-000E
2546
72
CAGGACCUCAUGGAUGGGC
B cAGGAccucAuGGAuGGGcTT B
1596


R-008308505-000T
2124
73
GUGAACUUGCUCAGGACAA
UUGuccuGAGcAAGuucAcUU
1599


R-008308505-000T
2124
73
GUGAACUUGCUCAGGACAA
B GuGAAcuuGcucAGGAcAATT B
1598


R-008308733-000X
2545
74
CCAGGACCUCAUGGAUGGG
CCCAuccAuGAGGuccuGGUU
1601


R-008308733-000X
2545
74
CCAGGACCUCAUGGAUGGG
B ccAGGAccucAuGGAuGGGTT B
1600


R-008308544-000D
643
75
GGCUGAACCAUCACAGAUG
B GGcuGAAccAucAcAGAuGTT B
1602


R-008308544-000D
643
75
GGCUGAACCAUCACAGAUG
CAUcuGuGAuGGuucAGccUU
1603


R-008308643-000E
2501
76
GGUGCUGACUAUCCAGUUG
B GGuGcuGAcuAuccAGuuGTT B
1604


R-008308643-000E
2501
76
GGUGCUGACUAUCCAGUUG
CAAcuGGAuAGucAGcAccUU
1605


R-008308712-000D
2330
77
AUGGCUUGGAAUGAGACUG
B AuGGcuuGGAAuGAGAcuGTT B
1606


R-008308712-000D
2330
77
AUGGCUUGGAAUGAGACUG
CAGucucAuuccAAGccAuUU
1607


R-008308568-000Y
1638
78
GGGAAGACAUCACUGAGCC
GGCucAGuGAuGucuucccUU
1609


R-008308568-000Y
1638
78
GGGAAGACAUCACUGAGCC
B GGGAAGAcAucAcuGAGccTT B
1608


R-008308640-000D
1630
79
UGGUGACAGGGAAGACAUC
B uGGuGAcAGGGAAGAcAucTT B
1610


R-008308640-000D
1630
79
UGGUGACAGGGAAGACAUC
GAUGucuucccuGucAccAUU
1611


R-008308541-000C
616
80
UGCUCAUCCCACUAAUGUC
GACAuuAGuGGGAuGAGcAUU
1613


R-008308541-000C
616
80
UGCUCAUCCCACUAAUGUC
B uGcucAucccAcuAAuGucTT B
1612


R-008308679-000J
2509
81
CUAUCCAGUUGAUGGGCUG
B cuAuccAGuuGAuGGGcuGTT B
1614


R-008308679-000J
2509
81
CUAUCCAGUUGAUGGGCUG
CAGcccAucAAcuGGAuAGUU
1615


R-008308565-000X
2548
82
GGACCUCAUGGAUGGGCUG
B GGAccucAuGGAuGGGcuGTT B
1616


R-008308565-000X
2548
82
GGACCUCAUGGAUGGGCUG
CAGcccAuccAuGAGGuccUU
1617


R-008308538-000W
1773
83
CCCACUGGCCUCUGAUAAA
UUUAucAGAGGccAGuGGGUU
1619


R-008308538-000W
1773
83
CCCACUGGCCUCUGAUAAA
B cccAcuGGccucuGAuAAATT B
1618


R-008308535-000V
2247
84
UCCGAAUGUCUGAGGACAA
UUGuccucAGAcAuucGGAUU
1621


R-008308535-000V
2247
84
UCCGAAUGUCUGAGGACAA
B uccGAAuGucuGAGGAcAATT B 
1620


R-008308637-000X
2331
85
UGGCUUGGAAUGAGACUGC
B uGGcuuGGAAuGAGAcuGcTT B
1622


R-008308637-000X
2331
85
UGGCUUGGAAUGAGACUGC
GCAGucucAuuccAAGccAUU
1623


R-008309111-000F
1498
86
UUCAGAUGAUAUAAAUGUG
CACAuuuAuAucAucuGAAUU
1625


R-008309111-000F
1498
86
UUCAGAUGAUAUAAAUGUG
B uucAGAuGAuAuAAAuGuGTT B
1624


R-008309108-000Z
2267
87
CCACAAGAUUACAAGAAAC
B ccAcAAGAuuAcAAGAAAcTT B
1626


R-008309108-000Z
2267
87
CCACAAGAUUACAAGAAAC
GUUucuuGuAAucuuGuGGUU
1627


R-008308994-000E
1547
88
CUCACUUGCAAUAAUUAUA
UAUAAuuAuuGcAAGuGAGUU
1629


R-008308994-000E
1547
88
CUCACUUGCAAUAAUUAUA
B cucAcuuGcAAuAAuuAuATT B
1628


R-008309075-000K
1549
89
CACUUGCAAUAAUUAUAAG
CUUAuAAuuAuuGcAAGuGUU
1631


R-008309075-000K
1549
89
CACUUGCAAUAAUUAUAAG
B cAcuuGcAAuAAuuAuAAGTT B
1630


R-008309045-000H
867
90
GUACCAUGCAGAAUACAAA
UUUGuAuucuGcAuGGuAcUU
1633


R-008309045-000H
867
90
GUACCAUGCAGAAUACAAA
B GuAccAuGcAGAAuAcAAATT B
1632


R-008309072-000J
1390
91
UCAACGUCUUGUUCAGAAC
B ucAAcGucuuGuucAGAAcTT B
1634


R-008309072-000J
1390
91
UCAACGUCUUGUUCAGAAC
GUUcuGAAcAAGAcGuuGAUU
1635


R-008309027-000R
593
92
AUCCCAUCUACACAGUUUG
CAAAcuGuGuAGAuGGGAuUU
1637


R-008309027-000R
593
92
AUCCCAUCUACACAGUUUG
B AucccAucuAcAcAGuuuGTT B
1636


R-008309009-000Y
274
93
UACUCAAGCUGAUUUGAUG
CAUcAAAucAGcuuGAGuAUU
1639


R-008309009-000Y
274
93
UACUCAAGCUGAUUUGAUG
B uAcucAAGcuGAuuuGAuGTT B
1638


R-008309024-000P
759
94
ACCAGGUGGUGGUUAAUAA
B AccAGGuGGuGGuuAAuAATT B
1640


R-008309024-000P
759
94
ACCAGGUGGUGGUUAAUAA
UUAuuAAccAccAccuGGuUU
1641


R-008309093-000C
1439
95
GCUGCAACUAAACAGGAAG
B GcuGcAAcuAAAcAGGAAGTT B
1642


R-008309093-000C
1439
95
GCUGCAACUAAACAGGAAG
CUUccuGuuuAGuuGcAGcUU
1643


R-008309069-000C
1801
96
UGGAUUGAUUCGAAAUCUU
B uGGAuuGAuucGAAAucuuTT B
1644


R-008309069-000C
1801
96
UGGAUUGAUUCGAAAUCUU
AAGAuuucGAAucAAuccAUU
1645


R-008309021-000N
1500
97
CAGAUGAUAUAAAUGUGGU
B cAGAuGAuAuAAAuGuGGuTT B
1646


R-008309021-000N
1500
97
CAGAUGAUAUAAAUGUGGU
ACCAcAuuuAuAucAucuGUU
1647


R-008309066-000B
848
98
AUGGUGUCUGCUAUUGUAC
B AuGGuGucuGcuAuuGuAcTT B
1648


R-008309066-000B
848
98
AUGGUGUCUGCUAUUGUAC
GUAcAAuAGcAGAcAccAuUU
1649


R-008309105-000Y
2268
99
CACAAGAUUACAAGAAACG
CGUuucuuGuAAucuuGuGUU
1651


R-008309105-000Y
2268
99
CACAAGAUUACAAGAAACG
B cAcAAGAuuAcAAGAAAcGTT B
1650


R-008309042-000G
882
100
CAAAUGAUGUAGAAACAGC
GCUGuuucuAcAucAuuuGUU
1653


R-008309042-000G
882
100
CAAAUGAUGUAGAAACAGC
B cAAAuGAuGuAGAAAcAGcTT B
1652


R-008309063-000A
2266
101
GCCACAAGAUUACAAGAAA
UUUcuuGuAAucuuGuGGcUU
1655


R-008309063-000A
2266
101
GCCACAAGAUUACAAGAAA
B GccAcAAGAuuAcAAGAAATT B
1654


R-008309018-000G
880
102
UACAAAUGAUGUAGAAACA
B uAcAAAuGAuGuAGAAAcATT B 
1656


R-008309018-000G
880
102
UACAAAUGAUGUAGAAACA
UGUuucuAcAucAuuuGuAUU      
1657


R-008309039-000A
1810
103
UCGAAAUCUUGCCCUUUGU
ACAAAGGGcAAGAuuucGAUU
1659


R-008309039-000A
1810
103
UCGAAAUCUUGCCCUUUGU
B ucGAAAucuuGcccuuuGuTT B
1658


R-008309015-000F
685
104
GAUUAACUAUCAAGAUGAU
B GAuuAAcuAucAAGAuGAuTT B
1660


R-008309015-000F
685
104
GAUUAACUAUCAAGAUGAU
AUCAucuuGAuAGuuAAucUU
1661


R-008309060-000Z
1007
105
CCAGUGGAUUCUGUGUUGU
ACAAcAcAGAAuccAcuGGUU
1663


R-008309060-000Z
1007
105
CCAGUGGAUUCUGUGUUGU
B ccAGuGGAuucuGuGuuGuTT B
1662


R-008309057-000T
1789
106
AAAGGCUACUGUUGGAUUG
B AAAGGcuAcuGuuGGAuuGTT B
1664


R-008309057-000T
1789
106
AAAGGCUACUGUUGGAUUG
CAAuccAAcAGuAGccuuuUU
1665


R-008309054-000S
499
107
ACAAGUAGCUGAUAUUGAU
AUCAAuAucAGcuAcuuGuUU
1667


R-008309054-000S
499
107
ACAAGUAGCUGAUAUUGAU
B AcAAGuAGcuGAuAuuGAuTT B
1666


R-008309090-000B
2470
108
GAUGGAACAUGAGAUGGGU
B GAuGGAAcAuGAGAuGGGuTT B
1668


R-008309090-000B
2470
108
GAUGGAACAUGAGAUGGGU
ACCcAucucAuGuuccAucUU
1669


R-008309051-000R
694
109
UCAAGAUGAUGCAGAACUU
B ucAAGAuGAuGcAGAAcuuTT B
1670


R-008309051-000R
694
109
UCAAGAUGAUGCAGAACUU
AAGuucuGcAucAucuuGAUU
1671


R-008309036-000Z
278
110
CAAGCUGAUUUGAUGGAGU
ACUccAucAAAucAGcuuGUU
1673


R-008309036-000Z
278
110
CAAGCUGAUUUGAUGGAGU
B cAAGcuGAuuuGAuGGAGuTT B
1672


R-008309102-000X
1415
111
UGGACUCUCAGGAAUCUUU
B uGGAcucucAGGAAucuuuTT B
1674


R-008309102-000X
1415
111
UGGACUCUCAGGAAUCUUU
AAAGAuuccuGAGAGuccAUU
1675


R-008308991-000D
2046
112
UAAAUACCAUUCCAUUGUU
AACAAuGGAAuGGuAuuuAUU
1677


R-008308991-000D
2046
112
UAAAUACCAUUCCAUUGUU
B uAAAuAccAuuccAuuGuuTT B
1676


R-008309006-000X
1057
113
AUUACAUCAAGAAGGAGCU
AGCuccuucuuGAuGuAAuUU
1679


R-008309006-000X
1057
113
AUUACAUCAAGAAGGAGCU
B AuuAcAucAAGAAGGAGcuTT B
1678


R-008309087-000V
1422
114
UCAGGAAUCUUUCAGAUGC
B ucAGGAAucuuucAGAuGcTT B
1680


R-008309087-000V
1422
114
UCAGGAAUCUUUCAGAUGC
GCAucuGAAAGAuuccuGAUU
1681


R-008309084-000U
684
115
UGAUUAACUAUCAAGAUGA
UCAucuuGAuAGuuAAucAUU
1683


R-008309084-000U
684
115
UGAUUAACUAUCAAGAUGA
B uGAuuAAcuAucAAGAuGATT B
1682


R-008309099-000E
2197
116
ACUUCACUCUAGGAAUGAA
B AcuucAcucuAGGAAuGAATT B
1684


R-008309099-000E
2197
116
ACUUCACUCUAGGAAUGAA
UUCAuuccuAGAGuGAAGuUU
1685


R-008309003-000W
666
117
AACAUGCAGUUGUAAACUU
B AAcAuGcAGuuGuAAAcuuTT B
1686


R-008309003-000W
666
117
AACAUGCAGUUGUAAACUU
AAGuuuAcAAcuGcAuGuuUU
1687


R-008309012-000E
279
118
AAGCUGAUUUGAUGGAGUU
AACuccAucAAAucAGcuuUU
1689


R-008309012-000E
279
118
AAGCUGAUUUGAUGGAGUU
B AAGcuGAuuuGAuGGAGuuTT B
1688


R-008309033-000Y
1492
119
UCUGGGUUCAGAUGAUAUA
B ucuGGGuucAGAuGAuAuATT B
1690


R-008309033-000Y
1492
119
UCUGGGUUCAGAUGAUAUA
UAUAucAucuGAAcccAGAUU       
1691


R-008309081-000T
2195
120
UUACUUCACUCUAGGAAUG
CAUuccuAGAGuGAAGuAAUU       
1693


R-008309081-000T
2195
120
UUACUUCACUCUAGGAAUG
B uuAcuucAcucuAGGAAuGTT B
1692


R-008309048-000J
1424
121
AGGAAUCUUUCAGAUGCUG
B AGGAAucuuucAGAuGcuGTT B
1694


R-008309048-000J
1424
121
AGGAAUCUUUCAGAUGCUG
CAGcAucuGAAAGAuuccuUU
1695


R-008309000-000V
661
122
GCUGAAACAUGCAGUUGUA
UACAAcuGcAuGuuucAGcUU
1697


R-008309000-000V
661
122
GCUGAAACAUGCAGUUGUA
B GcuGAAAcAuGcAGuuGuATT B
1696


R-008309078-000L
1882
123
GUUGCUUGUUCGUGCACAU
B GuuGcuuGuucGuGcAcAuTT B
1698


R-008309078-000L
1882
123
GUUGCUUGUUCGUGCACAU
AUGuGcAcGAAcAAGcAAcUU
1699


R-008309096-000D
1966
124
GGAAGAAAUAGUUGAAGGU
B GGAAGAAAuAGuuGAAGGuTT B
1700


R-008309096-000D
1966
124
GGAAGAAAUAGUUGAAGGU
ACCuucAAcuAuuucuuccUU
1701


R-008308997-000F
2259
125
AGGACAAGCCACAAGAUUA
B AGGAcAAGccAcAAGAuuATT B
1702


R-008308997-000F
2259
125
AGGACAAGCCACAAGAUUA
UAAucuuGuGGcuuGuccuUU
1703


R-008309030-000X
832
126
CAUGCGUUCUCCUCAGAUG
B cAuGcGuucuccucAGAuGTT B
1704


R-008309030-000X
832
126
CAUGCGUUCUCCUCAGAUG
CAUcuGAGGAGAAcGcAuGUU
1705


R-008042849-001H
2346
127
GAUGAUCCCAGCUACCGUU
AACGGuAGcuGGGAucAucUU
1707


R-008042849-001H
2346
127
GAUGAUCCCAGCUACCGUU
B GAuGAucccAGcuAccGuuTT B
1706


R-008308601-000T
1653
128
AGCCUGCCAUCUGUGCUCU
B AGccuGccAucuGuGcucuTT B
1708


R-008308601-000T
1653
128
AGCCUGCCAUCUGUGCUCU
AGAGcAcAGAuGGcAGGcuUU
1709


R-008308562-000W
2389
129
UGGAUAUCGCCAGGAUGAU
B uGGAuAucGccAGGAuGAuTT B
1710


R-008308562-000W
2389
129
UGGAUAUCGCCAGGAUGAU
AUCAuccuGGcGAuAuccAUU
1711


R-008308709-000X
1669
130
UCUUCGUCAUCUGACCAGC
B ucuucGucAucuGAccAGcTT B
1712


R-008308709-000X
1669
130
UCUUCGUCAUCUGACCAGC
GCUGGucAGAuGAcGAAGAUU
1713


R-008308634-000W
2123
131
UGUGAACUUGCUCAGGACA
B uGuGAAcuuGcucAGGAcATT B
1714


R-008308634-000W
2123
131
UGUGAACUUGCUCAGGACA
UGUccuGAGcAAGuucAcAUU
1715


R-008308667-000Z
1521
132
CCUGUGCAGCUGGAAUUCU
B ccuGuGcAGcuGGAAuucuTT B
1716


R-008308667-000Z
1521
132
CCUGUGCAGCUGGAAUUCU
AGAAuuccAGcuGcAcAGGUU
1717


R-008308706-000W
2125
133
UGAACUUGCUCAGGACAAG
CUUGuccuGAGcAAGuucAUU
1719


R-008308706-000W
2125
133
UGAACUUGCUCAGGACAAG
B uGAAcuuGcucAGGAcAAGTT B
1718


R-008308724-000N
2503
134
UGCUGACUAUCCAGUUGAU
B uGcuGAcuAuccAGuuGAuTT B
1720


R-008308724-000N
2503
134
UGCUGACUAUCCAGUUGAU
AUCAAcuGGAuAGucAGcAUU
1721


R-008308703-000V
1502
135
GAUGAUAUAAAUGUGGUCA
UGAccAcAuuuAuAucAucUU
1723


R-008308703-000V
1502
135
GAUGAUAUAAAUGUGGUCA
B GAuGAuAuAAAuGuGGucATT B
1722


R-008308496-000Y
2502
136
GUGCUGACUAUCCAGUUGA
UCAAcuGGAuAGucAGcAcUU
1725


R-008308496-000Y
2502
136
GUGCUGACUAUCCAGUUGA
B GuGcuGAcuAuccAGuuGATT B
1724


R-008308625-000M
2506
137
UGACUAUCCAGUUGAUGGG
CCCAucAAcuGGAuAGucAUU      
1727


R-008308625-000M
2506
137
UGACUAUCCAGUUGAUGGG
B uGAcuAuccAGuuGAuGGGTT B   
1726


R-008308589-000S
2127
138
AACUUGCUCAGGACAAGGA
B AAcuuGcucAGGAcAAGGATT B
1728


R-008308589-000S
2127
138
AACUUGCUCAGGACAAGGA
UCCuuGuccuGAGcAAGuuUU
1729


R-008308586-000R
2505
139
CUGACUAUCCAGUUGAUGG
B cuGAcuAuccAGuuGAuGGTT B
1730


R-008308586-000R
2505
139
CUGACUAUCCAGUUGAUGG
CCAucAAcuGGAuAGucAGUU
1731


R-008308493-000X
617
140
GCUCAUCCCACUAAUGUCC
B GcucAucccAcuAAuGuccTT B
1732


R-008308493-000X
617
140
GCUCAUCCCACUAAUGUCC
GGAcAuuAGuGGGAuGAGcUU
1733


R-008308697-000B
2504
141
GCUGACUAUCCAGUUGAUG
B GcuGAcuAuccAGuuGAuGTT B
1734


R-008308697-000B
2504
141
GCUGACUAUCCAGUUGAUG
CAUcAAcuGGAuAGucAGcUU
1735


R-008308661-000X
1503
142
AUGAUAUAAAUGUGGUCAC
GUGAccAcAuuuAuAucAuUU
1737


R-008308661-000X
1503
142
AUGAUAUAAAUGUGGUCAC
B AuGAuAuAAAuGuGGucAcTT B
1736


R-008308526-000L
618
143
CUCAUCCCACUAAUGUCCA
UGGAcAuuAGuGGGAuGAGUU
1739


R-008308526-000L
618
143
CUCAUCCCACUAAUGUCCA
B cucAucccAcuAAuGuccATT B
1738


R-008308556-000N
2074
144
GCUUUAUUCUCCCAUUGAA
B GcuuuAuucucccAuuGAATT B
1740


R-008308556-000N
2074
144
GCUUUAUUCUCCCAUUGAA
UUCAAuGGGAGAAuAAAGcUU
1741


R-008308523-000K
2499
145
CUGGUGCUGACUAUCCAGU
B cuGGuGcuGAcuAuccAGuTT B
1742


R-008308523-000K
2499
145
CUGGUGCUGACUAUCCAGU
ACUGGAuAGucAGcAccAGUU
1743


R-008362860-000A
1406
146
AACUGUCUUUGGACUCUCA
B AAcuGucuuuGGAcucucATT B
1744


R-008362860-000A
1406
146
AACUGUCUUUGGACUCUCA
UGAGAGuccAAAGAcAGuuUU
1745


R-008362809-000Z
582
147
AGGGCAUGCAGAUCCCAUC
GAUGGGAucuGcAuGcccuUU
1747


R-008362809-000Z
582
147
AGGGCAUGCAGAUCCCAUC
B AGGGcAuGcAGAucccAucTT B
1746


R-008362908-000A
1505
148
GAUAUAAAUGUGGUCACCU
B GAuAuAAAuGuGGucAccuTT B
1748


R-008362908-000A
1505
148
GAUAUAAAUGUGGUCACCU
AGGuGAccAcAuuuAuAucUU
1749


R-008362713-000E
1432
149
UUCAGAUGCUGCAACUAAA
UUUAGuuGcAGcAucuGAAUU
1751


R-008362713-000E
1432
149
UUCAGAUGCUGCAACUAAA
B uucAGAuGcuGcAAcuAAATT B
1750


R-008363073-000K
1968
150
AAGAAAUAGUUGAAGGUUG
B AAGAAAuAGuuGAAGGuuGTT B
1752


R-008363073-000K
1968
150
AAGAAAUAGUUGAAGGUUG
CAAccuucAAcuAuuucuuUU
1753


R-008362947-000L
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuTT B
1754


R-008362947-000L
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcuAGGAucAuccuGGUU
1755


R-008363070-000J
954
152
UGGCCAUCUUUAAGUCUGG
CCAGAcuuAAAGAuGGccAUU
1757


R-008363070-000J
954
152
UGGCCAUCUUUAAGUCUGG
B uGGccAucuuuAAGucuGGTT B
1756


R-008362857-000U
505
153
AGCUGAUAUUGAUGGACAG
B AGcuGAuAuuGAuGGAcAGTT B
1758


R-008362857-000U
505
153
AGCUGAUAUUGAUGGACAG
CUGuccAucAAuAucAGcuUU
1759


R-008363067-000C
2011
154
UCGGGAUGUUCACAACCGA
B ucGGGAuGuucAcAAccGATT B
1760


R-008363067-000C
2011
154
UCGGGAUGUUCACAACCGA
UCGGuuGuGAAcAucccGAUU       
1761


R-008362944-000K
1339
155
UGUAGAAGCUGGUGGAAUG
B uGuAGAAGcuGGuGGAAuGTT B   
1762


R-008362944-000K
1339
155
UGUAGAAGCUGGUGGAAUG
CAUuccAccAGcuucuAcAUU
1763


R-008362761-000Z
1242
156
UAAAUAUAAUGAGGACCUA
B uAAAuAuAAuGAGGAccuATT B
1764


R-008362761-000Z
1242
156
UAAAUAUAAUGAGGACCUA
UAGGuccucAuuAuAuuuAUU
1765


R-008362758-000T
567
157
CUGAGACAUUAGAUGAGGG
B cuGAGAcAuuAGAuGAGGGTT B
1766


R-008362758-000T
567
157
CUGAGACAUUAGAUGAGGG
CCCucAucuAAuGucucAGUU
1767


R-008363007-000Y
1240
158
AGUAAAUAUAAUGAGGACC
B AGuAAAuAuAAuGAGGAccTT B
1768


R-008363007-000Y
1240
158
AGUAAAUAUAAUGAGGACC
GGUccucAuuAuAuuuAcuUU
1769


R-008362854-000T
438
159
UGGAUACCUCCCAAGUCCU
B uGGAuAccucccAAGuccuTT B
1770


R-008362854-000T
438
159
UGGAUACCUCCCAAGUCCU
AGGAcuuGGGAGGuAuccAUU
1771


R-008362755-000S
2445
160
AGGAUGCCUUGGGUAUGGA
UCCAuAcccAAGGcAuccuUU
1773


R-008362755-000S
2445
160
AGGAUGCCUUGGGUAUGGA
B AGGAuGccuuGGGuAuGGATT B
1772


R-008363064-000B
860
161
AUUGUACGUACCAUGCAGA
B AuuGuAcGuAccAuGcAGATT B
1774


R-008363064-000B
860
161
AUUGUACGUACCAUGCAGA
UCUGcAuGGuAcGuAcAAuUU
1775


R-008362752-000R
1413
162
UUUGGACUCUCAGGAAUCU
B uuuGGAcucucAGGAAucuTT B
1776


R-008362752-000R
1413
162
UUUGGACUCUCAGGAAUCU
AGAuuccuGAGAGuccAAAUU
1777


R-008363061-000A
1800
163
UUGGAUUGAUUCGAAAUCU
AGAuuucGAAucAAuccAAUU
1779


R-008363061-000A
1800
163
UUGGAUUGAUUCGAAAUCU
B uuGGAuuGAuucGAAAucuTT B
1778


R-008363004-000X
2037
164
UCAGAGGACUAAAUACCAU
AUGGuAuuuAGuccucuGAUU
1781


R-008363004-000X
2037
164
UCAGAGGACUAAAUACCAU
B ucAGAGGAcuAAAuAccAuTT B
1780


R-008362851-000S
2443
165
CCAGGAUGCCUUGGGUAUG
B ccAGGAuGccuuGGGuAuGTT B
1782


R-008362851-000S
2443
165
CCAGGAUGCCUUGGGUAUG
CAUAcccAAGGcAuccuGGUU
1783


R-008363001-000W
2471
166
AUGGAACAUGAGAUGGGUG
B AuGGAAcAuGAGAuGGGuGTT B
1784


R-008363001-000W
2471
166
AUGGAACAUGAGAUGGGUG
CACccAucucAuGuuccAuUU
1785


R-008362905-000Z
1792
167
GGCUACUGUUGGAUUGAUU
B GGcuAcuGuuGGAuuGAuuTT B
1786


R-008362905-000Z
1792
167
GGCUACUGUUGGAUUGAUU
AAUcAAuccAAcAGuAGccUU
1787


R-008362902-000Y
2547
168
AGGACCUCAUGGAUGGGCU
B AGGAccucAuGGAuGGGcuTT B
1788


R-008362902-000Y
2547
168
AGGACCUCAUGGAUGGGCU
AGCccAuccAuGAGGuccuUU
1789


R-008362998-000G
1662
169
UCUGUGCUCUUCGUCAUCU
AGAuGAcGAAGAGcAcAGAUU
1791


R-008362998-000G
1662
169
UCUGUGCUCUUCGUCAUCU
B ucuGuGcucuucGucAucuTT B
1790


R-008362848-000K
288
170
UGAUGGAGUUGGACAUGGC
GCCAuGuccAAcuccAucAUU
1793


R-008362848-000K
288
170
UGAUGGAGUUGGACAUGGC
B uGAuGGAGuuGGAcAuGGcTT B
1792


R-008362710-000D
579
171
AUGAGGGCAUGCAGAUCCC
GGGAucuGcAuGcccucAuUU
1795


R-008362710-000D
579
171
AUGAGGGCAUGCAGAUCCC
B AuGAGGGcAuGcAGAucccTT B
1794


R-008362707-000X
2508
172
ACUAUCCAGUUGAUGGGCU
AGCccAucAAcuGGAuAGuUU
1797


R-008362707-000X
2508
172
ACUAUCCAGUUGAUGGGCU
B AcuAuccAGuuGAuGGGcuTT B  
1796


R-008362806-000Y
580
173
UGAGGGCAUGCAGAUCCCA
B uGAGGGcAuGcAGAucccATT B 
1798


R-008362806-000Y
580
173
UGAGGGCAUGCAGAUCCCA
UGGGAucuGcAuGcccucAUU
1799


R-008362803-000X
2388
174
UUGGAUAUCGCCAGGAUGA
B uuGGAuAucGccAGGAuGATT B
1800


R-008362803-000X
2388
174
UUGGAUAUCGCCAGGAUGA
UCAuccuGGcGAuAuccAAUU
1801


R-008362899-000F
2543
175
GCCCAGGACCUCAUGGAUG
B GcccAGGAccucAuGGAuGTT B 
1802


R-008362899-000F
2543
175
GCCCAGGACCUCAUGGAUG
CAUccAuGAGGuccuGGGcUU
1803


R-008362749-000J
708
176
AACUUGCCACACGUGCAAU
B AAcuuGccAcAcGuGcAAuTT B
1804


R-008362749-000J
708
176
AACUUGCCACACGUGCAAU
AUUGcAcGuGuGGcAAGuuUU
1805


R-008362845-000J
447
177
CCCAAGUCCUGUAUGAGUG
B cccAAGuccuGuAuGAGuGTT B
1806


R-008362845-000J
447
177
CCCAAGUCCUGUAUGAGUG
CACucAuAcAGGAcuuGGGUU
1807


R-008362842-000H
654
178
CACAGAUGCUGAAACAUGC
GCAuGuuucAGcAucuGuGUU
1809


R-008362842-000H
654
178
CACAGAUGCUGAAACAUGC
B cAcAGAuGcuGAAAcAuGcTT B
1808


R-008362896-000E
912
179
CUGGGACCUUGCAUAACCU
B cuGGGAccuuGcAuAAccuTT B
1810


R-008362896-000E
912
179
CUGGGACCUUGCAUAACCU
AGGuuAuGcAAGGucccAGUU
1811


R-008363058-000U
1009
180
AGUGGAUUCUGUGUUGUUU
AAAcAAcAcAGAAuccAcuUU
1813


R-008363058-000U
1009
180
AGUGGAUUCUGUGUUGUUU
B AGuGGAuucuGuGuuGuuuTT B 
1812


R-008362941-000J
1354
181
AAUGCAAGCUUUAGGACUU
B AAuGcAAGcuuuAGGAcuuTT B 
1814


R-008362941-000J
1354
181
AAUGCAAGCUUUAGGACUU
AAGuccuAAAGcuuGcAuuUU
1815


R-008362839-000B
1969
182
AGAAAUAGUUGAAGGUUGU
B AGAAAuAGuuGAAGGuuGuTT B
1816


R-008362839-000B
1969
182
AGAAAUAGUUGAAGGUUGU
ACAAccuucAAcuAuuucuUU
1817


R-008363055-000T
1959
183
UCCGCAUGGAAGAAAUAGU
ACUAuuucuuccAuGcGGAUU
1819


R-008363055-000T
1959
183
UCCGCAUGGAAGAAAUAGU
B uccGcAuGGAAGAAAuAGuTT B
1818


R-008362836-000A
557
184
GCUAUGUUCCCUGAGACAU
B GcuAuGuucccuGAGAcAuTT B
1820


R-008362836-000A
557
184
GCUAUGUUCCCUGAGACAU
AUGucucAGGGAAcAuAGcUU
1821


R-008363052-000S
403
185
UCUGAGUGGUAAAGGCAAU
AUUGccuuuAccAcucAGAUU
1823


R-008363052-000S
403
185
UCUGAGUGGUAAAGGCAAU
B ucuGAGuGGuAAAGGcAAuTT B
1822


R-008363049-000K
1356
186
UGCAAGCUUUAGGACUUCA
B uGcAAGcuuuAGGAcuucATT B
1824


R-008363049-000K
1356
186
UGCAAGCUUUAGGACUUCA
UGAAGuccuAAAGcuuGcAUU
1825


R-008362893-000D
517
187
UGGACAGUAUGCAAUGACU
B uGGAcAGuAuGcAAuGAcuTT B
1826


R-008362893-000D
517
187
UGGACAGUAUGCAAUGACU
AGUcAuuGcAuAcuGuccAUU
1827


R-008362890-000C
1238
188
UUAGUAAAUAUAAUGAGGA
UCCucAuuAuAuuuAcuAAUU
1829


R-008362890-000C
1238
188
UUAGUAAAUAUAAUGAGGA
B uuAGuAAAuAuAAuGAGGATT B
1828


R-008362995-000F
843
189
CUCAGAUGGUGUCUGCUAU
B cucAGAuGGuGucuGcuAuTT B
1830


R-008362995-000F
843
189
CUCAGAUGGUGUCUGCUAU
AUAGcAGAcAccAucuGAGUU
1831


R-008362992-000E
496
190
AGAACAAGUAGCUGAUAUU
B AGAAcAAGuAGcuGAuAuuTT B 
1832


R-008362992-000E
496
190
AGAACAAGUAGCUGAUAUU
AAUAucAGcuAcuuGuucuUU
1833


R-008363046-000J
2387
191
CUUGGAUAUCGCCAGGAUG
B cuuGGAuAucGccAGGAuGTT B
1834


R-008363046-000J
2387
191
CUUGGAUAUCGCCAGGAUG
CAUccuGGcGAuAuccAAGUU
1835


R-008362704-000W
1660
192
CAUCUGUGCUCUUCGUCAU
AUGAcGAAGAGcAcAGAuGUU
1837


R-008362704-000W
1660
192
CAUCUGUGCUCUUCGUCAU
B cAucuGuGcucuucGucAuTT B
1836


R-008362938-000C
2497
193
CCCUGGUGCUGACUAUCCA
B cccuGGuGcuGAcuAuccATT B 
1838


R-008362938-000C
2497
193
CCCUGGUGCUGACUAUCCA
UGGAuAGucAGcAccAGGGUU
1839


R-008363043-000H
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuTT B
1840


R-008363043-000H
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUU
1841


R-008362746-000H
2353
195
UCUUGGACUUGAUAUUGGU
B ucuuGGAcuuGAuAuuGGuTT B
1842


R-008362746-000H
2353
195
UCUUGGACUUGAUAUUGGU
ACCAAuAucAAGuccAAGAUU
1843


R-008362743-000G
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuTT B
1844


R-008362743-000G
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAGcuAGGAucAuccUU
1845


R-008362887-000W
1238
188
UUAGUAAAUAUAAUGAGGA
B UUAGUAAAUAUAAUGAGGATT B
1846


R-008362887-000W
1238
188
UUAGUAAAUAUAAUGAGGA
UCCUCAUUAUAUUUACUAAUU
1847


R-008363040-000G
2125
133
UGAACUUGCUCAGGACAAG
B UGAACUUGCUCAGGACAAGTT B
1848


R-008363040-000G
2125
133
UGAACUUGCUCAGGACAAG
CUUGUCCUGAGCAAGUUCAUU
1849


R-008362935-000B
843
189
CUCAGAUGGUGUCUGCUAU
AUAGCAGACACCAUCUGAGUU
1851


R-008362935-000B
843
189
CUCAGAUGGUGUCUGCUAU
B CUCAGAUGGUGUCUGCUAUTT B
1850


R-008362740-000F
496
190
AGAACAAGUAGCUGAUAUU
AAUAUCAGCUACUUGUUCUUU
1853


R-008362740-000F
496
190
AGAACAAGUAGCUGAUAUU
B AGAACAAGUAGCUGAUAUUTT B
1852


R-008362884-000V
2074
144
GCUUUAUUCUCCCAUUGAA
UUCAAUGGGAGAAUAAAGCUU
1855


R-008362884-000V
2074
144
GCUUUAUUCUCCCAUUGAA
B GCUUUAUUCUCCCAUUGAATT B
1854


R-008362701-000V
2503
134
UGCUGACUAUCCAGUUGAU
B UGCUGACUAUCCAGUUGAUTT B
1856


R-008362701-000V
2503
134
UGCUGACUAUCCAGUUGAU
AUCAACUGGAUAGUCAGCAUU
1857


R-008362698-000C
2387
191
CUUGGAUAUCGCCAGGAUG
B CUUGGAUAUCGCCAGGAUGTT B
1858


R-008362698-000C
2387
191
CUUGGAUAUCGCCAGGAUG
CAUCCUGGCGAUAUCCAAGUU
1859


R-008362800-000W
1660
192
CAUCUGUGCUCUUCGUCAU
AUGACGAAGAGCACAGAUGUU
1861


R-008362800-000W
1660
192
CAUCUGUGCUCUUCGUCAU
B CAUCUGUGCUCUUCGUCAUTT B
1860


R-008362737-000Z
2497
193
CCCUGGUGCUGACUAUCCA
B CCCUGGUGCUGACUAUCCATT B
1862


R-008362737-000Z
2497
193
CCCUGGUGCUGACUAUCCA
UGGAUAGUCAGCACCAGGGUU
1863


R-008363037-000A
1503
142
AUGAUAUAAAUGUGGUCAC
B AUGAUAUAAAUGUGGUCACTT B 
1864


R-008363037-000A
1503
142
AUGAUAUAAAUGUGGUCAC
GUGACCACAUUUAUAUCAUUU
1865


R-008362734-000Y
2506
137
UGACUAUCCAGUUGAUGGG
CCCAUCAACUGGAUAGUCAUU
1867


R-008362734-000Y
2506
137
UGACUAUCCAGUUGAUGGG
B UGACUAUCCAGUUGAUGGGTT B  
1866


R-008362797-000D
2052
71
CCAUUCCAUUGUUUGUGCA
UGCACAAACAAUGGAAUGGUU
1869


R-008362797-000D
2052
71
CCAUUCCAUUGUUUGUGCA
B CCAUUCCAUUGUUUGUGCATT B
1868


R-008362731-000X
2389
129
UGGAUAUCGCCAGGAUGAU
B UGGAUAUCGCCAGGAUGAUTT B
1870


R-008362731-000X
2389
129
UGGAUAUCGCCAGGAUGAU
AUCAUCCUGGCGAUAUCCAUU
1871


R-008362794-000C
1406
146
AACUGUCUUUGGACUCUCA
B AACUGUCUUUGGACUCUCATT B
1872


R-008362794-000C
1406
146
AACUGUCUUUGGACUCUCA
UGAGAGUCCAAAGACAGUUUU
1873


R-008362833-000Z
1796
12
ACUGUUGGAUUGAUUCGAA
B ACUGUUGGAUUGAUUCGAATT B
1874


R-008362833-000Z
1796
12
ACUGUUGGAUUGAUUCGAA
UUCGAAUCAAUCCAACAGUUU
1875


R-008362989-000Y
2505
139
CUGACUAUCCAGUUGAUGG
B CUGACUAUCCAGUUGAUGGTT B
1876


R-008362989-000Y
2505
139
CUGACUAUCCAGUUGAUGG
CCAUCAACUGGAUAGUCAGUU
1877


R-008362791-000B
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAATT B
1878


R-008362791-000B
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUU
1879


R-008362881-000U
643
75
GGCUGAACCAUCACAGAUG
B GGCUGAACCAUCACAGAUGTT B
1880


R-008362881-000U
643
75
GGCUGAACCAUCACAGAUG
CAUCUGUGAUGGUUCAGCCUU
1881


R-008363034-000Z
582
147
AGGGCAUGCAGAUCCCAUC
GAUGGGAUCUGCAUGCCCUUU
1883


R-008363034-000Z
582
147
AGGGCAUGCAGAUCCCAUC
B AGGGCAUGCAGAUCCCAUCTT B
1882


R-008362830-000Y
2502
136
GUGCUGACUAUCCAGUUGA
B GUGCUGACUAUCCAGUUGATT B
1884


R-008362830-000Y
2502
136
GUGCUGACUAUCCAGUUGA
UCAACUGGAUAGUCAGCACUU
1885


R-008362827-000S
1505
148
GAUAUAAAUGUGGUCACCU
AGGUGACCACAUUUAUAUCUU
1887


R-008362827-000S
1505
148
GAUAUAAAUGUGGUCACCU
B GAUAUAAAUGUGGUCACCUTT B
1886


R-008362728-000R
1432
149
UUCAGAUGCUGCAACUAAA
B UUCAGAUGCUGCAACUAAATT B
1888


R-008362728-000R
1432
149
UUCAGAUGCUGCAACUAAA
UUUAGUUGCAGCAUCUGAAUU
1889


R-008362986-000X
1968
150
AAGAAAUAGUUGAAGGUUG
CAACCUUCAACUAUUUCUUUU
1891


R-008362986-000X
1968
150
AAGAAAUAGUUGAAGGUUG
B AAGAAAUAGUUGAAGGUUGTT B
1890


R-008362878-000M
694
109
UCAAGAUGAUGCAGAACUU
B UCAAGAUGAUGCAGAACUUTT B
1892


R-008362878-000M
694
109
UCAAGAUGAUGCAGAACUU
AAGUUCUGCAUCAUCUUGAUU
1893


R-008362824-000R
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUU
1895


R-008362824-000R
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUTT B
1894


R-008362932-000A
2259
125
AGGACAAGCCACAAGAUUA
UAAUCUUGUGGCUUGUCCUUU
1897


R-008362932-000A
2259
125
AGGACAAGCCACAAGAUUA
B AGGACAAGCCACAAGAUUATT B
1896


R-008362788-000V
954
152
UGGCCAUCUUUAAGUCUGG
B UGGCCAUCUUUAAGUCUGGTT B
1898


R-008362788-000V
954
152
UGGCCAUCUUUAAGUCUGG
CCAGACUUAAAGAUGGCCAUU
1899


R-008362983-000W
2197
116
ACUUCACUCUAGGAAUGAA
B ACUUCACUCUAGGAAUGAATT B
1900


R-008362983-000W
2197
116
ACUUCACUCUAGGAAUGAA
UUCAUUCCUAGAGUGAAGUUU
1901


R-008362929-000U
505
153
AGCUGAUAUUGAUGGACAG
B AGCUGAUAUUGAUGGACAGTT B
1902


R-008362929-000U
505
153
AGCUGAUAUUGAUGGACAG
CUGUCCAUCAAUAUCAGCUUU
1903


R-008362926-000T
2011
154
UCGGGAUGUUCACAACCGA
B UCGGGAUGUUCACAACCGATT B
1904


R-008362926-000T
2011
154
UCGGGAUGUUCACAACCGA
UCGGUUGUGAACAUCCCGAUU
1905


R-008362923-000S
1339
155
UGUAGAAGCUGGUGGAAUG
B UGUAGAAGCUGGUGGAAUGTT B
1906


R-008362923-000S
1339
155
UGUAGAAGCUGGUGGAAUG
CAUUCCACCAGCUUCUACAUU
1907


R-008362695-000B
1242
156
UAAAUAUAAUGAGGACCUA
B UAAAUAUAAUGAGGACCUATT B
1908


R-008362695-000B
1242
156
UAAAUAUAAUGAGGACCUA
UAGGUCCUCAUUAUAUUUAUU
1909


R-008362692-000A
499
107
ACAAGUAGCUGAUAUUGAU
B ACAAGUAGCUGAUAUUGAUTT B
1910


R-008362692-000A
499
107
ACAAGUAGCUGAUAUUGAU
AUCAAUAUCAGCUACUUGUUU
1911


R-008362689-000U
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUU
1913


R-008362689-000U
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUTT B
1912


R-008362785-000U
2353
195
UCUUGGACUUGAUAUUGGU
B UCUUGGACUUGAUAUUGGUTT B
1914


R-008362785-000U
2353
195
UCUUGGACUUGAUAUUGGU
ACCAAUAUCAAGUCCAAGAUU
1915


R-008363031-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUU
1917


R-008363031-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUTT B
1916


R-008362920-000R
878
197
AAUACAAAUGAUGUAGAAA
UUUCUACAUCAUUUGUAUUUU
1919


R-008362920-000R
878
197
AAUACAAAUGAUGUAGAAA
B AAUACAAAUGAUGUAGAAATT B
1918


R-008362917-000J
2046
112
UAAAUACCAUUCCAUUGUU
AACAAUGGAAUGGUAUUUAUU
1921


R-008362917-000J
2046
112
UAAAUACCAUUCCAUUGUU
B UAAAUACCAUUCCAUUGUUTT B
1920


R-008362980-000V
647
198
GAACCAUCACAGAUGCUGA
UCAGCAUCUGUGAUGGUUCUU
1923


R-008362980-000V
647
198
GAACCAUCACAGAUGCUGA
B GAACCAUCACAGAUGCUGATT B
1922


R-008362725-000P
1998
199
UUCACAUCCUAGCUCGGGA
B UUCACAUCCUAGCUCGGGATT B
1924


R-008362725-000P
1998
199
UUCACAUCCUAGCUCGGGA
UCCCGAGCUAGGAUGUGAAUU
1925


R-008363028-000S
588
200
UGCAGAUCCCAUCUACACA
UGUGUAGAUGGGAUCUGCAUU
1927


R-008363028-000S
588
200
UGCAGAUCCCAUCUACACA
B UGCAGAUCCCAUCUACACATT B
1926


R-008362782-000T
2042
201
GGACUAAAUACCAUUCCAU
AUGGAAUGGUAUUUAGUCCUU
1929


R-008362782-000T
2042
201
GGACUAAAUACCAUUCCAU
B GGACUAAAUACCAUUCCAUTT B
1928


R-008362977-000N
855
202
CUGCUAUUGUACGUACCAU
B CUGCUAUUGUACGUACCAUTT B
1930


R-008362977-000N
855
202
CUGCUAUUGUACGUACCAU
AUGGUACGUACAAUAGCAGUU
1931


R-008362686-000T
2038
203
CAGAGGACUAAAUACCAUU
AAUGGUAUUUAGUCCUCUGUU
1933


R-008362686-000T
2038
203
CAGAGGACUAAAUACCAUU
B CAGAGGACUAAAUACCAUUTT B
1932


R-008362875-000L
1786
204
GAUAAAGGCUACUGUUGGA
UCCAACAGUAGCCUUUAUCUU
1935


R-008362875-000L
1786
204
GAUAAAGGCUACUGUUGGA
B GAUAAAGGCUACUGUUGGATT B
1934


R-008363025-000R
1501
205
AGAUGAUAUAAAUGUGGUC
B AGAUGAUAUAAAUGUGGUCTT B
1936


R-008363025-000R
1501
205
AGAUGAUAUAAAUGUGGUC
GACCACAUUUAUAUCAUCUUU
1937


R-008362914-000H
1834
206
AAAUCAUGCACCUUUGCGU
ACGCAAAGGUGCAUGAUUUUU
1939


R-008362914-000H
1834
206
AAAUCAUGCACCUUUGCGU
B AAAUCAUGCACCUUUGCGUTT B
1938


R-008362872-000K
1157
207
ACGACAGACUGCCUUCAAA
B ACGACAGACUGCCUUCAAATT B
1940


R-008362872-000K
1157
207
ACGACAGACUGCCUUCAAA
UUUGAAGGCAGUCUGUCGUUU
1941


R-008362974-000M
1239
208
UAGUAAAUAUAAUGAGGAC
B UAGUAAAUAUAAUGAGGACTT B
1942


R-008362974-000M
1239
208
UAGUAAAUAUAAUGAGGAC
GUCCUCAUUAUAUUUACUAUU
1943


R-008362821-000P
1248
209
UAAUGAGGACCUAUACUUA
B UAAUGAGGACCUAUACUUATT B
1944


R-008362821-000P
1248
209
UAAUGAGGACCUAUACUUA
UAAGUAUAGGUCCUCAUUAUU
1945


R-008362683-000S
660
210
UGCUGAAACAUGCAGUUGU
B UGCUGAAACAUGCAGUUGUTT B
1946


R-008362683-000S
660
210
UGCUGAAACAUGCAGUUGU
ACAACUGCAUGUUUCAGCAUU
1947


R-008363022-000P
285
211
AUUUGAUGGAGUUGGACAU
B AUUUGAUGGAGUUGGACAUTT B
1948


R-008363022-000P
285
211
AUUUGAUGGAGUUGGACAU
AUGUCCAACUCCAUCAAAUUU
1949


R-008362779-000L
1582
212
CUGCCAAGUGGGUGGUAUA
B CUGCCAAGUGGGUGGUAUATT B
1950


R-008362779-000L
1582
212
CUGCCAAGUGGGUGGUAUA
UAUACCACCCACUUGGCAGUU
1951


R-008363019-000H
1735
213
UGGACUACCAGUUGUGGUU
AACCACAACUGGUAGUCCAUU
1953


R-008363019-000H
1735
213
UGGACUACCAGUUGUGGUU
B UGGACUACCAGUUGUGGUUTT B
1952


R-008362776-000K
771
214
UUAAUAAGGCUGCAGUUAU
AUAACUGCAGCCUUAUUAAUU
1955


R-008362776-000K
771
214
UUAAUAAGGCUGCAGUUAU
B UUAAUAAGGCUGCAGUUAUTT B
1954


R-008363016-000G
1060
215
ACAUCAAGAAGGAGCUAAA
B ACAUCAAGAAGGAGCUAAATT B
1956


R-008363016-000G
1060
215
ACAUCAAGAAGGAGCUAAA
UUUAGCUCCUUCUUGAUGUUU
1957


R-008362773-000J
2390
216
GGAUAUCGCCAGGAUGAUC
GAUCAUCCUGGCGAUAUCCUU
1959


R-008362773-000J
2390
216
GGAUAUCGCCAGGAUGAUC
B GGAUAUCGCCAGGAUGAUCTT B
1958


R-008362971-000L
2509
81
CUAUCCAGUUGAUGGGCUG
CAGCCCAUCAACUGGAUAGUU
1961


R-008362971-000L
2509
81
CUAUCCAGUUGAUGGGCUG
B CUAUCCAGUUGAUGGGCUGTT B
1960


R-008362722-000N
2186
217
CUGACAGAGUUACUUCACU
B CUGACAGAGUUACUUCACUTT B
1962


R-008362722-000N
2186
217
CUGACAGAGUUACUUCACU
AGUGAAGUAACUCUGUCAGUU
1963


R-008363013-000F
1632
218
GUGACAGGGAAGACAUCAC
B GUGACAGGGAAGACAUCACTT B
1964


R-008363013-000F
1632
218
GUGACAGGGAAGACAUCAC
GUGAUGUCUUCCCUGUCACUU
1965


R-008362818-000H
619
219
UCAUCCCACUAAUGUCCAG
CUGGACAUUAGUGGGAUGAUU
1967


R-008362818-000H
619
219
UCAUCCCACUAAUGUCCAG
B UCAUCCCACUAAUGUCCAGTT B
1966


R-008362968-000E
1656
220
CUGCCAUCUGUGCUCUUCG
B CUGCCAUCUGUGCUCUUCGTT B
1968


R-008362968-000E
1656
220
CUGCCAUCUGUGCUCUUCG
CGAAGAGCACAGAUGGCAGUU
1969


R-008362815-000G
1506
221
AUAUAAAUGUGGUCACCUG
B AUAUAAAUGUGGUCACCUGTT B
1970


R-008362815-000G
1506
221
AUAUAAAUGUGGUCACCUG
CAGGUGACCACAUUUAUAUUU
1971


R-008362869-000D
2501
76
GGUGCUGACUAUCCAGUUG
B GGUGCUGACUAUCCAGUUGTT B
1972


R-008362869-000D
2501
76
GGUGCUGACUAUCCAGUUG
CAACUGGAUAGUCAGCACCUU
1973


R-008362719-000G
2494
222
CCACCCUGGUGCUGACUAU
AUAGUCAGCACCAGGGUGGUU
1975


R-008362719-000G
2494
222
CCACCCUGGUGCUGACUAU
B CCACCCUGGUGCUGACUAUTT B
1974


R-008362770-000H
1666
223
UGCUCUUCGUCAUCUGACC
GGUCAGAUGACGAAGAGCAUU
1977


R-008362770-000H
1666
223
UGCUCUUCGUCAUCUGACC
B UGCUCUUCGUCAUCUGACCTT B
1976


R-008362680-000R
1635
224
ACAGGGAAGACAUCACUGA
B ACAGGGAAGACAUCACUGATT B
1978


R-008362680-000R
1635
224
ACAGGGAAGACAUCACUGA
UCAGUGAUGUCUUCCCUGUUU
1979


R-008362866-000C
294
225
AGUUGGACAUGGCCAUGGA
UCCAUGGCCAUGUCCAACUUU
1981


R-008362866-000C
294
225
AGUUGGACAUGGCCAUGGA
B AGUUGGACAUGGCCAUGGATT B
1980


R-008362863-000B
641
226
UUGGCUGAACCAUCACAGA
B UUGGCUGAACCAUCACAGATT B
1982


R-008362863-000B
641
226
UUGGCUGAACCAUCACAGA
UCUGUGAUGGUUCAGCCAAUU
1983


R-008362965-000D
576
227
UAGAUGAGGGCAUGCAGAU
AUCUGCAUGCCCUCAUCUAUU
1985


R-008362965-000D
576
227
UAGAUGAGGGCAUGCAGAU
B UAGAUGAGGGCAUGCAGAUTT B
1984


R-008362911-000G
577
228
AGAUGAGGGCAUGCAGAUC
B AGAUGAGGGCAUGCAGAUCTT B
1986


R-008362911-000G
577
228
AGAUGAGGGCAUGCAGAUC
GAUCUGCAUGCCCUCAUCUUU
1987


R-008362767-000B
1661
229
AUCUGUGCUCUUCGUCAUC
GAUGACGAAGAGCACAGAUUU
1989


R-008362767-000B
1661
229
AUCUGUGCUCUUCGUCAUC
B AUCUGUGCUCUUCGUCAUCTT B
1988


R-008362962-000C
707
230
GAACUUGCCACACGUGCAA
B GAACUUGCCACACGUGCAATT B
1990


R-008362962-000C
707
230
GAACUUGCCACACGUGCAA
UUGCACGUGUGGCAAGUUCUU
1991


R-008362677-000J
1659
231
CCAUCUGUGCUCUUCGUCA
B CCAUCUGUGCUCUUCGUCATT B
1992


R-008362677-000J
1659
231
CCAUCUGUGCUCUUCGUCA
UGACGAAGAGCACAGAUGGUU
1993


R-008362674-000H
1547
88
CUCACUUGCAAUAAUUAUA
UAUAAUUAUUGCAAGUGAGUU
1995


R-008362674-000H
1547
88
CUCACUUGCAAUAAUUAUA
B CUCACUUGCAAUAAUUAUATT B
1994


R-008362959-000W
867
90
GUACCAUGCAGAAUACAAA
UUUGUAUUCUGCAUGGUACUU
1997


R-008362959-000W
867
90
GUACCAUGCAGAAUACAAA
B GUACCAUGCAGAAUACAAATT B
1996


R-008362956-000V
1185
232
AUGGCAACCAAGAAAGCAA
UUGCUUUCUUGGUUGCCAUUU
1999


R-008362956-000V
1185
232
AUGGCAACCAAGAAAGCAA
B AUGGCAACCAAGAAAGCAATT B
1998


R-008362764-000A
664
233
GAAACAUGCAGUUGUAAAC
GUUUACAACUGCAUGUUUCUU
2001


R-008362764-000A
664
233
GAAACAUGCAGUUGUAAAC
B GAAACAUGCAGUUGUAAACTT B
2000


R-008362716-000F
820
18
CAGACACGCUAUCAUGCGU
B CAGACACGCUAUCAUGCGUTT B
2002


R-008362716-000F
820
18
CAGACACGCUAUCAUGCGU
ACGCAUGAUAGCGUGUCUGUU
2003


R-008362812-000F
2266
101
GCCACAAGAUUACAAGAAA
UUUCUUGUAAUCUUGUGGCUU
2005


R-008362812-000F
2266
101
GCCACAAGAUUACAAGAAA
B GCCACAAGAUUACAAGAAATT B
2004


R-008362671-000G
1749
234
UGGUUAAGCUCUUACACCC
GGGUGUAAGAGCUUAACCAUU
2007


R-008362671-000G
1749
234
UGGUUAAGCUCUUACACCC
B UGGUUAAGCUCUUACACCCTT B
2006


R-008362953-000U
1234
235
AGCUUUAGUAAAUAUAAUG
B AGCUUUAGUAAAUAUAAUGTT B
2008


R-008362953-000U
1234
235
AGCUUUAGUAAAUAUAAUG
CAUUAUAUUUACUAAAGCUUU
2009


R-008362950-000T
691
236
CUAUCAAGAUGAUGCAGAA
B CUAUCAAGAUGAUGCAGAATT B
2010


R-008362950-000T
691
236
CUAUCAAGAUGAUGCAGAA
UUCUGCAUCAUCUUGAUAGUU
2011


R-008363010-000E
1387
237
AAGUCAACGUCUUGUUCAG
B AAGUCAACGUCUUGUUCAGTT B
2012


R-008363010-000E
1387
237
AAGUCAACGUCUUGUUCAG
CUGAACAAGACGUUGACUUUU
2013


R-008381224-000R
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2015


R-008381224-000R
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2014


R-008381211-000X
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2017


R-008381211-000X
1797
5
CUGUUGGAUUGAUUCGAAA
uuucGAAucAAuccAAcAGUsU
2016


R-008381038-000Y
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAAucAAuccAAcAGUsU
2019


R-008381038-000Y
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2018


R-008381052-000F
1797
5
CUGUUGGAUUGAUUCGAAA
uuucGAAucAAuccAAcAGUsU
2016


R-008381052-000F
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008381158-000T
1797
5
CUGUUGGAUUGAUUCGAAA
uuucGAAucAAuccAAcAGUsU
2016


R-008381158-000T
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008381341-000J
1797
5
CUGUUGGAUUGAUUCGAAA
uuucGAAucAAuccAAcAGUsU
2016


R-008381341-000J
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008381109-000P
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008381109-000P
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2023


R-008380818-000X
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008380818-000X
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2023


R-008381199-000W
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2023


R-008381199-000W
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008381296-000E
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2024


R-008381296-000E
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008381042-000N
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2024


R-008381042-000N
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008380923-000F
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008380923-000F
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2024


R-008381104-000W
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2025


R-008381104-000W
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008381098-000C
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2025


R-008381098-000C
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008380916-000P
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008380916-000P
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2025


R-008380906-000X
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008380906-000X
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAAucAAuccAAcAGUsU
2019


R-008381291-000L
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAAucAAuccAAcAGUsU
2019


R-008381291-000L
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008381334-000T
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAAucAAuccAAcAGUsU
2019


R-008381334-000T
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008381330-000H
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008381330-000H
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2026


R-008381036-000F
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2026


R-008381036-000F
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008381287-000W
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008381287-000W
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2026


R-008381027-000X
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2027


R-008381027-000X
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2028


R-008380896-000U
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2029


R-008380896-000U
2398
151
CCAGGAUGAUCCUAGCUAU
AuAGcuAGGAucAuccuGGUsU
2030


R-008381153-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcuAGGAucAuccuGGUsU
2032


R-008381153-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2031


R-008381323-000S
2398
151
CCAGGAUGAUCCUAGCUAU
AuAGcuAGGAucAuccuGGUsU
2030


R-008381323-000S
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381315-000S
2398
151
CCAGGAUGAUCCUAGCUAU
AuAGcuAGGAucAuccuGGUsU
2030


R-008381315-000S
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008380888-000U
2398
151
CCAGGAUGAUCCUAGCUAU
AuAGcuAGGAucAuccuGGUsU
2030


R-008380888-000U
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008381013-000V
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381013-000V
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2036


R-008381007-000M
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2036


R-008381007-000M
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008380995-000V
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008380995-000V
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2036


R-008380878-000B
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2037


R-008380878-000B
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381143-000G
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2037


R-008381143-000G
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008381282-000C
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008381282-000C
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2037


R-008380985-000C
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2038


R-008380985-000C
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381278-000M
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2038


R-008381278-000M
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008381139-000S
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2038


R-008381139-000S
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008380871-000R
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcuAGGAucAuccuGGUsU
2032


R-008380871-000R
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381272-000K
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcuAGGAucAuccuGGUsU
2032


R-008381272-000K
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008381268-000V
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcuAGGAucAuccuGGUsU
2032


R-008381268-000V
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008381133-000P
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2039


R-008381133-000P
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381261-000J
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2039


R-008381261-000J
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008381091-000S
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008381091-000S
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2039


R-008380861-000Y
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2041


R-008380861-000Y
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2040


R-008380853-000Y
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2043


R-008380853-000Y
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2042


R-008380811-000L
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2044


R-008380811-000L
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2045


R-008380974-000B
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2043


R-008380974-000B
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008380966-000B
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2043


R-008380966-000B
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008381310-000Y
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2043


R-008381310-000Y
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008381194-000C
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008381194-000C
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2049


R-008380833-000N
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008380833-000N
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2049


R-008381115-000X
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2049


R-008381115-000X
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008381242-000H
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2050


R-008381242-000H
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008381235-000S
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008381235-000S
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2050


R-008381231-000G
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2050


R-008381231-000G
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008381304-000R
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2051


R-008381304-000R
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008380828-000P
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008380828-000P
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2051


R-008380926-000G
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2051


R-008380926-000G
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008381350-000T
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2045


R-008381350-000T
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008381162-000H
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008381162-000H
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2045


R-008380823-000W
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2045


R-008380823-000W
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008381068-000A
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2052


R-008381068-000A
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008381190-000T
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2052


R-008381190-000T
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008380959-000K
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2052


R-008380959-000K
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008381084-000A
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2054


R-008381084-000A
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2053


R-008380848-000Z
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2055


R-008380848-000Z
2401
196
GGAUGAUCCUAGCUAUCGU
AcGAuAGcuAGGAucAuccUsU
2056


R-008380807-000W
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2057


R-008380807-000W
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAGcuAGGAucAuccUsU
2058


R-008380843-000F
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008380843-000F
2401
196
GGAUGAUCCUAGCUAUCGU
AcGAuAGcuAGGAucAuccUsU
2056


R-008381185-000U
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008381185-000U
2401
196
GGAUGAUCCUAGCUAUCGU
AcGAuAGcuAGGAucAuccUsU
2056


R-008380951-000R
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008380951-000R
2401
196
GGAUGAUCCUAGCUAUCGU
AcGAuAGcuAGGAucAuccUsU
2056


R-008380804-000V
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008380804-000V
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2062


R-008381179-000L
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008381179-000L
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2062


R-008381127-000G
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2062


R-008381127-000G
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008380945-000H
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008380945-000H
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2063


R-008381071-000G
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008381071-000G
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2063


R-008381173-000J
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008381173-000J
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2063


R-008381122-000N
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008381122-000N
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2064


R-008380801-000U
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008380801-000U
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2064


R-008380839-000R
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008380839-000R
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2064


R-008380835-000F
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAGcuAGGAucAuccUsU
2058


R-008380835-000F
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008381258-000C
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAGcuAGGAucAuccUsU
2058


R-008381258-000C
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008381169-000U
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAGcuAGGAucAuccUsU
2058


R-008381169-000U
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008380937-000H
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008380937-000H
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2065


R-008381251-000S
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008381251-000S
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2065


R-008380933-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008380933-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2065


R-008381748-000J
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUuGGAUUGAUUCGaAAUsU B 
2066


R-008381748-000J
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGaAUCAauccaACAGUsU
2067


R-008381708-000P
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUuGGaUUGaUUCGAAaUsU B 
2069


R-008381708-000P
1797
5
CUGUUGGAUUGAUUCGAAA
uuucGAauCaAUCcAaCaGUsU
2068


R-008381704-000E
1797
5
CUGUUGGAUUGAUUCGAAA
uUUcgAaUCaAuCCAACAGUsU
2070


R-008381704-000E
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUuGgaUUGAUuCGaAAUsU B
2071


R-008381746-000S
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGaaUCAAUCcAacaGUsU
2073


R-008381746-000S
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUGgaUUGaUUCgAAAUsU B
2072


R-008381728-000Z
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUGGAUUGAUuCgAAAUsU B
2074


R-008381728-000Z
1797
5
CUGUUGGAUUGAUUCGAAA
UUucGaAUCAAUCcAAcagUsU
2075


R-008381686-000B
1797
5
CUGUUGGAUUGAUUCGAAA
uuUCGAAUcaaUCCAAcAgUsU
2076


R-008381686-000B
1797
5
CUGUUGGAUUGAUUCGAAA
B CuGUUGgaUUgAuUCGAaaUsU B
2077


R-008381726-000G
1797
5
CUGUUGGAUUGAUUCGAAA
uuUcGAAUCaaUcCAACaGUsU
2078


R-008381726-000G
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUgGaUUGAUUCGaaAUsU B
2079


R-008381629-000Y
1797
5
CUGUUGGAUUGAUUCGAAA
UUucGAAuCaaUCCAacAGUsU
2081


R-008381629-000Y
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGaUUCGAaAUsU B
2080


R-008381724-000P
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUGgAUugAUUCgAAaUsU B
2083


R-008381724-000P
1797
5
CUGUUGGAUUGAUUCGAAA
uuuCgaAUCAAUCcAACagUsU
2082


R-008381670-000G
1797
5
CUGUUGGAUUGAUUCGAAA
B CugUUGGAUUGaUUcgaaaUsU B
2084


R-008381670-000G
1797
5
CUGUUGGAUUGAUUCGAAA
UuuCgAAUCAAUCcaACAGUsU
2085


R-008381666-000S
1797
5
CUGUUGGAUUGAUUCGAAA
UuuCGaauCAaUccaACAGUsU
2087


R-008381666-000S
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUgGaUugAUuCGaAAUsU B
2086


R-008381722-000X
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUgGAUUGAUUCgAAAUsU B
2088


R-008381722-000X
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgAauCAAUCcAAcagUsU
2089


R-008381700-000V
1797
5
CUGUUGGAUUGAUUCGAAA
uUuCGAAUCAaUCcaaCAGUsU
2090


R-008381700-000V
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUggAUUgaUUCGaAAUsU B
2091


R-008381650-000X
1797
5
CUGUUGGAUUGAUUCGAAA
UuUCGAAUcaauCCaACaGUsU
2093


R-008381650-000X
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGaUUGaUUCgAAAUsU B
2092


R-008381647-000R
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGaUUgaUUCgAaaUsU B
2094


R-008381647-000R
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgAAuCAauCcaaCAgUsU
2095


R-008381624-000E
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGaAUCAauCCAaCAGUsU
2097


R-008381624-000E
1797
5
CUGUUGGAUUGAUUCGAAA
B CuGuUgGAUUgaUUCGAaAUsU B
2096


R-008381682-000S
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGgAUUGAUUCGaaaUsU B
2098


R-008381682-000S
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcgaAUcAAUcCAACagUsU
2099


R-008381622-000M
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAaUcaAUCcaACAgUsU
2101


R-008381622-000M
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUggaUUgaUUCgaaaUsU B
2100


R-008381680-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
AuaGCUAggAUCAuCCuGGUsU
2103


R-008381680-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUgaUcCUaGCUAUUsU B
2102


R-008381606-000M
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGgaUGaUCCUAgCUAUUsU B
2104


R-008381606-000M
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgcuaGgaUCAuCcUGgUsU
2105


R-008381714-000X
2398
151
CCAGGAUGAUCCUAGCUAU
aUagCUAGGaUCauccUGgUsU
2106


R-008381714-000X
2398
151
CCAGGAUGAUCCUAGCUAU
B CCagGAUgAUCCUAGCUaUUsU B
2107


R-008381642-000X
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUaUUsU B
2109


R-008381642-000X
2398
151
CCAGGAUGAUCCUAGCUAU
aUagCuagGAUCAucCugGUsU
2108


R-008381662-000G
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcUAgGAuCauCCUggUsU
2111


R-008381662-000G
2398
151
CCAGGAUGAUCCUAGCUAU
B cCAGgAUGaUCCUagCUAUUsU B
2110


R-008381618-000X
2398
151
CCAGGAUGAUCCUAGCUAU
auAgCUaGGAuCauCCUGGUsU
2112


R-008381618-000X
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2113


R-008381698-000L
2398
151
CCAGGAUGAUCCUAGCUAU
aUaGCuaggAUcaUcCUGGUsU
2114


R-008381698-000L
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUagCUaUUsU B
2115


R-008381742-000G
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAgGAUgaUCCUaGCUAUUsU B
2117


R-008381742-000G
2398
151
CCAGGAUGAUCCUAGCUAU
aUagCUAggAuCAuCCuGgUsU
2116


R-008381738-000S
2398
151
CCAGGAUGAUCCUAGCUAU
B CCaggaUgaUCCUagCUaUUsU B
2118


R-008381738-000S
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUaGGAUcauCCUgGUsU
2119


R-008381660-000P
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAgGAUGAUCCUAGcUAUUsU B
2121


R-008381660-000P
2398
151
CCAGGAUGAUCCUAGCUAU
aUagcUAGGAUcaUCCugGUsU
2120


R-008381696-000U
2398
151
CCAGGAUGAUCCUAGCUAU
B CCaGGaUGAUCCUAGCUAUUsU B
2123


R-008381696-000U
2398
151
CCAGGAUGAUCCUAGCUAU
auAGcUaggauCAUCCuGGUsU
2122


R-008381636-000P
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGgaUCauCcuGGUsU
2125


R-008381636-000P
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGaUGaUCCuAgCUAUUsU B
2124


R-008381634-000X
2398
151
CCAGGAUGAUCCUAGCUAU
AUaGCUagGAucAuCCUgGUsU
2127


R-008381634-000X
2398
151
CCAGGAUGAUCCUAGCUAU
B cCAGGaUGAuCCUaGCUaUUsU B
2126


R-008381632-000E
2398
151
CCAGGAUGAUCCUAGCUAU
B CCaGgAUgAuCCUAGcUAUUsU B
2129


R-008381632-000E
2398
151
CCAGGAUGAUCCUAGCUAU
aUAGCuAGGAUCAUCcUggUsU
2128


R-008381736-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
AUaGCuAGGaUcAUcCUggUsU
2131


R-008381736-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
B CcaggAugaUCCUAGCUaUUsU B
2130


R-008381600-000K
2398
151
CCAGGAUGAUCCUAGCUAU
aUaGcUaggAUCAucCUGGUsU
2132


R-008381600-000K
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAgGaUGAUcCUaGCUAUUsU B
2133


R-008381732-000P
2398
151
CCAGGAUGAUCCUAGCUAU
aUagCuAGGaUCAuCcUgGUsU
2134


R-008381732-000P
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAggaUGAUCCUAgCUAuUsU B
2135


R-008381656-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGgAUgAUCCUAGcuaUUsU B
2136


R-008381656-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
AuagCUAgGauCAUcCUGGUsU
2137


R-008381750-000G
1870
194
ACGACUAGUUCAGUUGCUU
aagCAaCUGaAcuAGUCgUUsU
2138


R-008381750-000G
1870
194
ACGACUAGUUCAGUUGCUU
B ACgACuAgUUcAGUUGCUUUsU B
2139


R-008381690-000S
1870
194
ACGACUAGUUCAGUUGCUU
aAGcAACUgAaCUaGUCguUsU
2140


R-008381690-000S
1870
194
ACGACUAGUUCAGUUGCUU
B aCGACUAGuUCAgUugcUUUsU B
2141


R-008381616-000E
1870
194
ACGACUAGUUCAGUUGCUU
AAGcaACuGaaCUaGuCGUUsU
2143


R-008381616-000E
1870
194
ACGACUAGUUCAGUUGCUU
B aCGACUagUUCaGUUgCUUUsU B
2142


R-008381688-000U
1870
194
ACGACUAGUUCAGUUGCUU
aAgCaAcUGAACUAgUcGUUsU
2144


R-008381688-000U
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCuAGUuCAgUUgcUUUsU B
2145


R-008381614-000M
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCUAguUCAGUUGCUUUsU B
2147


R-008381614-000M
1870
194
ACGACUAGUUCAGUUGCUU
aaGCAAcUgAaCuagUcGUUsU
2146


R-008381706-000X
1870
194
ACGACUAGUUCAGUUGCUU
B ACGaCUAGUUCAGUUGCuUUsU B
2148


R-008381706-000X
1870
194
ACGACUAGUUCAGUUGCUU
AAgCAAcUGaACUaGUcgUUsU
2149


R-008381672-000Z
1870
194
ACGACUAGUUCAGUUGCUU
AAgCAacugAAcUagUCGUUsU
2151


R-008381672-000Z
1870
194
ACGACUAGUUCAGUUGCUU
B ACgACUAGUUCaGUUGcUUUsU B
2150


R-008381730-000X
1870
194
ACGACUAGUUCAGUUGCUU
AagcAaCUgaaCUAGucgUUsU
2153


R-008381730-000X
1870
194
ACGACUAGUUCAGUUGCUU
B acGACUagUUCagUuGCuUUsU B
2152


R-008381612-000V
1870
194
ACGACUAGUUCAGUUGCUU
B aCGAcUAGUUCAGUUgCUUUsU B
2154


R-008381612-000V
1870
194
ACGACUAGUUCAGUUGCUU
AaGCaAcUGAacUaGUcGUUsU
2155


R-008381702-000M
1870
194
ACGACUAGUUCAGUUGCUU
AAgcaaCUGAACuaGUCGUUsU
2157


R-008381702-000M
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUaGUUCaGUUgCUUUsU B
2156


R-008381744-000Z
1870
194
ACGACUAGUUCAGUUGCUU
B ACGaCUaGUUCAGUUGcUUUsU B
2158


R-008381744-000Z
1870
194
ACGACUAGUUCAGUUGCUU
AaGCAACUgaACUAGuCGUUsU
2159


R-008381610-000C
1870
194
ACGACUAGUUCAGUUGCUU
aAgCAACUGAacUaGuCgUUsU
2160


R-008381610-000C
1870
194
ACGACUAGUUCAGUUGCUU
B ACgACUAgUUCAgUUgCUUUsU B
2161


R-008381608-000E
1870
194
ACGACUAGUUCAGUUGCUU
B ACGaCUaGuUCagUUGCUUUsU B
2162


R-008381608-000E
1870
194
ACGACUAGUUCAGUUGCUU
AAgCAACUGaACUaGUCguUsU
2163


R-008381654-000G
1870
194
ACGACUAGUUCAGUUGCUU
aAgCAaCuGaAcuaGUCgUUsU
2164


R-008381654-000G
1870
194
ACGACUAGUUCAGUUGCUU
B ACGaCUaGUUCaguUgCUuUsU B
2165


R-008381668-000J
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2167


R-008381668-000J
1870
194
ACGACUAGUUCAGUUGCUU
aAgCAACugAACuaguCgUUsU
2166


R-008381627-000F
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCUAGUUCaGUUGCUUUsU B
2169


R-008381627-000F
1870
194
ACGACUAGUUCAGUUGCUU
aAGCAacUgaACUaGUcGUUsU
2168


R-008381719-000R
1870
194
ACGACUAGUUCAGUUGCUU
B ACgAcUAgUuCAgUUGCUUUsU B
2170


R-008381719-000R
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAAcUGAaCUaGUCGuUsU
2171


R-008381717-000Y
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCUagUUCagUUgCUUUsU B
2173


R-008381717-000Y
1870
194
ACGACUAGUUCAGUUGCUU
aaGCAACuGaACUagUcGuUsU
2172


R-008381652-000P
2401
196
GGAUGAUCCUAGCUAUCGU
ACgaUAGcuAGgauCAUCcUsU
2175


R-008381652-000P
2401
196
GGAUGAUCCUAGCUAUCGU
B gGaugaUcCUaGCuAUCgUUsU B
2174


R-008381684-000J
2401
196
GGAUGAUCCUAGCUAUCGU
B GgAUGaUCCuagcUAUCgUUsU B
2177


R-008381684-000J
2401
196
GGAUGAUCCUAGCUAUCGU
aCgAUagcuaGGAUcAUCCUsU
2176


R-008381664-000Z
2401
196
GGAUGAUCCUAGCUAUCGU
B gGAUgAUCCUAGCuaUCGUUsU B
2179


R-008381664-000Z
2401
196
GGAUGAUCCUAGCUAUCGU
aCGauAGCuAgGaUcauCCUsU
2178


R-008381645-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
acgAUAGCUaGgAUCAuCCUsU
2180


R-008381645-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
B gGAUGAUCCUAgCUauCGUUsU B
2181


R-008381678-000B
2401
196
GGAUGAUCCUAGCUAUCGU
ACgaUAgCUaGGAuCAUCcUsU
2183


R-008381678-000B
2401
196
GGAUGAUCCUAGCUAUCGU
B ggaUgaUCCUagCUaUCgUUsU B
2182


R-008381620-000V
2401
196
GGAUGAUCCUAGCUAUCGU
aCgauAgCUAggAucaUcCUsU
2184


R-008381620-000V
2401
196
GGAUGAUCCUAGCUAUCGU
B GGaUGAUCCUAGCUaUCgUUsU B
2185


R-008381712-000E
2401
196
GGAUGAUCCUAGCUAUCGU
aCGAuaGCuAGGAuCaUCCUsU
2186


R-008381712-000E
2401
196
GGAUGAUCCUAGCUAUCGU
B GGaUGAUCCUaGCUAUCgUUsU B
2187


R-008381710-000M
2401
196
GGAUGAUCCUAGCUAUCGU
B gGaUgAUCCUaGCUAUCGUUsU B
2188


R-008381710-000M
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAgcUaGGAUCauCCUsU
2189


R-008381676-000J
2401
196
GGAUGAUCCUAGCUAUCGU
aCGAuaGCUAGgAUCaUccUsU
2190


R-008381676-000J
2401
196
GGAUGAUCCUAGCUAUCGU
B GgAUGauCCUAGCUAUCguUsU B
2191


R-008381604-000V
2401
196
GGAUGAUCCUAGCUAUCGU
B GgaUgAUCcUagCUaUCGuUsU B
2192


R-008381604-000V
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAgCUagGAuCAUCcUsU
2193


R-008381640-000E
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGaUCCUaGCUaUcgUUsU B
2194


R-008381640-000E
2401
196
GGAUGAUCCUAGCUAUCGU
AcGAUAGCUAGgaucaUCCUsU
2195


R-008381740-000P
2401
196
GGAUGAUCCUAGCUAUCGU
acgAuaGCUagGauCAUcCUsU
2196


R-008381740-000P
2401
196
GGAUGAUCCUAGCUAUCGU
B GgAUGAUCCUagCUAUCGUUsU B
2197


R-008381674-000S
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAuCCUaGCUAUCGUUsU B
2199


R-008381674-000S
2401
196
GGAUGAUCCUAGCUAUCGU
aCgAUagcUAGGAuCAuCCUsU
2198


R-008381694-000B
2401
196
GGAUGAUCCUAGCUAUCGU
B GgaUGaUCCUAgCUAUCGUUsU B
2201


R-008381694-000B
2401
196
GGAUGAUCCUAGCUAUCGU
aCGAUaGCuAGGauCauCCUsU
2200


R-008381638-000G
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUgAUCCUAgcUAUCgUUsU B
2203


R-008381638-000G
2401
196
GGAUGAUCCUAGCUAUCGU
aCGaUagcUAgGAUcAuCcUsU
2202


R-008381602-000C
2401
196
GGAUGAUCCUAGCUAUCGU
B GGaUgaUCCuAGCuAUCGUUsU B
2204


R-008381602-000C
2401
196
GGAUGAUCCUAGCUAUCGU
AcGAUaGCUaGGauCAUccUsU
2205


R-008381692-000J
2401
196
GGAUGAUCCUAGCUAUCGU
AcgaUagCUAGGAUcAucCUsU
2207


R-008381692-000J
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUagCUAuCGUUsU B
2206


R-008381658-000S
2401
196
GGAUGAUCCUAGCUAUCGU
B gGAUgaUCCUAGCUaUCGUUsU B
2208


R-008381658-000S
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUAGcuaggAuCAUcCUsU
2209


R-008381178-000C
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008381178-000C
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGaAUCAauccaACAGUsU
2067


R-008380929-000H
1797
5
CUGUUGGAUUGAUUCGAAA
uuucGAauCaAUCcAaCaGUsU
2068


R-008380929-000H
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008381019-000X
1797
5
CUGUUGGAUUGAUUCGAAA
uUUcgAaUCaAuCCAACAGUsU
2070


R-008381019-000X
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008381256-000K
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008381256-000K
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGaaUCAAUCcAacaGUsU
2073


R-008381552-000E
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008381552-000E
1797
5
CUGUUGGAUUGAUUCGAAA
UUucGaAUCAAUCcAAcagUsU
2075


R-008381002-000U
1797
5
CUGUUGGAUUGAUUCGAAA
uuUCGAAUcaaUCCAAcAgUsU
2076


R-008381002-000U
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008381394-000X
1797
5
CUGUUGGAUUGAUUCGAAA
uuUcGAAUCaaUcCAACaGUsU
2078


R-008381394-000X
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008381383-000W
1797
5
CUGUUGGAUUGAUUCGAAA
UUucGAAuCaaUCCAacAGUsU
2081


R-008381383-000W
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008381093-000J
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008381093-000J
1797
5
CUGUUGGAUUGAUUCGAAA
uuuCgaAUCAAUCcAACagUsU
2082


R-008381375-000W
1797
5
CUGUUGGAUUGAUUCGAAA
UuuCgAAUCAAUCcaACAGUsU
2085


R-008381375-000W
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008381543-000W
1797
5
CUGUUGGAUUGAUUCGAAA
UuuCGaauCAaUccaACAGUsU
2087


R-008381543-000W
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008381535-000W
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgAauCAAUCcAAcagUsU
2089


R-008381535-000W
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008381528-000E
1797
5
CUGUUGGAUUGAUUCGAAA
uUuCGAAUCAaUCcaaCAGUsU
2090


R-008381528-000E
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008381365-000D
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008381365-000D
1797
5
CUGUUGGAUUGAUUCGAAA
UuUCGAAUcaauCCaACaGUsU
2093


R-008381520-000K
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgAAuCAauCcaaCAgUsU
2095


R-008381520-000K
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008380915-000F
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2020


R-008380915-000F
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGaAUCAauCCAaCAGUsU
2097


R-008381359-000W
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcgaAUcAAUcCAACagUsU
2099


R-008381359-000W
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUsU B
2021


R-008381249-000U
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAAUsU B
2022


R-008381249-000U
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAaUcaAUCcaACAgUsU
2101


R-008381082-000H
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381082-000H
2398
151
CCAGGAUGAUCCUAGCUAU
AuaGCUAggAUCAuCCuGGUsU
2103


R-008381240-000R
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008381240-000R
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgcuaGgaUCAuCcUGgUsU
2105


R-008380907-000F
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008380907-000F
2398
151
CCAGGAUGAUCCUAGCUAU
aUagCUAGGaUCauccUGgUsU
2106


R-008381164-000A
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381164-000A
2398
151
CCAGGAUGAUCCUAGCUAU
aUagCuagGAUCAucCugGUsU
2108


R-008381072-000R
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008381072-000R
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcUAgGAuCauCCUggUsU
2111


R-008381450-000C
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008381450-000C
2398
151
CCAGGAUGAUCCUAGCUAU
auAgCUaGGAuCauCCUGGUsU
2112


R-008381059-000S
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381059-000S
2398
151
CCAGGAUGAUCCUAGCUAU
aUaGCuaggAUcaUcCUGGUsU
2114


R-008381154-000H
2398
151
CCAGGAUGAUCCUAGCUAU
aUagCUAggAuCAuCCuGgUsU
2116


R-008381154-000H
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008381443-000L
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUaGGAUcauCCUgGUsU
2119


R-008381443-000L
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008381049-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381049-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
aUagcUAGGAUcaUCCugGUsU
2120


R-008381292-000V
2398
151
CCAGGAUGAUCCUAGCUAU
auAGcUaggauCAUCCuGGUsU
2122


R-008381292-000V
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008381010-000U
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGgaUCauCcuGGUsU
2125


R-008381010-000U
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008381284-000V
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381284-000V
2398
151
CCAGGAUGAUCCUAGCUAU
AUaGCUagGrAucAuCCUgGUsU
2127


R-008381417-000U
2398
151
CCAGGAUGAUCCUAGCUAU
aUAGCuAGGAUCAUCcUggUsU
2128


R-008381417-000U
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008381265-000U
2398
151
CCAGGAUGAUCCUAGCUAU
AUaGCuAGGaUcAUcCUggUsU
2131


R-008381265-000U
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008381464-000E
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2033


R-008381464-000E
2398
151
CCAGGAUGAUCCUAGCUAU
aUaGcUaggAUCAucCUGGUsU
2132


R-008381170-000H
2398
151
CCAGGAUGAUCCUAGCUAU
aUagCuAGGaUCAuCcUgGUsU
2134


R-008381170-000H
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2034


R-008381408-000K
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuUsU B
2035


R-008381408-000K
2398
151
CCAGGAUGAUCCUAGCUAU
AuagCUAgGauCAUcCUGGUsU
2137


R-008381110-000D
1870
194
ACGACUAGUUCAGUUGCUU
aagCAaCUGaAcuAGUCgUUsU
2138


R-008381110-000D
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008381558-000G
1870
194
ACGACUAGUUCAGUUGCUU
aAGcAACUgAaCUaGUCguUsU
2140


R-008381558-000G
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008381456-000E
1870
194
ACGACUAGUUCAGUUGCUU
AAGcaACuGaaCUaGuCGUUsU
2143


R-008381456-000E
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008381401-000Z
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008381401-000Z
1870
194
ACGACUAGUUCAGUUGCUU
aAgCaAcUGAACUAgUcGUUsU
2144


R-008380922-000X
1870
194
ACGACUAGUUCAGUUGCUU
aaGCAAcUgAaCuagUcGUUsU
2146


R-008380922-000X
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008381101-000V
1870
194
ACGACUAGUUCAGUUGCUU
AAgCAAcUGaACUaGUcgUUsU
2149


R-008381101-000V
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008381556-000P
1870
194
ACGACUAGUUCAGUUGCUU
AAgCAacugAAcUagUCGUUsU
2151


R-008381556-000P
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008381426-000C
1870
194
ACGACUAGUUCAGUUGCUU
AagcAaCUgaaCUAGucgUUsU
2153


R-008381426-000C
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008380979-000V
1870
194
ACGACUAGUUCAGUUGCUU
AaGCaAcUGAacUaGUcGUUsU
2155


R-008380979-000V
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008380882-000S
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008380882-000S
1870
194
ACGACUAGUUCAGUUGCUU
AAgcaaCUGAACuaGUCGUUsU
2157


R-008381204-000F
1870
194
ACGACUAGUUCAGUUGCUU
AaGCAACUgaACUAGuCGUUsU
2159


R-008381204-000F
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008381471-000W
1870
194
ACGACUAGUUCAGUUGCUU
aAgCAACUGAacUaGuCgUUsU
2160


R-008381471-000W
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008381197-000D
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008381197-000D
1870
194
ACGACUAGUUCAGUUGCUU
AAgCAACUGaACUaGUCguUsU
2163


R-008380970-000S
1870
194
ACGACUAGUUCAGUUGCUU
aAgCAaCuGaAcuaGUCgUUsU
2164


R-008380970-000S
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008381511-000B
1870
194
ACGACUAGUUCAGUUGCUU
aAgCAACugAACuaguCgUUsU
2166


R-008381511-000B
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008380992-000U
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2046


R-008380992-000U
1870
194
ACGACUAGUUCAGUUGCUU
aAGCAacUgaACUaGUcGUUsU
2168


R-008381233-000Z
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAAcUGAaCUaGUCGuUsU
2171


R-008381233-000Z
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2047


R-008381352-000K
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuUsU B
2048


R-008381352-000K
1870
194
ACGACUAGUUCAGUUGCUU
aaGCAACuGaACUagUcGuUsU
2172


R-008380987-000V
2401
196
GGAUGAUCCUAGCUAUCGU
ACgaUAGcuAGgauCAUCcUsU
2175


R-008380987-000V
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008381345-000U
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008381345-000U
2401
196
GGAUGAUCCUAGCUAUCGU
aCgAUagcuaGGAUcAUCCUsU
2176


R-008381146-000H
2401
196
GGAUGAUCCUAGCUAUCGU
aCGauAGCuAgGaUcauCCUsU
2178


R-008381146-000H
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008381503-000B
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008381503-000B
2401
196
GGAUGAUCCUAGCUAUCGU
acgAUAGCUaGgAUCAuCCUsU
2180


R-008381137-000Z
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008381137-000Z
2401
196
GGAUGAUCCUAGCUAUCGU
ACgaUAgCUaGGAuCAUCcUsU
2183


R-008381337-000U
2401
196
GGAUGAUCCUAGCUAUCGU
aCgauAgCUAggAucaUcCUsU
2184


R-008381337-000U
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008380900-000V
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008380900-000V
2401
196
GGAUGAUCCUAGCUAUCGU
aCGAuaGCuAGGAuCaUCCUsU
2186


R-008381328-000K
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008381328-000K
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAgcUaGGAUCauCCUsU
2189


R-008381222-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008381222-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
aCGAuaGCUAGgAUCaUccUsU
2190


R-008381494-000G
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAgCUagGAuCAUCcUsU
2193


R-008381494-000G
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008381212-000F
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008381212-000F
2401
196
GGAUGAUCCUAGCUAUCGU
AcGAUAGCUAGgaucaUCCUsU
2195


R-008381434-000C
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008381434-000C
2401
196
GGAUGAUCCUAGCUAUCGU
acgAuaGCUagGauCAUcCUsU
2196


R-008380895-000K
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008380895-000K
2401
196
GGAUGAUCCUAGCUAUCGU
aCgAUagcUAGGAuCAuCCUsU
2198


R-008381488-000Z
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008381488-000Z
2401
196
GGAUGAUCCUAGCUAUCGU
aCGAUaGCuAGGauCauCCUsU
2200


R-008381126-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
aCGaUagcUAgGAUcAuCcUsU
2202


R-008381126-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008381479-000R
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2059


R-008381479-000R
2401
196
GGAUGAUCCUAGCUAUCGU
AcGAUaGCUaGGauCAUccUsU
2205


R-008381319-000B
2401
196
GGAUGAUCCUAGCUAUCGU
AcgaUagCUAGGAUcAucCUsU
2207


R-008381319-000B
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUAGCUAUCGUUsU B
2060


R-008380889-000C
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuUsU B
2061


R-008380889-000C
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUAGcuaggAuCAUcCUsU
2209


R-008381831-000R
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUuGGAUUGAUUCGaAAUsU B
2066


R-008381831-000R
1797
5
CUGUUGGAUUGAUUCGAAA
uuucGAAucAAuccAAcAGUsU
2016


R-008381842-000S
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUuGGaUUGaUUCGAAaUsU B
2069


R-008381842-000S
1797
5
CUGUUGGAUUGAUUCGAAA
uuucGAAucAAuccAAcAGUsU
2016


R-008381850-000S
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUuGgaUUGAUuCGaAAUsU B
2071


R-008381850-000S
1797
5
CUGUUGGAUUGAUUCGAAA
uuucGAAucAAuccAAcAGUsU
2016


R-008381815-000R
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2023


R-008381815-000R
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUGgaUUGaUUCgAAAUsU B
2072


R-008381783-000K
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUGGAUUGAUuCgAAAUsU B 
2074


R-008381783-000K
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2023


R-008381799-000E
1797
5
CUGUUGGAUUGAUUCGAAA
B CuGUUGgaUUgAuUCGAaaUsU B
2077


R-008381799-000E
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2023


R-008381814-000G
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUgGaUUGAUUCGaaAUsU B
2079


R-008381814-000G
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2024


R-008381780-000J
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2024


R-008381780-000J
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGaUUCGAaAUsU B
2080


R-008381841-000H
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUGgAUugAUUCgAAaUsU B
2083


R-008381841-000H
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2024


R-008381791-000K
1797
5
CUGUUGGAUUGAUUCGAAA
B CugUUGGAUUGaUUcgaaaUsU B
2084


R-008381791-000K
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2025


R-008381839-000K
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2025


R-008381839-000K
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUgGaUugAUuCGaAAUsU B
2086


R-008381796-000D
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUgGAUUGAUUCgAAAUsU B
2088


R-008381796-000D
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCGAAUCAAUCCAACAGUsU
2025


R-008381838-000B
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAAucAAuccAAcAGUsU
2019


R-008381838-000B
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUggAUUgaUUCGaAAUsU B
2091


R-008381790-000B
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGaUUGaUUCgAAAUsU B
2092


R-008381790-000B
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAAucAAuccAAcAGUsU
2019


R-008381825-000H
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGaUUgaUUCgAaaUsU B
2094


R-008381825-000H
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAAucAAuccAAcAGUsU
2019


R-008381789-000M
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2026


R-008381789-000M
1797
5
CUGUUGGAUUGAUUCGAAA
B CuGuUgGAUUgaUUCGAaAUsU B 
2096


R-008381805-000Y
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2026


R-008381805-000Y
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGgAUUGAUUCGaaaUsU B
2098


R-008381788-000D
1797
5
CUGUUGGAUUGAUUCGAAA
UUUCgaaUCaaUCCaaCagUsU
2026


R-008381788-000D
1797
5
CUGUUGGAUUGAUUCGAAA
B CUgUUggaUUgaUUCgaaaUsU B
2100


R-008381847-000K
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUgaUcCUaGCUAUUsU B
2102


R-008381847-000K
2398
151
CCAGGAUGAUCCUAGCUAU
AuAGcuAGGAucAuccuGGUsU
2030


R-008381837-000T
2398
151
CCAGGAUGAUCCUAGCUAU
AuAGcuAGGAucAuccuGGUsU
2030


R-008381837-000T
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGgaUGaUCCUAgCUAUUsU B 
2104


R-008381824-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
B CCagGAUgAUCCUAGCUaUUsU B
2107


R-008381824-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
AuAGcuAGGAucAuccuGGUsU
2030


R-008381810-000X
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUaUUsU B
2109


R-008381810-000X
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2036


R-008381802-000X
2398
151
CCAGGAUGAUCCUAGCUAU
B cCAGgAUGaUCCUagCUAUUsU B
2110


R-008381802-000X
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2036


R-008381820-000P
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2036


R-008381820-000P
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUAGCUAUUsU B
2113


R-008381819-000A
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2037


R-008381819-000A
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGAUGAUCCUagCUaUUsU B
2115


R-008381787-000V
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2037


R-008381787-000V
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAgGAUgaUCCUaGCUAUUsU B
2117


R-008381835-000A
2398
151
CCAGGAUGAUCCUAGCUAU
B CCaggaUgaUCCUagCUaUUsU B
2118


R-008381835-000A
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2037


R-008381844-000J
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2038


R-008381844-000J
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAgGAUGAUCCUAGcUAUUsU B
2121


R-008381853-000T
2398
151
CCAGGAUGAUCCUAGCUAU
B CCaGGaUGAUCCUAGCUAUUsU B
2123


R-008381853-000T
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2038


R-008381833-000H
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGGaUGaUCCuAgCUAUUsU B
2124


R-008381833-000H
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGCUAGGAUCAUCCUGGUsU
2038


R-008381817-000H
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcuAGGAucAuccuGGUsU
2032


R-008381817-000H
2398
151
CCAGGAUGAUCCUAGCUAU
B cCAGGaUGAuCCUaGCUaUUsU B
2126


R-008381786-000L
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcuAGGAucAuccuGGUsU
2032


R-008381786-000L
2398
151
CCAGGAUGAUCCUAGCUAU
B CCaGgAUgAuCCUAGcUAUUsU B
2129


R-008381851-000A
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcuAGGAucAuccuGGUsU
2032


R-008381851-000A
2398
151
CCAGGAUGAUCCUAGCUAU
B CcaggAugaUCCUAGCUaUUsU B
2130


R-008381809-000H
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2039


R-008381809-000H
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAgGaUGAUcCUaGCUAUUsU B
2133


R-008381808-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAggaUGAUCCUAgCUAuUsU B
2135


R-008381808-000Z
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2039


R-008381784-000U
2398
151
CCAGGAUGAUCCUAGCUAU
AUAgCUaggaUCaUCCUggUsU
2039


R-008381784-000U
2398
151
CCAGGAUGAUCCUAGCUAU
B CCAGgAUgAUCCUAGcuaUUsU B
2136


R-008381793-000C
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2043


R-008381793-000C
1870
194
ACGACUAGUUCAGUUGCUU
B ACgACuAgUUcAGUUGCUUUsU B
2139


R-008381807-000R
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2043


R-008381807-000R
1870
194
ACGACUAGUUCAGUUGCUU
B aCGACUAGuUCAgUugcUUUsU B
2141


R-008381816-000Z
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2043


R-008381816-000Z
1870
194
ACGACUAGUUCAGUUGCUU
B aCGACUagUUCaGUUgCUUUsU B
2142


R-008381830-000G
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2049


R-008381830-000G
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCuAGUuCAgUUgcUUUsU B
2145


R-008381782-000B
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCUAguUCAGUUGCUUUsU B
2147


R-008381782-000B
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2049


R-008381849-000C
1870
194
ACGACUAGUUCAGUUGCUU
B ACGaCUAGUUCAGUUGCuUUsU B
2148


R-008381849-000C
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2049


R-008381781-000T
1870
194
ACGACUAGUUCAGUUGCUU
B ACgACUAGUUCaGUUGcUUUsU B
2150


R-008381781-000T
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2050


R-008381829-000T
1870
194
ACGACUAGUUCAGUUGCUU
B acGACUagUUCagUuGCuUUsU B
2152


R-008381829-000T
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2050


R-008381792-000U
1870
194
ACGACUAGUUCAGUUGCUU
B aCGAcUAGUUCAGUUgCUUUsU B
2154


R-008381792-000U
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2050


R-008381798-000W
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2051


R-008381798-000W
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUaGUUCaGUUgCUUUsU B
2156


R-008381828-000J
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2051


R-008381828-000J
1870
194
ACGACUAGUUCAGUUGCUU
B ACGaCUaGUUCAGUUGcUUUsU B
2158


R-008381840-000Z
1870
194
ACGACUAGUUCAGUUGCUU
AAGCAACUGAACUAGUCGUUsU
2051


R-008381840-000Z
1870
194
ACGACUAGUUCAGUUGCUU
B ACgACUAgUUCAgUUgCUUUsU B
2161


R-008381797-000M
1870
194
ACGACUAGUUCAGUUGCUU
B ACGaCUaGuUCagUUGCUUUsU B
2162


R-008381797-000M
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2045


R-008381813-000Y
1870
194
ACGACUAGUUCAGUUGCUU
B ACGaCUaGUUCaguUgCUuUsU B
2165


R-008381813-000Y
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2045


R-008381827-000A
1870
194
ACGACUAGUUCAGUUGCUU
B ACGACUAGUUCAGUUGCUUUsU B
2167


R-008381827-000A
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUsU
2045


R-008381812-000P
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCUAGUUCaGUUGCUUUsU B
2169


R-008381812-000P
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2052


R-008381848-000U
1870
194
ACGACUAGUUCAGUUGCUU
B ACgAcUAgUuCAgUUGCUUUsU B
2170


R-008381848-000U
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2052


R-008381779-000V
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCUagUUCagUUgCUUUsU B
2173


R-008381779-000V
1870
194
ACGACUAGUUCAGUUGCUU
AAGCaaCUgaaCUagUCgUUsU
2052


R-008381846-000B
2401
196
GGAUGAUCCUAGCUAUCGU
AcGAuAGcuAGGAucAuccUsU
2056


R-008381846-000B
2401
196
GGAUGAUCCUAGCUAUCGU
B gGaugaUcCUaGCuAUCgUUsU B
2174


R-008381811-000F
2401
196
GGAUGAUCCUAGCUAUCGU
B GgAUGaUCCuagcUAUCgUUsU B
2177


R-008381811-000F
2401
196
GGAUGAUCCUAGCUAUCGU
AcGAuAGcuAGGAucAuccUsU
2056


R-008381845-000T
2401
196
GGAUGAUCCUAGCUAUCGU
B gGAUgAUCCUAGCuaUCGUUsU B
2179


R-008381845-000T
2401
196
GGAUGAUCCUAGCUAUCGU
AcGAuAGcuAGGAucAuccUsU
2056


R-008381795-000V
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2062


R-008381795-000V
2401
196
GGAUGAUCCUAGCUAUCGU
B gGAUGAUCCUAgCUauCGUUsU B
2181


R-008381823-000R
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2062


R-008381823-000R
2401
196
GGAUGAUCCUAGCUAUCGU
B ggaUgaUCCUagCUaUCgUUsU B
2182


R-008381803-000F
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2062


R-008381803-000F
2401
196
GGAUGAUCCUAGCUAUCGU
B GGaUGAUCCUAGCUaUCgUUsU B
2185


R-008381822-000G
2401
196
GGAUGAUCCUAGCUAUCGU
B GGaUGAUCCUaGCUAUCgUUsU B
2187


R-008381822-000G
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2063


R-008381836-000J
2401
196
GGAUGAUCCUAGCUAUCGU
B gGaUgAUCCUaGCUAUCGUUsU B
2188


R-008381836-000J
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2063


R-008381854-000B
2401
196
GGAUGAUCCUAGCUAUCGU
B GgAUGauCCUAGCUAUCguUsU B
2191


R-008381854-000B
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2063


R-008381801-000N
2401
196
GGAUGAUCCUAGCUAUCGU
B GgaUgAUCcUagCUaUCGuUsU B
2192


R-008381801-000N
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2064


R-008381800-000E
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGaUCCUaGCUaUcgUUsU B
2194


R-008381800-000E
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2064


R-008381834-000S
2401
196
GGAUGAUCCUAGCUAUCGU
B GgAUGAUCCUagCUAUCGUUsU B
2197


R-008381834-000S
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAUAGCUAGGAUCAUCCUsU
2064


R-008381852-000J
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAGcuAGGAucAuccUsU
2058


R-008381852-000J
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAuCCUaGCUAUCGUUsU B
2199


R-008381843-000A
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAGcuAGGAucAuccUsU
2058


R-008381843-000A
2401
196
GGAUGAUCCUAGCUAUCGU
B GgaUGaUCCUAgCUAUCGUUsU B
2201


R-008381832-000Z
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAGcuAGGAucAuccUsU
2058


R-008381832-000Z
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUgAUCCUAgcUAUCgUUsU B
2203


R-008381818-000S
2401
196
GGAUGAUCCUAGCUAUCGU
B GGaUgaUCCuAGCuAUCGUUsU B
2204


R-008381818-000S
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2065


R-008381785-000C
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAUGAUCCUagCUAuCGUUsU B
2206


R-008381785-000C
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2065


R-008381794-000L
2401
196
GGAUGAUCCUAGCUAUCGU
ACGaUagCUaggaUCaUCCUsU
2065


R-008381794-000L
2401
196
GGAUGAUCCUAGCUAUCGU
B gGAUgaUCCUAGCUaUCGUUsU B
2208


R-008395187-000D
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAATT B
2210


R-008395187-000D
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAAucAAuccAAcAGUU
1463


R-008395244-000T
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAATT B
2210


R-008395244-000T
1797
5
CUGUUGGAUUGAUUCGAAA
IUUcGAAucAAuccAAcAGUU
2211


R-008395198-000E
1797
5
CUGUUGGAUUGAUUCGAAA
UIUcGAAucAAuccAAcAGUU
2212


R-008395198-000E
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAATT B
2210


R-008395222-000R
1797
5
CUGUUGGAUUGAUUCGAAA
UUIcGAAucAAuccAAcAGUU
2213


R-008395222-000R
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAATT B
2210


R-008395155-000J
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAATT B
2210


R-008395155-000J
1797
5
CUGUUGGAUUGAUUCGAAA
UUUIGAAucAAuccAAcAGUU
2214


R-008395242-000A
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAATT B
2210


R-008395242-000A
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcIAAucAAuccAAcAGUU
2215


R-008395267-000D
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAATT B
2210


R-008395267-000D
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGIAucAAuccAAcAGUU
2216


R-008395153-000S
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAATT B
2210


R-008395153-0005
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAIucAAuccAAcAGUU
2217


R-008395286-000E
1797
5
CUGUUGGAUUGAUUCGAAA
B cuGuuGGAuuGAuucGAAATT B
2210


R-008395286-000E
1797
5
CUGUUGGAUUGAUUCGAAA
UUUcGAAIcAAuccAAcAGUU
2218


R-008395196-000M
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuTT B
2219


R-008395196-000M
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcuGAAcuAGucGuUU
1841


R-008395168-000C
1870
194
ACGACUAGUUCAGUUGCUU
IAGcAAcuGAAcuAGucGuUU
2220


R-008395168-000C
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuTT B
2219


R-008395265-000L
1870
194
ACGACUAGUUCAGUUGCUU
AIGcAAcuGAAcuAGucGuUU
2221


R-008395265-000L
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuTT B
2219


R-008395150-000R
1870
194
ACGACUAGUUCAGUUGCUU
AAIcAAcuGAAcuAGucGuUU
2222


R-008395150-000R
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuTT B
2219


R-008395263-000U
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuTT B
2219


R-008395263-000U
1870
194
ACGACUAGUUCAGUUGCUU
AAGIAAcuGAAcuAGucGuUU
2223


R-008395172-000T
1870
194
ACGACUAGUUCAGUUGCUU
AAGcIAcuGAAcuAGucGuUU
2224


R-008395172-000T
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuTT B
2219


R-008395170-000A
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuTT B
2219


R-008395170-000A
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAIcuGAAcuAGucGuUU
2225


R-008395226-000A
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuTT B
2219


R-008395226-000A
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAIuGAAcuAGucGuUU
2226


R-008395207-000Z
1870
194
ACGACUAGUUCAGUUGCUU
AAGcAAcIGAAcuAGucGuUU
2227


R-008395207-000Z
1870
194
ACGACUAGUUCAGUUGCUU
B AcGAcuAGuucAGuuGcuuTT B
2219


R-008395205-000G
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcuAGGAucAuccuGGUU
1755


R-008395205-000G
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuTT B
2228


R-008395250-000A
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuTT B
2228


R-008395250-000A
2398
151
CCAGGAUGAUCCUAGCUAU
IUAGcuAGGAucAuccuGGUU
2229


R-008395248-000C
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuTT B
2228


R-008395248-000C
2398
151
CCAGGAUGAUCCUAGCUAU
AIAGcuAGGAucAuccuGGUU
2230


R-008395275-000D
2398
151
CCAGGAUGAUCCUAGCUAU
AUIGcuAGGAucAuccuGGUU
2231


R-008395275-000D
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuTT B
2228


R-008395163-000J
2398
151
CCAGGAUGAUCCUAGCUAU
AUAIcuAGGAucAuccuGGUU
2232


R-008395163-000J
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuTT B
2228


R-008395224-000H
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuTT B
2228


R-008395224-000H
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGIuAGGAucAuccuGGUU
2233


R-008395161-000S
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcIAGGAucAuccuGGUU
2234


R-008395161-000S
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuTT B
2228


R-008395290-000V
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuTT B
2228


R-008395290-000V
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcuIGGAucAuccuGGUU
2235


R-008395273-000L
2398
151
CCAGGAUGAUCCUAGCUAU
B ccAGGAuGAuccuAGcuAuTT B
2228


R-008395273-000L
2398
151
CCAGGAUGAUCCUAGCUAU
AUAGcuAIGAucAuccuGGUU
2236


R-008395188-000M
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAGcuAGGAucAuccUU
1845


R-008395188-000M
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuTT B
2237


R-008395204-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
ICGAuAGcuAGGAucAuccUU
2238


R-008395204-000Y
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuTT B
2237


R-008395202-000F
2401
196
GGAUGAUCCUAGCUAUCGU
AIGAuAGcuAGGAucAuccUU
2239


R-008395202-000F
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuTT B
2237


R-008395158-000K
2401
196
GGAUGAUCCUAGCUAUCGU
ACIAuAGcuAGGAucAuccUU
2240


R-008395158-000K
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuTT B
2237


R-008395246-000K
2401
196
GGAUGAUCCUAGCUAUCGU
ACGIuAGcuAGGAucAuccUU
2241


R-008395246-000K
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuTT B
2237


R-008395271-000U
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuTT B
2237


R-008395271-000U
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAIAGcuAGGAucAuccUU
2242


R-008395200-000N
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuIGcuAGGAucAuccUU
2243


R-008395200-000N
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuTT B
2237


R-008395288-000X
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuTT B
2237


R-008395288-000X
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAIcuAGGAucAuccUU
2244


R-008395269-000W
2401
196
GGAUGAUCCUAGCUAUCGU
ACGAuAGIuAGGAucAuccUU
2245


R-008395269-000W
2401
196
GGAUGAUCCUAGCUAUCGU
B GGAuGAuccuAGcuAucGuTT B
2237


R-008397891-000B
1382
238
GAUCCAAGUCAACGUCUUG
B GAUCCAAGUCAACGUCUUGTT B
2246


R-008397891-000B
1382
238
GAUCCAAGUCAACGUCUUG
CAAGACGUUGACUUGGAUCUU
2247


R-008397894-000C
828
239
CUAUCAUGCGUUCUCCUCA
B CUAUCAUGCGUUCUCCUCATT B
2248


R-008397894-000C
828
239
CUAUCAUGCGUUCUCCUCA
UGAGGAGAACGCAUGAUAGUU
2249


R-008396925-000E
1244
240
AAUAUAAUGAGGACCUAUA
B AAUAUAAUGAGGACCUAUATT B
2250


R-008396925-000E
1244
240
AAUAUAAUGAGGACCUAUA
UAUAGGUCCUCAUUAUAUUUU
2251


R-008395941-000K
1304
241
GUGCUAUCUGUCUGCUCUA
B GUGCUAUCUGUCUGCUCUATT B
2252


R-008395941-000K
1304
241
GUGCUAUCUGUCUGCUCUA
UAGAGCAGACAGAUAGCACUU
2253


R-008395944-000L
812
242
GAAGCUUCCAGACACGCUA
B GAAGCUUCCAGACACGCUATT B
2254


R-008395944-000L
812
242
GAAGCUUCCAGACACGCUA
UAGCGUGUCUGGAAGCUUCUU
2255


R-008397498-000Y
1558
243
UAAUUAUAAGAACAAGAUG
B UAAUUAUAAGAACAAGAUGTT B
2256


R-008397498-000Y
1558
243
UAAUUAUAAGAACAAGAUG
CAUCUUGUUCUUAUAAUUAUU
2257


R-008397501-000R
879
244
AUACAAAUGAUGUAGAAAC
B AUACAAAUGAUGUAGAAACTT B
2258


R-008397501-000R
879
244
AUACAAAUGAUGUAGAAAC
GUUUCUACAUCAUUUGUAUUU
2259


R-008396451-000Y
1311
245
CUGUCUGCUCUAGUAAUAA
UUAUUACUAGAGCAGACAGUU
2261


R-008396451-000Y
1311
245
CUGUCUGCUCUAGUAAUAA
B CUGUCUGCUCUAGUAAUAATT B
2260


R-008397504-000S
856
246
UGCUAUUGUACGUACCAUG
B UGCUAUUGUACGUACCAUGTT B
2262


R-008397504-000S
856
246
UGCUAUUGUACGUACCAUG
CAUGGUACGUACAAUAGCAUU
2263


R-008396961-000P
1296
247
UGCUGAAGGUGCUAUCUGU
B UGCUGAAGGUGCUAUCUGUTT B
2264


R-008396961-000P
1296
247
UGCUGAAGGUGCUAUCUGU
ACAGAUAGCACCUUCAGCAUU
2265


R-008396967-000S
1235
39
GCUUUAGUAAAUAUAAUGA
B GCUUUAGUAAAUAUAAUGATT B
2266


R-008396967-000S
1235
39
GCUUUAGUAAAUAUAAUGA
UCAUUAUAUUUACUAAAGCUU
2267


R-008396463-000H
960
248
UCUUUAAGUCUGGAGGCAU
AUGCCUCCAGACUUAAAGAUU
2269


R-008396463-000H
960
248
UCUUUAAGUCUGGAGGCAU
B UCUUUAAGUCUGGAGGCAUTT B
2268


R-008398998-000S
2049
249
AUACCAUUCCAUUGUUUGU
B AUACCAUUCCAUUGUUUGUTT B
2270


R-008398998-000S
2049
249
AUACCAUUCCAUUGUUUGU
ACAAACAAUGGAAUGGUAUUU
2271


R-008398515-000M
1791
250
AGGCUACUGUUGGAUUGAU
AUCAAUCCAACAGUAGCCUUU
2273


R-008398515-000M
1791
250
AGGCUACUGUUGGAUUGAU
B AGGCUACUGUUGGAUUGAUTT B
2272


R-008395947-000M
783
251
CAGUUAUGGUCCAUCAGCU
B CAGUUAUGGUCCAUCAGCUTT B
2274


R-008395947-000M
783
251
CAGUUAUGGUCCAUCAGCU
AGCUGAUGGACCAUAACUGUU
2275


R-008396466-000J
1569
252
ACAAGAUGAUGGUCUGCCA
B ACAAGAUGAUGGUCUGCCATT B
2276


R-008396466-000J
1569
252
ACAAGAUGAUGGUCUGCCA
UGGCAGACCAUCAUCUUGUUU
2277


R-008396970-000Y
2224
253
GACAUAUGCAGCUGCUGUU
AACAGCAGCUGCAUAUGUCUU
2279


R-008396970-000Y
2224
253
GACAUAUGCAGCUGCUGUU
B GACAUAUGCAGCUGCUGUUTT B
2278


R-008395989-000Z
1882
123
GUUGCUUGUUCGUGCACAU
B GUUGCUUGUUCGUGCACAUTT B
2280


R-008395989-000Z
1882
123
GUUGCUUGUUCGUGCACAU
AUGUGCACGAACAAGCAACUU
2281


R-008398626-000Y
934
254
CCAUCAUCGUGAGGGCUUA
B CCAUCAUCGUGAGGGCUUATT B
2282


R-008398626-000Y
934
254
CCAUCAUCGUGAGGGCUUA
UAAGCCCUCACGAUGAUGGUU
2283


R-008396121-000S
1378
255
GACAGAUCCAAGUCAACGU
B GACAGAUCCAAGUCAACGUTT B
2284


R-008396121-000S
1378
255
GACAGAUCCAAGUCAACGU
ACGUUGACUUGGAUCUGUCUU
2285


R-008396001-000X
569
256
GAGACAUUAGAUGAGGGCA
UGCCCUCAUCUAAUGUCUCUU
2287


R-008396001-000X
569
256
GAGACAUUAGAUGAGGGCA
B GAGACAUUAGAUGAGGGCATT B
2286


R-008396007-000Z
1722
257
UUCGCCUUCACUAUGGACU
B UUCGCCUUCACUAUGGACUTT B
2288


R-008396007-000Z
1722
257
UUCGCCUUCACUAUGGACU
AGUCCAUAGUGAAGGCGAAUU
2289


R-008396547-000T
1483
258
UGUUCAGCUUCUGGGUUCA
B UGUUCAGCUUCUGGGUUCATT B
2290


R-008396547-000T
1483
258
UGUUCAGCUUCUGGGUUCA
UGAACCCAGAAGCUGAACAUU
2291


R-008399088-000F
2352
259
AUCUUGGACUUGAUAUUGG
CCAAUAUCAAGUCCAAGAUUU
2293


R-008399088-000F
2352
259
AUCUUGGACUUGAUAUUGG
B AUCUUGGACUUGAUAUUGGTT B
2292


R-008398596-000K
719
260
CGUGCAAUCCCUGAACUGA
B CGUGCAAUCCCUGAACUGATT B
2294


R-008398596-000K
719
260
CGUGCAAUCCCUGAACUGA
UCAGUUCAGGGAUUGCACGUU
2295


R-008399094-000N
762
261
AGGUGGUGGUUAAUAAGGC
B AGGUGGUGGUUAAUAAGGCTT B
2296


R-008399094-000N
762
261
AGGUGGUGGUUAAUAAGGC
GCCUUAUUAACCACCACCUUU
2297


R-008397585-000P
599
262
UCUACACAGUUUGAUGCUG
B UCUACACAGUUUGAUGCUGTT B
2298


R-008397585-000P
599
262
UCUACACAGUUUGAUGCUG
CAGCAUCAAACUGUGUAGAUU
2299


R-008396073-000L
1704
263
AGAUGGCCCAGAAUGCAGU
B AGAUGGCCCAGAAUGCAGUTT B
2300


R-008396073-000L
1704
263
AGAUGGCCCAGAAUGCAGU
ACUGCAUUCUGGGCCAUCUUU
2301


R-008398599-000L
2270
264
CAAGAUUACAAGAAACGGC
GCCGUUUCUUGUAAUCUUGUU
2303


R-008398599-000L
2270
264
CAAGAUUACAAGAAACGGC
B CAAGAUUACAAGAAACGGCTT B
2302


R-008399532-000R
1810
103
UCGAAAUCUUGCCCUUUGU
ACAAAGGGCAAGAUUUCGAUU
2305


R-008399532-000R
1810
103
UCGAAAUCUUGCCCUUUGU
B UCGAAAUCUUGCCCUUUGUTT B
2304


R-008398602-000D
662
265
CUGAAACAUGCAGUUGUAA
B CUGAAACAUGCAGUUGUAATT B
2306


R-008398602-000D
662
265
CUGAAACAUGCAGUUGUAA
UUACAACUGCAUGUUUCAGUU
2307


R-008399106-000J
396
266
CUCCUUCUCUGAGUGGUAA
UUACCACUCAGAGAAGGAGUU
2309


R-008399106-000J
396
266
CUCCUUCUCUGAGUGGUAA
B CUCCUUCUCUGAGUGGUAATT B
2308


R-008398053-000R
1199
267
AGCAAGCUCAUCAUACUGG
CCAGUAUGAUGAGCUUGCUUU
2311


R-008398053-000R
1199
267
AGCAAGCUCAUCAUACUGG
B AGCAAGCUCAUCAUACUGGTT B
2310


R-008396583-000C
1560
268
AUUAUAAGAACAAGAUGAU
B AUUAUAAGAACAAGAUGAUTT B
2312


R-008396583-000C
1560
268
AUUAUAAGAACAAGAUGAU
AUCAUCUUGUUCUUAUAAUUU
2313


R-008399028-000B
593
92
AUCCCAUCUACACAGUUUG
CAAACUGUGUAGAUGGGAUUU
2315


R-008399028-000B
593
92
AUCCCAUCUACACAGUUUG
B AUCCCAUCUACACAGUUUGTT B
2314


R-008398104-000X
1310
269
UCUGUCUGCUCUAGUAAUA
B UCUGUCUGCUCUAGUAAUATT B
2316


R-008398104-000X
1310
269
UCUGUCUGCUCUAGUAAUA
UAUUACUAGAGCAGACAGAUU
2317


R-008398113-000F
1233
270
AAGCUUUAGUAAAUAUAAU
B AAGCUUUAGUAAAUAUAAUTT B
2318


R-008398113-000F
1233
270
AAGCUUUAGUAAAUAUAAU
AUUAUAUUUACUAAAGCUUUU
2319


R-008399622-000H
1330
271
GCCGGCUAUUGUAGAAGCU
B GCCGGCUAUUGUAGAAGCUTT B
2320


R-008399622-000H
1330
271
GCCGGCUAUUGUAGAAGCU
AGCUUCUACAAUAGCCGGCUU
2321


R-008399151-000C
1312
272
UGUCUGCUCUAGUAAUAAG
B UGUCUGCUCUAGUAAUAAGTT B
2322


R-008399151-000C
1312
272
UGUCUGCUCUAGUAAUAAG
CUUAUUACUAGAGCAGACAUU
2323


R-008396127-000U
1556
273
AAUAAUUAUAAGAACAAGA
UCUUGUUCUUAUAAUUAUUUU
2325


R-008396127-000U
1556
273
AAUAAUUAUAAGAACAAGA
B AAUAAUUAUAAGAACAAGATT B
2324


R-008395707-000Y
2438
274
UAUGGCCAGGAUGCCUUGG
B UAUGGCCAGGAUGCCUUGGTT B
2326


R-008395707-000Y
2438
274
UAUGGCCAGGAUGCCUUGG
CCAAGGCAUCCUGGCCAUAUU
2327


R-008395710-000E
1826
275
UGUCCCGCAAAUCAUGCAC
GUGCAUGAUUUGCGGGACAUU
2329


R-008395710-000E
1826
275
UGUCCCGCAAAUCAUGCAC
B UGUCCCGCAAAUCAUGCACTT B
2328


R-008395713-000F
1397
276
CUUGUUCAGAACUGUCUUU
B CUUGUUCAGAACUGUCUUUTT B
2330


R-008395713-000F
1397
276
CUUGUUCAGAACUGUCUUU
AAAGACAGUUCUGAACAAGUU
2331


R-008395716-000G
3181
277
GCUGUGAUACGAUGCUUCA
UGAAGCAUCGUAUCACAGCUU
2333


R-008395716-000G
3181
277
GCUGUGAUACGAUGCUUCA
B GCUGUGAUACGAUGCUUCATT B
2332


R-008395719-000H
1912
278
GCGCCGUACGUCCAUGGGU
B GCGCCGUACGUCCAUGGGUTT B
2334


R-008395719-000H
1912
278
GCGCCGUACGUCCAUGGGU
ACCCAUGGACGUACGGCGCUU
2335


R-008395722-000P
846
279
AGAUGGUGUCUGCUAUUGU
B AGAUGGUGUCUGCUAUUGUTT B
2336


R-008395722-000P
846
279
AGAUGGUGUCUGCUAUUGU
ACAAUAGCAGACACCAUCUUU
2337


R-008395725-000R
1404
280
AGAACUGUCUUUGGACUCU
B AGAACUGUCUUUGGACUCUTT B
2338


R-008395725-000R
1404
280
AGAACUGUCUUUGGACUCU
AGAGUCCAAAGACAGUUCUUU
2339


R-008395728-000S
586
281
CAUGCAGAUCCCAUCUACA
UGUAGAUGGGAUCUGCAUGUU
2341


R-008395728-000S
586
281
CAUGCAGAUCCCAUCUACA
B CAUGCAGAUCCCAUCUACATT B
2340


R-008395731-000Y
1469
282
CUCCUUGGGACUCUUGUUC
GAACAAGAGUCCCAAGGAGUU
2343


R-008395731-000Y
1469
282
CUCCUUGGGACUCUUGUUC
B CUCCUUGGGACUCUUGUUCTT B
2342


R-008395734-000Z
380
283
GGUGCCACUACCACAGCUC
B GGUGCCACUACCACAGCUCTT B
2344


R-008395734-000Z
380
283
GGUGCCACUACCACAGCUC
GAGCUGUGGUAGUGGCACCUU
2345


R-008395737-000A
1345
284
AGCUGGUGGAAUGCAAGCU
B AGCUGGUGGAAUGCAAGCUTT B
2346


R-008395737-000A
1345
284
AGCUGGUGGAAUGCAAGCU
AGCUUGCAUUCCACCAGCUUU
2347


R-008395740-000G
1863
285
CCAUUCCACGACUAGUUCA
B CCAUUCCACGACUAGUUCATT B
2348


R-008395740-000G
1863
285
CCAUUCCACGACUAGUUCA
UGAACUAGUCGUGGAAUGGUU
2349


R-008395743-000H
635
286
CAGCGUUUGGCUGAACCAU
AUGGUUCAGCCAAACGCUGUU
2351


R-008395743-000H
635
286
CAGCGUUUGGCUGAACCAU
B CAGCGUUUGGCUGAACCAUTT B
2350


R-008395746-000J
959
287
AUCUUUAAGUCUGGAGGCA
UGCCUCCAGACUUAAAGAUUU
2353


R-008395746-000J
959
287
AUCUUUAAGUCUGGAGGCA
B AUCUUUAAGUCUGGAGGCATT B
2352


R-008395749-000K
2440
288
UGGCCAGGAUGCCUUGGGU
B UGGCCAGGAUGCCUUGGGUTT B
2354


R-008395749-000K
2440
288
UGGCCAGGAUGCCUUGGGU
ACCCAAGGCAUCCUGGCCAUU
2355


R-008395752-000S
877
289
GAAUACAAAUGAUGUAGAA
UUCUACAUCAUUUGUAUUCUU
2357


R-008395752-000S
877
289
GAAUACAAAUGAUGUAGAA
B GAAUACAAAUGAUGUAGAATT B
2356


R-008395755-000T
2556
290
UGGAUGGGCUGCCUCCAGG
CCUGGAGGCAGCCCAUCCAUU
2359


R-008395755-000T
2556
290
UGGAUGGGCUGCCUCCAGG
B UGGAUGGGCUGCCUCCAGGTT B
2358


R-008395758-000U
1916
291
CGUACGUCCAUGGGUGGGA
B CGUACGUCCAUGGGUGGGATT B
2360


R-008395758-000U
1916
291
CGUACGUCCAUGGGUGGGA
UCCCACCCAUGGACGUACGUU
2361


R-008395761-000A
850
292
GGUGUCUGCUAUUGUACGU
B GGUGUCUGCUAUUGUACGUTT B
2362


R-008395761-000A
850
292
GGUGUCUGCUAUUGUACGU
ACGUACAAUAGCAGACACCUU
2363


R-008395764-000B
1303
293
GGUGCUAUCUGUCUGCUCU
B GGUGCUAUCUGUCUGCUCUTT B
2364


R-008395764-000B
1303
293
GGUGCUAUCUGUCUGCUCU
AGAGCAGACAGAUAGCACCUU
2365


R-008395767-000C
1726
294
CCUUCACUAUGGACUACCA
UGGUAGUCCAUAGUGAAGGUU
2367


R-008395767-000C
1726
294
CCUUCACUAUGGACUACCA
B CCUUCACUAUGGACUACCATT B
2366


R-008395770-000J
1477
295
GACUCUUGUUCAGCUUCUG
CAGAAGCUGAACAAGAGUCUU
2369


R-008395770-000J
1477
295
GACUCUUGUUCAGCUUCUG
B GACUCUUGUUCAGCUUCUGTT B
2368


R-008395773-000K
598
296
AUCUACACAGUUUGAUGCU
B AUCUACACAGUUUGAUGCUTT B 
2370


R-008395773-000K
598
296
AUCUACACAGUUUGAUGCU
AGCAUCAAACUGUGUAGAUUU
2371


R-008395776-000L
2062
297
GUUUGUGCAGCUGCUUUAU
B GUUUGUGCAGCUGCUUUAUTT B
2372


R-008395776-000L
2062
297
GUUUGUGCAGCUGCUUUAU
AUAAAGCAGCUGCACAAACUU
2373


R-008395779-000M
2278
298
CAAGAAACGGCUUUCAGUU
B CAAGAAACGGCUUUCAGUUTT B
2374


R-008395779-000M
2278
298
CAAGAAACGGCUUUCAGUU
AACUGAAAGCCGUUUCUUGUU
2375


R-008395782-000U
1877
299
GUUCAGUUGCUUGUUCGUG
CACGAACAAGCAACUGAACUU
2377


R-008395782-000U
1877
299
GUUCAGUUGCUUGUUCGUG
B GUUCAGUUGCUUGUUCGUGTT B
2376


R-008395785-000V
1499
300
UCAGAUGAUAUAAAUGUGG
B UCAGAUGAUAUAAAUGUGGTT B
2378


R-008395785-000V
1499
300
UCAGAUGAUAUAAAUGUGG
CCACAUUUAUAUCAUCUGAUU
2379


R-008395788-000W
1136
301
AAUGUUAAAUUCUUGGCUA
B AAUGUUAAAUUCUUGGCUATT B
2380


R-008395788-000W
1136
301
AAUGUUAAAUUCUUGGCUA
UAGCCAAGAAUUUAACAUUUU
2381


R-008395791-000C
1494
302
UGGGUUCAGAUGAUAUAAA
UUUAUAUCAUCUGAACCCAUU
2383


R-008395791-000C
1494
302
UGGGUUCAGAUGAUAUAAA
B UGGGUUCAGAUGAUAUAAATT B
2382


R-008395794-000D
1972
303
AAUAGUUGAAGGUUGUACC
B AAUAGUUGAAGGUUGUACCTT B
2384


R-008395794-000D
1972
303
AAUAGUUGAAGGUUGUACC
GGUACAACCUUCAACUAUUUU
2385


R-008395797-000E
668
304
CAUGCAGUUGUAAACUUGA
UCAAGUUUACAACUGCAUGUU
2387


R-008395797-000E
668
304
CAUGCAGUUGUAAACUUGA
B CAUGCAGUUGUAAACUUGATT B
2386


R-008395800-000X
2945
305
AAUCUGAAUAAAGUGUAAC
GUUACACUUUAUUCAGAUUUU
2389


R-008395800-000X
2945
305
AAUCUGAAUAAAGUGUAAC
B AAUCUGAAUAAAGUGUAACTT B 
2388


R-008395803-000Y
2492
306
CACCACCCUGGUGCUGACU
B CACCACCCUGGUGCUGACUTT B
2390


R-008395803-000Y
2492
306
CACCACCCUGGUGCUGACU
AGUCAGCACCAGGGUGGUGUU
2391


R-008395806-000Z
293
307
GAGUUGGACAUGGCCAUGG
B GAGUUGGACAUGGCCAUGGTT B
2392


R-008395806-000Z
293
307
GAGUUGGACAUGGCCAUGG
CCAUGGCCAUGUCCAACUCUU
2393


R-008395809-000A
1905
308
AUACCCAGCGCCGUACGUC
B AUACCCAGCGCCGUACGUCTT B
2394


R-008395809-000A
1905
308
AUACCCAGCGCCGUACGUC
GACGUACGGCGCUGGGUAUUU
2395


R-008395812-000G
944
309
GAGGGCUUACUGGCCAUCU
AGAUGGCCAGUAAGCCCUCUU
2397


R-008395812-000G
944
309
GAGGGCUUACUGGCCAUCU
B GAGGGCUUACUGGCCAUCUTT B
2396


R-008395815-000H
581
310
GAGGGCAUGCAGAUCCCAU
B GAGGGCAUGCAGAUCCCAUTT B
2398


R-008395815-000H
581
310
GAGGGCAUGCAGAUCCCAU
AUGGGAUCUGCAUGCCCUCUU
2399


R-008395818-000J
1454
311
GAAGGGAUGGAAGGUCUCC
B GAAGGGAUGGAAGGUCUCCTT B
2400


R-008395818-000J
1454
311
GAAGGGAUGGAAGGUCUCC
GGAGACCUUCCAUCCCUUCUU
2401


R-008395821-000R
2254
312
GUCUGAGGACAAGCCACAA
B GUCUGAGGACAAGCCACAATT B
2402


R-008395821-000R
2254
312
GUCUGAGGACAAGCCACAA
UUGUGGCUUGUCCUCAGACUU
2403


R-008395824-000S
1837
313
UCAUGCACCUUUGCGUGAG
CUCACGCAAAGGUGCAUGAUU
2405


R-008395824-000S
1837
313
UCAUGCACCUUUGCGUGAG
B UCAUGCACCUUUGCGUGAGTT B
2404


R-008395827-000T
1425
314
GGAAUCUUUCAGAUGCUGC
B GGAAUCUUUCAGAUGCUGCTT B
2406


R-008395827-000T
1425
314
GGAAUCUUUCAGAUGCUGC
GCAGCAUCUGAAAGAUUCCUU
2407


R-008395830-000Z
1372
315
UCACCUGACAGAUCCAAGU
ACUUGGAUCUGUCAGGUGAUU
2409


R-008395830-000Z
1372
315
UCACCUGACAGAUCCAAGU
B UCACCUGACAGAUCCAAGUTT B
2408


R-008395833-000A
1298
316
CUGAAGGUGCUAUCUGUCU
B CUGAAGGUGCUAUCUGUCUTT B
2410


R-008395833-000A
1298
316
CUGAAGGUGCUAUCUGUCU
AGACAGAUAGCACCUUCAGUU
2411


R-008395836-000B
1674
317
GUCAUCUGACCAGCCGACA
B GUCAUCUGACCAGCCGACATT B
2412


R-008395836-000B
1674
317
GUCAUCUGACCAGCCGACA
UGUCGGCUGGUCAGAUGACUU
2413


R-008395839-000C
1864
318
CAUUCCACGACUAGUUCAG
CUGAACUAGUCGUGGAAUGUU
2415


R-008395839-000C
1864
318
CAUUCCACGACUAGUUCAG
B CAUUCCACGACUAGUUCAGTT B
2414


R-008395842-000J
2404
319
UGAUCCUAGCUAUCGUUCU
AGAACGAUAGCUAGGAUCAUU
2417


R-008395842-000J
2404
319
UGAUCCUAGCUAUCGUUCU
B UGAUCCUAGCUAUCGUUCUTT B
2416


R-008395845-000K
1992
320
GAGCCCUUCACAUCCUAGC
GCUAGGAUGUGAAGGGCUCUU
2419


R-008395845-000K
1992
320
GAGCCCUUCACAUCCUAGC
B GAGCCCUUCACAUCCUAGCTT B
2418


R-008395848-000L
2124
73
GUGAACUUGCUCAGGACAA
UUGUCCUGAGCAAGUUCACUU
2421


R-008395848-000L
2124
73
GUGAACUUGCUCAGGACAA
B GUGAACUUGCUCAGGACAATT B
2420


R-008395851-000T
578
321
GAUGAGGGCAUGCAGAUCC
GGAUCUGCAUGCCCUCAUCUU
2423


R-008395851-000T
578
321
GAUGAGGGCAUGCAGAUCC
B GAUGAGGGCAUGCAGAUCCTT B
2422


R-008395854-000U
3091
322
AUGGGUAGGGUAAAUCAGU
B AUGGGUAGGGUAAAUCAGUTT B
2424


R-008395854-000U
3091
322
AUGGGUAGGGUAAAUCAGU
ACUGAUUUACCCUACCCAUUU
2425


R-008395857-000V
720
323
GUGCAAUCCCUGAACUGAC
B GUGCAAUCCCUGAACUGACTT B
2426


R-008395857-000V
720
323
GUGCAAUCCCUGAACUGAC
GUCAGUUCAGGGAUUGCACUU
2427


R-008395860-000B
2054
324
AUUCCAUUGUUUGUGCAGC
B AUUCCAUUGUUUGUGCAGCTT B
2428


R-008395860-000B
2054
324
AUUCCAUUGUUUGUGCAGC
GCUGCACAAACAAUGGAAUUU
2429


R-008395863-000C
1237
42
UUUAGUAAAUAUAAUGAGG
CCUCAUUAUAUUUACUAAAUU
2431


R-008395863-000C
1237
42
UUUAGUAAAUAUAAUGAGG
B UUUAGUAAAUAUAAUGAGGTT B
2430


R-008395866-000D
374
325
CAUUCUGGUGCCACUACCA
UGGUAGUGGCACCAGAAUGUU
2433


R-008395866-000D
374
325
CAUUCUGGUGCCACUACCA
B CAUUCUGGUGCCACUACCATT B
2432


R-008395869-000E
868
326
UACCAUGCAGAAUACAAAU
AUUUGUAUUCUGCAUGGUAUU
2435


R-008395869-000E
868
326
UACCAUGCAGAAUACAAAU
B UACCAUGCAGAAUACAAAUTT B
2434


R-008395872-000L
626
23
ACUAAUGUCCAGCGUUUGG
CCAAACGCUGGACAUUAGUUU
2437


R-008395872-000L
626
23
ACUAAUGUCCAGCGUUUGG
B ACUAAUGUCCAGCGUUUGGTT B
2436


R-008395875-000M
1716
327
AUGCAGUUCGCCUUCACUA
B AUGCAGUUCGCCUUCACUATT B
2438


R-008395875-000M
1716
327
AUGCAGUUCGCCUUCACUA
UAGUGAAGGCGAACUGCAUUU
2439


R-008395878-000N
950
328
UUACUGGCCAUCUUUAAGU
B UUACUGGCCAUCUUUAAGUTT B
2440


R-008395878-000N
950
328
UUACUGGCCAUCUUUAAGU
ACUUAAAGAUGGCCAGUAAUU
2441


R-008395881-000V
1489
329
GCUUCUGGGUUCAGAUGAU
B GCUUCUGGGUUCAGAUGAUTT B
2442


R-008395881-000V
1489
329
GCUUCUGGGUUCAGAUGAU
AUCAUCUGAACCCAGAAGCUU
2443


R-008395884-000W
1451
330
CAGGAAGGGAUGGAAGGUC
B CAGGAAGGGAUGGAAGGUCTT B
2444


R-008395884-000W
1451
330
CAGGAAGGGAUGGAAGGUC
GACCUUCCAUCCCUUCCUGUU
2445


R-008395887-000X
438
159
UGGAUACCUCCCAAGUCCU
AGGACUUGGGAGGUAUCCAUU
2447


R-008395887-000X
438
159
UGGAUACCUCCCAAGUCCU
B UGGAUACCUCCCAAGUCCUTT B
2446


R-008395890-000D
1181
331
GCUUAUGGCAACCAAGAAA
UUUCUUGGUUGCCAUAAGCUU
2449


R-008395890-000D
1181
331
GCUUAUGGCAACCAAGAAA
B GCUUAUGGCAACCAAGAAATT B
2448


R-008395893-000E
1633
332
UGACAGGGAAGACAUCACU
AGUGAUGUCUUCCCUGUCAUU
2451


R-008395893-000E
1633
332
UGACAGGGAAGACAUCACU
B UGACAGGGAAGACAUCACUTT B
2450


R-008395896-000F
2394
333
AUCGCCAGGAUGAUCCUAG
CUAGGAUCAUCCUGGCGAUUU
2453


R-008395896-000F
2394
333
AUCGCCAGGAUGAUCCUAG
B AUCGCCAGGAUGAUCCUAGTT B
2452


R-008395899-000G
1322
334
AGUAAUAAGCCGGCUAUUG
B AGUAAUAAGCCGGCUAUUGTT B
2454


R-008395899-000G
1322
334
AGUAAUAAGCCGGCUAUUG
CAAUAGCCGGCUUAUUACUUU
2455


R-008395902-000Z
884
335
AAUGAUGUAGAAACAGCUC
GAGCUGUUUCUACAUCAUUUU
2457


R-008395902-000Z
884
335
AAUGAUGUAGAAACAGCUC
B AAUGAUGUAGAAACAGCUCTT B
2456


R-008395905-000A
2255
336
UCUGAGGACAAGCCACAAG
B UCUGAGGACAAGCCACAAGTT B
2458


R-008395905-000A
2255
336
UCUGAGGACAAGCCACAAG
CUUGUGGCUUGUCCUCAGAUU
2459


R-008395908-000B
1466
337
GGUCUCCUUGGGACUCUUG
CAAGAGUCCCAAGGAGACCUU
2461


R-008395908-000B
1466
337
GGUCUCCUUGGGACUCUUG
B GGUCUCCUUGGGACUCUUGTT B
2460


R-008395911-000H
1399
338
UGUUCAGAACUGUCUUUGG
CCAAAGACAGUUCUGAACAUU
2463


R-008395911-000H
1399
338
UGUUCAGAACUGUCUUUGG
B UGUUCAGAACUGUCUUUGGTT B
2462


R-008395914-000J
378
339
CUGGUGCCACUACCACAGC
B CUGGUGCCACUACCACAGCTT B
2464


R-008395914-000J
378
339
CUGGUGCCACUACCACAGC
GCUGUGGUAGUGGCACCAGUU
2465


R-008395917-000K
1921
340
GUCCAUGGGUGGGACACAG
CUGUGUCCCACCCAUGGACUU
2467


R-008395917-000K
1921
340
GUCCAUGGGUGGGACACAG
B GUCCAUGGGUGGGACACAGTT B
2466


R-008395920-000S
1085
341
GUGCGUUUAGCUGGUGGGC
B GUGCGUUUAGCUGGUGGGCTT B
2468


R-008395920-000S
1085
341
GUGCGUUUAGCUGGUGGGC
GCCCACCAGCUAAACGCACUU
2469


R-008395923-000T
865
342
ACGUACCAUGCAGAAUACA
B ACGUACCAUGCAGAAUACATT B
2470


R-008395923-000T
865
342
ACGUACCAUGCAGAAUACA
UGUAUUCUGCAUGGUACGUUU
2471


R-008395926-000U
2015
343
GAUGUUCACAACCGAAUUG
B GAUGUUCACAACCGAAUUGTT B
2472


R-008395926-000U
2015
343
GAUGUUCACAACCGAAUUG
CAAUUCGGUUGUGAACAUCUU
2473


R-008395929-000V
1195
344
AGAAAGCAAGCUCAUCAUA
B AGAAAGCAAGCUCAUCAUATT B
2474


R-008395929-000V
1195
344
AGAAAGCAAGCUCAUCAUA
UAUGAUGAGCUUGCUUUCUUU
2475


R-008395932-000B
1484
345
GUUCAGCUUCUGGGUUCAG
CUGAACCCAGAAGCUGAACUU
2477


R-008395932-000B
1484
345
GUUCAGCUUCUGGGUUCAG
B GUUCAGCUUCUGGGUUCAGTT B
2476


R-008395935-000C
1855
346
GCAGGGUGCCAUUCCACGA
B GCAGGGUGCCAUUCCACGATT B
2478


R-008395935-000C
1855
346
GCAGGGUGCCAUUCCACGA
UCGUGGAAUGGCACCCUGCUU
2479


R-008395938-000D
1341
347
UAGAAGCUGGUGGAAUGCA
B UAGAAGCUGGUGGAAUGCATT B
2480


R-008395938-000D
1341
347
UAGAAGCUGGUGGAAUGCA
UGCAUUCCACCAGCUUCUAUU
2481


R-008395950-000U
1963
348
CAUGGAAGAAAUAGUUGAA
UUCAACUAUUUCUUCCAUGUU
2483


R-008395950-000U
1963
348
CAUGGAAGAAAUAGUUGAA
B CAUGGAAGAAAUAGUUGAATT B
2482


R-008395953-000V
2362
349
UGAUAUUGGUGCCCAGGGA
B UGAUAUUGGUGCCCAGGGATT B
2484


R-008395953-000V
2362
349
UGAUAUUGGUGCCCAGGGA
UCCCUGGGCACCAAUAUCAUU
2485


R-008395956-000W
584
350
GGCAUGCAGAUCCCAUCUA
B GGCAUGCAGAUCCCAUCUATT B
2486


R-008395956-000W
584
350
GGCAUGCAGAUCCCAUCUA
UAGAUGGGAUCUGCAUGCCUU
2487


R-008395959-000X
1613
351
CGUACUGUCCUUCGGGCUG
B CGUACUGUCCUUCGGGCUGTT B
2488


R-008395959-000X
1613
351
CGUACUGUCCUUCGGGCUG
CAGCCCGAAGGACAGUACGUU
2489


R-008395962-000D
1155
352
UUACGACAGACUGCCUUCA
UGAAGGCAGUCUGUCGUAAUU
2491


R-008395962-000D
1155
352
UUACGACAGACUGCCUUCA
B UUACGACAGACUGCCUUCATT B
2490


R-008395965-000E
334
353
UAGUCACUGGCAGCAACAG
B UAGUCACUGGCAGCAACAGTT B
2492


R-008395965-000E
334
353
UAGUCACUGGCAGCAACAG
CUGUUGCUGCCAGUGACUAUU
2493


R-008395968-000F
1031
354
GCCAUUACAACUCUCCACA
B GCCAUUACAACUCUCCACATT B
2494


R-008395968-000F
1031
354
GCCAUUACAACUCUCCACA
UGUGGAGAGUUGUAAUGGCUU
2495


R-008395971-000M
1725
355
GCCUUCACUAUGGACUACC
B GCCUUCACUAUGGACUACCTT B
2496


R-008395971-000M
1725
355
GCCUUCACUAUGGACUACC
GGUAGUCCAUAGUGAAGGCUU
2497


R-008395974-000N
2018
356
GUUCACAACCGAAUUGUUA
B GUUCACAACCGAAUUGUUATT B
2498


R-008395974-000N
2018
356
GUUCACAACCGAAUUGUUA
UAACAAUUCGGUUGUGAACUU
2499


R-008395977-000P
914
357
GGGACCUUGCAUAACCUUU
AAAGGUUAUGCAAGGUCCCUU
2501


R-008395977-000P
914
357
GGGACCUUGCAUAACCUUU
B GGGACCUUGCAUAACCUUUTT B
2500


R-008395980-000W
2264
358
AAGCCACAAGAUUACAAGA
B AAGCCACAAGAUUACAAGATT B
2502


R-008395980-000W
2264
358
AAGCCACAAGAUUACAAGA
UCUUGUAAUCUUGUGGCUUUU
2503


R-008395983-000X
343
359
GCAGCAACAGUCUUACCUG
CAGGUAAGACUGUUGCUGCUU
2505


R-008395983-000X
343
359
GCAGCAACAGUCUUACCUG
B GCAGCAACAGUCUUACCUGTT B
2504


R-008395986-000Y
1056
360
UAUUACAUCAAGAAGGAGC
B UAUUACAUCAAGAAGGAGCTT B
2506


R-008395986-000Y
1056
360
UAUUACAUCAAGAAGGAGC
GCUCCUUCUUGAUGUAAUAUU
2507


R-008395992-000F
772
361
UAAUAAGGCUGCAGUUAUG
B UAAUAAGGCUGCAGUUAUGTT B
2508


R-008395992-000F
772
361
UAAUAAGGCUGCAGUUAUG
CAUAACUGCAGCCUUAUUAUU
2509


R-008395995-000G
1390
91
UCAACGUCUUGUUCAGAAC
GUUCUGAACAAGACGUUGAUU
2511


R-008395995-000G
1390
91
UCAACGUCUUGUUCAGAAC
B UCAACGUCUUGUUCAGAACTT B
2510


R-008395998-000H
1959
183
UCCGCAUGGAAGAAAUAGU
ACUAUUUCUUCCAUGCGGAUU
2513


R-008395998-000H
1959
183
UCCGCAUGGAAGAAAUAGU
B UCCGCAUGGAAGAAAUAGUTT B
2512


R-008396004-000Y
763
362
GGUGGUGGUUAAUAAGGCU
B GGUGGUGGUUAAUAAGGCUTT B
2514


R-008396004-000Y
763
362
GGUGGUGGUUAAUAAGGCU
AGCCUUAUUAACCACCACCUU
2515


R-008396010-000F
628
363
UAAUGUCCAGCGUUUGGCU
B UAAUGUCCAGCGUUUGGCUTT B
2516


R-008396010-000F
628
363
UAAUGUCCAGCGUUUGGCU
AGCCAAACGCUGGACAUUAUU
2517


R-008396013-000G
399
364
CUUCUCUGAGUGGUAAAGG
B CUUCUCUGAGUGGUAAAGGTT B
2518


R-008396013-000G
399
364
CUUCUCUGAGUGGUAAAGG
CCUUUACCACUCAGAGAAGUU
2519


R-008396016-000H
1682
365
ACCAGCCGACACCAAGAAG
CUUCUUGGUGUCGGCUGGUUU
2521


R-008396016-000H
1682
365
ACCAGCCGACACCAAGAAG
B ACCAGCCGACACCAAGAAGTT B
2520


R-008396019-000J
441
366
AUACCUCCCAAGUCCUGUA
B AUACCUCCCAAGUCCUGUATT B
2522


R-008396019-000J
441
366
AUACCUCCCAAGUCCUGUA
UACAGGACUUGGGAGGUAUUU
2523


R-008396022-000R
1729
367
UCACUAUGGACUACCAGUU
B UCACUAUGGACUACCAGUUTT B
2524


R-008396022-000R
1729
367
UCACUAUGGACUACCAGUU
AACUGGUAGUCCAUAGUGAUU
2525


R-008396025-000S
1902
368
AGGAUACCCAGCGCCGUAC
GUACGGCGCUGGGUAUCCUUU
2527


R-008396025-000S
1902
368
AGGAUACCCAGCGCCGUAC
B AGGAUACCCAGCGCCGUACTT B
2526


R-008396028-000T
1637
369
AGGGAAGACAUCACUGAGC
B AGGGAAGACAUCACUGAGCTT B
2528


R-008396028-000T
1637
369
AGGGAAGACAUCACUGAGC
GCUCAGUGAUGUCUUCCCUUU
2529


R-008396031-000Z
2391
370
GAUAUCGCCAGGAUGAUCC
B GAUAUCGCCAGGAUGAUCCTT B
2530


R-008396031-000Z
2391
370
GAUAUCGCCAGGAUGAUCC
GGAUCAUCCUGGCGAUAUCUU
2531


R-008396034-000A
501
371
AAGUAGCUGAUAUUGAUGG
B AAGUAGCUGAUAUUGAUGGTT B
2532


R-008396034-000A
501
371
AAGUAGCUGAUAUUGAUGG
CCAUCAAUAUCAGCUACUUUU
2533


R-008396037-000B
1358
372
CAAGCUUUAGGACUUCACC
B CAAGCUUUAGGACUUCACCTT B
2534


R-008396037-000B
1358
372
CAAGCUUUAGGACUUCACC
GGUGAAGUCCUAAAGCUUGUU
2535


R-008396040-000H
1821
373
CCCUUUGUCCCGCAAAUCA
B CCCUUUGUCCCGCAAAUCATT B
2536


R-008396040-000H
1821
373
CCCUUUGUCCCGCAAAUCA
UGAUUUGCGGGACAAAGGGUU
2537


R-008396043-000J
575
374
UUAGAUGAGGGCAUGCAGA
B UUAGAUGAGGGCAUGCAGATT B
2538


R-008396043-000J
575
374
UUAGAUGAGGGCAUGCAGA
UCUGCAUGCCCUCAUCUAAUU
2539


R-008396046-000K
528
375
CAAUGACUCGAGCUCAGAG
B CAAUGACUCGAGCUCAGAGTT B
2540


R-008396046-000K
528
375
CAAUGACUCGAGCUCAGAG
CUCUGAGCUCGAGUCAUUGUU
2541


R-008396049-000L
2433
376
GUGGAUAUGGCCAGGAUGC
B GUGGAUAUGGCCAGGAUGCTT B
2542


R-008396049-000L
2433
376
GUGGAUAUGGCCAGGAUGC
GCAUCCUGGCCAUAUCCACUU
2543


R-008396052-000T
1497
377
GUUCAGAUGAUAUAAAUGU
ACAUUUAUAUCAUCUGAACUU
2545


R-008396052-000T
1497
377
GUUCAGAUGAUAUAAAUGU
B GUUCAGAUGAUAUAAAUGUTT B
2544


R-008396055-000U
2134
378
UCAGGACAAGGAAGCUGCA
B UCAGGACAAGGAAGCUGCATT B
2546


R-008396055-000U
2134
378
UCAGGACAAGGAAGCUGCA
UGCAGCUUCCUUGUCCUGAUU
2547


R-008396058-000V
2160
379
UUGAAGCUGAGGGAGCCAC
GUGGCUCCCUCAGCUUCAAUU
2549


R-008396058-000V
2160
379
UUGAAGCUGAGGGAGCCAC
B UUGAAGCUGAGGGAGCCACTT B
2548


R-008396061-000B
291
380
UGGAGUUGGACAUGGCCAU
AUGGCCAUGUCCAACUCCAUU
2551


R-008396061-000B
291
380
UGGAGUUGGACAUGGCCAU
B UGGAGUUGGACAUGGCCAUTT B
2550


R-008396064-000C
657
381
AGAUGCUGAAACAUGCAGU
B AGAUGCUGAAACAUGCAGUTT B
2552


R-008396064-000C
657
381
AGAUGCUGAAACAUGCAGU
ACUGCAUGUUUCAGCAUCUUU
2553


R-008396067-000D
1575
382
UGAUGGUCUGCCAAGUGGG
B UGAUGGUCUGCCAAGUGGGTT B
2554


R-008396067-000D
1575
382
UGAUGGUCUGCCAAGUGGG
CCCACUUGGCAGACCAUCAUU
2555


R-008396070-000K
667
383
ACAUGCAGUUGUAAACUUG
CAAGUUUACAACUGCAUGUUU
2557


R-008396070-000K
667
383
ACAUGCAGUUGUAAACUUG
B ACAUGCAGUUGUAAACUUGTT B
2556


R-008396076-000M
2190
384
CAGAGUUACUUCACUCUAG
B CAGAGUUACUUCACUCUAGTT B
2558


R-008396076-000M
2190
384
CAGAGUUACUUCACUCUAG
CUAGAGUGAAGUAACUCUGUU
2559


R-008396079-000N
532
385
GACUCGAGCUCAGAGGGUA
UACCCUCUGAGCUCGAGUCUU
2561


R-008396079-000N
532
385
GACUCGAGCUCAGAGGGUA
B GACUCGAGCUCAGAGGGUATT B
2560


R-008396082-000V
953
386
CUGGCCAUCUUUAAGUCUG
CAGACUUAAAGAUGGCCAGUU
2563


R-008396082-000V
953
386
CUGGCCAUCUUUAAGUCUG
B CUGGCCAUCUUUAAGUCUGTT B
2562


R-008396085-000W
3188
387
UACGAUGCUUCAAGAGAAA
UUUCUCUUGAAGCAUCGUAUU
2565


R-008396085-000W
3188
387
UACGAUGCUUCAAGAGAAA
B UACGAUGCUUCAAGAGAAATT B
2564


R-008396088-000X
2301
388
UGACCAGCUCUCUCUUCAG
B UGACCAGCUCUCUCUUCAGTT B
2566


R-008396088-000X
2301
388
UGACCAGCUCUCUCUUCAG
CUGAAGAGAGAGCUGGUCAUU
2567


R-008396091-000D
2310
389
CUCUCUUCAGAACAGAGCC
B CUCUCUUCAGAACAGAGCCTT B
2568


R-008396091-000D
2310
389
CUCUCUUCAGAACAGAGCC
GGCUCUGUUCUGAAGAGAGUU
2569


R-008396094-000E
2287
390
GCUUUCAGUUGAGCUGACC
B GCUUUCAGUUGAGCUGACCTT B
2570


R-008396094-000E
2287
390
GCUUUCAGUUGAGCUGACC
GGUCAGCUCAACUGAAAGCUU
2571


R-008396097-000F
1927
391
GGGUGGGACACAGCAGCAA
UUGCUGCUGUGUCCCACCCUU
2573


R-008396097-000F
1927
391
GGGUGGGACACAGCAGCAA
B GGGUGGGACACAGCAGCAATT B
2572


R-008396100-000Y
712
392
UGCCACACGUGCAAUCCCU
AGGGAUUGCACGUGUGGCAUU
2575


R-008396100-000Y
712
392
UGCCACACGUGCAAUCCCU
B UGCCACACGUGCAAUCCCUTT B
2574


R-008396103-000Z
2121
393
UCUGUGAACUUGCUCAGGA
B UCUGUGAACUUGCUCAGGATT B
2576


R-008396103-000Z
2121
393
UCUGUGAACUUGCUCAGGA
UCCUGAGCAAGUUCACAGAUU
2577


R-008396106-000A
2898
394
UGAGUAAUGGUGUAGAACA
B UGAGUAAUGGUGUAGAACATT B
2578


R-008396106-000A
2898
394
UGAGUAAUGGUGUAGAACA
UGUUCUACACCAUUACUCAUU
2579


R-008396109-000B
1799
395
GUUGGAUUGAUUCGAAAUC
B GUUGGAUUGAUUCGAAAUCTT B
2580


R-008396109-000B
1799
395
GUUGGAUUGAUUCGAAAUC
GAUUUCGAAUCAAUCCAACUU
2581


R-008396112-000H
1036
396
UACAACUCUCCACAACCUU
AAGGUUGUGGAGAGUUGUAUU
2583


R-008396112-000H
1036
396
UACAACUCUCCACAACCUU
B UACAACUCUCCACAACCUUTT B
2582


R-008396115-000J
449
397
CAAGUCCUGUAUGAGUGGG
CCCACUCAUACAGGACUUGUU
2585


R-008396115-000J
449
397
CAAGUCCUGUAUGAGUGGG
B CAAGUCCUGUAUGAGUGGGTT B
2584


R-008396118-000K
1452
398
AGGAAGGGAUGGAAGGUCU
B AGGAAGGGAUGGAAGGUCUTT B
2586


R-008396118-000K
1452
398
AGGAAGGGAUGGAAGGUCU
AGACCUUCCAUCCCUUCCUUU
2587


R-008396124-000T
1203
399
AGCUCAUCAUACUGGCUAG
B AGCUCAUCAUACUGGCUAGTT B
2588


R-008396124-000T
1203
399
AGCUCAUCAUACUGGCUAG
CUAGCCAGUAUGAUGAGCUUU
2589


R-008396130-000A
1357
400
GCAAGCUUUAGGACUUCAC
GUGAAGUCCUAAAGCUUGCUU
2591


R-008396130-000A
1357
400
GCAAGCUUUAGGACUUCAC
B GCAAGCUUUAGGACUUCACTT B
2590


R-008396133-000B
1512
401
AUGUGGUCACCUGUGCAGC
GCUGCACAGGUGACCACAUUU
2593


R-008396133-000B
1512
401
AUGUGGUCACCUGUGCAGC
B AUGUGGUCACCUGUGCAGCTT B
2592


R-008396136-000C
275
402
ACUCAAGCUGAUUUGAUGG
B ACUCAAGCUGAUUUGAUGGTT B
2594


R-008396136-000C
275
402
ACUCAAGCUGAUUUGAUGG
CCAUCAAAUCAGCUUGAGUUU
2595


R-008396139-000D
299
403
GACAUGGCCAUGGAACCAG
CUGGUUCCAUGGCCAUGUCUU
2597


R-008396139-000D
299
403
GACAUGGCCAUGGAACCAG
B GACAUGGCCAUGGAACCAGTT B
2596


R-008396142-000K
1241
404
GUAAAUAUAAUGAGGACCU
B GUAAAUAUAAUGAGGACCUTT B
2598


R-008396142-000K
1241
404
GUAAAUAUAAUGAGGACCU
AGGUCCUCAUUAUAUUUACUU
2599


R-008396145-000L
1961
405
CGCAUGGAAGAAAUAGUUG
CAACUAUUUCUUCCAUGCGUU
2601


R-008396145-000L
1961
405
CGCAUGGAAGAAAUAGUUG
B CGCAUGGAAGAAAUAGUUGTT B
2600


R-008396148-000M
1436
406
GAUGCUGCAACUAAACAGG
B GAUGCUGCAACUAAACAGGTT B
2602


R-008396148-000M
1436
406
GAUGCUGCAACUAAACAGG
CCUGUUUAGUUGCAGCAUCUU
2603


R-008396151-000U
2469
407
UGAUGGAACAUGAGAUGGG
B UGAUGGAACAUGAGAUGGGTT B
2604


R-008396151-000U
2469
407
UGAUGGAACAUGAGAUGGG
CCCAUCUCAUGUUCCAUCAUU
2605


R-008396154-000V
760
408
CCAGGUGGUGGUUAAUAAG
B CCAGGUGGUGGUUAAUAAGTT B
2606


R-008396154-000V
760
408
CCAGGUGGUGGUUAAUAAG
CUUAUUAACCACCACCUGGUU
2607


R-008396157-000W
2504
141
GCUGACUAUCCAGUUGAUG
CAUCAACUGGAUAGUCAGCUU
2609


R-008396157-000W
2504
141
GCUGACUAUCCAGUUGAUG
B GCUGACUAUCCAGUUGAUGTT B
2608


R-008396160-000C
2257
409
UGAGGACAAGCCACAAGAU
AUCUUGUGGCUUGUCCUCAUU
2611


R-008396160-000C
2257
409
UGAGGACAAGCCACAAGAU
B UGAGGACAAGCCACAAGAUTT B
2610


R-008396163-000D
952
410
ACUGGCCAUCUUUAAGUCU
AGACUUAAAGAUGGCCAGUUU
2613


R-008396163-000D
952
410
ACUGGCCAUCUUUAAGUCU
B ACUGGCCAUCUUUAAGUCUTT B
2612


R-008396166-000E
2283
411
AACGGCUUUCAGUUGAGCU
B AACGGCUUUCAGUUGAGCUTT B
2614


R-008396166-000E
2283
411
AACGGCUUUCAGUUGAGCU
AGCUCAACUGAAAGCCGUUUU
2615


R-008396169-000F
1649
62
ACUGAGCCUGCCAUCUGUG
B ACUGAGCCUGCCAUCUGUGTT B
2616


R-008396169-000F
1649
62
ACUGAGCCUGCCAUCUGUG
CACAGAUGGCAGGCUCAGUUU
2617


R-008396172-000M
2014
8
GGAUGUUCACAACCGAAUU
AAUUCGGUUGUGAACAUCCUU
2619


R-008396172-000M
2014
8
GGAUGUUCACAACCGAAUU
B GGAUGUUCACAACCGAAUUTT B
2618


R-008396175-000N
1794
412
CUACUGUUGGAUUGAUUCG
CGAAUCAAUCCAACAGUAGUU
2621


R-008396175-000N
1794
412
CUACUGUUGGAUUGAUUCG
B CUACUGUUGGAUUGAUUCGTT B
2620


R-008396178-000P
1745
413
GUUGUGGUUAAGCUCUUAC
B GUUGUGGUUAAGCUCUUACTT B
2622


R-008396178-000P
1745
413
GUUGUGGUUAAGCUCUUAC
GUAAGAGCUUAACCACAACUU
2623


R-008396181-000W
1211
414
AUACUGGCUAGUGGUGGAC
GUCCACCACUAGCCAGUAUUU
2625


R-008396181-000W
1211
414
AUACUGGCUAGUGGUGGAC
B AUACUGGCUAGUGGUGGACTT B
2624


R-008396184-000X
2549
415
GACCUCAUGGAUGGGCUGC
B GACCUCAUGGAUGGGCUGCTT B
2626


R-008396184-000X
2549
415
GACCUCAUGGAUGGGCUGC
GCAGCCCAUCCAUGAGGUCUU
2627


R-008396187-000Y
2007
416
UAGCUCGGGAUGUUCACAA
UUGUGAACAUCCCGAGCUAUU
2629


R-008396187-000Y
2007
416
UAGCUCGGGAUGUUCACAA
B UAGCUCGGGAUGUUCACAATT B
2628


R-008396190-000E
2474
417
GAACAUGAGAUGGGUGGCC
B GAACAUGAGAUGGGUGGCCTT B
2630


R-008396190-000E
2474
417
GAACAUGAGAUGGGUGGCC
GGCCACCCAUCUCAUGUUCUU
2631


R-008396193-000F
1712
418
CAGAAUGCAGUUCGCCUUC
GAAGGCGAACUGCAUUCUGUU
2633


R-008396193-000F
1712
418
CAGAAUGCAGUUCGCCUUC
B CAGAAUGCAGUUCGCCUUCTT B
2632


R-008396196-000G
1919
419
ACGUCCAUGGGUGGGACAC
B ACGUCCAUGGGUGGGACACTT B
2634


R-008396196-000G
1919
419
ACGUCCAUGGGUGGGACAC
GUGUCCCACCCAUGGACGUUU
2635


R-008396199-000H
1000
420
UGGUUCACCAGUGGAUUCU
AGAAUCCACUGGUGAACCAUU
2637


R-008396199-000H
1000
420
UGGUUCACCAGUGGAUUCU
B UGGUUCACCAGUGGAUUCUTT B
2636


R-008396202-000A
2392
421
AUAUCGCCAGGAUGAUCCU
AGGAUCAUCCUGGCGAUAUUU
2639


R-008396202-000A
2392
421
AUAUCGCCAGGAUGAUCCU
B AUAUCGCCAGGAUGAUCCUTT B
2638


R-008396205-000B
1449
422
AACAGGAAGGGAUGGAAGG
B AACAGGAAGGGAUGGAAGGTT B
2640


R-008396205-000B
1449
422
AACAGGAAGGGAUGGAAGG
CCUUCCAUCCCUUCCUGUUUU
2641


R-008396208-000C
2294
423
GUUGAGCUGACCAGCUCUC
GAGAGCUGGUCAGCUCAACUU
2643


R-008396208-000C
2294
423
GUUGAGCUGACCAGCUCUC
B GUUGAGCUGACCAGCUCUCTT B
2642


R-008396211-000J
1135
424
AAAUGUUAAAUUCUUGGCU
B AAAUGUUAAAUUCUUGGCUTT B
2644


R-008396211-000J
1135
424
AAAUGUUAAAUUCUUGGCU
AGCCAAGAAUUUAACAUUUUU
2645


R-008396214-000K
822
14
GACACGCUAUCAUGCGUUC
B GACACGCUAUCAUGCGUUCTT B
2646


R-008396214-000K
822
14
GACACGCUAUCAUGCGUUC
GAACGCAUGAUAGCGUGUCUU
2647


R-008396217-000L
1333
425
GGCUAUUGUAGAAGCUGGU
ACCAGCUUCUACAAUAGCCUU
2649


R-008396217-000L
1333
425
GGCUAUUGUAGAAGCUGGU
B GGCUAUUGUAGAAGCUGGUTT B
2648


R-008396220-000T
1743
426
CAGUUGUGGUUAAGCUCUU
AAGAGCUUAACCACAACUGUU
2651


R-008396220-000T
1743
426
CAGUUGUGGUUAAGCUCUU
B CAGUUGUGGUUAAGCUCUUTT B
2650


R-008396223-000U
600
427
CUACACAGUUUGAUGCUGC
GCAGCAUCAAACUGUGUAGUU
2653


R-008396223-000U
600
427
CUACACAGUUUGAUGCUGC
B CUACACAGUUUGAUGCUGCTT B
2652


R-008396226-000V
970
428
UGGAGGCAUUCCUGCCCUG
CAGGGCAGGAAUGCCUCCAUU
2655


R-008396226-000V
970
428
UGGAGGCAUUCCUGCCCUG
B UGGAGGCAUUCCUGCCCUGTT B
2654


R-008396229-000W
3137
429
GGACAGUUUACCAGUUGCC
B GGACAGUUUACCAGUUGCCTT B
2656


R-008396229-000W
3137
429
GGACAGUUUACCAGUUGCC
GGCAACUGGUAAACUGUCCUU
2657


R-008396232-000C
372
430
UCCAUUCUGGUGCCACUAC
GUAGUGGCACCAGAAUGGAUU
2659


R-008396232-000C
372
430
UCCAUUCUGGUGCCACUAC
B UCCAUUCUGGUGCCACUACTT B
2658


R-008396235-000D
1761
431
UACACCCACCAUCCCACUG
B UACACCCACCAUCCCACUGTT B
2660


R-008396235-000D
1761
431
UACACCCACCAUCCCACUG
CAGUGGGAUGGUGGGUGUAUU
2661


R-008396238-000E
1650
432
CUGAGCCUGCCAUCUGUGC
GCACAGAUGGCAGGCUCAGUU
2663


R-008396238-000E
1650
432
CUGAGCCUGCCAUCUGUGC
B CUGAGCCUGCCAUCUGUGCTT B
2662


R-008396241-000L
972
433
GAGGCAUUCCUGCCCUGGU
B GAGGCAUUCCUGCCCUGGUTT B
2664


R-008396241-000L
972
433
GAGGCAUUCCUGCCCUGGU
ACCAGGGCAGGAAUGCCUCUU
2665


R-008396244-000M
1147
434
CUUGGCUAUUACGACAGAC
GUCUGUCGUAAUAGCCAAGUU
2667


R-008396244-000M
1147
434
CUUGGCUAUUACGACAGAC
B CUUGGCUAUUACGACAGACTT B
2666


R-008396247-000N
565
435
CCCUGAGACAUUAGAUGAG
B CCCUGAGACAUUAGAUGAGTT B
2668


R-008396247-000N
565
435
CCCUGAGACAUUAGAUGAG
CUCAUCUAAUGUCUCAGGGUU
2669


R-008396250-000V
525
436
AUGCAAUGACUCGAGCUCA
B AUGCAAUGACUCGAGCUCATT B
2670


R-008396250-000V
525
436
AUGCAAUGACUCGAGCUCA
UGAGCUCGAGUCAUUGCAUUU
2671


R-008396253-000W
1599
437
UAGAGGCUCUUGUGCGUAC
B UAGAGGCUCUUGUGCGUACTT B
2672


R-008396253-000W
1599
437
UAGAGGCUCUUGUGCGUAC
GUACGCACAAGAGCCUCUAUU
2673


R-008396256-000X
2199
438
UUCACUCUAGGAAUGAAGG
B UUCACUCUAGGAAUGAAGGTT B
2674


R-008396256-000X
2199
438
UUCACUCUAGGAAUGAAGG
CCUUCAUUCCUAGAGUGAAUU
2675


R-008396259-000Y
2261
439
GACAAGCCACAAGAUUACA
B GACAAGCCACAAGAUUACATT B
2676


R-008396259-000Y
2261
439
GACAAGCCACAAGAUUACA
UGUAAUCUUGUGGCUUGUCUU
2677


R-008396262-000E
705
440
CAGAACUUGCCACACGUGC
B CAGAACUUGCCACACGUGCTT B
2678


R-008396262-000E
705
440
CAGAACUUGCCACACGUGC
GCACGUGUGGCAAGUUCUGUU
2679


R-008396265-000F
916
441
GACCUUGCAUAACCUUUCC
B GACCUUGCAUAACCUUUCCTT B
2680


R-008396265-000F
916
441
GACCUUGCAUAACCUUUCC
GGAAAGGUUAUGCAAGGUCUU
2681


R-008396268-000G
385
442
CACUACCACAGCUCCUUCU
AGAAGGAGCUGUGGUAGUGUU
2683


R-008396268-000G
385
442
CACUACCACAGCUCCUUCU
B CACUACCACAGCUCCUUCUTT B
2682


R-008396271-000N
3076
443
CUAUUUGGGAUAUGUAUGG
B CUAUUUGGGAUAUGUAUGGTT B
2684


R-008396271-000N
3076
443
CUAUUUGGGAUAUGUAUGG
CCAUACAUAUCCCAAAUAGUU
2685


R-008396274-000P
1396
444
UCUUGUUCAGAACUGUCUU
B UCUUGUUCAGAACUGUCUUTT B
2686


R-008396274-000P
1396
444
UCUUGUUCAGAACUGUCUU
AAGACAGUUCUGAACAAGAUU
2687


R-008396277-000R
2447
445
GAUGCCUUGGGUAUGGACC
GGUCCAUACCCAAGGCAUCUU
2689


R-008396277-000R
2447
445
GAUGCCUUGGGUAUGGACC
B GAUGCCUUGGGUAUGGACCTT B
2688


R-008396280-000X
1338
446
UUGUAGAAGCUGGUGGAAU
B UUGUAGAAGCUGGUGGAAUTT B
2690


R-008396280-000X
1338
446
UUGUAGAAGCUGGUGGAAU
AUUCCACCAGCUUCUACAAUU
2691


R-008396283-000Y
2215
447
AGGUGUGGCGACAUAUGCA
UGCAUAUGUCGCCACACCUUU
2693


R-008396283-000Y
2215
447
AGGUGUGGCGACAUAUGCA
B AGGUGUGGCGACAUAUGCATT B
2692


R-008396286-000Z
722
448
GCAAUCCCUGAACUGACAA
B GCAAUCCCUGAACUGACAATT B
2694


R-008396286-000Z
722
448
GCAAUCCCUGAACUGACAA
UUGUCAGUUCAGGGAUUGCUU
2695


R-008396289-000A
1316
449
UGCUCUAGUAAUAAGCCGG
CCGGCUUAUUACUAGAGCAUU
2697


R-008396289-000A
1316
449
UGCUCUAGUAAUAAGCCGG
B UGCUCUAGUAAUAAGCCGGTT B
2696


R-008396292-000G
1687
450
CCGACACCAAGAAGCAGAG
B CCGACACCAAGAAGCAGAGTT B
2698


R-008396292-000G
1687
450
CCGACACCAAGAAGCAGAG
CUCUGCUUCUUGGUGUCGGUU
2699


R-008396295-000H
697
451
AGAUGAUGCAGAACUUGCC
B AGAUGAUGCAGAACUUGCCTT B
2700


R-008396295-000H
697
451
AGAUGAUGCAGAACUUGCC
GGCAAGUUCUGCAUCAUCUUU
2701


R-008396298-000J
2517
452
UUGAUGGGCUGCCAGAUCU
B UUGAUGGGCUGCCAGAUCUTT B
2702


R-008396298-000J
2517
452
UUGAUGGGCUGCCAGAUCU
AGAUCUGGCAGCCCAUCAAUU
2703


R-008396301-000B
1685
453
AGCCGACACCAAGAAGCAG
B AGCCGACACCAAGAAGCAGTT B
2704


R-008396301-000B
1685
453
AGCCGACACCAAGAAGCAG
CUGCUUCUUGGUGUCGGCUUU
2705


R-008396304-000C
3090
454
UAUGGGUAGGGUAAAUCAG
CUGAUUUACCCUACCCAUAUU
2707


R-008396304-000C
3090
454
UAUGGGUAGGGUAAAUCAG
B UAUGGGUAGGGUAAAUCAGTT B
2706


R-008396307-000D
1205
455
CUCAUCAUACUGGCUAGUG
B CUCAUCAUACUGGCUAGUGTT B
2708


R-008396307-000D
1205
455
CUCAUCAUACUGGCUAGUG
CACUAGCCAGUAUGAUGAGUU
2709


R-008396310-000K
1153
456
UAUUACGACAGACUGCCUU
B UAUUACGACAGACUGCCUUTT B
2710


R-008396310-000K
1153
456
UAUUACGACAGACUGCCUU
AAGGCAGUCUGUCGUAAUAUU
2711


R-008396313-000L
723
457
CAAUCCCUGAACUGACAAA
B CAAUCCCUGAACUGACAAATT B
2712


R-008396313-000L
723
457
CAAUCCCUGAACUGACAAA
UUUGUCAGUUCAGGGAUUGUU
2713


R-008396316-000M
1468
458
UCUCCUUGGGACUCUUGUU
AACAAGAGUCCCAAGGAGAUU
2715


R-008396316-000M
1468
458
UCUCCUUGGGACUCUUGUU
B UCUCCUUGGGACUCUUGUUTT B
2714


R-008396319-000N
2480
459
GAGAUGGGUGGCCACCACC
B GAGAUGGGUGGCCACCACCTT B
2716


R-008396319-000N
2480
459
GAGAUGGGUGGCCACCACC
GGUGGUGGCCACCCAUCUCUU
2717


R-008396322-000V
1856
460
CAGGGUGCCAUUCCACGAC
B CAGGGUGCCAUUCCACGACTT B
2718


R-008396322-000V
1856
460
CAGGGUGCCAUUCCACGAC
GUCGUGGAAUGGCACCCUGUU
2719


R-008396325-000W
2193
461
AGUUACUUCACUCUAGGAA
B AGUUACUUCACUCUAGGAATT B
2720


R-008396325-000W
2193
461
AGUUACUUCACUCUAGGAA
UUCCUAGAGUGAAGUAACUUU
2721


R-008396328-000X
2355
462
UUGGACUUGAUAUUGGUGC
B UUGGACUUGAUAUUGGUGCTT B
2722


R-008396328-000X
2355
462
UUGGACUUGAUAUUGGUGC
GCACCAAUAUCAAGUCCAAUU
2723


R-008396331-000D
1995
463
CCCUUCACAUCCUAGCUCG
CGAGCUAGGAUGUGAAGGGUU
2725


R-008396331-000D
1995
463
CCCUUCACAUCCUAGCUCG
B CCCUUCACAUCCUAGCUCGTT B
2724


R-008396334-000E
821
464
AGACACGCUAUCAUGCGUU
B AGACACGCUAUCAUGCGUUTT B
2726


R-008396334-000E
821
464
AGACACGCUAUCAUGCGUU
AACGCAUGAUAGCGUGUCUUU
2727


R-008396337-000F
1715
465
AAUGCAGUUCGCCUUCACU
B AAUGCAGUUCGCCUUCACUTT B
2728


R-008396337-000F
1715
465
AAUGCAGUUCGCCUUCACU
AGUGAAGGCGAACUGCAUUUU
2729


R-008396340-000M
1182
466
CUUAUGGCAACCAAGAAAG
CUUUCUUGGUUGCCAUAAGUU
2731


R-008396340-000M
1182
466
CUUAUGGCAACCAAGAAAG
B CUUAUGGCAACCAAGAAAGTT B
2730


R-008396343-000N
445
467
CUCCCAAGUCCUGUAUGAG
B CUCCCAAGUCCUGUAUGAGTT B
2732


R-008396343-000N
445
467
CUCCCAAGUCCUGUAUGAG
CUCAUACAGGACUUGGGAGUU
2733


R-008396346-000P
1759
468
CUUACACCCACCAUCCCAC
GUGGGAUGGUGGGUGUAAGUU
2735


R-008396346-000P
1759
468
CUUACACCCACCAUCCCAC
B CUUACACCCACCAUCCCACTT B
2734


R-008396349-000R
1461
469
UGGAAGGUCUCCUUGGGAC
B UGGAAGGUCUCCUUGGGACTT B
2736


R-008396349-000R
1461
469
UGGAAGGUCUCCUUGGGAC
GUCCCAAGGAGACCUUCCAUU
2737


R-008396352-000X
1993
470
AGCCCUUCACAUCCUAGCU
AGCUAGGAUGUGAAGGGCUUU
2739


R-008396352-000X
1993
470
AGCCCUUCACAUCCUAGCU
B AGCCCUUCACAUCCUAGCUTT B
2738


R-008396355-000Y
2558
471
GAUGGGCUGCCUCCAGGUG
B GAUGGGCUGCCUCCAGGUGTT B
2740


R-008396355-000Y
2558
471
GAUGGGCUGCCUCCAGGUG
CACCUGGAGGCAGCCCAUCUU
2741


R-008396358-000Z
1488
472
AGCUUCUGGGUUCAGAUGA
B AGCUUCUGGGUUCAGAUGATT B
2742


R-008396358-000Z
1488
472
AGCUUCUGGGUUCAGAUGA
UCAUCUGAACCCAGAAGCUUU
2743


R-008396361-000F
1652
473
GAGCCUGCCAUCUGUGCUC
B GAGCCUGCCAUCUGUGCUCTT B
2744


R-008396361-000F
1652
473
GAGCCUGCCAUCUGUGCUC
GAGCACAGAUGGCAGGCUCUU
2745


R-008396364-000G
963
474
UUAAGUCUGGAGGCAUUCC
B UUAAGUCUGGAGGCAUUCCTT B
2746


R-008396364-000G
963
474
UUAAGUCUGGAGGCAUUCC
GGAAUGCCUCCAGACUUAAUU
2747


R-008396367-000H
1520
475
ACCUGUGCAGCUGGAAUUC
B ACCUGUGCAGCUGGAAUUCTT B
2748


R-008396367-000H
1520
475
ACCUGUGCAGCUGGAAUUC
GAAUUCCAGCUGCACAGGUUU
2749


R-008396370-000P
1828
476
UCCCGCAAAUCAUGCACCU
AGGUGCAUGAUUUGCGGGAUU
2751


R-008396370-000P
1828
476
UCCCGCAAAUCAUGCACCU
B UCCCGCAAAUCAUGCACCUTT B
2750


R-008396373-000R
2214
477
AAGGUGUGGCGACAUAUGC
B AAGGUGUGGCGACAUAUGCTT B
2752


R-008396373-000R
2214
477
AAGGUGUGGCGACAUAUGC
GCAUAUGUCGCCACACCUUUU
2753


R-008396376-000S
2155
478
AGCUAUUGAAGCUGAGGGA
UCCCUCAGCUUCAAUAGCUUU
2755


R-008396376-000S
2155
478
AGCUAUUGAAGCUGAGGGA
B AGCUAUUGAAGCUGAGGGATT B
2754


R-008396379-000T
332
479
GUUAGUCACUGGCAGCAAC
GUUGCUGCCAGUGACUAACUU
2757


R-008396379-000T
332
479
GUUAGUCACUGGCAGCAAC
B GUUAGUCACUGGCAGCAACTT B
2756


R-008396382-000Z
2545
74
CCAGGACCUCAUGGAUGGG
CCCAUCCAUGAGGUCCUGGUU
2759


R-008396382-000Z
2545
74
CCAGGACCUCAUGGAUGGG
B CCAGGACCUCAUGGAUGGGTT B
2758


R-008396385-000A
1878
480
UUCAGUUGCUUGUUCGUGC
B UUCAGUUGCUUGUUCGUGCTT B
2760


R-008396385-000A
1878
480
UUCAGUUGCUUGUUCGUGC
GCACGAACAAGCAACUGAAUU
2761


R-008396388-000B
1789
106
AAAGGCUACUGUUGGAUUG
CAAUCCAACAGUAGCCUUUUU
2763


R-008396388-000B
1789
106
AAAGGCUACUGUUGGAUUG
B AAAGGCUACUGUUGGAUUGTT B
2762


R-008396391-000H
2547
168
AGGACCUCAUGGAUGGGCU
B AGGACCUCAUGGAUGGGCUTT B
2764


R-008396391-000H
2547
168
AGGACCUCAUGGAUGGGCU
AGCCCAUCCAUGAGGUCCUUU
2765


R-008396394-000J
1573
481
GAUGAUGGUCUGCCAAGUG
B GAUGAUGGUCUGCCAAGUGTT B
2766


R-008396394-000J
1573
481
GAUGAUGGUCUGCCAAGUG
CACUUGGCAGACCAUCAUCUU
2767


R-008396397-000K
1446
482
CUAAACAGGAAGGGAUGGA
B CUAAACAGGAAGGGAUGGATT B
2768


R-008396397-000K
1446
482
CUAAACAGGAAGGGAUGGA
UCCAUCCCUUCCUGUUUAGUU
2769


R-008396400-000C
1868
483
CCACGACUAGUUCAGUUGC
GCAACUGAACUAGUCGUGGUU
2771


R-008396400-000C
1868
483
CCACGACUAGUUCAGUUGC
B CCACGACUAGUUCAGUUGCTT B
2770


R-008396403-000D
1873
484
ACUAGUUCAGUUGCUUGUU
AACAAGCAACUGAACUAGUUU
2773


R-008396403-000D
1873
484
ACUAGUUCAGUUGCUUGUU
B ACUAGUUCAGUUGCUUGUUTT B
2772


R-008396406-000E
1002
485
GUUCACCAGUGGAUUCUGU
B GUUCACCAGUGGAUUCUGUTT B
2774


R-008396406-000E
1002
485
GUUCACCAGUGGAUUCUGU
ACAGAAUCCACUGGUGAACUU
2775


R-008396409-000F
408
486
GUGGUAAAGGCAAUCCUGA
B GUGGUAAAGGCAAUCCUGATT B
2776


R-008396409-000F
408
486
GUGGUAAAGGCAAUCCUGA
UCAGGAUUGCCUUUACCACUU
2777


R-008396412-000M
287
487
UUGAUGGAGUUGGACAUGG
CCAUGUCCAACUCCAUCAAUU
2779


R-008396412-000M
287
487
UUGAUGGAGUUGGACAUGG
B UUGAUGGAGUUGGACAUGGTT B
2778


R-008396415-000N
1492
119
UCUGGGUUCAGAUGAUAUA
UAUAUCAUCUGAACCCAGAUU
2781


R-008396415-000N
1492
119
UCUGGGUUCAGAUGAUAUA
B UCUGGGUUCAGAUGAUAUATT B
2780


R-008396418-000P
517
187
UGGACAGUAUGCAAUGACU
B UGGACAGUAUGCAAUGACUTT B
2782


R-008396418-000P
517
187
UGGACAGUAUGCAAUGACU
AGUCAUUGCAUACUGUCCAUU
2783


R-008396421-000W
447
177
CCCAAGUCCUGUAUGAGUG
B CCCAAGUCCUGUAUGAGUGTT B
2784


R-008396421-000W
447
177
CCCAAGUCCUGUAUGAGUG
CACUCAUACAGGACUUGGGUU
2785


R-008396424-000X
2128
488
ACUUGCUCAGGACAAGGAA
UUCCUUGUCCUGAGCAAGUUU
2787


R-008396424-000X
2128
488
ACUUGCUCAGGACAAGGAA
B ACUUGCUCAGGACAAGGAATT B
2786


R-008396427-000Y
2513
489
CCAGUUGAUGGGCUGCCAG
B CCAGUUGAUGGGCUGCCAGTT B
2788


R-008396427-000Y
2513
489
CCAGUUGAUGGGCUGCCAG
CUGGCAGCCCAUCAACUGGUU
2789


R-008396430-000E
1196
490
GAAAGCAAGCUCAUCAUAC
GUAUGAUGAGCUUGCUUUCUU
2791


R-008396430-000E
1196
490
GAAAGCAAGCUCAUCAUAC
B GAAAGCAAGCUCAUCAUACTT B
2790


R-008396433-000F
572
491
ACAUUAGAUGAGGGCAUGC
B ACAUUAGAUGAGGGCAUGCTT B
2792


R-008396433-000F
572
491
ACAUUAGAUGAGGGCAUGC
GCAUGCCCUCAUCUAAUGUUU
2793


R-008396436-000G
622
492
UCCCACUAAUGUCCAGCGU
B UCCCACUAAUGUCCAGCGUTT B
2794


R-008396436-000G
622
492
UCCCACUAAUGUCCAGCGU
ACGCUGGACAUUAGUGGGAUU
2795


R-008396439-000H
1187
493
GGCAACCAAGAAAGCAAGC
GCUUGCUUUCUUGGUUGCCUU
2797


R-008396439-000H
1187
493
GGCAACCAAGAAAGCAAGC
B GGCAACCAAGAAAGCAAGCTT B
2796


R-008396442-000P
2098
49
CCAAAGAGUAGCUGCAGGG
B CCAAAGAGUAGCUGCAGGGTT B
2798


R-008396442-000P
2098
49
CCAAAGAGUAGCUGCAGGG
CCCUGCAGCUACUCUUUGGUU
2799


R-008396445-000R
1971
494
AAAUAGUUGAAGGUUGUAC
B AAAUAGUUGAAGGUUGUACTT B
2800


R-008396445-000R
1971
494
AAAUAGUUGAAGGUUGUAC
GUACAACCUUCAACUAUUUUU
2801


R-008396448-000S
3083
495
GGAUAUGUAUGGGUAGGGU
ACCCUACCCAUACAUAUCCUU
2803


R-008396448-000S
3083
495
GGAUAUGUAUGGGUAGGGU
B GGAUAUGUAUGGGUAGGGUTT B
2802


R-008396454-000Z
2944
496
UAAUCUGAAUAAAGUGUAA
UUACACUUUAUUCAGAUUAUU
2805


R-008396454-000Z
2944
496
UAAUCUGAAUAAAGUGUAA
B UAAUCUGAAUAAAGUGUAATT B
2804


R-008396457-000A
1894
497
UGCACAUCAGGAUACCCAG
B UGCACAUCAGGAUACCCAGTT B
2806


R-008396457-000A
1894
497
UGCACAUCAGGAUACCCAG
CUGGGUAUCCUGAUGUGCAUU
2807


R-008396460-000G
1323
498
GUAAUAAGCCGGCUAUUGU
B GUAAUAAGCCGGCUAUUGUTT B
2808


R-008396460-000G
1323
498
GUAAUAAGCCGGCUAUUGU
ACAAUAGCCGGCUUAUUACUU
2809


R-008396469-000K
1202
499
AAGCUCAUCAUACUGGCUA
B AAGCUCAUCAUACUGGCUATT B
2810


R-008396469-000K
1202
499
AAGCUCAUCAUACUGGCUA
UAGCCAGUAUGAUGAGCUUUU
2811


R-008396472-000S
718
500
ACGUGCAAUCCCUGAACUG
CAGUUCAGGGAUUGCACGUUU
2813


R-008396472-000S
718
500
ACGUGCAAUCCCUGAACUG
B ACGUGCAAUCCCUGAACUGTT B
2812


R-008396475-000T
2097
46
UCCAAAGAGUAGCUGCAGG
CCUGCAGCUACUCUUUGGAUU
2815


R-008396475-000T
2097
46
UCCAAAGAGUAGCUGCAGG
B UCCAAAGAGUAGCUGCAGGTT B
2814


R-008396478-000U
1744
501
AGUUGUGGUUAAGCUCUUA
B AGUUGUGGUUAAGCUCUUATT B
2816


R-008396478-000U
1744
501
AGUUGUGGUUAAGCUCUUA
UAAGAGCUUAACCACAACUUU
2817


R-008396481-000A
756
502
AGGACCAGGUGGUGGUUAA
UUAACCACCACCUGGUCCUUU
2819


R-008396481-000A
756
502
AGGACCAGGUGGUGGUUAA
B AGGACCAGGUGGUGGUUAATT B
2818


R-008396484-000B
1317
503
GCUCUAGUAAUAAGCCGGC
GCCGGCUUAUUACUAGAGCUU
2821


R-008396484-000B
1317
503
GCUCUAGUAAUAAGCCGGC
B GCUCUAGUAAUAAGCCGGCTT B
2820


R-008396487-000C
284
504
GAUUUGAUGGAGUUGGACA
B GAUUUGAUGGAGUUGGACATT B
2822


R-008396487-000C
284
504
GAUUUGAUGGAGUUGGACA
UGUCCAACUCCAUCAAAUCUU
2823


R-008396490-000J
886
505
UGAUGUAGAAACAGCUCGU
B UGAUGUAGAAACAGCUCGUTT B
2824


R-008396490-000J
886
505
UGAUGUAGAAACAGCUCGU
ACGAGCUGUUUCUACAUCAUU
2825


R-008396493-000K
2430
506
CUGGUGGAUAUGGCCAGGA
B CUGGUGGAUAUGGCCAGGATT B
2826


R-008396493-000K
2430
506
CUGGUGGAUAUGGCCAGGA
UCCUGGCCAUAUCCACCAGUU
2827


R-008396496-000L
1207
507
CAUCAUACUGGCUAGUGGU
B CAUCAUACUGGCUAGUGGUTT B
2828


R-008396496-000L
1207
507
CAUCAUACUGGCUAGUGGU
ACCACUAGCCAGUAUGAUGUU
2829


R-008396499-000M
592
508
GAUCCCAUCUACACAGUUU
AAACUGUGUAGAUGGGAUCUU
2831


R-008396499-000M
592
508
GAUCCCAUCUACACAGUUU
B GAUCCCAUCUACACAGUUUTT B
2830


R-008396502-000E
824
509
CACGCUAUCAUGCGUUCUC
GAGAACGCAUGAUAGCGUGUU
2833


R-008396502-000E
824
509
CACGCUAUCAUGCGUUCUC
B CACGCUAUCAUGCGUUCUCTT B
2832


R-008396505-000F
519
510
GACAGUAUGCAAUGACUCG
B GACAGUAUGCAAUGACUCGTT B
2834


R-008396505-000F
519
510
GACAGUAUGCAAUGACUCG
CGAGUCAUUGCAUACUGUCUU
2835


R-008396508-000G
3166
511
AAGUUGUUGUAACCUGCUG
CAGCAGGUUACAACAACUUUU
2837


R-008396508-000G
3166
511
AAGUUGUUGUAACCUGCUG
B AAGUUGUUGUAACCUGCUGTT B
2836


R-008396511-000N
1151
512
GCUAUUACGACAGACUGCC
B GCUAUUACGACAGACUGCCTT B
2838


R-008396511-000N
1151
512
GCUAUUACGACAGACUGCC
GGCAGUCUGUCGUAAUAGCUU
2839


R-008396514-000P
2566
513
GCCUCCAGGUGACAGCAAU
B GCCUCCAGGUGACAGCAAUTT B
2840


R-008396514-000P
2566
513
GCCUCCAGGUGACAGCAAU
AUUGCUGUCACCUGGAGGCUU
2841


R-008396517-000R
453
514
UCCUGUAUGAGUGGGAACA
UGUUCCCACUCAUACAGGAUU
2843


R-008396517-000R
453
514
UCCUGUAUGAGUGGGAACA
B UCCUGUAUGAGUGGGAACATT B
2842


R-008396520-000X
587
515
AUGCAGAUCCCAUCUACAC
GUGUAGAUGGGAUCUGCAUUU
2845


R-008396520-000X
587
515
AUGCAGAUCCCAUCUACAC
B AUGCAGAUCCCAUCUACACTT B
2844


R-008396523-000Y
930
516
UUUCCCAUCAUCGUGAGGG
B UUUCCCAUCAUCGUGAGGGTT B
2846


R-008396523-000Y
930
516
UUUCCCAUCAUCGUGAGGG
CCCUCACGAUGAUGGGAAAUU
2847


R-008396526-000Z
1585
517
CCAAGUGGGUGGUAUAGAG
B CCAAGUGGGUGGUAUAGAGTT B
2848


R-008396526-000Z
1585
517
CCAAGUGGGUGGUAUAGAG
CUCUAUACCACCCACUUGGUU
2849


R-008396529-000A
915
518
GGACCUUGCAUAACCUUUC
B GGACCUUGCAUAACCUUUCTT B
2850


R-008396529-000A
915
518
GGACCUUGCAUAACCUUUC
GAAAGGUUAUGCAAGGUCCUU
2851


R-008396532-000G
446
519
UCCCAAGUCCUGUAUGAGU
ACUCAUACAGGACUUGGGAUU
2853


R-008396532-000G
446
519
UCCCAAGUCCUGUAUGAGU
B UCCCAAGUCCUGUAUGAGUTT B
2852


R-008396535-000H
1869
520
CACGACUAGUUCAGUUGCU
AGCAACUGAACUAGUCGUGUU
2855


R-008396535-000H
1869
520
CACGACUAGUUCAGUUGCU
B CACGACUAGUUCAGUUGCUTT B
2854


R-008396538-000J
1960
521
CCGCAUGGAAGAAAUAGUU
AACUAUUUCUUCCAUGCGGUU
2857


R-008396538-000J
1960
521
CCGCAUGGAAGAAAUAGUU
B CCGCAUGGAAGAAAUAGUUTT B
2856


R-008396541-000R
1708
522
GGCCCAGAAUGCAGUUCGC
B GGCCCAGAAUGCAGUUCGCTT B
2858


R-008396541-000R
1708
522
GGCCCAGAAUGCAGUUCGC
GCGAACUGCAUUCUGGGCCUU
2859


R-008396544-000S
306
523
CCAUGGAACCAGACAGAAA
UUUCUGUCUGGUUCCAUGGUU
2861


R-008396544-000S
306
523
CCAUGGAACCAGACAGAAA
B CCAUGGAACCAGACAGAAATT B
2860


R-008396550-000Z
2281
524
GAAACGGCUUUCAGUUGAG
B GAAACGGCUUUCAGUUGAGTT B
2862


R-008396550-000Z
2281
524
GAAACGGCUUUCAGUUGAG
CUCAACUGAAAGCCGUUUCUU
2863


R-008396553-000A
3082
525
GGGAUAUGUAUGGGUAGGG
B GGGAUAUGUAUGGGUAGGGTT B
2864


R-008396553-000A
3082
525
GGGAUAUGUAUGGGUAGGG
CCCUACCCAUACAUAUCCCUU
2865


R-008396556-000B
1473
526
UUGGGACUCUUGUUCAGCU
AGCUGAACAAGAGUCCCAAUU
2867


R-008396556-000B
1473
526
UUGGGACUCUUGUUCAGCU
B UUGGGACUCUUGUUCAGCUTT B
2866


R-008396559-000C
559
527
UAUGUUCCCUGAGACAUUA
UAAUGUCUCAGGGAACAUAUU
2869


R-008396559-000C
559
527
UAUGUUCCCUGAGACAUUA
B UAUGUUCCCUGAGACAUUATT B
2868


R-008396562-000J
1416
528
GGACUCUCAGGAAUCUUUC
B GGACUCUCAGGAAUCUUUCTT B
2870


R-008396562-000J
1416
528
GGACUCUCAGGAAUCUUUC
GAAAGAUUCCUGAGAGUCCUU
2871


R-008396565-000K
2145
529
AAGCUGCAGAAGCUAUUGA
B AAGCUGCAGAAGCUAUUGATT B
2872


R-008396565-000K
2145
529
AAGCUGCAGAAGCUAUUGA
UCAAUAGCUUCUGCAGCUUUU
2873


R-008396568-000L
1994
530
GCCCUUCACAUCCUAGCUC
B GCCCUUCACAUCCUAGCUCTT B
2874


R-008396568-000L
1994
530
GCCCUUCACAUCCUAGCUC
GAGCUAGGAUGUGAAGGGCUU
2875


R-008396571-000T
1611
27
UGCGUACUGUCCUUCGGGC
B UGCGUACUGUCCUUCGGGCTT B
2876


R-008396571-000T
1611
27
UGCGUACUGUCCUUCGGGC
GCCCGAAGGACAGUACGCAUU
2877


R-008396574-000U
1702
531
AGAGAUGGCCCAGAAUGCA
B AGAGAUGGCCCAGAAUGCATT B
2878


R-008396574-000U
1702
531
AGAGAUGGCCCAGAAUGCA
UGCAUUCUGGGCCAUCUCUUU
2879


R-008396577-000V
417
532
GCAAUCCUGAGGAAGAGGA
B GCAAUCCUGAGGAAGAGGATT B
2880


R-008396577-000V
417
532
GCAAUCCUGAGGAAGAGGA
UCCUCUUCCUCAGGAUUGCUU
2881


R-008396580-000B
2444
533
CAGGAUGCCUUGGGUAUGG
B CAGGAUGCCUUGGGUAUGGTT B
2882


R-008396580-000B
2444
533
CAGGAUGCCUUGGGUAUGG
CCAUACCCAAGGCAUCCUGUU
2883


R-008396586-000D
555
534
CUGCUAUGUUCCCUGAGAC
B CUGCUAUGUUCCCUGAGACTT B
2884


R-008396586-000D
555
534
CUGCUAUGUUCCCUGAGAC
GUCUCAGGGAACAUAGCAGUU
2885


R-008396589-000E
2019
535
UUCACAACCGAAUUGUUAU
B UUCACAACCGAAUUGUUAUTT B
2886


R-008396589-000E
2019
535
UUCACAACCGAAUUGUUAU
AUAACAAUUCGGUUGUGAAUU
2887


R-008396592-000L
1197
536
AAAGCAAGCUCAUCAUACU
B AAAGCAAGCUCAUCAUACUTT B
2888


R-008396592-000L
1197
536
AAAGCAAGCUCAUCAUACU
AGUAUGAUGAGCUUGCUUUUU
2889


R-008396595-000M
415
537
AGGCAAUCCUGAGGAAGAG
CUCUUCCUCAGGAUUGCCUUU
2891


R-008396595-000M
415
537
AGGCAAUCCUGAGGAAGAG
B AGGCAAUCCUGAGGAAGAGTT B
2890


R-008396598-000N
2061
538
UGUUUGUGCAGCUGCUUUA
B UGUUUGUGCAGCUGCUUUATT B
2892


R-008396598-000N
2061
538
UGUUUGUGCAGCUGCUUUA
UAAAGCAGCUGCACAAACAUU
2893


R-008396601-000F
1352
539
GGAAUGCAAGCUUUAGGAC
B GGAAUGCAAGCUUUAGGACTT B
2894


R-008396601-000F
1352
539
GGAAUGCAAGCUUUAGGAC
GUCCUAAAGCUUGCAUUCCUU
2895


R-008396604-000G
1502
135
GAUGAUAUAAAUGUGGUCA
UGACCACAUUUAUAUCAUCUU
2897


R-008396604-000G
1502
135
GAUGAUAUAAAUGUGGUCA
B GAUGAUAUAAAUGUGGUCATT B
2896


R-008396607-000H
1331
540
CCGGCUAUUGUAGAAGCUG
B CCGGCUAUUGUAGAAGCUGTT B
2898


R-008396607-000H
1331
540
CCGGCUAUUGUAGAAGCUG
CAGCUUCUACAAUAGCCGGUU
2899


R-008396610-000P
1325
541
AAUAAGCCGGCUAUUGUAG
B AAUAAGCCGGCUAUUGUAGTT B
2900


R-008396610-000P
1325
541
AAUAAGCCGGCUAUUGUAG
CUACAAUAGCCGGCUUAUUUU
2901


R-008396613-000R
1486
542
UCAGCUUCUGGGUUCAGAU
B UCAGCUUCUGGGUUCAGAUTT B
2902


R-008396613-000R
1486
542
UCAGCUUCUGGGUUCAGAU
AUCUGAACCCAGAAGCUGAUU
2903


R-008396616-000S
454
543
CCUGUAUGAGUGGGAACAG
B CCUGUAUGAGUGGGAACAGTT B
2904


R-008396616-000S
454
543
CCUGUAUGAGUGGGAACAG
CUGUUCCCACUCAUACAGGUU
2905


R-008396619-000T
490
544
CACUCAAGAACAAGUAGCU
B CACUCAAGAACAAGUAGCUTT B
2906


R-008396619-000T
490
544
CACUCAAGAACAAGUAGCU
AGCUACUUGUUCUUGAGUGUU
2907


R-008396622-000Z
1996
545
CCUUCACAUCCUAGCUCGG
B CCUUCACAUCCUAGCUCGGTT B
2908


R-008396622-000Z
1996
545
CCUUCACAUCCUAGCUCGG
CCGAGCUAGGAUGUGAAGGUU
2909


R-008396625-000A
1839
546
AUGCACCUUUGCGUGAGCA
B AUGCACCUUUGCGUGAGCATT B
2910


R-008396625-000A
1839
546
AUGCACCUUUGCGUGAGCA
UGCUCACGCAAAGGUGCAUUU
2911


R-008396628-000B
1888
547
UGUUCGUGCACAUCAGGAU
AUCCUGAUGUGCACGAACAUU
2913


R-008396628-000B
1888
547
UGUUCGUGCACAUCAGGAU
B UGUUCGUGCACAUCAGGAUTT B
2912


R-008396631-000H
1879
548
UCAGUUGCUUGUUCGUGCA
B UCAGUUGCUUGUUCGUGCATT B
2914


R-008396631-000H
1879
548
UCAGUUGCUUGUUCGUGCA
UGCACGAACAAGCAACUGAUU
2915


R-008396634-000J
2508
172
ACUAUCCAGUUGAUGGGCU
B ACUAUCCAGUUGAUGGGCUTT B
2916


R-008396634-000J
2508
172
ACUAUCCAGUUGAUGGGCU
AGCCCAUCAACUGGAUAGUUU
2917


R-008396637-000K
1829
549
CCCGCAAAUCAUGCACCUU
AAGGUGCAUGAUUUGCGGGUU
2919


R-008396637-000K
1829
549
CCCGCAAAUCAUGCACCUU
B CCCGCAAAUCAUGCACCUUTT B
2918


R-008396640-000S
281
550
GCUGAUUUGAUGGAGUUGG
B GCUGAUUUGAUGGAGUUGGTT B
2920


R-008396640-000S
281
550
GCUGAUUUGAUGGAGUUGG
CCAACUCCAUCAAAUCAGCUU
2921


R-008396643-000T
1598
551
AUAGAGGCUCUUGUGCGUA
UACGCACAAGAGCCUCUAUUU
2923


R-008396643-000T
1598
551
AUAGAGGCUCUUGUGCGUA
B AUAGAGGCUCUUGUGCGUATT B
2922


R-008396646-000U
2135
552
CAGGACAAGGAAGCUGCAG
B CAGGACAAGGAAGCUGCAGTT B
2924


R-008396646-000U
2135
552
CAGGACAAGGAAGCUGCAG
CUGCAGCUUCCUUGUCCUGUU
2925


R-008396649-000V
642
67
UGGCUGAACCAUCACAGAU
AUCUGUGAUGGUUCAGCCAUU
2927


R-008396649-000V
642
67
UGGCUGAACCAUCACAGAU
B UGGCUGAACCAUCACAGAUTT B
2926


R-008396652-000B
1755
553
AGCUCUUACACCCACCAUC
B AGCUCUUACACCCACCAUCTT B
2928


R-008396652-000B
1755
553
AGCUCUUACACCCACCAUC
GAUGGUGGGUGUAAGAGCUUU
2929


R-008396655-000C
651
554
CAUCACAGAUGCUGAAACA
B CAUCACAGAUGCUGAAACATT B
2930


R-008396655-000C
651
554
CAUCACAGAUGCUGAAACA
UGUUUCAGCAUCUGUGAUGUU
2931


R-008396658-000D
1335
555
CUAUUGUAGAAGCUGGUGG
C CACCAGCUUCUACAAUAGUU
2933


R-008396658-000D
1335
555
CUAUUGUAGAAGCUGGUGG
B CUAUUGUAGAAGCUGGUGGTT B
2932


R-008396661-000K
2541
556
AUGCCCAGGACCUCAUGGA
UCCAUGAGGUCCUGGGCAUUU
2935


R-008396661-000K
2541
556
AUGCCCAGGACCUCAUGGA
B AUGCCCAGGACCUCAUGGATT B
2934


R-008396664-000L
531
557
UGACUCGAGCUCAGAGGGU
B UGACUCGAGCUCAGAGGGUTT B
2936


R-008396664-000L
531
557
UGACUCGAGCUCAGAGGGU
ACCCUCUGAGCUCGAGUCAUU
2937


R-008396667-000M
606
558
AGUUUGAUGCUGCUCAUCC
B AGUUUGAUGCUGCUCAUCCTT B
2938


R-008396667-000M
606
558
AGUUUGAUGCUGCUCAUCC
GGAUGAGCAGCAUCAAACUUU
2939


R-008396670-000U
1620
559
UCCUUCGGGCUGGUGACAG
B UCCUUCGGGCUGGUGACAGTT B
2940


R-008396670-000U
1620
559
UCCUUCGGGCUGGUGACAG
CUGUCACCAGCCCGAAGGAUU
2941


R-008396673-000V
2211
560
AUGAAGGUGUGGCGACAUA
B AUGAAGGUGUGGCGACAUATT B
2942


R-008396673-000V
2211
560
AUGAAGGUGUGGCGACAUA
UAUGUCGCCACACCUUCAUUU
2943


R-008396676-000W
2293
561
AGUUGAGCUGACCAGCUCU
B AGUUGAGCUGACCAGCUCUTT B
2944


R-008396676-000W
2293
561
AGUUGAGCUGACCAGCUCU
AGAGCUGGUCAGCUCAACUUU
2945


R-008396679-000X
1511
65
AAUGUGGUCACCUGUGCAG
B AAUGUGGUCACCUGUGCAGTT B
2946


R-008396679-000X
1511
65
AAUGUGGUCACCUGUGCAG
CUGCACAGGUGACCACAUUUU
2947


R-008396682-000D
455
562
CUGUAUGAGUGGGAACAGG
B CUGUAUGAGUGGGAACAGGTT B
2948


R-008396682-000D
455
562
CUGUAUGAGUGGGAACAGG
CCUGUUCCCACUCAUACAGUU
2949


R-008396685-000E
540
563
CUCAGAGGGUACGAGCUGC
B CUCAGAGGGUACGAGCUGCTT B
2950


R-008396685-000E
540
563
CUCAGAGGGUACGAGCUGC
GCAGCUCGUACCCUCUGAGUU
2951


R-008396688-000F
416
564
GGCAAUCCUGAGGAAGAGG
CCUCUUCCUCAGGAUUGCCUU
2953


R-008396688-000F
416
564
GGCAAUCCUGAGGAAGAGG
B GGCAAUCCUGAGGAAGAGGTT B
2952


R-008396691-000M
1669
130
UCUUCGUCAUCUGACCAGC
GCUGGUCAGAUGACGAAGAUU
2955


R-008396691-000M
1669
130
UCUUCGUCAUCUGACCAGC
B UCUUCGUCAUCUGACCAGCTT B
2954


R-008396694-000N
1210
565
CAUACUGGCUAGUGGUGGA
B CAUACUGGCUAGUGGUGGATT B
2956


R-008396694-000N
1210
565
CAUACUGGCUAGUGGUGGA
UCCACCACUAGCCAGUAUGUU
2957


R-008396697-000P
2262
566
ACAAGCCACAAGAUUACAA
UUGUAAUCUUGUGGCUUGUUU
2959


R-008396697-000P
2262
566
ACAAGCCACAAGAUUACAA
B ACAAGCCACAAGAUUACAATT B
2958


R-008396700-000G
1604
567
GCUCUUGUGCGUACUGUCC
GGACAGUACGCACAAGAGCUU
2961


R-008396700-000G
1604
567
GCUCUUGUGCGUACUGUCC
B GCUCUUGUGCGUACUGUCCTT B
2960


R-008396703-000H
435
568
AUGUGGAUACCUCCCAAGU
B AUGUGGAUACCUCCCAAGUTT B
2962


R-008396703-000H
435
568
AUGUGGAUACCUCCCAAGU
ACUUGGGAGGUAUCCACAUUU
2963


R-008396706-000J
2060
569
UUGUUUGUGCAGCUGCUUU
B UUGUUUGUGCAGCUGCUUUTT B
2964


R-008396706-000J
2060
569
UUGUUUGUGCAGCUGCUUU
AAAGCAGCUGCACAAACAAUU
2965


R-008396709-000K
2225
570
ACAUAUGCAGCUGCUGUUU
B ACAUAUGCAGCUGCUGUUUTT B
2966


R-008396709-000K
2225
570
ACAUAUGCAGCUGCUGUUU
AAACAGCAGCUGCAUAUGUUU
2967


R-008396712-000S
2510
47
UAUCCAGUUGAUGGGCUGC
B UAUCCAGUUGAUGGGCUGCTT B
2968


R-008396712-000S
2510
47
UAUCCAGUUGAUGGGCUGC
GCAGCCCAUCAACUGGAUAUU
2969


R-008396715-000T
481
571
UCAGUCCUUCACUCAAGAA
UUCUUGAGUGAAGGACUGAUU
2971


R-008396715-000T
481
571
UCAGUCCUUCACUCAAGAA
B UCAGUCCUUCACUCAAGAATT B
2970


R-008396718-000U
917
572
ACCUUGCAUAACCUUUCCC
B ACCUUGCAUAACCUUUCCCTT B
2972


R-008396718-000U
917
572
ACCUUGCAUAACCUUUCCC
GGGAAAGGUUAUGCAAGGUUU
2973


R-008396721-000A
2221
573
GGCGACAUAUGCAGCUGCU
B GGCGACAUAUGCAGCUGCUTT B
2974


R-008396721-000A
2221
573
GGCGACAUAUGCAGCUGCU
AGCAGCUGCAUAUGUCGCCUU
2975


R-008396724-000B
849
574
UGGUGUCUGCUAUUGUACG
CGUACAAUAGCAGACACCAUU
2977


R-008396724-000B
849
574
UGGUGUCUGCUAUUGUACG
B UGGUGUCUGCUAUUGUACGTT B
2976


R-008396727-000C
562
575
GUUCCCUGAGACAUUAGAU
B GUUCCCUGAGACAUUAGAUTT B
2978


R-008396727-000C
562
575
GUUCCCUGAGACAUUAGAU
AUCUAAUGUCUCAGGGAACUU
2979


R-008396730-000J
617
140
GCUCAUCCCACUAAUGUCC
GGACAUUAGUGGGAUGAGCUU
2981


R-008396730-000J
617
140
GCUCAUCCCACUAAUGUCC
B GCUCAUCCCACUAAUGUCCTT B
2980


R-008396733-000K
1787
576
AUAAAGGCUACUGUUGGAU
B AUAAAGGCUACUGUUGGAUTT B
2982


R-008396733-000K
1787
576
AUAAAGGCUACUGUUGGAU
AUCCAACAGUAGCCUUUAUUU
2983


R-008396736-000L
1860
577
GUGCCAUUCCACGACUAGU
ACUAGUCGUGGAAUGGCACUU
2985


R-008396736-000L
1860
577
GUGCCAUUCCACGACUAGU
B GUGCCAUUCCACGACUAGUTT B
2984


R-008396739-000M
1590
578
UGGGUGGUAUAGAGGCUCU
B UGGGUGGUAUAGAGGCUCUTT B
2986


R-008396739-000M
1590
578
UGGGUGGUAUAGAGGCUCU
AGAGCCUCUAUACCACCCAUU
2987


R-008396742-000U
955
579
GGCCAUCUUUAAGUCUGGA
UCCAGACUUAAAGAUGGCCUU
2989


R-008396742-000U
955
579
GGCCAUCUUUAAGUCUGGA
B GGCCAUCUUUAAGUCUGGATT B
2988


R-008396745-000V
2365
580
UAUUGGUGCCCAGGGAGAA
B UAUUGGUGCCCAGGGAGAATT B
2990


R-008396745-000V
2365
580
UAUUGGUGCCCAGGGAGAA
UUCUCCCUGGGCACCAAUAUU
2991


R-008396748-000W
534
581
CUCGAGCUCAGAGGGUACG
B CUCGAGCUCAGAGGGUACGTT B
2992


R-008396748-000W
534
581
CUCGAGCUCAGAGGGUACG
CGUACCCUCUGAGCUCGAGUU
2993


R-008396751-000C
706
582
AGAACUUGCCACACGUGCA
UGCACGUGUGGCAAGUUCUUU
2995


R-008396751-000C
706
582
AGAACUUGCCACACGUGCA
B AGAACUUGCCACACGUGCATT B
2994


R-008396754-000D
1740
583
UACCAGUUGUGGUUAAGCU
B UACCAGUUGUGGUUAAGCUTT B
2996


R-008396754-000D
1740
583
UACCAGUUGUGGUUAAGCU
AGCUUAACCACAACUGGUAUU
2997


R-008396757-000E
638
584
CGUUUGGCUGAACCAUCAC
B CGUUUGGCUGAACCAUCACTT B
2998


R-008396757-000E
638
584
CGUUUGGCUGAACCAUCAC
GUGAUGGUUCAGCCAAACGUU
2999


R-008396760-000L
1334
585
GCUAUUGUAGAAGCUGGUG
CACCAGCUUCUACAAUAGCUU
3001


R-008396760-000L
1334
585
GCUAUUGUAGAAGCUGGUG
B GCUAUUGUAGAAGCUGGUGTT B 
3000


R-008396763-000M
971
586
GGAGGCAUUCCUGCCCUGG
B GGAGGCAUUCCUGCCCUGGTT B
3002


R-008396763-000M
971
586
GGAGGCAUUCCUGCCCUGG
CCAGGGCAGGAAUGCCUCCUU
3003


R-008396766-000N
2493
587
ACCACCCUGGUGCUGACUA
UAGUCAGCACCAGGGUGGUUU
3005


R-008396766-000N
2493
587
ACCACCCUGGUGCUGACUA
B ACCACCCUGGUGCUGACUATT B
3004


R-008396769-000P
1814
588
AAUCUUGCCCUUUGUCCCG
B AAUCUUGCCCUUUGUCCCGTT B
3006


R-008396769-000P
1814
588
AAUCUUGCCCUUUGUCCCG
CGGGACAAAGGGCAAGAUUUU
3007


R-008396772-000W
1088
589
CGUUUAGCUGGUGGGCUGC
GCAGCCCACCAGCUAAACGUU
3009


R-008396772-000W
1088
589
CGUUUAGCUGGUGGGCUGC
B CGUUUAGCUGGUGGGCUGCTT B
3008


R-008396775-000X
2292
590
CAGUUGAGCUGACCAGCUC
GAGCUGGUCAGCUCAACUGUU
3011


R-008396775-000X
2292
590
CAGUUGAGCUGACCAGCUC
B CAGUUGAGCUGACCAGCUCTT B
3010


R-008396778-000Y
1504
591
UGAUAUAAAUGUGGUCACC
GGUGACCACAUUUAUAUCAUU
3013


R-008396778-000Y
1504
591
UGAUAUAAAUGUGGUCACC
B UGAUAUAAAUGUGGUCACCTT B
3012


R-008396781-000E
404
592
CUGAGUGGUAAAGGCAAUC
GAUUGCCUUUACCACUCAGUU
3015


R-008396781-000E
404
592
CUGAGUGGUAAAGGCAAUC
B CUGAGUGGUAAAGGCAAUCTT B
3014


R-008396784-000F
1301
593
AAGGUGCUAUCUGUCUGCU
AGCAGACAGAUAGCACCUUUU
3017


R-008396784-000F
1301
593
AAGGUGCUAUCUGUCUGCU
B AAGGUGCUAUCUGUCUGCUTT B
3016


R-008396787-000G
2004
594
UCCUAGCUCGGGAUGUUCA
UGAACAUCCCGAGCUAGGAUU
3019


R-008396787-000G
2004
594
UCCUAGCUCGGGAUGUUCA
B UCCUAGCUCGGGAUGUUCATT B
3018


R-008396790-000N
853
6
GUCUGCUAUUGUACGUACC
GGUACGUACAAUAGCAGACUU
3021


R-008396790-000N
853
6
GUCUGCUAUUGUACGUACC
B GUCUGCUAUUGUACGUACCTT B
3020


R-008396793-000P
277
595
UCAAGCUGAUUUGAUGGAG
B UCAAGCUGAUUUGAUGGAGTT B
3022


R-008396793-000P
277
595
UCAAGCUGAUUUGAUGGAG
CUCCAUCAAAUCAGCUUGAUU
3023


R-008396796-000R
2304
596
CCAGCUCUCUCUUCAGAAC
GUUCUGAAGAGAGAGCUGGUU
3025


R-008396796-000R
2304
596
CCAGCUCUCUCUUCAGAAC
B CCAGCUCUCUCUUCAGAACTT B
3024


R-008396799-000S
300
597
ACAUGGCCAUGGAACCAGA
B ACAUGGCCAUGGAACCAGATT B
3026


R-008396799-000S
300
597
ACAUGGCCAUGGAACCAGA
UCUGGUUCCAUGGCCAUGUUU
3027


R-008396802-000J
1906
598
UACCCAGCGCCGUACGUCC
B UACCCAGCGCCGUACGUCCTT B
3028


R-008396802-000J
1906
598
UACCCAGCGCCGUACGUCC
GGACGUACGGCGCUGGGUAUU
3029


R-008396805-000K
1973
599
AUAGUUGAAGGUUGUACCG
CGGUACAACCUUCAACUAUUU
3031


R-008396805-000K
1973
599
AUAGUUGAAGGUUGUACCG
B AUAGUUGAAGGUUGUACCGTT B
3030


R-008396808-000L
1360
600
AGCUUUAGGACUUCACCUG
B AGCUUUAGGACUUCACCUGTT B
3032


R-008396808-000L
1360
600
AGCUUUAGGACUUCACCUG
CAGGUGAAGUCCUAAAGCUUU
3033


R-008396811-000T
2094
601
ACAUCCAAAGAGUAGCUGC
GCAGCUACUCUUUGGAUGUUU
3035


R-008396811-000T
2094
601
ACAUCCAAAGAGUAGCUGC
B ACAUCCAAAGAGUAGCUGCTT B
3034


R-008396814-000U
920
602
UUGCAUAACCUUUCCCAUC
B UUGCAUAACCUUUCCCAUCTT B
3036


R-008396814-000U
920
602
UUGCAUAACCUUUCCCAUC
GAUGGGAAAGGUUAUGCAAUU
3037


R-008396817-000V
1707
603
UGGCCCAGAAUGCAGUUCG
CGAACUGCAUUCUGGGCCAUU
3039


R-008396817-000V
1707
603
UGGCCCAGAAUGCAGUUCG
B UGGCCCAGAAUGCAGUUCGTT B 
3038


R-008396820-000B
1808
604
AUUCGAAAUCUUGCCCUUU
B AUUCGAAAUCUUGCCCUUUTT B 
3040


R-008396820-000B
1808
604
AUUCGAAAUCUUGCCCUUU
AAAGGGCAAGAUUUCGAAUUU
3041


R-008396823-000C
1326
605
AUAAGCCGGCUAUUGUAGA
UCUACAAUAGCCGGCUUAUUU
3043


R-008396823-000C
1326
605
AUAAGCCGGCUAUUGUAGA
B AUAAGCCGGCUAUUGUAGATT B
3042


R-008396826-000D
1158
606
CGACAGACUGCCUUCAAAU
B CGACAGACUGCCUUCAAAUTT B 
3044


R-008396826-000D
1158
606
CGACAGACUGCCUUCAAAU
AUUUGAAGGCAGUCUGUCGUU
3045


R-008396829-000E
781
607
UGCAGUUAUGGUCCAUCAG
B UGCAGUUAUGGUCCAUCAGTT B 
3046


R-008396829-000E
781
607
UGCAGUUAUGGUCCAUCAG
CUGAUGGACCAUAACUGCAUU
3047


R-008396832-000L
607
608
GUUUGAUGCUGCUCAUCCC
B GUUUGAUGCUGCUCAUCCCTT B 
3048


R-008396832-000L
607
608
GUUUGAUGCUGCUCAUCCC
GGGAUGAGCAGCAUCAAACUU
3049


R-008396835-000M
627
609
CUAAUGUCCAGCGUUUGGC
GCCAAACGCUGGACAUUAGUU
3051


R-008396835-000M
627
609
CUAAUGUCCAGCGUUUGGC
B CUAAUGUCCAGCGUUUGGCTT B
3050


R-008396838-000N
500
610
CAAGUAGCUGAUAUUGAUG
B CAAGUAGCUGAUAUUGAUGTT B 
3052


R-008396838-000N
500
610
CAAGUAGCUGAUAUUGAUG
CAUCAAUAUCAGCUACUUGUU
3053


R-008396841-000V
2185
611
UCUGACAGAGUUACUUCAC
B UCUGACAGAGUUACUUCACTT B 
3054


R-008396841-000V
2185
611
UCUGACAGAGUUACUUCAC
GUGAAGUAACUCUGUCAGAUU
3055


R-008396844-000W
1592
612
GGUGGUAUAGAGGCUCUUG
B GGUGGUAUAGAGGCUCUUGTT B 
3056


R-008396844-000W
1592
612
GGUGGUAUAGAGGCUCUUG
CAAGAGCCUCUAUACCACCUU
3057


R-008396847-000X
758
613
GACCAGGUGGUGGUUAAUA
B GACCAGGUGGUGGUUAAUATT B
3058


R-008396847-000X
758
613
GACCAGGUGGUGGUUAAUA
UAUUAACCACCACCUGGUCUU
3059


R-008396850-000D
2551
614
CCUCAUGGAUGGGCUGCCU
B CCUCAUGGAUGGGCUGCCUTT B 
3060


R-008396850-000D
2551
614
CCUCAUGGAUGGGCUGCCU
AGGCAGCCCAUCCAUGAGGUU
3061


R-008396853-000E
1409
615
UGUCUUUGGACUCUCAGGA
B UGUCUUUGGACUCUCAGGATT B 
3062


R-008396853-000E
1409
615
UGUCUUUGGACUCUCAGGA
UCCUGAGAGUCCAAAGACAUU
3063


R-008396856-000F
497
616
GAACAAGUAGCUGAUAUUG
B GAACAAGUAGCUGAUAUUGTT B 
3064


R-008396856-000F
497
616
GAACAAGUAGCUGAUAUUG
CAAUAUCAGCUACUUGUUCUU
3065


R-008396859-000G
381
617
GUGCCACUACCACAGCUCC
B GUGCCACUACCACAGCUCCTT B
3066


R-008396859-000G
381
617
GUGCCACUACCACAGCUCC
GGAGCUGUGGUAGUGGCACUU
3067


R-008396862-000N
1841
618
GCACCUUUGCGUGAGCAGG
CCUGCUCACGCAAAGGUGCUU
3069


R-008396862-000N
1841
618
GCACCUUUGCGUGAGCAGG
B GCACCUUUGCGUGAGCAGGTT B 
3068


R-008396865-000P
1368
619
GACUUCACCUGACAGAUCC
B GACUUCACCUGACAGAUCCTT B 
3070


R-008396865-000P
1368
619
GACUUCACCUGACAGAUCC
GGAUCUGUCAGGUGAAGUCUU
3071


R-008396868-000R
2047
620
AAAUACCAUUCCAUUGUUU
AAACAAUGGAAUGGUAUUUUU
3073


R-008396868-000R
2047
620
AAAUACCAUUCCAUUGUUU
B AAAUACCAUUCCAUUGUUUTT B 
3072


R-008396871-000X
492
621
CUCAAGAACAAGUAGCUGA
B CUCAAGAACAAGUAGCUGATT B 
3074


R-008396871-000X
492
621
CUCAAGAACAAGUAGCUGA
UCAGCUACUUGUUCUUGAGUU
3075


R-008396874-000Y
832
126
CAUGCGUUCUCCUCAGAUG
B CAUGCGUUCUCCUCAGAUGTT B
3076


R-008396874-000Y
832
126
CAUGCGUUCUCCUCAGAUG
CAUCUGAGGAGAACGCAUGUU
3077


R-008396877-000Z
2118
622
UCCUCUGUGAACUUGCUCA
B UCCUCUGUGAACUUGCUCATT B
3078


R-008396877-000Z
2118
622
UCCUCUGUGAACUUGCUCA
UGAGCAAGUUCACAGAGGAUU
3079


R-008396880-000F
968
623
UCUGGAGGCAUUCCUGCCC
GGGCAGGAAUGCCUCCAGAUU
3081


R-008396880-000F
968
623
UCUGGAGGCAUUCCUGCCC
B UCUGGAGGCAUUCCUGCCCTT B 
3080


R-008396883-000G
965
624
AAGUCUGGAGGCAUUCCUG
CAGGAAUGCCUCCAGACUUUU
3083


R-008396883-000G
965
624
AAGUCUGGAGGCAUUCCUG
B AAGUCUGGAGGCAUUCCUGTT B 
3082


R-008396886-000H
1977
625
UUGAAGGUUGUACCGGAGC
GCUCCGGUACAACCUUCAAUU
3085


R-008396886-000H
1977
625
UUGAAGGUUGUACCGGAGC
B UUGAAGGUUGUACCGGAGCTT B
3084


R-008396889-000J
2001
626
ACAUCCUAGCUCGGGAUGU
B ACAUCCUAGCUCGGGAUGUTT B 
3086


R-008396889-000J
2001
626
ACAUCCUAGCUCGGGAUGU
ACAUCCCGAGCUAGGAUGUUU
3087


R-008396892-000R
1191
627
ACCAAGAAAGCAAGCUCAU
B ACCAAGAAAGCAAGCUCAUTT B 
3088


R-008396892-000R
1191
627
ACCAAGAAAGCAAGCUCAU
AUGAGCUUGCUUUCUUGGUUU
3089


R-008396895-000S
640
628
UUUGGCUGAACCAUCACAG
B UUUGGCUGAACCAUCACAGTT B 
3090


R-008396895-000S
640
628
UUUGGCUGAACCAUCACAG
CUGUGAUGGUUCAGCCAAAUU
3091


R-008396898-000T
715
629
CACACGUGCAAUCCCUGAA
B CACACGUGCAAUCCCUGAATT B 
3092


R-008396898-000T
715
629
CACACGUGCAAUCCCUGAA
UUCAGGGAUUGCACGUGUGUU
3093


R-008396901-000K
1204
630
GCUCAUCAUACUGGCUAGU
ACUAGCCAGUAUGAUGAGCUU
3095


R-008396901-000K
1204
630
GCUCAUCAUACUGGCUAGU
B GCUCAUCAUACUGGCUAGUTT B 
3094


R-008396904-000L
3093
631
GGGUAGGGUAAAUCAGUAA
B GGGUAGGGUAAAUCAGUAATT B 
3096


R-008396904-000L
3093
631
GGGUAGGGUAAAUCAGUAA
UUACUGAUUUACCCUACCCUU
3097


R-008396907-000M
1371
632
UUCACCUGACAGAUCCAAG
CUUGGAUCUGUCAGGUGAAUU
3099


R-008396907-000M
1371
632
UUCACCUGACAGAUCCAAG
B UUCACCUGACAGAUCCAAGTT B 
3098


R-008396910-000U
1424
121
AGGAAUCUUUCAGAUGCUG
B AGGAAUCUUUCAGAUGCUGTT B
3100


R-008396910-000U
1424
121
AGGAAUCUUUCAGAUGCUG
CAGCAUCUGAAAGAUUCCUUU
3101


R-008396913-000V
860
161
AUUGUACGUACCAUGCAGA
B AUUGUACGUACCAUGCAGATT B 
3102


R-008396913-000V
860
161
AUUGUACGUACCAUGCAGA
UCUGCAUGGUACGUACAAUUU
3103


R-008396916-000W
409
633
UGGUAAAGGCAAUCCUGAG
B UGGUAAAGGCAAUCCUGAGTT B 
3104


R-008396916-000W
409
633
UGGUAAAGGCAAUCCUGAG
CUCAGGAUUGCCUUUACCAUU
3105


R-008396919-000X
1143
7
AAUUCUUGGCUAUUACGAC
GUCGUAAUAGCCAAGAAUUUU
3107


R-008396919-000X
1143
7
AAUUCUUGGCUAUUACGAC
B AAUUCUUGGCUAUUACGACTT B
3106


R-008396922-000D
2405
634
GAUCCUAGCUAUCGUUCUU
B GAUCCUAGCUAUCGUUCUUTT B
3108


R-008396922-000D
2405
634
GAUCCUAGCUAUCGUUCUU
AAGAACGAUAGCUAGGAUCUU
3109


R-008396928-000F
1671
635
UUCGUCAUCUGACCAGCCG
CGGCUGGUCAGAUGACGAAUU
3111


R-008396928-000F
1671
635
UUCGUCAUCUGACCAGCCG
B UUCGUCAUCUGACCAGCCGTT B
3110


R-008396931-000M
1427
636
AAUCUUUCAGAUGCUGCAA
B AAUCUUUCAGAUGCUGCAATT B
3112


R-008396931-000M
1427
636
AAUCUUUCAGAUGCUGCAA
UUGCAGCAUCUGAAAGAUUUU
3113


R-008396934-000N
1717
637
UGCAGUUCGCCUUCACUAU
AUAGUGAAGGCGAACUGCAUU
3115


R-008396934-000N
1717
637
UGCAGUUCGCCUUCACUAU
B UGCAGUUCGCCUUCACUAUTT B
3114


R-008396937-000P
2400
638
AGGAUGAUCCUAGCUAUCG
CGAUAGCUAGGAUCAUCCUUU
3117


R-008396937-000P
2400
638
AGGAUGAUCCUAGCUAUCG
B AGGAUGAUCCUAGCUAUCGTT B
3116


R-008396940-000W
2305
639
CAGCUCUCUCUUCAGAACA
B CAGCUCUCUCUUCAGAACATT B
3118


R-008396940-000W
2305
639
CAGCUCUCUCUUCAGAACA
UGUUCUGAAGAGAGAGCUGUU
3119


R-008396943-000X
1928
640
GGUGGGACACAGCAGCAAU
B GGUGGGACACAGCAGCAAUTT B
3120


R-008396943-000X
1928
640
GGUGGGACACAGCAGCAAU
AUUGCUGCUGUGUCCCACCUU
3121


R-008396946-000Y
2399
641
CAGGAUGAUCCUAGCUAUC
B CAGGAUGAUCCUAGCUAUCTT B 
3122


R-008396946-000Y
2399
641
CAGGAUGAUCCUAGCUAUC
GAUAGCUAGGAUCAUCCUGUU
3123


R-008396949-000Z
426
642
AGGAAGAGGAUGUGGAUAC
B AGGAAGAGGAUGUGGAUACTT B 
3124


R-008396949-000Z
426
642
AGGAAGAGGAUGUGGAUAC
GUAUCCACAUCCUCUUCCUUU
3125


R-008396952-000F
1309
643
AUCUGUCUGCUCUAGUAAU
AUUACUAGAGCAGACAGAUUU
3127


R-008396952-000F
1309
643
AUCUGUCUGCUCUAGUAAU
B AUCUGUCUGCUCUAGUAAUTT B
3126


R-008396955-000G
925
644
UAACCUUUCCCAUCAUCGU
B UAACCUUUCCCAUCAUCGUTT B
3128


R-008396955-000G
925
644
UAACCUUUCCCAUCAUCGU
ACGAUGAUGGGAAAGGUUAUU
3129


R-008396958-000H
2072
645
CUGCUUUAUUCUCCCAUUG
CAAUGGGAGAAUAAAGCAGUU
3131


R-008396958-000H
2072
645
CUGCUUUAUUCUCCCAUUG
B CUGCUUUAUUCUCCCAUUGTT B
3130


R-008396964-000R
2939
646
AAUUGUAAUCUGAAUAAAG
B AAUUGUAAUCUGAAUAAAGTT B
3132


R-008396964-000R
2939
646
AAUUGUAAUCUGAAUAAAG
CUUUAUUCAGAUUACAAUUUU
3133


R-008396973-000Z
1480
647
UCUUGUUCAGCUUCUGGGU
B UCUUGUUCAGCUUCUGGGUTT B
3134


R-008396973-000Z
1480
647
UCUUGUUCAGCUUCUGGGU
ACCCAGAAGCUGAACAAGAUU
3135


R-008396976-000A
1889
648
GUUCGUGCACAUCAGGAUA
B GUUCGUGCACAUCAGGAUATT B
3136


R-008396976-000A
1889
648
GUUCGUGCACAUCAGGAUA
UAUCCUGAUGUGCACGAACUU
3137


R-008396979-000B
699
649
AUGAUGCAGAACUUGCCAC
B AUGAUGCAGAACUUGCCACTT B
3138


R-008396979-000B
699
649
AUGAUGCAGAACUUGCCAC
GUGGCAAGUUCUGCAUCAUUU
3139


R-008396982-000H
506
650
GCUGAUAUUGAUGGACAGU
B GCUGAUAUUGAUGGACAGUTT B
3140


R-008396982-000H
506
650
GCUGAUAUUGAUGGACAGU
ACUGUCCAUCAAUAUCAGCUU
3141


R-008396985-000J
1750
651
GGUUAAGCUCUUACACCCA
UGGGUGUAAGAGCUUAACCUU
3143


R-008396985-000J
1750
651
GGUUAAGCUCUUACACCCA
B GGUUAAGCUCUUACACCCATT B
3142


R-008396988-000K
1820
652
GCCCUUUGUCCCGCAAAUC
B GCCCUUUGUCCCGCAAAUCTT B
3144


R-008396988-000K
1820
652
GCCCUUUGUCCCGCAAAUC
GAUUUGCGGGACAAAGGGCUU
3145


R-008396991-000S
541
653
UCAGAGGGUACGAGCUGCU
AGCAGCUCGUACCCUCUGAUU
3147


R-008396991-000S
541
653
UCAGAGGGUACGAGCUGCU
B UCAGAGGGUACGAGCUGCUTT B
3146


R-008396994-000T
880
102
UACAAAUGAUGUAGAAACA
B UACAAAUGAUGUAGAAACATT B
3148


R-008396994-000T
880
102
UACAAAUGAUGUAGAAACA
UGUUUCUACAUCAUUUGUAUU
3149


R-008396997-000U
665
654
AAACAUGCAGUUGUAAACU
B AAACAUGCAGUUGUAAACUTT B
3150


R-008396997-000U
665
654
AAACAUGCAGUUGUAAACU
AGUUUACAACUGCAUGUUUUU
3151


R-008397000-000H
1817
655
CUUGCCCUUUGUCCCGCAA
UUGCGGGACAAAGGGCAAGUU
3153


R-008397000-000H
1817
655
CUUGCCCUUUGUCCCGCAA
B CUUGCCCUUUGUCCCGCAATT B
3152


R-008397003-000J
2275
656
UUACAAGAAACGGCUUUCA
UGAAAGCCGUUUCUUGUAAUU
3155


R-008397003-000J
2275
656
UUACAAGAAACGGCUUUCA
B UUACAAGAAACGGCUUUCATT B
3154


R-008397006-000K
2426
657
CACUCUGGUGGAUAUGGCC
GGCCAUAUCCACCAGAGUGUU
3157


R-008397006-000K
2426
657
CACUCUGGUGGAUAUGGCC
B CACUCUGGUGGAUAUGGCCTT B
3156


R-008397009-000L
958
658
CAUCUUUAAGUCUGGAGGC
B CAUCUUUAAGUCUGGAGGCTT B
3158


R-008397009-000L
958
658
CAUCUUUAAGUCUGGAGGC
GCCUCCAGACUUAAAGAUGUU
3159


R-008397012-000T
1657
659
UGCCAUCUGUGCUCUUCGU
B UGCCAUCUGUGCUCUUCGUTT B
3160


R-008397012-000T
1657
659
UGCCAUCUGUGCUCUUCGU
ACGAAGAGCACAGAUGGCAUU
3161


R-008397015-000U
1146
660
UCUUGGCUAUUACGACAGA
UCUGUCGUAAUAGCCAAGAUU
3163


R-008397015-000U
1146
660
UCUUGGCUAUUACGACAGA
B UCUUGGCUAUUACGACAGATT B
3162


R-008397018-000V
3078
661
AUUUGGGAUAUGUAUGGGU
B AUUUGGGAUAUGUAUGGGUTT B
3164


R-008397018-000V
3078
661
AUUUGGGAUAUGUAUGGGU
ACCCAUACAUAUCCCAAAUUU
3165


R-008397021-000B
1008
662
CAGUGGAUUCUGUGUUGUU
AACAACACAGAAUCCACUGUU
3167


R-008397021-000B
1008
662
CAGUGGAUUCUGUGUUGUU
B CAGUGGAUUCUGUGUUGUUTT B
3166


R-008397024-000C
1621
663
CCUUCGGGCUGGUGACAGG
CCUGUCACCAGCCCGAAGGUU
3169


R-008397024-000C
1621
663
CCUUCGGGCUGGUGACAGG
B CCUUCGGGCUGGUGACAGGTT B
3168


R-008397027-000D
1932
664
GGACACAGCAGCAAUUUGU
B GGACACAGCAGCAAUUUGUTT B
3170


R-008397027-000D
1932
664
GGACACAGCAGCAAUUUGU
ACAAAUUGCUGCUGUGUCCUU
3171


R-008397030-000K
1909
665
CCAGCGCCGUACGUCCAUG
CAUGGACGUACGGCGCUGGUU
3173


R-008397030-000K
1909
665
CCAGCGCCGUACGUCCAUG
B CCAGCGCCGUACGUCCAUGTT B
3172


R-008397033-000L
2279
666
AAGAAACGGCUUUCAGUUG
CAACUGAAAGCCGUUUCUUUU
3175


R-008397033-000L
2279
666
AAGAAACGGCUUUCAGUUG
B AAGAAACGGCUUUCAGUUGTT B
3174


R-008397036-000M
574
667
AUUAGAUGAGGGCAUGCAG
B AUUAGAUGAGGGCAUGCAGTT B
3176


R-008397036-000M
574
667
AUUAGAUGAGGGCAUGCAG
CUGCAUGCCCUCAUCUAAUUU
3177


R-008397039-000N
2303
668
ACCAGCUCUCUCUUCAGAA
UUCUGAAGAGAGAGCUGGUUU
3179


R-008397039-000N
2303
668
ACCAGCUCUCUCUUCAGAA
B ACCAGCUCUCUCUUCAGAATT B 
3178


R-008397042-000V
784
669
AGUUAUGGUCCAUCAGCUU
B AGUUAUGGUCCAUCAGCUUTT B 
3180


R-008397042-000V
784
669
AGUUAUGGUCCAUCAGCUU
AAGCUGAUGGACCAUAACUUU
3181


R-008397045-000W
2507
670
GACUAUCCAGUUGAUGGGC
GCCCAUCAACUGGAUAGUCUU
3183


R-008397045-000W
2507
670
GACUAUCCAGUUGAUGGGC
B GACUAUCCAGUUGAUGGGCTT B
3182


R-008397048-000X
995
671
AUGCUUGGUUCACCAGUGG
B AUGCUUGGUUCACCAGUGGTT B 
3184


R-008397048-000X
995
671
AUGCUUGGUUCACCAGUGG
CCACUGGUGAACCAAGCAUUU
3185


R-008397051-000D
2006
672
CUAGCUCGGGAUGUUCACA
UGUGAACAUCCCGAGCUAGUU
3187


R-008397051-000D
2006
672
CUAGCUCGGGAUGUUCACA
B CUAGCUCGGGAUGUUCACATT B 
3186


R-008397054-000E
1757
673
CUCUUACACCCACCAUCCC
GGGAUGGUGGGUGUAAGAGUU
3189


R-008397054-000E
1757
673
CUCUUACACCCACCAUCCC
B CUCUUACACCCACCAUCCCTT B
3188


R-008397057-000F
2129
674
CUUGCUCAGGACAAGGAAG
B CUUGCUCAGGACAAGGAAGTT B 
3190


R-008397057-000F
2129
674
CUUGCUCAGGACAAGGAAG
CUUCCUUGUCCUGAGCAAGUU
3191


R-008397060-000M
2272
675
AGAUUACAAGAAACGGCUU
B AGAUUACAAGAAACGGCUUTT B 
3192


R-008397060-000M
2272
675
AGAUUACAAGAAACGGCUU
AAGCCGUUUCUUGUAAUCUUU
3193


R-008397063-000N
389
676
ACCACAGCUCCUUCUCUGA
B ACCACAGCUCCUUCUCUGATT B 
3194


R-008397063-000N
389
676
ACCACAGCUCCUUCUCUGA
UCAGAGAAGGAGCUGUGGUUU
3195


R-008397066-000P
708
176
AACUUGCCACACGUGCAAU
B AACUUGCCACACGUGCAAUTT B 
3196


R-008397066-000P
708
176
AACUUGCCACACGUGCAAU
AUUGCACGUGUGGCAAGUUUU
3197


R-008397069-000R
1435
677
AGAUGCUGCAACUAAACAG
CUGUUUAGUUGCAGCAUCUUU
3199


R-008397069-000R
1435
677
AGAUGCUGCAACUAAACAG
B AGAUGCUGCAACUAAACAGTT B 
3198


R-008397072-000X
1247
34
AUAAUGAGGACCUAUACUU
B AUAAUGAGGACCUAUACUUTT B 
3200


R-008397072-000X
1247
34
AUAAUGAGGACCUAUACUU
AAGUAUAGGUCCUCAUUAUUU
3201


R-008397075-000Y
1752
678
UUAAGCUCUUACACCCACC
GGUGGGUGUAAGAGCUUAAUU
3203


R-008397075-000Y
1752
678
UUAAGCUCUUACACCCACC
B UUAAGCUCUUACACCCACCTT B
3202


R-008397078-000Z
773
679
AAUAAGGCUGCAGUUAUGG
CCAUAACUGCAGCCUUAUUUU
3205


R-008397078-000Z
773
679
AAUAAGGCUGCAGUUAUGG
B AAUAAGGCUGCAGUUAUGGTT B 
3204


R-008397081-000F
3080
680
UUGGGAUAUGUAUGGGUAG
CUACCCAUACAUAUCCCAAUU
3207


R-008397081-000F
3080
680
UUGGGAUAUGUAUGGGUAG
B UUGGGAUAUGUAUGGGUAGTT B 
3206


R-008397084-000G
3174
681
GUAACCUGCUGUGAUACGA
B GUAACCUGCUGUGAUACGATT B 
3208


R-008397084-000G
3174
681
GUAACCUGCUGUGAUACGA
UCGUAUCACAGCAGGUUACUU
3209


R-008397087-000H
1578
682
UGGUCUGCCAAGUGGGUGG
B UGGUCUGCCAAGUGGGUGGTT B 
3210


R-008397087-000H
1578
682
UGGUCUGCCAAGUGGGUGG
C CACCCACUUGGCAGACCAUU 
3211


R-008397090-000P
398
683
CCUUCUCUGAGUGGUAAAG
B CCUUCUCUGAGUGGUAAAGTT B 
3212


R-008397090-000P
398
683
CCUUCUCUGAGUGGUAAAG
CUUUACCACUCAGAGAAGGUU
3213


R-008397093-000R
2153
684
GAAGCUAUUGAAGCUGAGG
CCUCAGCUUCAAUAGCUUCUU
3215


R-008397093-000R
2153
684
GAAGCUAUUGAAGCUGAGG
B GAAGCUAUUGAAGCUGAGGTT B 
3214


R-008397096-000S
702
685
AUGCAGAACUUGCCACACG
CGUGUGGCAAGUUCUGCAUUU
3217


R-008397096-000S
702
685
AUGCAGAACUUGCCACACG
B AUGCAGAACUUGCCACACGTT B 
3216


R-008397099-000T
503
686
GUAGCUGAUAUUGAUGGAC
B GUAGCUGAUAUUGAUGGACTT B
3218


R-008397099-000T
503
686
GUAGCUGAUAUUGAUGGAC
GUCCAUCAAUAUCAGCUACUU
3219


R-008397102-000K
276
687
CUCAAGCUGAUUUGAUGGA
B CUCAAGCUGAUUUGAUGGATT B
3220


R-008397102-000K
276
687
CUCAAGCUGAUUUGAUGGA
UCCAUCAAAUCAGCUUGAGUU
3221


R-008397105-000L
1962
688
GCAUGGAAGAAAUAGUUGA
B GCAUGGAAGAAAUAGUUGATT B 
3222


R-008397105-000L
1962
688
GCAUGGAAGAAAUAGUUGA
UCAACUAUUUCUUCCAUGCUU
3223


R-008397108-000M
1347
689
CUGGUGGAAUGCAAGCUUU
B CUGGUGGAAUGCAAGCUUUTT B 
3224


R-008397108-000M
1347
689
CUGGUGGAAUGCAAGCUUU
AAAGCUUGCAUUCCACCAGUU
3225


R-008397111-000U
2544
690
CCCAGGACCUCAUGGAUGG
CCAUCCAUGAGGUCCUGGGUU
3227


R-008397111-000U
2544
690
CCCAGGACCUCAUGGAUGG
B CCCAGGACCUCAUGGAUGGTT B 
3226


R-008397114-000V
3079
691
UUUGGGAUAUGUAUGGGUA
B UUUGGGAUAUGUAUGGGUATT B 
3228


R-008397114-000V
3079
691
UUUGGGAUAUGUAUGGGUA
UACCCAUACAUAUCCCAAAUU
3229


R-008397117-000W
3164
692
CAAAGUUGUUGUAACCUGC
GCAGGUUACAACAACUUUGUU
3231


R-008397117-000W
3164
692
CAAAGUUGUUGUAACCUGC
B CAAAGUUGUUGUAACCUGCTT B 
3230


R-008397120-000C
2026
693
CCGAAUUGUUAUCAGAGGA
B CCGAAUUGUUAUCAGAGGATT B
3232


R-008397120-000C
2026
693
CCGAAUUGUUAUCAGAGGA
UCCUCUGAUAACAAUUCGGUU
3233


R-008397123-000D
2938
694
UAAUUGUAAUCUGAAUAAA
B UAAUUGUAAUCUGAAUAAATT B 
3234


R-008397123-000D
2938
694
UAAUUGUAAUCUGAAUAAA
UUUAUUCAGAUUACAAUUAUU
3235


R-008397126-000E
2940
695
AUUGUAAUCUGAAUAAAGU
ACUUUAUUCAGAUUACAAUUU
3237


R-008397126-000E
2940
695
AUUGUAAUCUGAAUAAAGU
B AUUGUAAUCUGAAUAAAGUTT B 
3236


R-008397129-000F
2027
696
CGAAUUGUUAUCAGAGGAC
B CGAAUUGUUAUCAGAGGACTT B
3238


R-008397129-000F
2027
696
CGAAUUGUUAUCAGAGGAC
GUCCUCUGAUAACAAUUCGUU
3239


R-008397132-000M
448
697
CCAAGUCCUGUAUGAGUGG
CCACUCAUACAGGACUUGGUU
3241


R-008397132-000M
448
697
CCAAGUCCUGUAUGAGUGG
B CCAAGUCCUGUAUGAGUGGTT B 
3240


R-008397135-000N
1328
698
AAGCCGGCUAUUGUAGAAG
B AAGCCGGCUAUUGUAGAAGTT B 
3242


R-008397135-000N
1328
698
AAGCCGGCUAUUGUAGAAG
CUUCUACAAUAGCCGGCUUUU
3243


R-008397138-000P
1970
33
GAAAUAGUUGAAGGUUGUA
UACAACCUUCAACUAUUUCUU
3245


R-008397138-000P
1970
33
GAAAUAGUUGAAGGUUGUA
B GAAAUAGUUGAAGGUUGUATT B 
3244


R-008397141-000W
2406
699
AUCCUAGCUAUCGUUCUUU
AAAGAACGAUAGCUAGGAUUU
3247


R-008397141-000W
2406
699
AUCCUAGCUAUCGUUCUUU
B AUCCUAGCUAUCGUUCUUUTT B
3246


R-008397144-000X
924
700
AUAACCUUUCCCAUCAUCG
B AUAACCUUUCCCAUCAUCGTT B
3248


R-008397144-000X
924
700
AUAACCUUUCCCAUCAUCG
CGAUGAUGGGAAAGGUUAUUU
3249


R-008397147-000Y
1584
701
GCCAAGUGGGUGGUAUAGA
UCUAUACCACCCACUUGGCUU
3251


R-008397147-000Y
1584
701
GCCAAGUGGGUGGUAUAGA
B GCCAAGUGGGUGGUAUAGATT B
3250


R-008397150-000E
1871
702
CGACUAGUUCAGUUGCUUG
B CGACUAGUUCAGUUGCUUGTT B
3252


R-008397150-000E
1871
702
CGACUAGUUCAGUUGCUUG
CAAGCAACUGAACUAGUCGUU
3253


R-008397153-000F
999
703
UUGGUUCACCAGUGGAUUC
B UUGGUUCACCAGUGGAUUCTT B
3254


R-008397153-000F
999
703
UUGGUUCACCAGUGGAUUC
GAAUCCACUGGUGAACCAAUU
3255


R-008397156-000G
1400
704
GUUCAGAACUGUCUUUGGA
UCCAAAGACAGUUCUGAACUU
3257


R-008397156-000G
1400
704
GUUCAGAACUGUCUUUGGA
B GUUCAGAACUGUCUUUGGATT B
3256


R-008397159-000H
3180
705
UGCUGUGAUACGAUGCUUC
GAAGCAUCGUAUCACAGCAUU
3259


R-008397159-000H
3180
705
UGCUGUGAUACGAUGCUUC
B UGCUGUGAUACGAUGCUUCTT B
3258


R-008397162-000P
2569
706
UCCAGGUGACAGCAAUCAG
CUGAUUGCUGUCACCUGGAUU
3261


R-008397162-000P
2569
706
UCCAGGUGACAGCAAUCAG
B UCCAGGUGACAGCAAUCAGTT B
3260


R-008397165-000R
787
707
UAUGGUCCAUCAGCUUUCU
AGAAAGCUGAUGGACCAUAUU
3263


R-008397165-000R
787
707
UAUGGUCCAUCAGCUUUCU
B UAUGGUCCAUCAGCUUUCUTT B
3262


R-008397168-000S
1861
708
UGCCAUUCCACGACUAGUU
B UGCCAUUCCACGACUAGUUTT B
3264


R-008397168-000S
1861
708
UGCCAUUCCACGACUAGUU
AACUAGUCGUGGAAUGGCAUU
3265


R-008397171-000Y
1190
709
AACCAAGAAAGCAAGCUCA
UGAGCUUGCUUUCUUGGUUUU
3267


R-008397171-000Y
1190
709
AACCAAGAAAGCAAGCUCA
B AACCAAGAAAGCAAGCUCATT B
3266


R-008397174-000Z
1557
710
AUAAUUAUAAGAACAAGAU
AUCUUGUUCUUAUAAUUAUUU
3269


R-008397174-000Z
1557
710
AUAAUUAUAAGAACAAGAU
B AUAAUUAUAAGAACAAGAUTT B
3268


R-008397177-000A
1751
711
GUUAAGCUCUUACACCCAC
B GUUAAGCUCUUACACCCACTT B
3270


R-008397177-000A
1751
711
GUUAAGCUCUUACACCCAC
GUGGGUGUAAGAGCUUAACUU
3271


R-008397180-000G
2897
712
UUGAGUAAUGGUGUAGAAC
B UUGAGUAAUGGUGUAGAACTT B
3272


R-008397180-000G
2897
712
UUGAGUAAUGGUGUAGAAC
GUUCUACACCAUUACUCAAUU
3273


R-008397183-000H
2217
713
GUGUGGCGACAUAUGCAGC
GCUGCAUAUGUCGCCACACUU
3275


R-008397183-000H
2217
713
GUGUGGCGACAUAUGCAGC
B GUGUGGCGACAUAUGCAGCTT B
3274


R-008397186-000J
2302
714
GACCAGCUCUCUCUUCAGA
UCUGAAGAGAGAGCUGGUCUU
3277


R-008397186-000J
2302
714
GACCAGCUCUCUCUUCAGA
B GACCAGCUCUCUCUUCAGATT B
3276


R-008397189-000K
1984
715
UUGUACCGGAGCCCUUCAC
GUGAAGGGCUCCGGUACAAUU
3279


R-008397189-000K
1984
715
UUGUACCGGAGCCCUUCAC
B UUGUACCGGAGCCCUUCACTT B
3278


R-008397192-000S
302
716
AUGGCCAUGGAACCAGACA
B AUGGCCAUGGAACCAGACATT B
3280


R-008397192-000S
302
716
AUGGCCAUGGAACCAGACA
UGUCUGGUUCCAUGGCCAUUU
3281


R-008397195-000T
2431
717
UGGUGGAUAUGGCCAGGAU
B UGGUGGAUAUGGCCAGGAUTT B 
3282


R-008397195-000T
2431
717
UGGUGGAUAUGGCCAGGAU
AUCCUGGCCAUAUCCACCAUU
3283


R-008397198-000U
2183
718
CCUCUGACAGAGUUACUUC
GAAGUAACUCUGUCAGAGGUU
3285


R-008397198-000U
2183
718
CCUCUGACAGAGUUACUUC
B CCUCUGACAGAGUUACUUCTT B
3284


R-008397201-000L
2403
719
AUGAUCCUAGCUAUCGUUC
GAACGAUAGCUAGGAUCAUUU
3287


R-008397201-000L
2403
719
AUGAUCCUAGCUAUCGUUC
B AUGAUCCUAGCUAUCGUUCTT B
3286


R-008397204-000M
788
720
AUGGUCCAUCAGCUUUCUA
B AUGGUCCAUCAGCUUUCUATT B 
3288


R-008397204-000M
788
720
AUGGUCCAUCAGCUUUCUA
UAGAAAGCUGAUGGACCAUUU
3289


R-008397207-000N
1476
721
GGACUCUUGUUCAGCUUCU
B GGACUCUUGUUCAGCUUCUTT B 
3290


R-008397207-000N
1476
721
GGACUCUUGUUCAGCUUCU
AGAAGCUGAACAAGAGUCCUU
3291


R-008397210-000V
827
722
GCUAUCAUGCGUUCUCCUC
B GCUAUCAUGCGUUCUCCUCTT B 
3292


R-008397210-000V
827
722
GCUAUCAUGCGUUCUCCUC
GAGGAGAACGCAUGAUAGCUU
3293


R-008397213-000W
2299
723
GCUGACCAGCUCUCUCUUC
B GCUGACCAGCUCUCUCUUCTT B 
3294


R-008397213-000W
2299
723
GCUGACCAGCUCUCUCUUC
GAAGAGAGAGCUGGUCAGCUU
3295


R-008397216-000X
1891
724
UCGUGCACAUCAGGAUACC
B UCGUGCACAUCAGGAUACCTT B
3296


R-008397216-000X
1891
724
UCGUGCACAUCAGGAUACC
GGUAUCCUGAUGUGCACGAUU
3297


R-008397219-000Y
2196
725
UACUUCACUCUAGGAAUGA
UCAUUCCUAGAGUGAAGUAUU
3299


R-008397219-000Y
2196
725
UACUUCACUCUAGGAAUGA
B UACUUCACUCUAGGAAUGATT B 
3298


R-008397222-000E
663
726
UGAAACAUGCAGUUGUAAA
UUUACAACUGCAUGUUUCAUU
3301


R-008397222-000E
663
726
UGAAACAUGCAGUUGUAAA
B UGAAACAUGCAGUUGUAAATT B 
3300


R-008397225-000F
1028
727
UAUGCCAUUACAACUCUCC
GGAGAGUUGUAAUGGCAUAUU
3303


R-008397225-000F
1028
727
UAUGCCAUUACAACUCUCC
B UAUGCCAUUACAACUCUCCTT B 
3302


R-008397228-000G
2032
728
UGUUAUCAGAGGACUAAAU
AUUUAGUCCUCUGAUAACAUU
3305


R-008397228-000G
2032
728
UGUUAUCAGAGGACUAAAU
B UGUUAUCAGAGGACUAAAUTT B 
3304


R-008397231-000N
1459
729
GAUGGAAGGUCUCCUUGGG
B GAUGGAAGGUCUCCUUGGGTT B 
3306


R-008397231-000N
1459
729
GAUGGAAGGUCUCCUUGGG
CCCAAGGAGACCUUCCAUCUU
3307


R-008397234-000P
2095
730
CAUCCAAAGAGUAGCUGCA
UGCAGCUACUCUUUGGAUGUU
3309


R-008397234-000P
2095
730
CAUCCAAAGAGUAGCUGCA
B CAUCCAAAGAGUAGCUGCATT B 
3308


R-008397237-000R
1686
731
GCCGACACCAAGAAGCAGA
B GCCGACACCAAGAAGCAGATT B
3310


R-008397237-000R
1686
731
GCCGACACCAAGAAGCAGA
UCUGCUUCUUGGUGUCGGCUU
3311


R-008397240-000X
1412
732
CUUUGGACUCUCAGGAAUC
B CUUUGGACUCUCAGGAAUCTT B
3312


R-008397240-000X
1412
732
CUUUGGACUCUCAGGAAUC
GAUUCCUGAGAGUCCAAAGUU
3313


R-008397243-000Y
2473
733
GGAACAUGAGAUGGGUGGC
GCCACCCAUCUCAUGUUCCUU
3315


R-008397243-000Y
2473
733
GGAACAUGAGAUGGGUGGC
B GGAACAUGAGAUGGGUGGCTT B
3314


R-008397246-000Z
1080
734
UGGCAGUGCGUUUAGCUGG
CCAGCUAAACGCACUGCCAUU
3317


R-008397246-000Z
1080
734
UGGCAGUGCGUUUAGCUGG
B UGGCAGUGCGUUUAGCUGGTT B 
3316


R-008397249-000A
2143
735
GGAAGCUGCAGAAGCUAUU
AAUAGCUUCUGCAGCUUCCUU
3319


R-008397249-000A
2143
735
GGAAGCUGCAGAAGCUAUU
B GGAAGCUGCAGAAGCUAUUTT B 
3318


R-008397252-000G
2203
736
CUCUAGGAAUGAAGGUGUG
B CUCUAGGAAUGAAGGUGUGTT B 
3320


R-008397252-000G
2203
736
CUCUAGGAAUGAAGGUGUG
CACACCUUCAUUCCUAGAGUU
3321


R-008397255-000H
548
737
GUACGAGCUGCUAUGUUCC
B GUACGAGCUGCUAUGUUCCTT B
3322


R-008397255-000H
548
737
GUACGAGCUGCUAUGUUCC
GGAACAUAGCAGCUCGUACUU
3323


R-008397258-000J
2050
45
UACCAUUCCAUUGUUUGUG
CACAAACAAUGGAAUGGUAUU
3325


R-008397258-000J
2050
45
UACCAUUCCAUUGUUUGUG
B UACCAUUCCAUUGUUUGUGTT B 
3324


R-008397261-000R
1867
738
UCCACGACUAGUUCAGUUG
B UCCACGACUAGUUCAGUUGTT B 
3326


R-008397261-000R
1867
738
UCCACGACUAGUUCAGUUG
CAACUGAACUAGUCGUGGAUU
3327


R-008397264-000S
842
739
CCUCAGAUGGUGUCUGCUA
B CCUCAGAUGGUGUCUGCUATT B 
3328


R-008397264-000S
842
739
CCUCAGAUGGUGUCUGCUA
UAGCAGACACCAUCUGAGGUU
3329


R-008397267-000T
2120
740
CUCUGUGAACUUGCUCAGG
CCUGAGCAAGUUCACAGAGUU
3331


R-008397267-000T
2120
740
CUCUGUGAACUUGCUCAGG
B CUCUGUGAACUUGCUCAGGTT B 
3330


R-008397270-000Z
782
741
GCAGUUAUGGUCCAUCAGC
B GCAGUUAUGGUCCAUCAGCTT B
3332


R-008397270-000Z
782
741
GCAGUUAUGGUCCAUCAGC
GCUGAUGGACCAUAACUGCUU
3333


R-008397273-000A
1758
742
UCUUACACCCACCAUCCCA
UGGGAUGGUGGGUGUAAGAUU
3335


R-008397273-000A
1758
742
UCUUACACCCACCAUCCCA
B UCUUACACCCACCAUCCCATT B 
3334


R-008397276-000B
2396
743
CGCCAGGAUGAUCCUAGCU
B CGCCAGGAUGAUCCUAGCUTT B 
3336


R-008397276-000B
2396
743
CGCCAGGAUGAUCCUAGCU
AGCUAGGAUCAUCCUGGCGUU
3337


R-008397279-000C
1373
744
CACCUGACAGAUCCAAGUC
GACUUGGAUCUGUCAGGUGUU
3339


R-008397279-000C
1373
744
CACCUGACAGAUCCAAGUC
B CACCUGACAGAUCCAAGUCTT B 
3338


R-008397282-000J
1518
745
UCACCUGUGCAGCUGGAAU
B UCACCUGUGCAGCUGGAAUTT B 
3340


R-008397282-000J
1518
745
UCACCUGUGCAGCUGGAAU
AUUCCAGCUGCACAGGUGAUU
3341


R-008397285-000K
2557
746
GGAUGGGCUGCCUCCAGGU
ACCUGGAGGCAGCCCAUCCUU
3343


R-008397285-000K
2557
746
GGAUGGGCUGCCUCCAGGU
B GGAUGGGCUGCCUCCAGGUTT B 
3342


R-008397288-000L
1987
747
UACCGGAGCCCUUCACAUC
B UACCGGAGCCCUUCACAUCTT B 
3344


R-008397288-000L
1987
747
UACCGGAGCCCUUCACAUC
GAUGUGAAGGGCUCCGGUAUU
3345


R-008397291-000T
568
748
UGAGACAUUAGAUGAGGGC
GCCCUCAUCUAAUGUCUCAUU
3347


R-008397291-000T
568
748
UGAGACAUUAGAUGAGGGC
B UGAGACAUUAGAUGAGGGCTT B
3346


R-008397294-000U
2201
749
CACUCUAGGAAUGAAGGUG
B CACUCUAGGAAUGAAGGUGTT B 
3348


R-008397294-000U
2201
749
CACUCUAGGAAUGAAGGUG
CACCUUCAUUCCUAGAGUGUU
3349


R-008397297-000V
609
750
UUGAUGCUGCUCAUCCCAC
GUGGGAUGAGCAGCAUCAAUU
3351


R-008397297-000V
609
750
UUGAUGCUGCUCAUCCCAC
B UUGAUGCUGCUCAUCCCACTT B 
3350


R-008397300-000M
400
751
UUCUCUGAGUGGUAAAGGC
GCCUUUACCACUCAGAGAAUU
3353


R-008397300-000M
400
751
UUCUCUGAGUGGUAAAGGC
B UUCUCUGAGUGGUAAAGGCTT B
3352


R-008397303-000N
331
752
UGUUAGUCACUGGCAGCAA
UUGCUGCCAGUGACUAACAUU
3355


R-008397303-000N
331
752
UGUUAGUCACUGGCAGCAA
B UGUUAGUCACUGGCAGCAATT B 
3354


R-008397306-000P
1967
753
GAAGAAAUAGUUGAAGGUU
AACCUUCAACUAUUUCUUCUU
3357


R-008397306-000P
1967
753
GAAGAAAUAGUUGAAGGUU
B GAAGAAAUAGUUGAAGGUUTT B 
3356


R-008397309-000R
2198
754
CUUCACUCUAGGAAUGAAG
CUUCAUUCCUAGAGUGAAGUU
3359


R-008397309-000R
2198
754
CUUCACUCUAGGAAUGAAG
B CUUCACUCUAGGAAUGAAGTT B 
3358


R-008397312-000X
1493
755
CUGGGUUCAGAUGAUAUAA
UUAUAUCAUCUGAACCCAGUU
3361


R-008397312-000X
1493
755
CUGGGUUCAGAUGAUAUAA
B CUGGGUUCAGAUGAUAUAATT B
3360


R-008397315-000Y
2260
756
GGACAAGCCACAAGAUUAC
GUAAUCUUGUGGCUUGUCCUU
3363


R-008397315-000Y
2260
756
GGACAAGCCACAAGAUUAC
B GGACAAGCCACAAGAUUACTT B
3362


R-008397318-000Z
2496
757
ACCCUGGUGCUGACUAUCC
B ACCCUGGUGCUGACUAUCCTT B 
3364


R-008397318-000Z
2496
757
ACCCUGGUGCUGACUAUCC
GGAUAGUCAGCACCAGGGUUU
3365


R-008397321-000F
2361
758
UUGAUAUUGGUGCCCAGGG
B UUGAUAUUGGUGCCCAGGGTT B 
3366


R-008397321-000F
2361
758
UUGAUAUUGGUGCCCAGGG
CCCUGGGCACCAAUAUCAAUU
3367


R-008397324-000G
443
759
ACCUCCCAAGUCCUGUAUG
CAUACAGGACUUGGGAGGUUU
3369


R-008397324-000G
443
759
ACCUCCCAAGUCCUGUAUG
B ACCUCCCAAGUCCUGUAUGTT B 
3368


R-008397327-000H
523
760
GUAUGCAAUGACUCGAGCU
B GUAUGCAAUGACUCGAGCUTT B 
3370


R-008397327-000H
523
760
GUAUGCAAUGACUCGAGCU
AGCUCGAGUCAUUGCAUACUU
3371


R-008397330-000P
1742
761
CCAGUUGUGGUUAAGCUCU
B CCAGUUGUGGUUAAGCUCUTT B 
3372


R-008397330-000P
1742
761
CCAGUUGUGGUUAAGCUCU
AGAGCUUAACCACAACUGGUU
3373


R-008397333-000R
530
762
AUGACUCGAGCUCAGAGGG
B AUGACUCGAGCUCAGAGGGTT B 
3374


R-008397333-000R
530
762
AUGACUCGAGCUCAGAGGG
CCCUCUGAGCUCGAGUCAUUU
3375


R-008397336-000S
3169
763
UUGUUGUAACCUGCUGUGA
B UUGUUGUAACCUGCUGUGATT B 
3376


R-008397336-000S
3169
763
UUGUUGUAACCUGCUGUGA
UCACAGCAGGUUACAACAAUU
3377


R-008397339-000T
1385
764
CCAAGUCAACGUCUUGUUC
B CCAAGUCAACGUCUUGUUCTT B
3378


R-008397339-000T
1385
764
CCAAGUCAACGUCUUGUUC
GAACAAGACGUUGACUUGGUU
3379


R-008397342-000Z
2123
131
UGUGAACUUGCUCAGGACA
B UGUGAACUUGCUCAGGACATT B 
3380


R-008397342-000Z
2123
131
UGUGAACUUGCUCAGGACA
UGUCCUGAGCAAGUUCACAUU
3381


R-008397345-000A
2036
765
AUCAGAGGACUAAAUACCA
B AUCAGAGGACUAAAUACCATT B 
3382


R-008397345-000A
2036
765
AUCAGAGGACUAAAUACCA
UGGUAUUUAGUCCUCUGAUUU
3383


R-008397348-000B
3088
766
UGUAUGGGUAGGGUAAAUC
GAUUUACCCUACCCAUACAUU
3385


R-008397348-000B
3088
766
UGUAUGGGUAGGGUAAAUC
B UGUAUGGGUAGGGUAAAUCTT B
3384


R-008397351-000H
2051
56
ACCAUUCCAUUGUUUGUGC
GCACAAACAAUGGAAUGGUUU
3387


R-008397351-000H
2051
56
ACCAUUCCAUUGUUUGUGC
B ACCAUUCCAUUGUUUGUGCTT B
3386


R-008397354-000J
288
170
UGAUGGAGUUGGACAUGGC
GCCAUGUCCAACUCCAUCAUU
3389


R-008397354-000J
288
170
UGAUGGAGUUGGACAUGGC
B UGAUGGAGUUGGACAUGGCTT B 
3388


R-008397357-000K
1850
767
CGUGAGCAGGGUGCCAUUC
B CGUGAGCAGGGUGCCAUUCTT B 
3390


R-008397357-000K
1850
767
CGUGAGCAGGGUGCCAUUC
GAAUGGCACCCUGCUCACGUU
3391


R-008397360-000S
2548
82
GGACCUCAUGGAUGGGCUG
B GGACCUCAUGGAUGGGCUGTT B
3392


R-008397360-000S
2548
82
GGACCUCAUGGAUGGGCUG
CAGCCCAUCCAUGAGGUCCUU
3393


R-008397363-000T
2518
768
UGAUGGGCUGCCAGAUCUG
B UGAUGGGCUGCCAGAUCUGTT B
3394


R-008397363-000T
2518
768
UGAUGGGCUGCCAGAUCUG
CAGAUCUGGCAGCCCAUCAUU
3395


R-008397366-000U
1886
769
CUUGUUCGUGCACAUCAGG
B CUUGUUCGUGCACAUCAGGTT B
3396


R-008397366-000U
1886
769
CUUGUUCGUGCACAUCAGG
CCUGAUGUGCACGAACAAGUU
3397


R-008397369-000V
650
770
CCAUCACAGAUGCUGAAAC
GUUUCAGCAUCUGUGAUGGUU
3399


R-008397369-000V
650
770
CCAUCACAGAUGCUGAAAC
B CCAUCACAGAUGCUGAAACTT B
3398


R-008397372-000B
3139
771
ACAGUUUACCAGUUGCCUU
AAGGCAACUGGUAAACUGUUU
3401


R-008397372-000B
3139
771
ACAGUUUACCAGUUGCCUU
B ACAGUUUACCAGUUGCCUUTT B
3400


R-008397375-000C
2025
772
ACCGAAUUGUUAUCAGAGG
CCUCUGAUAACAAUUCGGUUU
3403


R-008397375-000C
2025
772
ACCGAAUUGUUAUCAGAGG
B ACCGAAUUGUUAUCAGAGGTT B
3402


R-008397378-000D
1082
773
GCAGUGCGUUUAGCUGGUG
CACCAGCUAAACGCACUGCUU
3405


R-008397378-000D
1082
773
GCAGUGCGUUUAGCUGGUG
B GCAGUGCGUUUAGCUGGUGTT B
3404


R-008397381-000K
2475
774
AACAUGAGAUGGGUGGCCA
UGGCCACCCAUCUCAUGUUUU
3407


R-008397381-000K
2475
774
AACAUGAGAUGGGUGGCCA
B AACAUGAGAUGGGUGGCCATT B 
3406


R-008397384-000L
1375
775
CCUGACAGAUCCAAGUCAA
UUGACUUGGAUCUGUCAGGUU
3409


R-008397384-000L
1375
775
CCUGACAGAUCCAAGUCAA
B CCUGACAGAUCCAAGUCAATT B 
3408


R-008397387-000M
2013
776
GGGAUGUUCACAACCGAAU
B GGGAUGUUCACAACCGAAUTT B
3410


R-008397387-000M
2013
776
GGGAUGUUCACAACCGAAU
AUUCGGUUGUGAACAUCCCUU
3411


R-008397390-000U
1236
41
CUUUAGUAAAUAUAAUGAG
CUCAUUAUAUUUACUAAAGUU
3413


R-008397390-000U
1236
41
CUUUAGUAAAUAUAAUGAG
B CUUUAGUAAAUAUAAUGAGTT B
3412


R-008397393-000V
1653
128
AGCCUGCCAUCUGUGCUCU
B AGCCUGCCAUCUGUGCUCUTT B
3414


R-008397393-000V
1653
128
AGCCUGCCAUCUGUGCUCU
AGAGCACAGAUGGCAGGCUUU
3415


R-008397396-000W
1802
777
GGAUUGAUUCGAAAUCUUG
B GGAUUGAUUCGAAAUCUUGTT B
3416


R-008397396-000W
1802
777
GGAUUGAUUCGAAAUCUUG
CAAGAUUUCGAAUCAAUCCUU
3417


R-008397399-000X
2144
778
GAAGCUGCAGAAGCUAUUG
CAAUAGCUUCUGCAGCUUCUU
3419


R-008397399-000X
2144
778
GAAGCUGCAGAAGCUAUUG
B GAAGCUGCAGAAGCUAUUGTT B
3418


R-008397402-000P
529
779
AAUGACUCGAGCUCAGAGG
B AAUGACUCGAGCUCAGAGGTT B
3420


R-008397402-000P
529
779
AAUGACUCGAGCUCAGAGG
CCUCUGAGCUCGAGUCAUUUU
3421


R-008397405-000R
1482
780
UUGUUCAGCUUCUGGGUUC
GAACCCAGAAGCUGAACAAUU
3423


R-008397405-000R
1482
780
UUGUUCAGCUUCUGGGUUC
B UUGUUCAGCUUCUGGGUUCTT B
3422


R-008397408-000S
1546
781
CCUCACUUGCAAUAAUUAU
B CCUCACUUGCAAUAAUUAUTT B 
3424


R-008397408-000S
1546
781
CCUCACUUGCAAUAAUUAU
AUAAUUAUUGCAAGUGAGGUU
3425


R-008397411-000Y
845
782
CAGAUGGUGUCUGCUAUUG
CAAUAGCAGACACCAUCUGUU
3427


R-008397411-000Y
845
782
CAGAUGGUGUCUGCUAUUG
B CAGAUGGUGUCUGCUAUUGTT B 
3426


R-008397414-000Z
487
783
CUUCACUCAAGAACAAGUA
B CUUCACUCAAGAACAAGUATT B 
3428


R-008397414-000Z
487
783
CUUCACUCAAGAACAAGUA
UACUUGUUCUUGAGUGAAGUU
3429


R-008397417-000A
652
784
AUCACAGAUGCUGAAACAU
AUGUUUCAGCAUCUGUGAUUU
3431


R-008397417-000A
652
784
AUCACAGAUGCUGAAACAU
B AUCACAGAUGCUGAAACAUTT B 
3430


R-008397420-000G
1720
785
AGUUCGCCUUCACUAUGGA
UCCAUAGUGAAGGCGAACUUU
3433


R-008397420-000G
1720
785
AGUUCGCCUUCACUAUGGA
B AGUUCGCCUUCACUAUGGATT B 
3432


R-008397423-000H
951
786
UACUGGCCAUCUUUAAGUC
GACUUAAAGAUGGCCAGUAUU
3435


R-008397423-000H
951
786
UACUGGCCAUCUUUAAGUC
B UACUGGCCAUCUUUAAGUCTT B
3434


R-008397426-000J
1232
787
CAAGCUUUAGUAAAUAUAA
UUAUAUUUACUAAAGCUUGUU
3437


R-008397426-000J
1232
787
CAAGCUUUAGUAAAUAUAA
B CAAGCUUUAGUAAAUAUAATT B
3436


R-008397429-000K
2269
28
ACAAGAUUACAAGAAACGG
B ACAAGAUUACAAGAAACGGTT B 
3438


R-008397429-000K
2269
28
ACAAGAUUACAAGAAACGG
CCGUUUCUUGUAAUCUUGUUU
3439


R-008397432-000S
2265
788
AGCCACAAGAUUACAAGAA
B AGCCACAAGAUUACAAGAATT B 
3440


R-008397432-000S
2265
788
AGCCACAAGAUUACAAGAA
UUCUUGUAAUCUUGUGGCUUU
3441


R-008397435-000T
1698
789
AAGCAGAGAUGGCCCAGAA
B AAGCAGAGAUGGCCCAGAATT B 
3442


R-008397435-000T
1698
789
AAGCAGAGAUGGCCCAGAA
UUCUGGGCCAUCUCUGCUUUU
3443


R-008397438-000U
701
790
GAUGCAGAACUUGCCACAC
GUGUGGCAAGUUCUGCAUCUU
3445


R-008397438-000U
701
790
GAUGCAGAACUUGCCACAC
B GAUGCAGAACUUGCCACACTT B
3444


R-008397441-000A
1428
791
AUCUUUCAGAUGCUGCAAC
GUUGCAGCAUCUGAAAGAUUU
3447


R-008397441-000A
1428
791
AUCUUUCAGAUGCUGCAAC
B AUCUUUCAGAUGCUGCAACTT B
3446


R-008397444-000B
1930
792
UGGGACACAGCAGCAAUUU
B UGGGACACAGCAGCAAUUUTT B 
3448


R-008397444-000B
1930
792
UGGGACACAGCAGCAAUUU
AAAUUGCUGCUGUGUCCCAUU
3449


R-008397447-000C
1379
793
ACAGAUCCAAGUCAACGUC
GACGUUGACUUGGAUCUGUUU
3451


R-008397447-000C
1379
793
ACAGAUCCAAGUCAACGUC
B ACAGAUCCAAGUCAACGUCTT B
3450


R-008397450-000J
1936
794
ACAGCAGCAAUUUGUGGAG
B ACAGCAGCAAUUUGUGGAGTT B 
3452


R-008397450-000J
1936
794
ACAGCAGCAAUUUGUGGAG
CUCCACAAAUUGCUGCUGUUU
3453


R-008397453-000K
1441
795
UGCAACUAAACAGGAAGGG
CCCUUCCUGUUUAGUUGCAUU
3455


R-008397453-000K
1441
795
UGCAACUAAACAGGAAGGG
B UGCAACUAAACAGGAAGGGTT B 
3454


R-008397456-000L
2132
796
GCUCAGGACAAGGAAGCUG
CAGCUUCCUUGUCCUGAGCUU
3457


R-008397456-000L
2132
796
GCUCAGGACAAGGAAGCUG
B GCUCAGGACAAGGAAGCUGTT B
3456


R-008397459-000M
2443
165
CCAGGAUGCCUUGGGUAUG
B CCAGGAUGCCUUGGGUAUGTT B 
3458


R-008397459-000M
2443
165
CCAGGAUGCCUUGGGUAUG
CAUACCCAAGGCAUCCUGGUU
3459


R-008397462-000U
1800
163
UUGGAUUGAUUCGAAAUCU
AGAUUUCGAAUCAAUCCAAUU
3461


R-008397462-000U
1800
163
UUGGAUUGAUUCGAAAUCU
B UUGGAUUGAUUCGAAAUCUTT B 
3460


R-008397465-000V
403
185
UCUGAGUGGUAAAGGCAAU
AUUGCCUUUACCACUCAGAUU
3463


R-008397465-000V
403
185
UCUGAGUGGUAAAGGCAAU
B UCUGAGUGGUAAAGGCAAUTT B 
3462


R-008397468-000W
1007
105
CCAGUGGAUUCUGUGUUGU
ACAACACAGAAUCCACUGGUU
3465


R-008397468-000W
1007
105
CCAGUGGAUUCUGUGUUGU
B CCAGUGGAUUCUGUGUUGUTT B
3464


R-008397471-000C
1057
113
AUUACAUCAAGAAGGAGCU
AGCUCCUUCUUGAUGUAAUUU
3467


R-008397471-000C
1057
113
AUUACAUCAAGAAGGAGCU
B AUUACAUCAAGAAGGAGCUTT B 
3466


R-008397474-000D
2267
87
CCACAAGAUUACAAGAAAC
B CCACAAGAUUACAAGAAACTT B
3468


R-008397474-000D
2267
87
CCACAAGAUUACAAGAAAC
GUUUCUUGUAAUCUUGUGGUU
3469


R-008397477-000E
1240
158
AGUAAAUAUAAUGAGGACC
B AGUAAAUAUAAUGAGGACCTT B
3470


R-008397477-000E
1240
158
AGUAAAUAUAAUGAGGACC
GGUCCUCAUUAUAUUUACUUU
3471


R-008397480-000L
2043
797
GACUAAAUACCAUUCCAUU
AAUGGAAUGGUAUUUAGUCUU
3473


R-008397480-000L
2043
797
GACUAAAUACCAUUCCAUU
B GACUAAAUACCAUUCCAUUTT B 
3472


R-008397483-000M
608
798
UUUGAUGCUGCUCAUCCCA
UGGGAUGAGCAGCAUCAAAUU
3475


R-008397483-000M
608
798
UUUGAUGCUGCUCAUCCCA
B UUUGAUGCUGCUCAUCCCATT B 
3474


R-008397486-000N
341
799
UGGCAGCAACAGUCUUACC
B UGGCAGCAACAGUCUUACCTT B
3476


R-008397486-000N
341
799
UGGCAGCAACAGUCUUACC
GGUAAGACUGUUGCUGCCAUU
3477


R-008397489-000P
1194
800
AAGAAAGCAAGCUCAUCAU
B AAGAAAGCAAGCUCAUCAUTT B 
3478


R-008397489-000P
1194
800
AAGAAAGCAAGCUCAUCAU
AUGAUGAGCUUGCUUUCUUUU
3479


R-008397492-000W
2350
801
UGAUCUUGGACUUGAUAUU
B UGAUCUUGGACUUGAUAUUTT B 
3480


R-008397492-000W
2350
801
UGAUCUUGGACUUGAUAUU
AAUAUCAAGUCCAAGAUCAUU
3481


R-008397495-000X
2948
802
CUGAAUAAAGUGUAACAAU
B CUGAAUAAAGUGUAACAAUTT B 
3482


R-008397495-000X
2948
802
CUGAAUAAAGUGUAACAAU
AUUGUUACACUUUAUUCAGUU
3483


R-008397507-000T
2044
803
ACUAAAUACCAUUCCAUUG
B ACUAAAUACCAUUCCAUUGTT B 
3484


R-008397507-000T
2044
803
ACUAAAUACCAUUCCAUUG
CAAUGGAAUGGUAUUUAGUUU
3485


R-008397510-000Z
621
804
AUCCCACUAAUGUCCAGCG
CGCUGGACAUUAGUGGGAUUU
3487


R-008397510-000Z
621
804
AUCCCACUAAUGUCCAGCG
B AUCCCACUAAUGUCCAGCGTT B 
3486


R-008397513-000A
384
805
CCACUACCACAGCUCCUUC
B CCACUACCACAGCUCCUUCTT B
3488


R-008397513-000A
384
805
CCACUACCACAGCUCCUUC
GAAGGAGCUGUGGUAGUGGUU
3489


R-008397516-000B
1898
806
CAUCAGGAUACCCAGCGCC
B CAUCAGGAUACCCAGCGCCTT B
3490


R-008397516-000B
1898
806
CAUCAGGAUACCCAGCGCC
GGCGCUGGGUAUCCUGAUGUU
3491


R-008397519-000C
1795
15
UACUGUUGGAUUGAUUCGA
UCGAAUCAAUCCAACAGUAUU
3493


R-008397519-000C
1795
15
UACUGUUGGAUUGAUUCGA
B UACUGUUGGAUUGAUUCGATT B
3492


R-008397522-000J
653
807
UCACAGAUGCUGAAACAUG
CAUGUUUCAGCAUCUGUGAUU
3495


R-008397522-000J
653
807
UCACAGAUGCUGAAACAUG
B UCACAGAUGCUGAAACAUGTT B 
3494


R-008397525-000K
1846
808
UUUGCGUGAGCAGGGUGCC
GGCACCCUGCUCACGCAAAUU
3497


R-008397525-000K
1846
808
UUUGCGUGAGCAGGGUGCC
B UUUGCGUGAGCAGGGUGCCTT B
3496


R-008397528-000L
2348
809
GCUGAUCUUGGACUUGAUA
UAUCAAGUCCAAGAUCAGCUU
3499


R-008397528-000L
2348
809
GCUGAUCUUGGACUUGAUA
B GCUGAUCUUGGACUUGAUATT B
3498


R-008397531-000T
1798
19
UGUUGGAUUGAUUCGAAAU
AUUUCGAAUCAAUCCAACAUU
3501


R-008397531-000T
1798
19
UGUUGGAUUGAUUCGAAAU
B UGUUGGAUUGAUUCGAAAUTT B 
3500


R-008397534-000U
1150
810
GGCUAUUACGACAGACUGC
B GGCUAUUACGACAGACUGCTT B
3502


R-008397534-000U
1150
810
GGCUAUUACGACAGACUGC
GCAGUCUGUCGUAAUAGCCUU
3503


R-008397537-000V
1009
180
AGUGGAUUCUGUGUUGUUU
AAACAACACAGAAUCCACUUU
3505


R-008397537-000V
1009
180
AGUGGAUUCUGUGUUGUUU
B AGUGGAUUCUGUGUUGUUUTT B 
3504


R-008397540-000B
654
178
CACAGAUGCUGAAACAUGC
B CACAGAUGCUGAAACAUGCTT B
3506


R-008397540-000B
654
178
CACAGAUGCUGAAACAUGC
GCAUGUUUCAGCAUCUGUGUU
3507


R-008397543-000C
298
811
GGACAUGGCCAUGGAACCA
B GGACAUGGCCAUGGAACCATT B
3508


R-008397543-000C
298
811
GGACAUGGCCAUGGAACCA
UGGUUCCAUGGCCAUGUCCUU
3509


R-008397546-000D
1568
812
AACAAGAUGAUGGUCUGCC
B AACAAGAUGAUGGUCUGCCTT B
3510


R-008397546-000D
1568
812
AACAAGAUGAUGGUCUGCC
GGCAGACCAUCAUCUUGUUUU
3511


R-008397549-000E
1058
813
UUACAUCAAGAAGGAGCUA
B UUACAUCAAGAAGGAGCUATT B
3512


R-008397549-000E
1058
813
UUACAUCAAGAAGGAGCUA
UAGCUCCUUCUUGAUGUAAUU
3513


R-008397552-000L
1835
814
AAUCAUGCACCUUUGCGUG
B AAUCAUGCACCUUUGCGUGTT B 
3514


R-008397552-000L
1835
814
AAUCAUGCACCUUUGCGUG
CACGCAAAGGUGCAUGAUUUU
3515


R-008397555-000M
1832
815
GCAAAUCAUGCACCUUUGC
B GCAAAUCAUGCACCUUUGCTT B
3516


R-008397555-000M
1832
815
GCAAAUCAUGCACCUUUGC
GCAAAGGUGCAUGAUUUGCUU
3517


R-008397558-000N
2550
55
ACCUCAUGGAUGGGCUGCC
GGCAGCCCAUCCAUGAGGUUU
3519


R-008397558-000N
2550
55
ACCUCAUGGAUGGGCUGCC
B ACCUCAUGGAUGGGCUGCCTT B
3518


R-008397561-000V
406
816
GAGUGGUAAAGGCAAUCCU
AGGAUUGCCUUUACCACUCUU
3521


R-008397561-000V
406
816
GAGUGGUAAAGGCAAUCCU
B GAGUGGUAAAGGCAAUCCUTT B 
3520


R-008397564-000W
1723
817
UCGCCUUCACUAUGGACUA
B UCGCCUUCACUAUGGACUATT B
3522


R-008397564-000W
1723
817
UCGCCUUCACUAUGGACUA
UAGUCCAUAGUGAAGGCGAUU
3523


R-008397567-000X
371
818
AUCCAUUCUGGUGCCACUA
UAGUGGCACCAGAAUGGAUUU
3525


R-008397567-000X
371
818
AUCCAUUCUGGUGCCACUA
B AUCCAUUCUGGUGCCACUATT B 
3524


R-008397570-000D
1899
819
AUCAGGAUACCCAGCGCCG
CGGCGCUGGGUAUCCUGAUUU
3527


R-008397570-000D
1899
819
AUCAGGAUACCCAGCGCCG
B AUCAGGAUACCCAGCGCCGTT B 
3526


R-008397573-000E
522
820
AGUAUGCAAUGACUCGAGC
B AGUAUGCAAUGACUCGAGCTT B
3528


R-008397573-000E
522
820
AGUAUGCAAUGACUCGAGC
GCUCGAGUCAUUGCAUACUUU
3529


R-008397576-000F
2285
821
CGGCUUUCAGUUGAGCUGA
B CGGCUUUCAGUUGAGCUGATT B 
3530


R-008397576-000F
2285
821
CGGCUUUCAGUUGAGCUGA
UCAGCUCAACUGAAAGCCGUU
3531


R-008397579-000G
779
822
GCUGCAGUUAUGGUCCAUC
GAUGGACCAUAACUGCAGCUU
3533


R-008397579-000G
779
822
GCUGCAGUUAUGGUCCAUC
B GCUGCAGUUAUGGUCCAUCTT B
3532


R-008397582-000N
2896
823
AUUGAGUAAUGGUGUAGAA
B AUUGAGUAAUGGUGUAGAATT B 
3534


R-008397582-000N
2896
823
AUUGAGUAAUGGUGUAGAA
UUCUACACCAUUACUCAAUUU
3535


R-008397588-000R
2943
824
GUAAUCUGAAUAAAGUGUA
UACACUUUAUUCAGAUUACUU
3537


R-008397588-000R
2943
824
GUAAUCUGAAUAAAGUGUA
B GUAAUCUGAAUAAAGUGUATT B 
3536


R-008397591-000X
513
825
UUGAUGGACAGUAUGCAAU
B UUGAUGGACAGUAUGCAAUTT B 
3538


R-008397591-000X
513
825
UUGAUGGACAGUAUGCAAU
AUUGCAUACUGUCCAUCAAUU
3539


R-008397594-000Y
3084
826
GAUAUGUAUGGGUAGGGUA
B GAUAUGUAUGGGUAGGGUATT B 
3540


R-008397594-000Y
3084
826
GAUAUGUAUGGGUAGGGUA
UACCCUACCCAUACAUAUCUU
3541


R-008397597-000Z
1567
827
GAACAAGAUGAUGGUCUGC
B GAACAAGAUGAUGGUCUGCTT B
3542


R-008397597-000Z
1567
827
GAACAAGAUGAUGGUCUGC
GCAGACCAUCAUCUUGUUCUU
3543


R-008397600-000S
2034
828
UUAUCAGAGGACUAAAUAC
B UUAUCAGAGGACUAAAUACTT B
3544


R-008397600-000S
2034
828
UUAUCAGAGGACUAAAUAC
GUAUUUAGUCCUCUGAUAAUU
3545


R-008397603-000T
1003
829
UUCACCAGUGGAUUCUGUG
B UUCACCAGUGGAUUCUGUGTT B 
3546


R-008397603-000T
1003
829
UUCACCAGUGGAUUCUGUG
CACAGAAUCCACUGGUGAAUU
3547


R-008397606-000U
1980
830
AAGGUUGUACCGGAGCCCU
AGGGCUCCGGUACAACCUUUU
3549


R-008397606-000U
1980
830
AAGGUUGUACCGGAGCCCU
B AAGGUUGUACCGGAGCCCUTT B 
3548


R-008397609-000V
1340
831
GUAGAAGCUGGUGGAAUGC
GCAUUCCACCAGCUUCUACUU
3551


R-008397609-000V
1340
831
GUAGAAGCUGGUGGAAUGC
B GUAGAAGCUGGUGGAAUGCTT B
3550


R-008397612-000B
1437
832
AUGCUGCAACUAAACAGGA
B AUGCUGCAACUAAACAGGATT B 
3552


R-008397612-000B
1437
832
AUGCUGCAACUAAACAGGA
UCCUGUUUAGUUGCAGCAUUU
3553


R-008397615-000C
2499
145
CUGGUGCUGACUAUCCAGU
B CUGGUGCUGACUAUCCAGUTT B 
3554


R-008397615-000C
2499
145
CUGGUGCUGACUAUCCAGU
ACUGGAUAGUCAGCACCAGUU
3555


R-008397618-000D
785
64
GUUAUGGUCCAUCAGCUUU
AAAGCUGAUGGACCAUAACUU
3557


R-008397618-000D
785
64
GUUAUGGUCCAUCAGCUUU
B GUUAUGGUCCAUCAGCUUUTT B 
3556


R-008397621-000K
2425
833
UCACUCUGGUGGAUAUGGC
B UCACUCUGGUGGAUAUGGCTT B
3558


R-008397621-000K
2425
833
UCACUCUGGUGGAUAUGGC
GCCAUAUCCACCAGAGUGAUU
3559


R-008397624-000L
282
834
CUGAUUUGAUGGAGUUGGA
UCCAACUCCAUCAAAUCAGUU
3561


R-008397624-000L
282
834
CUGAUUUGAUGGAGUUGGA
B CUGAUUUGAUGGAGUUGGATT B 
3560


R-008397627-000M
1206
835
UCAUCAUACUGGCUAGUGG
B UCAUCAUACUGGCUAGUGGTT B 
3562


R-008397627-000M
1206
835
UCAUCAUACUGGCUAGUGG
CCACUAGCCAGUAUGAUGAUU
3563


R-008397630-000U
1885
836
GCUUGUUCGUGCACAUCAG
CUGAUGUGCACGAACAAGCUU
3565


R-008397630-000U
1885
836
GCUUGUUCGUGCACAUCAG
B GCUUGUUCGUGCACAUCAGTT B 
3564


R-008397633-000V
1314
837
UCUGCUCUAGUAAUAAGCC
B UCUGCUCUAGUAAUAAGCCTT B
3566


R-008397633-000V
1314
837
UCUGCUCUAGUAAUAAGCC
GGCUUAUUACUAGAGCAGAUU
3567


R-008397636-000W
2388
174
UUGGAUAUCGCCAGGAUGA
B UUGGAUAUCGCCAGGAUGATT B 
3568


R-008397636-000W
2388
174
UUGGAUAUCGCCAGGAUGA
UCAUCCUGGCGAUAUCCAAUU
3569


R-008397639-000X
1308
838
UAUCUGUCUGCUCUAGUAA
B UAUCUGUCUGCUCUAGUAATT B 
3570


R-008397639-000X
1308
838
UAUCUGUCUGCUCUAGUAA
UUACUAGAGCAGACAGAUAUU
3571


R-008397642-000D
1200
839
GCAAGCUCAUCAUACUGGC
GCCAGUAUGAUGAGCUUGCUU
3573


R-008397642-000D
1200
839
GCAAGCUCAUCAUACUGGC
B GCAAGCUCAUCAUACUGGCTT B
3572


R-008397645-000E
543
840
AGAGGGUACGAGCUGCUAU
B AGAGGGUACGAGCUGCUAUTT B 
3574


R-008397645-000E
543
840
AGAGGGUACGAGCUGCUAU
AUAGCAGCUCGUACCCUCUUU
3575


R-008397648-000F
1609
841
UGUGCGUACUGUCCUUCGG
B UGUGCGUACUGUCCUUCGGTT B 
3576


R-008397648-000F
1609
841
UGUGCGUACUGUCCUUCGG
CCGAAGGACAGUACGCACAUU
3577


R-008397651-000M
1453
842
GGAAGGGAUGGAAGGUCUC
B GGAAGGGAUGGAAGGUCUCTT B
3578


R-008397651-000M
1453
842
GGAAGGGAUGGAAGGUCUC
GAGACCUUCCAUCCCUUCCUU
3579


R-008397654-000N
2127
138
AACUUGCUCAGGACAAGGA
B AACUUGCUCAGGACAAGGATT B 
3580


R-008397654-000N
2127
138
AACUUGCUCAGGACAAGGA
UCCUUGUCCUGAGCAAGUUUU
3581


R-008397657-000P
833
843
AUGCGUUCUCCUCAGAUGG
B AUGCGUUCUCCUCAGAUGGTT B 
3582


R-008397657-000P
833
843
AUGCGUUCUCCUCAGAUGG
CCAUCUGAGGAGAACGCAUUU
3583


R-008397660-000W
2188
844
GACAGAGUUACUUCACUCU
B GACAGAGUUACUUCACUCUTT B 
3584


R-008397660-000W
2188
844
GACAGAGUUACUUCACUCU
AGAGUGAAGUAACUCUGUCUU
3585


R-008397663-000X
1148
845
UUGGCUAUUACGACAGACU
B UUGGCUAUUACGACAGACUTT B 
3586


R-008397663-000X
1148
845
UUGGCUAUUACGACAGACU
AGUCUGUCGUAAUAGCCAAUU
3587


R-008397666-000Y
1736
846
GGACUACCAGUUGUGGUUA
B GGACUACCAGUUGUGGUUATT B
3588


R-008397666-000Y
1736
846
GGACUACCAGUUGUGGUUA
UAACCACAACUGGUAGUCCUU
3589


R-008397669-000Z
1401
847
UUCAGAACUGUCUUUGGAC
GUCCAAAGACAGUUCUGAAUU
3591


R-008397669-000Z
1401
847
UUCAGAACUGUCUUUGGAC
B UUCAGAACUGUCUUUGGACTT B
3590


R-008397672-000F
1677
848
AUCUGACCAGCCGACACCA
UGGUGUCGGCUGGUCAGAUUU
3593


R-008397672-000F
1677
848
AUCUGACCAGCCGACACCA
B AUCUGACCAGCCGACACCATT B 
3592


R-008397675-000G
1934
849
ACACAGCAGCAAUUUGUGG
B ACACAGCAGCAAUUUGUGGTT B 
3594


R-008397675-000G
1934
849
ACACAGCAGCAAUUUGUGG
CCACAAAUUGCUGCUGUGUUU
3595


R-008397678-000H
388
850
UACCACAGCUCCUUCUCUG
CAGAGAAGGAGCUGUGGUAUU
3597


R-008397678-000H
388
850
UACCACAGCUCCUUCUCUG
B UACCACAGCUCCUUCUCUGTT B 
3596


R-008397681-000P
1920
851
CGUCCAUGGGUGGGACACA
B CGUCCAUGGGUGGGACACATT B 
3598


R-008397681-000P
1920
851
CGUCCAUGGGUGGGACACA
UGUGUCCCACCCAUGGACGUU 
3599


R-008397684-000R
1747
852
UGUGGUUAAGCUCUUACAC
GUGUAAGAGCUUAACCACAUU
3601


R-008397684-000R
1747
852
UGUGGUUAAGCUCUUACAC
B UGUGGUUAAGCUCUUACACTT B
3600


R-008397687-000S
861
853
UUGUACGUACCAUGCAGAA
B UUGUACGUACCAUGCAGAATT B 
3602


R-008397687-000S
861
853
UUGUACGUACCAUGCAGAA
UUCUGCAUGGUACGUACAAUU
3603


R-008397690-000Y
1904
854
GAUACCCAGCGCCGUACGU
B GAUACCCAGCGCCGUACGUTT B 
3604


R-008397690-000Y
1904
854
GAUACCCAGCGCCGUACGU
ACGUACGGCGCUGGGUAUCUU
3605


R-008397693-000Z
831
855
UCAUGCGUUCUCCUCAGAU
B UCAUGCGUUCUCCUCAGAUTT B 
3606


R-008397693-000Z
831
855
UCAUGCGUUCUCCUCAGAU
AUCUGAGGAGAACGCAUGAUU
3607


R-008397696-000A
1895
856
GCACAUCAGGAUACCCAGC
GCUGGGUAUCCUGAUGUGCUU
3609


R-008397696-000A
1895
856
GCACAUCAGGAUACCCAGC
B GCACAUCAGGAUACCCAGCTT B 
3608


R-008397699-000B
2273
857
GAUUACAAGAAACGGCUUU
AAAGCCGUUUCUUGUAAUCUU
3611


R-008397699-000B
2273
857
GAUUACAAGAAACGGCUUU
B GAUUACAAGAAACGGCUUUTT B 
3610


R-008397702-000U
1738
858
ACUACCAGUUGUGGUUAAG
B ACUACCAGUUGUGGUUAAGTT B 
3612


R-008397702-000U
1738
858
ACUACCAGUUGUGGUUAAG
CUUAACCACAACUGGUAGUUU
3613


R-008397705-000V
1395
859
GUCUUGUUCAGAACUGUCU
B GUCUUGUUCAGAACUGUCUTT B 
3614


R-008397705-000V
1395
859
GUCUUGUUCAGAACUGUCU
AGACAGUUCUGAACAAGACUU
3615


R-008397708-000W
1675
860
UCAUCUGACCAGCCGACAC
B UCAUCUGACCAGCCGACACTT B
3616


R-008397708-000W
1675
860
UCAUCUGACCAGCCGACAC
GUGUCGGCUGGUCAGAUGAUU
3617


R-008397711-000C
1845
861
CUUUGCGUGAGCAGGGUGC
B CUUUGCGUGAGCAGGGUGCTT B
3618


R-008397711-000C
1845
861
CUUUGCGUGAGCAGGGUGC
GCACCCUGCUCACGCAAAGUU
3619


R-008397714-000D
1408
862
CUGUCUUUGGACUCUCAGG
CCUGAGAGUCCAAAGACAGUU
3621


R-008397714-000D
1408
862
CUGUCUUUGGACUCUCAGG
B CUGUCUUUGGACUCUCAGGTT B 
3620


R-008397717-000E
1059
863
UACAUCAAGAAGGAGCUAA
B UACAUCAAGAAGGAGCUAATT B
3622


R-008397717-000E
1059
863
UACAUCAAGAAGGAGCUAA
UUAGCUCCUUCUUGAUGUAUU
3623


R-008397720-000L
1381
864
AGAUCCAAGUCAACGUCUU
AAGACGUUGACUUGGAUCUUU
3625


R-008397720-000L
1381
864
AGAUCCAAGUCAACGUCUU
B AGAUCCAAGUCAACGUCUUTT B 
3624


R-008397723-000M 
1386
865
CAAGUCAACGUCUUGUUCA
B CAAGUCAACGUCUUGUUCATT B 
3626


R-008397723-000M
1386
865
CAAGUCAACGUCUUGUUCA
UGAACAAGACGUUGACUUGUU
3627


R-008397726-000N
1470
866
UCCUUGGGACUCUUGUUCA
UGAACAAGAGUCCCAAGGAUU
3629


R-008397726-000N
1470
866
UCCUUGGGACUCUUGUUCA
B UCCUUGGGACUCUUGUUCATT B
3628


R-008397729-000P
1349
867
GGUGGAAUGCAAGCUUUAG
CUAAAGCUUGCAUUCCACCUU
3631


R-008397729-000P
1349
867
GGUGGAAUGCAAGCUUUAG
B GGUGGAAUGCAAGCUUUAGTT B 
3630


R-008397732-000W
1440
868
CUGCAACUAAACAGGAAGG
CCUUCCUGUUUAGUUGCAGUU
3633


R-008397732-000W
1440
868
CUGCAACUAAACAGGAAGG
B CUGCAACUAAACAGGAAGGTT B 
3632


R-008397735-000X
1364
869
UUAGGACUUCACCUGACAG
CUGUCAGGUGAAGUCCUAAUU
3635


R-008397735-000X
1364
869
UUAGGACUUCACCUGACAG
B UUAGGACUUCACCUGACAGTT B
3634


R-008397738-000Y
502
870
AGUAGCUGAUAUUGAUGGA
B AGUAGCUGAUAUUGAUGGATT B 
3636


R-008397738-000Y
502
870
AGUAGCUGAUAUUGAUGGA
UCCAUCAAUAUCAGCUACUUU
3637


R-008397741-000E
1246
871
UAUAAUGAGGACCUAUACU
AGUAUAGGUCCUCAUUAUAUU
3639


R-008397741-000E
1246
871
UAUAAUGAGGACCUAUACU
B UAUAAUGAGGACCUAUACUTT B 
3638


R-008397744-000F
3178
872
CCUGCUGUGAUACGAUGCU
AGCAUCGUAUCACAGCAGGUU
3641


R-008397744-000F
3178
872
CCUGCUGUGAUACGAUGCU
B CCUGCUGUGAUACGAUGCUTT B 
3640


R-008397747-000G
2483
873
AUGGGUGGCCACCACCCUG
B AUGGGUGGCCACCACCCUGTT B 
3642


R-008397747-000G
2483
873
AUGGGUGGCCACCACCCUG
CAGGGUGGUGGCCACCCAUUU
3643


R-008397750-000N
1417
874
GACUCUCAGGAAUCUUUCA
B GACUCUCAGGAAUCUUUCATT B 
3644


R-008397750-000N
1417
874
GACUCUCAGGAAUCUUUCA
UGAAAGAUUCCUGAGAGUCUU
3645


R-008397753-000P
1893
875
GUGCACAUCAGGAUACCCA
B GUGCACAUCAGGAUACCCATT B 
3646


R-008397753-000P
1893
875
GUGCACAUCAGGAUACCCA
UGGGUAUCCUGAUGUGCACUU
3647


R-008397756-000R
817
876
UUCCAGACACGCUAUCAUG
CAUGAUAGCGUGUCUGGAAUU
3649


R-008397756-000R
817
876
UUCCAGACACGCUAUCAUG
B UUCCAGACACGCUAUCAUGTT B
3648


R-008397759-000S
711
877
UUGCCACACGUGCAAUCCC
GGGAUUGCACGUGUGGCAAUU
3651


R-008397759-000S
711
877
UUGCCACACGUGCAAUCCC
B UUGCCACACGUGCAAUCCCTT B
3650


R-008397762-000Y
1433
878
UCAGAUGCUGCAACUAAAC
GUUUAGUUGCAGCAUCUGAUU
3653


R-008397762-000Y
1433
878
UCAGAUGCUGCAACUAAAC
B UCAGAUGCUGCAACUAAACTT B
3652


R-008397765-000Z
1362
879
CUUUAGGACUUCACCUGAC
GUCAGGUGAAGUCCUAAAGUU
3655


R-008397765-000Z
1362
879
CUUUAGGACUUCACCUGAC
B CUUUAGGACUUCACCUGACTT B
3654


R-008397768-000A
1838
880
CAUGCACCUUUGCGUGAGC
B CAUGCACCUUUGCGUGAGCTT B
3656


R-008397768-000A
1838
880
CAUGCACCUUUGCGUGAGC
GCUCACGCAAAGGUGCAUGUU
3657


R-008397771-000G
1037
881
ACAACUCUCCACAACCUUU
AAAGGUUGUGGAGAGUUGUUU
3659


R-008397771-000G
1037
881
ACAACUCUCCACAACCUUU
B ACAACUCUCCACAACCUUUTT B 
3658


R-008397774-000H
1474
882
UGGGACUCUUGUUCAGCUU
B UGGGACUCUUGUUCAGCUUTT B 
3660


R-008397774-000H
1474
882
UGGGACUCUUGUUCAGCUU
AAGCUGAACAAGAGUCCCAUU
3661


R-008397777-000J
997
883
GCUUGGUUCACCAGUGGAU
B GCUUGGUUCACCAGUGGAUTT B 
3662


R-008397777-000J
997
883
GCUUGGUUCACCAGUGGAU
AUCCACUGGUGAACCAAGCUU
3663


R-008397780-000R
931
884
UUCCCAUCAUCGUGAGGGC
B UUCCCAUCAUCGUGAGGGCTT B
3664


R-008397780-000R
931
884
UUCCCAUCAUCGUGAGGGC
GCCCUCACGAUGAUGGGAAUU
3665


R-008397783-000S
1313
885
GUCUGCUCUAGUAAUAAGC
GCUUAUUACUAGAGCAGACUU
3667


R-008397783-000S
1313
885
GUCUGCUCUAGUAAUAAGC
B GUCUGCUCUAGUAAUAAGCTT B
3666


R-008397786-000T
1487
886
CAGCUUCUGGGUUCAGAUG
B CAGCUUCUGGGUUCAGAUGTT B 
3668


R-008397786-000T
1487
886
CAGCUUCUGGGUUCAGAUG
CAUCUGAACCCAGAAGCUGUU
3669


R-008397789-000U
1673
887
CGUCAUCUGACCAGCCGAC
B CGUCAUCUGACCAGCCGACTT B
3670


R-008397789-000U
1673
887
CGUCAUCUGACCAGCCGAC
GUCGGCUGGUCAGAUGACGUU
3671


R-008397792-000A
561
888
UGUUCCCUGAGACAUUAGA
UCUAAUGUCUCAGGGAACAUU
3673


R-008397792-000A
561
888
UGUUCCCUGAGACAUUAGA
B UGUUCCCUGAGACAUUAGATT B 
3672


R-008397795-000B
1188
889
GCAACCAAGAAAGCAAGCU
B GCAACCAAGAAAGCAAGCUTT B 
3674


R-008397795-000B
1188
889
GCAACCAAGAAAGCAAGCU
AGCUUGCUUUCUUGGUUGCUU
3675


R-008397798-000C
292
890
GGAGUUGGACAUGGCCAUG
B GGAGUUGGACAUGGCCAUGTT B 
3676


R-008397798-000C
292
890
GGAGUUGGACAUGGCCAUG
CAUGGCCAUGUCCAACUCCUU
3677


R-008397801-000V
1958
891
GUCCGCAUGGAAGAAAUAG
B GUCCGCAUGGAAGAAAUAGTT B 
3678


R-008397801-000V
1958
891
GUCCGCAUGGAAGAAAUAG
CUAUUUCUUCCAUGCGGACUU
3679


R-008397804-000W
2349
892
CUGAUCUUGGACUUGAUAU
B CUGAUCUUGGACUUGAUAUTT B 
3680


R-008397804-000W
2349
892
CUGAUCUUGGACUUGAUAU
AUAUCAAGUCCAAGAUCAGUU
3681


R-008397807-000X
1460
893
AUGGAAGGUCUCCUUGGGA
UCCCAAGGAGACCUUCCAUUU
3683


R-008397807-000X
1460
893
AUGGAAGGUCUCCUUGGGA
B AUGGAAGGUCUCCUUGGGATT B 
3682


R-008397810-000D
1576
894
GAUGGUCUGCCAAGUGGGU
B GAUGGUCUGCCAAGUGGGUTT B 
3684


R-008397810-000D
1576
894
GAUGGUCUGCCAAGUGGGU
ACCCACUUGGCAGACCAUCUU
3685


R-008397813-000E
536
4
CGAGCUCAGAGGGUACGAG
B CGAGCUCAGAGGGUACGAGTT B 
3686


R-008397813-000E
536
4
CGAGCUCAGAGGGUACGAG
CUCGUACCCUCUGAGCUCGUU
3687


R-008397816-000F
690
895
ACUAUCAAGAUGAUGCAGA
UCUGCAUCAUCUUGAUAGUUU
3689


R-008397816-000F
690
895
ACUAUCAAGAUGAUGCAGA
B ACUAUCAAGAUGAUGCAGATT B
3688


R-008397819-000G
655
896
ACAGAUGCUGAAACAUGCA
B ACAGAUGCUGAAACAUGCATT B 
3690


R-008397819-000G
655
896
ACAGAUGCUGAAACAUGCA
UGCAUGUUUCAGCAUCUGUUU
3691


R-008397822-000N
2290
897
UUCAGUUGAGCUGACCAGC
GCUGGUCAGCUCAACUGAAUU
3693


R-008397822-000N
2290
897
UUCAGUUGAGCUGACCAGC
B UUCAGUUGAGCUGACCAGCTT B
3692


R-008397825-000P
1600
898
AGAGGCUCUUGUGCGUACU
B AGAGGCUCUUGUGCGUACUTT B 
3694


R-008397825-000P
1600
898
AGAGGCUCUUGUGCGUACU
AGUACGCACAAGAGCCUCUUU
3695


R-008397828-000R
2432
899
GGUGGAUAUGGCCAGGAUG
CAUCCUGGCCAUAUCCACCUU
3697


R-008397828-000R
2432
899
GGUGGAUAUGGCCAGGAUG
B GGUGGAUAUGGCCAGGAUGTT B 
3696


R-008397831-000X
710
900
CUUGCCACACGUGCAAUCC
B CUUGCCACACGUGCAAUCCTT B
3698


R-008397831-000X
710
900
CUUGCCACACGUGCAAUCC
GGAUUGCACGUGUGGCAAGUU
3699


R-008397834-000Y
1714
901
GAAUGCAGUUCGCCUUCAC
B GAAUGCAGUUCGCCUUCACTT B
3700


R-008397834-000Y
1714
901
GAAUGCAGUUCGCCUUCAC
GUGAAGGCGAACUGCAUUCUU
3701


R-008397837-000Z
2005
902
CCUAGCUCGGGAUGUUCAC
B CCUAGCUCGGGAUGUUCACTT B
3702


R-008397837-000Z
2005
902
CCUAGCUCGGGAUGUUCAC
GUGAACAUCCCGAGCUAGGUU
3703


R-008397840-000F
1728
903
UUCACUAUGGACUACCAGU
B UUCACUAUGGACUACCAGUTT B 
3704


R-008397840-000F
1728
903
UUCACUAUGGACUACCAGU
ACUGGUAGUCCAUAGUGAAUU
3705


R-008397843-000G
2482
904
GAUGGGUGGCCACCACCCU
AGGGUGGUGGCCACCCAUCUU
3707


R-008397843-000G
2482
904
GAUGGGUGGCCACCACCCU
B GAUGGGUGGCCACCACCCUTT B 
3706


R-008397846-000H
768
905
UGGUUAAUAAGGCUGCAGU
B UGGUUAAUAAGGCUGCAGUTT B 
3708


R-008397846-000H
768
905
UGGUUAAUAAGGCUGCAGU
ACUGCAGCCUUAUUAACCAUU
3709


R-008397849-000J
693
906
AUCAAGAUGAUGCAGAACU
B AUCAAGAUGAUGCAGAACUTT B 
3710


R-008397849-000J
693
906
AUCAAGAUGAUGCAGAACU
AGUUCUGCAUCAUCUUGAUUU
3711


R-008397852-000R
3179
907
CUGCUGUGAUACGAUGCUU
B CUGCUGUGAUACGAUGCUUTT B 
3712


R-008397852-000R
3179
907
CUGCUGUGAUACGAUGCUU
AAGCAUCGUAUCACAGCAGUU
3713


R-008397855-000S
1549
89
CACUUGCAAUAAUUAUAAG
CUUAUAAUUAUUGCAAGUGUU
3715


R-008397855-000S
1549
89
CACUUGCAAUAAUUAUAAG
B CACUUGCAAUAAUUAUAAGTT B 
3714


R-008397858-000T
1792
167
GGCUACUGUUGGAUUGAUU
AAUCAAUCCAACAGUAGCCUU
3717


R-008397858-000T
1792
167
GGCUACUGUUGGAUUGAUU
B GGCUACUGUUGGAUUGAUUTT B 
3716


R-008397861-000Z
2448
908
AUGCCUUGGGUAUGGACCC
GGGUCCAUACCCAAGGCAUUU
3719


R-008397861-000Z
2448
908
AUGCCUUGGGUAUGGACCC
B AUGCCUUGGGUAUGGACCCTT B
3718


R-008397864-000A
3183
909
UGUGAUACGAUGCUUCAAG
B UGUGAUACGAUGCUUCAAGTT B 
3720


R-008397864-000A
3183
909
UGUGAUACGAUGCUUCAAG
CUUGAAGCAUCGUAUCACAUU
3721


R-008397867-000B
1293
910
GAGUGCUGAAGGUGCUAUC
GAUAGCACCUUCAGCACUCUU
3723


R-008397867-000B
1293
910
GAGUGCUGAAGGUGCUAUC
B GAGUGCUGAAGGUGCUAUCTT B
3722


R-008397870-000H
544
911
GAGGGUACGAGCUGCUAUG
CAUAGCAGCUCGUACCCUCUU
3725


R-008397870-000H
544
911
GAGGGUACGAGCUGCUAUG
B GAGGGUACGAGCUGCUAUGTT B 
3724


R-008397873-000J
1676
26
CAUCUGACCAGCCGACACC
GGUGUCGGCUGGUCAGAUGUU
3727


R-008397873-000J
1676
26
CAUCUGACCAGCCGACACC
B CAUCUGACCAGCCGACACCTT B
3726


R-008397876-000K
2937
912
UUAAUUGUAAUCUGAAUAA
B UUAAUUGUAAUCUGAAUAATT B 
3728


R-008397876-000K
2937
912
UUAAUUGUAAUCUGAAUAA
UUAUUCAGAUUACAAUUAAUU
3729


R-008397879-000L
1691
913
CACCAAGAAGCAGAGAUGG
CCAUCUCUGCUUCUUGGUGUU
3731


R-008397879-000L
1691
913
CACCAAGAAGCAGAGAUGG
B CACCAAGAAGCAGAGAUGGTT B 
3730


R-008397882-000T
2195
120
UUACUUCACUCUAGGAAUG
B UUACUUCACUCUAGGAAUGTT B 
3732


R-008397882-000T
2195
120
UUACUUCACUCUAGGAAUG
CAUUCCUAGAGUGAAGUAAUU
3733


R-008397885-000U
1356
186
UGCAAGCUUUAGGACUUCA
B UGCAAGCUUUAGGACUUCATT B 
3734


R-008397885-000U
1356
186
UGCAAGCUUUAGGACUUCA
UGAAGUCCUAAAGCUUGCAUU
3735


R-008397888-000V
557
184
GCUAUGUUCCCUGAGACAU
AUGUCUCAGGGAACAUAGCUU
3737


R-008397888-000V
557
184
GCUAUGUUCCCUGAGACAU
B GCUAUGUUCCCUGAGACAUTT B 
3736


R-008397897-000D
1353
914
GAAUGCAAGCUUUAGGACU
AGUCCUAAAGCUUGCAUUCUU
3739


R-008397897-000D
1353
914
GAAUGCAAGCUUUAGGACU
B GAAUGCAAGCUUUAGGACUTT B 
3738


R-008397900-000W
1843
915
ACCUUUGCGUGAGCAGGGU
B ACCUUUGCGUGAGCAGGGUTT B 
3740


R-008397900-000W
1843
915
ACCUUUGCGUGAGCAGGGU
ACCCUGCUCACGCAAAGGUUU
3741


R-008397903-000X
1302
916
AGGUGCUAUCUGUCUGCUC
B AGGUGCUAUCUGUCUGCUCTT B
3742


R-008397903-000X
1302
916
AGGUGCUAUCUGUCUGCUC
GAGCAGACAGAUAGCACCUUU
3743


R-008397906-000Y
2130
917
UUGCUCAGGACAAGGAAGC
B UUGCUCAGGACAAGGAAGCTT B 
3744


R-008397906-000Y
2130
917
UUGCUCAGGACAAGGAAGC
GCUUCCUUGUCCUGAGCAAUU
3745


R-008397909-000Z
2165
918
GCUGAGGGAGCCACAGCUC
B GCUGAGGGAGCCACAGCUCTT B
3746


R-008397909-000Z
2165
918
GCUGAGGGAGCCACAGCUC
GAGCUGUGGCUCCCUCAGCUU
3747


R-008397912-000F
387
919
CUACCACAGCUCCUUCUCU
B CUACCACAGCUCCUUCUCUTT B 
3748


R-008397912-000F
387
919
CUACCACAGCUCCUUCUCU
AGAGAAGGAGCUGUGGUAGUU
3749


R-008397915-000G
2472
920
UGGAACAUGAGAUGGGUGG
CCACCCAUCUCAUGUUCCAUU 
3751


R-008397915-000G
2472
920
UGGAACAUGAGAUGGGUGG
B UGGAACAUGAGAUGGGUGGTT B 
3750


R-008397918-000H
857
921
GCUAUUGUACGUACCAUGC
B GCUAUUGUACGUACCAUGCTT B
3752


R-008397918-000H
857
921
GCUAUUGUACGUACCAUGC
GCAUGGUACGUACAAUAGCUU
3753


R-008397921-000P
1816
922
UCUUGCCCUUUGUCCCGCA
UGCGGGACAAAGGGCAAGAUU
3755


R-008397921-000P
1816
922
UCUUGCCCUUUGUCCCGCA
B UCUUGCCCUUUGUCCCGCATT B 
3754


R-008397924-000R
1561
923
UUAUAAGAACAAGAUGAUG
CAUCAUCUUGUUCUUAUAAUU
3757


R-008397924-000R
1561
923
UUAUAAGAACAAGAUGAUG
B UUAUAAGAACAAGAUGAUGTT B 
3756


R-008397927-000S
811
924
GGAAGCUUCCAGACACGCU
B GGAAGCUUCCAGACACGCUTT B 
3758


R-008397927-000S
811
924
GGAAGCUUCCAGACACGCU
AGCGUGUCUGGAAGCUUCCUU
3759


R-008397930-000Y
1327
925
UAAGCCGGCUAUUGUAGAA
B UAAGCCGGCUAUUGUAGAATT B
3760


R-008397930-000Y
1327
925
UAAGCCGGCUAUUGUAGAA
UUCUACAAUAGCCGGCUUAUU
3761


R-008397933-000Z
757
926
GGACCAGGUGGUGGUUAAU
B GGACCAGGUGGUGGUUAAUTT B 
3762


R-008397933-000Z
757
926
GGACCAGGUGGUGGUUAAU
AUUAACCACCACCUGGUCCUU
3763


R-008397936-000A
507
927
CUGAUAUUGAUGGACAGUA
B CUGAUAUUGAUGGACAGUATT B
3764


R-008397936-000A
507
927
CUGAUAUUGAUGGACAGUA
UACUGUCCAUCAAUAUCAGUU
3765


R-008397939-000B
3092
928
UGGGUAGGGUAAAUCAGUA
B UGGGUAGGGUAAAUCAGUATT B 
3766


R-008397939-000B
3092
928
UGGGUAGGGUAAAUCAGUA
UACUGAUUUACCCUACCCAUU
3767


R-008397942-000H
2359
929
ACUUGAUAUUGGUGCCCAG
B ACUUGAUAUUGGUGCCCAGTT B 
3768


R-008397942-000H
2359
929
ACUUGAUAUUGGUGCCCAG
CUGGGCACCAAUAUCAAGUUU
3769


R-008397945-000J
1753
930
UAAGCUCUUACACCCACCA
B UAAGCUCUUACACCCACCATT B 
3770


R-008397945-000J
1753
930
UAAGCUCUUACACCCACCA
UGGUGGGUGUAAGAGCUUAUU
3771


R-008397948-000K
273
931
CUACUCAAGCUGAUUUGAU
AUCAAAUCAGCUUGAGUAGUU
3773


R-008397948-000K
273
931
CUACUCAAGCUGAUUUGAU
B CUACUCAAGCUGAUUUGAUTT B 
3772


R-008397951-000S
1859
932
GGUGCCAUUCCACGACUAG
CUAGUCGUGGAAUGGCACCUU
3775


R-008397951-000S
1859
932
GGUGCCAUUCCACGACUAG
B GGUGCCAUUCCACGACUAGTT B 
3774


R-008397954-000T
296
933
UUGGACAUGGCCAUGGAAC
B UUGGACAUGGCCAUGGAACTT B
3776


R-008397954-000T
296
933
UUGGACAUGGCCAUGGAAC
GUUCCAUGGCCAUGUCCAAUU
3777


R-008397957-000U
615
934
CUGCUCAUCCCACUAAUGU
ACAUUAGUGGGAUGAGCAGUU
3779


R-008397957-000U
615
934
CUGCUCAUCCCACUAAUGU
B CUGCUCAUCCCACUAAUGUTT B 
3778


R-008397960-000A
301
935
CAUGGCCAUGGAACCAGAC
GUCUGGUUCCAUGGCCAUGUU
3781


R-008397960-000A
301
935
CAUGGCCAUGGAACCAGAC
B CAUGGCCAUGGAACCAGACTT B
3780


R-008397963-000B
1184
936
UAUGGCAACCAAGAAAGCA
B UAUGGCAACCAAGAAAGCATT B 
3782


R-008397963-000B
1184
936
UAUGGCAACCAAGAAAGCA
UGCUUUCUUGGUUGCCAUAUU
3783


R-008397966-000C
1006
937
ACCAGUGGAUUCUGUGUUG
B ACCAGUGGAUUCUGUGUUGTT B 
3784


R-008397966-000C
1006
937
ACCAGUGGAUUCUGUGUUG
CAACACAGAAUCCACUGGUUU
3785


R-008397969-000D
2189
938
ACAGAGUUACUUCACUCUA
B ACAGAGUUACUUCACUCUATT B 
3786


R-008397969-000D
2189
938
ACAGAGUUACUUCACUCUA
UAGAGUGAAGUAACUCUGUUU
3787


R-008397972-000K
1365
939
UAGGACUUCACCUGACAGA
UCUGUCAGGUGAAGUCCUAUU
3789


R-008397972-000K
1365
939
UAGGACUUCACCUGACAGA
B UAGGACUUCACCUGACAGATT B
3788


R-008397975-000L
2442
940
GCCAGGAUGCCUUGGGUAU
B GCCAGGAUGCCUUGGGUAUTT B 
3790


R-008397975-000L
2442
940
GCCAGGAUGCCUUGGGUAU
AUACCCAAGGCAUCCUGGCUU
3791


R-008397978-000M
1249
941
AAUGAGGACCUAUACUUAC
B AAUGAGGACCUAUACUUACTT B
3792


R-008397978-000M
1249
941
AAUGAGGACCUAUACUUAC
GUAAGUAUAGGUCCUCAUUUU
3793


R-008397981-000U
1144
942
AUUCUUGGCUAUUACGACA
B AUUCUUGGCUAUUACGACATT B 
3794


R-008397981-000U
1144
942
AUUCUUGGCUAUUACGACA
UGUCGUAAUAGCCAAGAAUUU
3795


R-008397984-000V
2075
943
CUUUAUUCUCCCAUUGAAA
B CUUUAUUCUCCCAUUGAAATT B 
3796


R-008397984-000V
2075
943
CUUUAUUCUCCCAUUGAAA
UUUCAAUGGGAGAAUAAAGUU
3797


R-008397987-000W
759
94
ACCAGGUGGUGGUUAAUAA
B ACCAGGUGGUGGUUAAUAATT B
3798


R-008397987-000W
759
94
ACCAGGUGGUGGUUAAUAA
UUAUUAACCACCACCUGGUUU
3799


R-008397990-000C
1545
44
ACCUCACUUGCAAUAAUUA
B ACCUCACUUGCAAUAAUUATT B 
3800


R-008397990-000C
1545
44
ACCUCACUUGCAAUAAUUA
UAAUUAUUGCAAGUGAGGUUU
3801


R-008397993-000D
504
944
UAGCUGAUAUUGAUGGACA
UGUCCAUCAAUAUCAGCUAUU
3803


R-008397993-000D
504
944
UAGCUGAUAUUGAUGGACA
B UAGCUGAUAUUGAUGGACATT B 
3802


R-008397996-000E
1405
945
GAACUGUCUUUGGACUCUC
B GAACUGUCUUUGGACUCUCTT B
3804


R-008397996-000E
1405
945
GAACUGUCUUUGGACUCUC
GAGAGUCCAAAGACAGUUCUU
3805


R-008397999-000F
333
946
UUAGUCACUGGCAGCAACA
UGUUGCUGCCAGUGACUAAUU
3807


R-008397999-000F
333
946
UUAGUCACUGGCAGCAACA
B UUAGUCACUGGCAGCAACATT B 
3806


R-008398002-000V
1032
947
CCAUUACAACUCUCCACAA
B CCAUUACAACUCUCCACAATT B 
3808


R-008398002-000V
1032
947
CCAUUACAACUCUCCACAA
UUGUGGAGAGUUGUAAUGGUU
3809


R-008398005-000W
1748
948
GUGGUUAAGCUCUUACACC
B GUGGUUAAGCUCUUACACCTT B
3810


R-008398005-000W
1748
948
GUGGUUAAGCUCUUACACC
GGUGUAAGAGCUUAACCACUU
3811


R-008398008-000X
283
949
UGAUUUGAUGGAGUUGGAC
GUCCAACUCCAUCAAAUCAUU
3813


R-008398008-000X
283
949
UGAUUUGAUGGAGUUGGAC
B UGAUUUGAUGGAGUUGGACTT B
3812


R-008398011-000D
1700
950
GCAGAGAUGGCCCAGAAUG
B GCAGAGAUGGCCCAGAAUGTT B 
3814


R-008398011-000D
1700
950
GCAGAGAUGGCCCAGAAUG
CAUUCUGGGCCAUCUCUGCUU
3815


R-008398014-000E
1445
951
ACUAAACAGGAAGGGAUGG
B ACUAAACAGGAAGGGAUGGTT B 
3816


R-008398014-000E
1445
951
ACUAAACAGGAAGGGAUGG
CCAUCCCUUCCUGUUUAGUUU
3817


R-008398017-000F
1133
952
ACAAAUGUUAAAUUCUUGG
CCAAGAAUUUAACAUUUGUUU
3819


R-008398017-000F
1133
952
ACAAAUGUUAAAUUCUUGG
B ACAAAUGUUAAAUUCUUGGTT B
3818


R-008398020-000M
527
953
GCAAUGACUCGAGCUCAGA
UCUGAGCUCGAGUCAUUGCUU
3821


R-008398020-000M
527
953
GCAAUGACUCGAGCUCAGA
B GCAAUGACUCGAGCUCAGATT B 
3820


R-008398023-000N
2010
954
CUCGGGAUGUUCACAACCG
CGGUUGUGAACAUCCCGAGUU
3823


R-008398023-000N
2010
954
CUCGGGAUGUUCACAACCG
B CUCGGGAUGUUCACAACCGTT B 
3822


R-008398026-000P
851
955
GUGUCUGCUAUUGUACGUA
UACGUACAAUAGCAGACACUU
3825


R-008398026-000P
851
955
GUGUCUGCUAUUGUACGUA
B GUGUCUGCUAUUGUACGUATT B
3824


R-008398029-000R
436
956
UGUGGAUACCUCCCAAGUC
B UGUGGAUACCUCCCAAGUCTT B
3826


R-008398029-000R
436
956
UGUGGAUACCUCCCAAGUC
GACUUGGGAGGUAUCCACAUU
3827


R-008398032-000X
1601
2
GAGGCUCUUGUGCGUACUG
B GAGGCUCUUGUGCGUACUGTT B 
3828


R-008398032-000X
1601
2
GAGGCUCUUGUGCGUACUG
CAGUACGCACAAGAGCCUCUU
3829


R-008398035-000Y
2446
957
GGAUGCCUUGGGUAUGGAC
B GGAUGCCUUGGGUAUGGACTT B
3830


R-008398035-000Y
2446
957
GGAUGCCUUGGGUAUGGAC
GUCCAUACCCAAGGCAUCCUU
3831


R-008398038-000Z
1142
958
AAAUUCUUGGCUAUUACGA
B AAAUUCUUGGCUAUUACGATT B
3832


R-008398038-000Z
1142
958
AAAUUCUUGGCUAUUACGA
UCGUAAUAGCCAAGAAUUUUU
3833


R-008398041-000F
549
959
UACGAGCUGCUAUGUUCCC
B UACGAGCUGCUAUGUUCCCTT B
3834


R-008398041-000F
549
959
UACGAGCUGCUAUGUUCCC
GGGAACAUAGCAGCUCGUAUU
3835


R-008398044-000G
1083
960
CAGUGCGUUUAGCUGGUGG
CCACCAGCUAAACGCACUGUU
3837


R-008398044-000G
1083
960
CAGUGCGUUUAGCUGGUGG
B CAGUGCGUUUAGCUGGUGGTT B
3836


R-008398047-000H
695
961
CAAGAUGAUGCAGAACUUG
CAAGUUCUGCAUCAUCUUGUU
3839


R-008398047-000H
695
961
CAAGAUGAUGCAGAACUUG
B CAAGAUGAUGCAGAACUUGTT B
3838


R-008398050-000P
885
962
AUGAUGUAGAAACAGCUCG
B AUGAUGUAGAAACAGCUCGTT B
3840


R-008398050-000P
885
962
AUGAUGUAGAAACAGCUCG
CGAGCUGUUUCUACAUCAUUU
3841


R-008398056-000S
2067
963
UGCAGCUGCUUUAUUCUCC
B UGCAGCUGCUUUAUUCUCCTT B
3842


R-008398056-000S
2067
963
UGCAGCUGCUUUAUUCUCC
GGAGAAUAAAGCAGCUGCAUU
3843


R-008398059-000T
390
964
CCACAGCUCCUUCUCUGAG
CUCAGAGAAGGAGCUGUGGUU
3845


R-008398059-000T
390
964
CCACAGCUCCUUCUCUGAG
B CCACAGCUCCUUCUCUGAGTT B 
3844


R-008398062-000Z
1719
965
CAGUUCGCCUUCACUAUGG
B CAGUUCGCCUUCACUAUGGTT B
3846


R-008398062-000Z
1719
965
CAGUUCGCCUUCACUAUGG
CCAUAGUGAAGGCGAACUGUU
3847


R-008398065-000A
813
966
AAGCUUCCAGACACGCUAU
AUAGCGUGUCUGGAAGCUUUU
3849


R-008398065-000A
813
966
AAGCUUCCAGACACGCUAU
B AAGCUUCCAGACACGCUAUTT B 
3848


R-008398068-000B
2289
967
UUUCAGUUGAGCUGACCAG
B UUUCAGUUGAGCUGACCAGTT B 
3850


R-008398068-000B
2289
967
UUUCAGUUGAGCUGACCAG
CUGGUCAGCUCAACUGAAAUU
3851


R-008398071-000H
377
968
UCUGGUGCCACUACCACAG
B UCUGGUGCCACUACCACAGTT B 
3852


R-008398071-000H
377
968
UCUGGUGCCACUACCACAG
CUGUGGUAGUGGCACCAGAUU
3853


R-008398074-000J
826
969
CGCUAUCAUGCGUUCUCCU
AGGAGAACGCAUGAUAGCGUU
3855


R-008398074-000J
826
969
CGCUAUCAUGCGUUCUCCU
B CGCUAUCAUGCGUUCUCCUTT B 
3854


R-008398077-000K
1634
970
GACAGGGAAGACAUCACUG
CAGUGAUGUCUUCCCUGUCUU
3857


R-008398077-000K
1634
970
GACAGGGAAGACAUCACUG
B GACAGGGAAGACAUCACUGTT B 
3856


R-008398080-000S
1208
971
AUCAUACUGGCUAGUGGUG
B AUCAUACUGGCUAGUGGUGTT B 
3858


R-008398080-000S
1208
971
AUCAUACUGGCUAGUGGUG
CACCACUAGCCAGUAUGAUUU
3859


R-008398083-000T
1628
972
GCUGGUGACAGGGAAGACA
UGUCUUCCCUGUCACCAGCUU
3861


R-008398083-000T
1628
972
GCUGGUGACAGGGAAGACA
B GCUGGUGACAGGGAAGACATTB
3860


R-008398086-000U
2003
973
AUCCUAGCUCGGGAUGUUC
GAACAUCCCGAGCUAGGAUUU
3863


R-008398086-000U
2003
973
AUCCUAGCUCGGGAUGUUC
B AUCCUAGCUCGGGAUGUUCTT B
3862


R-008398089-000V
452
974
GUCCUGUAUGAGUGGGAAC
B GUCCUGUAUGAGUGGGAACTT B
3864


R-008398089-000V
452
974
GUCCUGUAUGAGUGGGAAC
GUUCCCACUCAUACAGGACUU
3865


R-008398092-000B
2543
175
GCCCAGGACCUCAUGGAUG
CAUCCAUGAGGUCCUGGGCUU
3867


R-008398092-000B
2543
175
GCCCAGGACCUCAUGGAUG
B GCCCAGGACCUCAUGGAUGTT B
3866


R-008398095-000C
3081
975
UGGGAUAUGUAUGGGUAGG
CCUACCCAUACAUAUCCCAUU
3869


R-008398095-000C
3081
975
UGGGAUAUGUAUGGGUAGG
B UGGGAUAUGUAUGGGUAGGTT B 
3868


R-008398098-000D
2354
976
CUUGGACUUGAUAUUGGUG
B CUUGGACUUGAUAUUGGUGTT B 
3870


R-008398098-000D
2354
976
CUUGGACUUGAUAUUGGUG
CACCAAUAUCAAGUCCAAGUU
3871


R-008398101-000W
1822
977
CCUUUGUCCCGCAAAUCAU
B CCUUUGUCCCGCAAAUCAUTT B
3872


R-008398101-000W
1822
977
CCUUUGUCCCGCAAAUCAU
AUGAUUUGCGGGACAAAGGUU
3873


R-008398107-000Y
1299
978
UGAAGGUGCUAUCUGUCUG
CAGACAGAUAGCACCUUCAUU
3875


R-008398107-000Y
1299
978
UGAAGGUGCUAUCUGUCUG
B UGAAGGUGCUAUCUGUCUGTT B 
3874


R-008398110-000E
486
979
CCUUCACUCAAGAACAAGU
B CCUUCACUCAAGAACAAGUTT B
3876


R-008398110-000E
486
979
CCUUCACUCAAGAACAAGU
ACUUGUUCUUGAGUGAAGGUU
3877


R-008398116-000G
1463
980
GAAGGUCUCCUUGGGACUC
B GAAGGUCUCCUUGGGACUCTT B
3878


R-008398116-000G
1463
980
GAAGGUCUCCUUGGGACUC
GAGUCCCAAGGAGACCUUCUU
3879


R-008398119-000H
2280
981
AGAAACGGCUUUCAGUUGA
B AGAAACGGCUUUCAGUUGATT B 
3880


R-008398119-000H
2280
981
AGAAACGGCUUUCAGUUGA
UCAACUGAAAGCCGUUUCUUU
3881


R-008398122-000P
1907
982
ACCCAGCGCCGUACGUCCA
B ACCCAGCGCCGUACGUCCATT B 
3882


R-008398122-000P
1907
982
ACCCAGCGCCGUACGUCCA
UGGACGUACGGCGCUGGGUUU
3883


R-008398125-000R
923
983
CAUAACCUUUCCCAUCAUC
B CAUAACCUUUCCCAUCAUCTT B 
3884


R-008398125-000R
923
983
CAUAACCUUUCCCAUCAUC
GAUGAUGGGAAAGGUUAUGUU
3885


R-008398128-000S
1979
984
GAAGGUUGUACCGGAGCCC
B GAAGGUUGUACCGGAGCCCTT B
3886


R-008398128-000S
1979
984
GAAGGUUGUACCGGAGCCC
GGGCUCCGGUACAACCUUCUU
3887


R-008398131-000Y
1827
985
GUCCCGCAAAUCAUGCACC
B GUCCCGCAAAUCAUGCACCTT B
3888


R-008398131-000Y
1827
985
GUCCCGCAAAUCAUGCACC
GGUGCAUGAUUUGCGGGACUU
3889


R-008398134-000Z
1201
986
CAAGCUCAUCAUACUGGCU
AGCCAGUAUGAUGAGCUUGUU
3891


R-008398134-000Z
1201
986
CAAGCUCAUCAUACUGGCU
B CAAGCUCAUCAUACUGGCUTT B 
3890


R-008398137-000A
1913
987
CGCCGUACGUCCAUGGGUG
B CGCCGUACGUCCAUGGGUGTT B 
3892


R-008398137-000A
1913
987
CGCCGUACGUCCAUGGGUG
CACCCAUGGACGUACGGCGUU
3893


R-008398140-000G
2191
988
AGAGUUACUUCACUCUAGG
CCUAGAGUGAAGUAACUCUUU
3895


R-008398140-000G
2191
988
AGAGUUACUUCACUCUAGG
B AGAGUUACUUCACUCUAGGTT B 
3894


R-008398143-000H
295
989
GUUGGACAUGGCCAUGGAA
UUCCAUGGCCAUGUCCAACUU
3897


R-008398143-000H
295
989
GUUGGACAUGGCCAUGGAA
B GUUGGACAUGGCCAUGGAATT B 
3896


R-008398146-000J
1149
990
UGGCUAUUACGACAGACUG
B UGGCUAUUACGACAGACUGTT B 
3898


R-008398146-000J
1149
990
UGGCUAUUACGACAGACUG
CAGUCUGUCGUAAUAGCCAUU
3899


R-008398149-000K
533
991
ACUCGAGCUCAGAGGGUAC
B ACUCGAGCUCAGAGGGUACTT B
3900


R-008398149-000K
533
991
ACUCGAGCUCAGAGGGUAC
GUACCCUCUGAGCUCGAGUUU
3901


R-008398152-000S
604
992
ACAGUUUGAUGCUGCUCAU
B ACAGUUUGAUGCUGCUCAUTT B 
3902


R-008398152-000S
604
992
ACAGUUUGAUGCUGCUCAU
AUGAGCAGCAUCAAACUGUUU
3903


R-008398155-000T
766
993
GGUGGUUAAUAAGGCUGCA
B GGUGGUUAAUAAGGCUGCATT B 
3904


R-008398155-000T
766
993
GGUGGUUAAUAAGGCUGCA
UGCAGCCUUAUUAACCACCUU
3905


R-008398158-000U
1823
994
CUUUGUCCCGCAAAUCAUG
B CUUUGUCCCGCAAAUCAUGTT B 
3906


R-008398158-000U
1823
994
CUUUGUCCCGCAAAUCAUG
CAUGAUUUGCGGGACAAAGUU
3907


R-008398161-000A
2048
995
AAUACCAUUCCAUUGUUUG
CAAACAAUGGAAUGGUAUUUU
3909


R-008398161-000A
2048
995
AAUACCAUUCCAUUGUUUG
B AAUACCAUUCCAUUGUUUGTT B 
3908


R-008398164-000B
714
996
CCACACGUGCAAUCCCUGA
B CCACACGUGCAAUCCCUGATT B 
3910


R-008398164-000B
714
996
CCACACGUGCAAUCCCUGA
UCAGGGAUUGCACGUGUGGUU
3911


R-008398167-000C
2439
997
AUGGCCAGGAUGCCUUGGG
CCCAAGGCAUCCUGGCCAUUU
3913


R-008398167-000C
2439
997
AUGGCCAGGAUGCCUUGGG
B AUGGCCAGGAUGCCUUGGGTT B 
3912


R-008398170-000J
1903
998
GGAUACCCAGCGCCGUACG
B GGAUACCCAGCGCCGUACGTT B 
3914


R-008398170-000J
1903
998
GGAUACCCAGCGCCGUACG
CGUACGGCGCUGGGUAUCCUU
3915


R-008398173-000K
2395
999
UCGCCAGGAUGAUCCUAGC
GCUAGGAUCAUCCUGGCGAUU
3917


R-008398173-000K
2395
999
UCGCCAGGAUGAUCCUAGC
B UCGCCAGGAUGAUCCUAGCTT B
3916


R-008398176-000L
789
1000
UGGUCCAUCAGCUUUCUAA
UUAGAAAGCUGAUGGACCAUU
3919


R-008398176-000L
789
1000
UGGUCCAUCAGCUUUCUAA
B UGGUCCAUCAGCUUUCUAATT B 
3918


R-008398179-000M
3085
1001
AUAUGUAUGGGUAGGGUAA
UUACCCUACCCAUACAUAUUU
3921


R-008398179-000M
3085
1001
AUAUGUAUGGGUAGGGUAA
B AUAUGUAUGGGUAGGGUAATT B 
3920


R-008398182-000U
1710
1002
CCCAGAAUGCAGUUCGCCU
B CCCAGAAUGCAGUUCGCCUTT B 
3922


R-008398182-000U
1710
1002
CCCAGAAUGCAGUUCGCCU
AGGCGAACUGCAUUCUGGGUU
3923


R-008398185-000V
1336
1003
UAUUGUAGAAGCUGGUGGA
B UAUUGUAGAAGCUGGUGGATT B 
3924


R-008398185-000V
1336
1003
UAUUGUAGAAGCUGGUGGA
UCCACCAGCUUCUACAAUAUU
3925


R-008398188-000W
3089
1004
GUAUGGGUAGGGUAAAUCA
UGAUUUACCCUACCCAUACUU
3927


R-008398188-000W
3089
1004
GUAUGGGUAGGGUAAAUCA
B GUAUGGGUAGGGUAAAUCATT B 
3926


R-008398191-000C
2351
1005
GAUCUUGGACUUGAUAUUG
B GAUCUUGGACUUGAUAUUGTT B
3928


R-008398191-000C
2351
1005
GAUCUUGGACUUGAUAUUG
CAAUAUCAAGUCCAAGAUCUU
3929


R-008398194-000D
716
1006
ACACGUGCAAUCCCUGAAC
B ACACGUGCAAUCCCUGAACTT B
3930


R-008398194-000D
716
1006
ACACGUGCAAUCCCUGAAC
GUUCAGGGAUUGCACGUGUUU
3931


R-008398197-000E
1911
1007
AGCGCCGUACGUCCAUGGG
B AGCGCCGUACGUCCAUGGGTT B 
3932


R-008398197-000E
1911
1007
AGCGCCGUACGUCCAUGGG
CCCAUGGACGUACGGCGCUUU
3933


R-008398200-000X
1985
1008
UGUACCGGAGCCCUUCACA
UGUGAAGGGCUCCGGUACAUU
3935


R-008398200-000X
1985
1008
UGUACCGGAGCCCUUCACA
B UGUACCGGAGCCCUUCACATT B 
3934


R-008398203-000Y
2516
1009
GUUGAUGGGCUGCCAGAUC
B GUUGAUGGGCUGCCAGAUCTT B
3936


R-008398203-000Y
2516
1009
GUUGAUGGGCUGCCAGAUC
GAUCUGGCAGCCCAUCAACUU
3937


R-008398206-000Z
1762
1010
ACACCCACCAUCCCACUGG
CCAGUGGGAUGGUGGGUGUUU
3939


R-008398206-000Z
1762
1010
ACACCCACCAUCCCACUGG
B ACACCCACCAUCCCACUGGTT B
3938


R-008398209-000A
1156
1011
UACGACAGACUGCCUUCAA
B UACGACAGACUGCCUUCAATT B
3940


R-008398209-000A
1156
1011
UACGACAGACUGCCUUCAA
UUGAAGGCAGUCUGUCGUAUU
3941


R-008398212-000G
1887
1012
UUGUUCGUGCACAUCAGGA
B UUGUUCGUGCACAUCAGGATT B 
3942


R-008398212-000G
1887
1012
UUGUUCGUGCACAUCAGGA
UCCUGAUGUGCACGAACAAUU
3943


R-008398215-000H
1833
1013
CAAAUCAUGCACCUUUGCG
CGCAAAGGUGCAUGAUUUGUU
3945


R-008398215-000H
1833
1013
CAAAUCAUGCACCUUUGCG
B CAAAUCAUGCACCUUUGCGTT B 
3944


R-008398218-000J
967
1014
GUCUGGAGGCAUUCCUGCC
GGCAGGAAUGCCUCCAGACUU
3947


R-008398218-000J
967
1014
GUCUGGAGGCAUUCCUGCC
B GUCUGGAGGCAUUCCUGCCTT B
3946


R-008398221-000R
1730
1015
CACUAUGGACUACCAGUUG
CAACUGGUAGUCCAUAGUGUU
3949


R-008398221-000R
1730
1015
CACUAUGGACUACCAGUUG
B CACUAUGGACUACCAGUUGTT B 
3948


R-008398224-000S
829
1016
UAUCAUGCGUUCUCCUCAG
CUGAGGAGAACGCAUGAUAUU
3951


R-008398224-000S
829
1016
UAUCAUGCGUUCUCCUCAG
B UAUCAUGCGUUCUCCUCAGTT B 
3950


R-008398227-000T
890
1017
GUAGAAACAGCUCGUUGUA
B GUAGAAACAGCUCGUUGUATT B 
3952


R-008398227-000T
890
1017
GUAGAAACAGCUCGUUGUA
UACAACGAGCUGUUUCUACUU
3953


R-008398230-000Z
2181
1018
CUCCUCUGACAGAGUUACU
AGUAACUCUGUCAGAGGAGUU
3955


R-008398230-000Z
2181
1018
CUCCUCUGACAGAGUUACU
B CUCCUCUGACAGAGUUACUTT B 
3954


R-008398233-000A
2131
1019
UGCUCAGGACAAGGAAGCU
B UGCUCAGGACAAGGAAGCUTT B 
3956


R-008398233-000A
2131
1019
UGCUCAGGACAAGGAAGCU
AGCUUCCUUGUCCUGAGCAUU
3957


R-008398236-000B
1586
1020
CAAGUGGGUGGUAUAGAGG
B CAAGUGGGUGGUAUAGAGGTT B 
3958


R-008398236-000B
1586
1020
CAAGUGGGUGGUAUAGAGG
C CUCUAUACCACCCACUUGUU 
3959


R-008398239-000C
765
1021
UGGUGGUUAAUAAGGCUGC
B UGGUGGUUAAUAAGGCUGCTT B
3960


R-008398239-000C
765
1021
UGGUGGUUAAUAAGGCUGC
GCAGCCUUAUUAACCACCAUU
3961


R-008398242-000J
1369
1022
ACUUCACCUGACAGAUCCA
B ACUUCACCUGACAGAUCCATT B 
3962


R-008398242-000J
1369
1022
ACUUCACCUGACAGAUCCA
UGGAUCUGUCAGGUGAAGUUU
3963


R-008398245-000K
1724
1023
CGCCUUCACUAUGGACUAC
GUAGUCCAUAGUGAAGGCGUU
3965


R-008398245-000K
1724
1023
CGCCUUCACUAUGGACUAC
B CGCCUUCACUAUGGACUACTT B
3964


R-008398248-000L
834
1024
UGCGUUCUCCUCAGAUGGU
ACCAUCUGAGGAGAACGCAUU
3967


R-008398248-000L
834
1024
UGCGUUCUCCUCAGAUGGU
B UGCGUUCUCCUCAGAUGGUTT B 
3966


R-008398251-000T
1983
1025
GUUGUACCGGAGCCCUUCA
B GUUGUACCGGAGCCCUUCATT B
3968


R-008398251-000T
1983
1025
GUUGUACCGGAGCCCUUCA
UGAAGGGCUCCGGUACAACUU
3969


R-008398254-000U
1688
1026
CGACACCAAGAAGCAGAGA
B CGACACCAAGAAGCAGAGATT B 
3970


R-008398254-000U
1688
1026
CGACACCAAGAAGCAGAGA
UCUCUGCUUCUUGGUGUCGUU
3971


R-008398257-000V
1004
1027
UCACCAGUGGAUUCUGUGU
B UCACCAGUGGAUUCUGUGUTT B 
3972


R-008398257-000V
1004
1027
UCACCAGUGGAUUCUGUGU
ACACAGAAUCCACUGGUGAUU
3973


R-008398260-000B
1631
1028
GGUGACAGGGAAGACAUCA
UGAUGUCUUCCCUGUCACCUU
3975


R-008398260-000B
1631
1028
GGUGACAGGGAAGACAUCA
B GGUGACAGGGAAGACAUCATT B
3974


R-008398263-000C
1319
1029
UCUAGUAAUAAGCCGGCUA
UAGCCGGCUUAUUACUAGAUU
3977


R-008398263-000C
1319
1029
UCUAGUAAUAAGCCGGCUA
B UCUAGUAAUAAGCCGGCUATT B 
3976


R-008398266-000D
767
1030
GUGGUUAAUAAGGCUGCAG
B GUGGUUAAUAAGGCUGCAGTT B 
3978


R-008398266-000D
767
1030
GUGGUUAAUAAGGCUGCAG
CUGCAGCCUUAUUAACCACUU
3979


R-008398269-000E
841
1031
UCCUCAGAUGGUGUCUGCU
AGCAGACACCAUCUGAGGAUU
3981


R-008398269-000E
841
1031
UCCUCAGAUGGUGUCUGCU
B UCCUCAGAUGGUGUCUGCUTT B 
3980


R-008398272-000L
516
1032
AUGGACAGUAUGCAAUGAC
B AUGGACAGUAUGCAAUGACTT B
3982


R-008398272-000L
516
1032
AUGGACAGUAUGCAAUGAC
GUCAUUGCAUACUGUCCAUUU
3983


R-008398275-000M
1848
1033
UGCGUGAGCAGGGUGCCAU
AUGGCACCCUGCUCACGCAUU
3985


R-008398275-000M
1848
1033
UGCGUGAGCAGGGUGCCAU
B UGCGUGAGCAGGGUGCCAUTT B 
3984


R-008398278-000N
2202
1034
ACUCUAGGAAUGAAGGUGU
B ACUCUAGGAAUGAAGGUGUTT B 
3986


R-008398278-000N
2202
1034
ACUCUAGGAAUGAAGGUGU
ACACCUUCAUUCCUAGAGUUU
3987


R-008398281-000V
571
1035
GACAUUAGAUGAGGGCAUG
B GACAUUAGAUGAGGGCAUGTT B 
3988


R-008398281-000V
571
1035
GACAUUAGAUGAGGGCAUG
CAUGCCCUCAUCUAAUGUCUU
3989


R-008398284-000W
1629
1036
CUGGUGACAGGGAAGACAU
B CUGGUGACAGGGAAGACAUTT B 
3990


R-008398284-000W
1629
1036
CUGGUGACAGGGAAGACAU
AUGUCUUCCCUGUCACCAGUU
3991


R-008398287-000X
1806
1037
UGAUUCGAAAUCUUGCCCU
B UGAUUCGAAAUCUUGCCCUTT B 
3992


R-008398287-000X
1806
1037
UGAUUCGAAAUCUUGCCCU
AGGGCAAGAUUUCGAAUCAUU
3993


R-008398290-000D
1756
1038
GCUCUUACACCCACCAUCC
B GCUCUUACACCCACCAUCCTT B
3994


R-008398290-000D
1756
1038
GCUCUUACACCCACCAUCC
GGAUGGUGGGUGUAAGAGCUU
3995


R-008398293-000E
1619
1039
GUCCUUCGGGCUGGUGACA
UGUCACCAGCCCGAAGGACUU
3997


R-008398293-000E
1619
1039
GUCCUUCGGGCUGGUGACA
B GUCCUUCGGGCUGGUGACATT B 
3996


R-008398296-000F
1610
1040
GUGCGUACUGUCCUUCGGG
B GUGCGUACUGUCCUUCGGGTT B 
3998


R-008398296-000F
1610
1040
GUGCGUACUGUCCUUCGGG
CCCGAAGGACAGUACGCACUU
3999


R-008398299-000G
2500
1041
UGGUGCUGACUAUCCAGUU
B UGGUGCUGACUAUCCAGUUTT B
4000


R-008398299-000G
2500
1041
UGGUGCUGACUAUCCAGUU
AACUGGAUAGUCAGCACCAUU
4001


R-008398302-000Z
2156
1042
GCUAUUGAAGCUGAGGGAG
B GCUAUUGAAGCUGAGGGAGTT B
4002


R-008398302-000Z
2156
1042
GCUAUUGAAGCUGAGGGAG
CUCCCUCAGCUUCAAUAGCUU
4003


R-008398305-000A
1189
1043
CAACCAAGAAAGCAAGCUC
GAGCUUGCUUUCUUGGUUGUU
4005


R-008398305-000A
1189
1043
CAACCAAGAAAGCAAGCUC
B CAACCAAGAAAGCAAGCUCTT B
4004


R-008398308-000B
2066
1044
GUGCAGCUGCUUUAUUCUC
GAGAAUAAAGCAGCUGCACUU
4007


R-008398308-000B
2066
1044
GUGCAGCUGCUUUAUUCUC
B GUGCAGCUGCUUUAUUCUCTT B
4006


R-008398311-000H
1307
1045
CUAUCUGUCUGCUCUAGUA
UACUAGAGCAGACAGAUAGUU
4009


R-008398311-000H
1307
1045
CUAUCUGUCUGCUCUAGUA
B CUAUCUGUCUGCUCUAGUATT B
4008


R-008398314-000J
1448
1046
AAACAGGAAGGGAUGGAAG
CUUCCAUCCCUUCCUGUUUUU
4011


R-008398314-000J
1448
1046
AAACAGGAAGGGAUGGAAG
B AAACAGGAAGGGAUGGAAGTT B
4010


R-008398317-000K
1213
1047
ACUGGCUAGUGGUGGACCC
B ACUGGCUAGUGGUGGACCCTT B
4012


R-008398317-000K
1213
1047
ACUGGCUAGUGGUGGACCC
GGGUCCACCACUAGCCAGUUU
4013


R-008398320-000S
2119
1048
CCUCUGUGAACUUGCUCAG
B CCUCUGUGAACUUGCUCAGTT B
4014


R-008398320-000S
2119
1048
CCUCUGUGAACUUGCUCAG
CUGAGCAAGUUCACAGAGGUU
4015


R-008398323-000T
2546
72
CAGGACCUCAUGGAUGGGC
B CAGGACCUCAUGGAUGGGCTT B
4016


R-008398323-000T
2546
72
CAGGACCUCAUGGAUGGGC
GCCCAUCCAUGAGGUCCUGUU
4017


R-008398326-000U
889
1049
UGUAGAAACAGCUCGUUGU
B UGUAGAAACAGCUCGUUGUTT B
4018


R-008398326-000U
889
1049
UGUAGAAACAGCUCGUUGU
ACAACGAGCUGUUUCUACAUU
4019


R-008398329-000V
1376
1050
CUGACAGAUCCAAGUCAAC
B CUGACAGAUCCAAGUCAACTT B
4020


R-008398329-000V
1376
1050
CUGACAGAUCCAAGUCAAC
GUUGACUUGGAUCUGUCAGUU
4021


R-008398332-000B
427
1051
GGAAGAGGAUGUGGAUACC
GGUAUCCACAUCCUCUUCCUU
4023


R-008398332-000B
427
1051
GGAAGAGGAUGUGGAUACC
B GGAAGAGGAUGUGGAUACCTT B
4022


R-008398335-000C
649
1052
ACCAUCACAGAUGCUGAAA
B ACCAUCACAGAUGCUGAAATT B
4024


R-008398335-000C
649
1052
ACCAUCACAGAUGCUGAAA
UUUCAGCAUCUGUGAUGGUUU
4025


R-008398338-000D
1915
1053
CCGUACGUCCAUGGGUGGG
B CCGUACGUCCAUGGGUGGGTT B
4026


R-008398338-000D
1915
1053
CCGUACGUCCAUGGGUGGG
CCCACCCAUGGACGUACGGUU
4027


R-008398341-000K
2053
1054
CAUUCCAUUGUUUGUGCAG
B CAUUCCAUUGUUUGUGCAGTT B
4028


R-008398341-000K
2053
1054
CAUUCCAUUGUUUGUGCAG
CUGCACAAACAAUGGAAUGUU
4029


R-008398344-000L
2000
24
CACAUCCUAGCUCGGGAUG
CAUCCCGAGCUAGGAUGUGUU
4031


R-008398344-000L
2000
24
CACAUCCUAGCUCGGGAUG
B CACAUCCUAGCUCGGGAUGTT B
4030


R-008398347-000M
2568
1055
CUCCAGGUGACAGCAAUCA
B CUCCAGGUGACAGCAAUCATT B
4032


R-008398347-000M
2568
1055
CUCCAGGUGACAGCAAUCA
UGAUUGCUGUCACCUGGAGUU
4033


R-008398350-000U
1739
1056
CUACCAGUUGUGGUUAAGC
GCUUAACCACAACUGGUAGUU
4035


R-008398350-000U
1739
1056
CUACCAGUUGUGGUUAAGC
B CUACCAGUUGUGGUUAAGCTT B
4034


R-008398353-000V
1746
1057
UUGUGGUUAAGCUCUUACA
B UUGUGGUUAAGCUCUUACATT B
4036


R-008398353-000V
1746
1057
UUGUGGUUAAGCUCUUACA
UGUAAGAGCUUAACCACAAUU
4037


R-008398356-000W
1321
1058
UAGUAAUAAGCCGGCUAUU
AAUAGCCGGCUUAUUACUAUU
4039


R-008398356-000W
1321
1058
UAGUAAUAAGCCGGCUAUU
B UAGUAAUAAGCCGGCUAUUTT B
4038


R-008398359-000X
482
1059
CAGUCCUUCACUCAAGAAC
GUUCUUGAGUGAAGGACUGUU
4041


R-008398359-000X
482
1059
CAGUCCUUCACUCAAGAAC
B CAGUCCUUCACUCAAGAACTT B
4040


R-008398362-000D
280
1060
AGCUGAUUUGAUGGAGUUG
CAACUCCAUCAAAUCAGCUUU
4043


R-008398362-000D
280
1060
AGCUGAUUUGAUGGAGUUG
B AGCUGAUUUGAUGGAGUUGTT B
4042


R-008398365-000E
1465
1061
AGGUCUCCUUGGGACUCUU
B AGGUCUCCUUGGGACUCUUTT B
4044


R-008398365-000E
1465
1061
AGGUCUCCUUGGGACUCUU
AAGAGUCCCAAGGAGACCUUU
4045


R-008398368-000F
1731
1062
ACUAUGGACUACCAGUUGU
ACAACUGGUAGUCCAUAGUUU
4047


R-008398368-000F
1731
1062
ACUAUGGACUACCAGUUGU
B ACUAUGGACUACCAGUUGUTT B
4046


R-008398371-000M
1937
1063
CAGCAGCAAUUUGUGGAGG
B CAGCAGCAAUUUGUGGAGGTT B
4048


R-008398371-000M
1937
1063
CAGCAGCAAUUUGUGGAGG
CCUCCACAAAUUGCUGCUGUU
4049


R-008398374-000N
1892
1064
CGUGCACAUCAGGAUACCC
B CGUGCACAUCAGGAUACCCTT B
4050


R-008398374-000N
1892
1064
CGUGCACAUCAGGAUACCC
GGGUAUCCUGAUGUGCACGUU
4051


R-008398377-000P
836
1065
CGUUCUCCUCAGAUGGUGU
B CGUUCUCCUCAGAUGGUGUTT B
4052


R-008398377-000P
836
1065
CGUUCUCCUCAGAUGGUGU
ACACCAUCUGAGGAGAACGUU
4053


R-008398380-000W
521
1066
CAGUAUGCAAUGACUCGAG
CUCGAGUCAUUGCAUACUGUU
4055


R-008398380-000W
521
1066
CAGUAUGCAAUGACUCGAG
B CAGUAUGCAAUGACUCGAGTT B
4054


R-008398383-000X
1595
1067
GGUAUAGAGGCUCUUGUGC
GCACAAGAGCCUCUAUACCUU
4057


R-008398383-000X
1595
1067
GGUAUAGAGGCUCUUGUGC
B GGUAUAGAGGCUCUUGUGCTT B
4056


R-008398386-000Y
2511
1068
AUCCAGUUGAUGGGCUGCC
GGCAGCCCAUCAACUGGAUUU
4059


R-008398386-000Y
2511
1068
AUCCAGUUGAUGGGCUGCC
B AUCCAGUUGAUGGGCUGCCTT B
4058


R-008398389-000Z
1583
1069
UGCCAAGUGGGUGGUAUAG
B UGCCAAGUGGGUGGUAUAGTT B
4060


R-008398389-000Z
1583
1069
UGCCAAGUGGGUGGUAUAG
CUAUACCACCCACUUGGCAUU
4061


R-008398392-000F
1897
1070
ACAUCAGGAUACCCAGCGC
GCGCUGGGUAUCCUGAUGUUU
4063


R-008398392-000F
1897
1070
ACAUCAGGAUACCCAGCGC
B ACAUCAGGAUACCCAGCGCTT B
4062


R-008398395-000G
956
1071
GCCAUCUUUAAGUCUGGAG
CUCCAGACUUAAAGAUGGCUU
4065


R-008398395-000G
956
1071
GCCAUCUUUAAGUCUGGAG
B GCCAUCUUUAAGUCUGGAGTT B
4064


R-008398398-000H
926
1072
AACCUUUCCCAUCAUCGUG
B AACCUUUCCCAUCAUCGUGTT B
4066


R-008398398-000H
926
1072
AACCUUUCCCAUCAUCGUG
CACGAUGAUGGGAAAGGUUUU
4067


R-008398401-000A
1874
1073
CUAGUUCAGUUGCUUGUUC
GAACAAGCAACUGAACUAGUU
4069


R-008398401-000A
1874
1073
CUAGUUCAGUUGCUUGUUC
B CUAGUUCAGUUGCUUGUUCTT B
4068


R-008398404-000B
488
1074
UUCACUCAAGAACAAGUAG
B UUCACUCAAGAACAAGUAGTT B
4070


R-008398404-000B
488
1074
UUCACUCAAGAACAAGUAG
CUACUUGUUCUUGAGUGAAUU
4071


R-008398407-000C
1602
21
AGGCUCUUGUGCGUACUGU
B AGGCUCUUGUGCGUACUGUTT B
4072


R-008398407-000C
1602
21
AGGCUCUUGUGCGUACUGU
ACAGUACGCACAAGAGCCUUU
4073


R-008398410-000J
1695
1075
AAGAAGCAGAGAUGGCCCA
UGGGCCAUCUCUGCUUCUUUU
4075


R-008398410-000J
1695
1075
AAGAAGCAGAGAUGGCCCA
B AAGAAGCAGAGAUGGCCCATT B
4074


R-008398413-000K
2182
1076
UCCUCUGACAGAGUUACUU
B UCCUCUGACAGAGUUACUUTT B
4076


R-008398413-000K
2182
1076
UCCUCUGACAGAGUUACUU
AAGUAACUCUGUCAGAGGAUU
4077


R-008398416-000L
2029
1077
AAUUGUUAUCAGAGGACUA
UAGUCCUCUGAUAACAAUUUU
4079


R-008398416-000L
2029
1077
AAUUGUUAUCAGAGGACUA
B AAUUGUUAUCAGAGGACUATT B
4078


R-008398419-000M
479
1078
UCUCAGUCCUUCACUCAAG
B UCUCAGUCCUUCACUCAAGTT B
4080


R-008398419-000M
479
1078
UCUCAGUCCUUCACUCAAG
CUUGAGUGAAGGACUGAGAUU
4081


R-008398422-000U
818
1079
UCCAGACACGCUAUCAUGC
GCAUGAUAGCGUGUCUGGAUU
4083


R-008398422-000U
818
1079
UCCAGACACGCUAUCAUGC
B UCCAGACACGCUAUCAUGCTT B
4082


R-008398425-000V
625
1080
CACUAAUGUCCAGCGUUUG
B CACUAAUGUCCAGCGUUUGTT B
4084


R-008398425-000V
625
1080
CACUAAUGUCCAGCGUUUG
CAAACGCUGGACAUUAGUGUU
4085


R-008398428-000W
3172
1081
UUGUAACCUGCUGUGAUAC
B UUGUAACCUGCUGUGAUACTT B
4086


R-008398428-000W
3172
1081
UUGUAACCUGCUGUGAUAC
GUAUCACAGCAGGUUACAAUU
4087


R-008398431-000C
1490
1082
CUUCUGGGUUCAGAUGAUA
B CUUCUGGGUUCAGAUGAUATT B
4088


R-008398431-000C
1490
1082
CUUCUGGGUUCAGAUGAUA
UAUCAUCUGAACCCAGAAGUU
4089


R-008398434-000D
1914
1083
GCCGUACGUCCAUGGGUGG
B GCCGUACGUCCAUGGGUGGTT B
4090


R-008398434-000D
1914
1083
GCCGUACGUCCAUGGGUGG
CCACCCAUGGACGUACGGCUU
4091


R-008398437-000E
882
100
CAAAUGAUGUAGAAACAGC
GCUGUUUCUACAUCAUUUGUU
4093


R-008398437-000E
882
100
CAAAUGAUGUAGAAACAGC
B CAAAUGAUGUAGAAACAGCTT B
4092


R-008398440-000L
1974
1084
UAGUUGAAGGUUGUACCGG
CCGGUACAACCUUCAACUAUU
4095


R-008398440-000L
1974
1084
UAGUUGAAGGUUGUACCGG
B UAGUUGAAGGUUGUACCGGTT B
4094


R-008398443-000M
2258
1085
GAGGACAAGCCACAAGAUU
B GAGGACAAGCCACAAGAUUTT B
4096


R-008398443-000M
2258
1085
GAGGACAAGCCACAAGAUU
AAUCUUGUGGCUUGUCCUCUU
4097


R-008398446-000N
2170
1086
GGGAGCCACAGCUCCUCUG
CAGAGGAGCUGUGGCUCCCUU
4099


R-008398446-000N
2170
1086
GGGAGCCACAGCUCCUCUG
B GGGAGCCACAGCUCCUCUGTT B
4098


R-008398449-000P
1370
1087
CUUCACCUGACAGAUCCAA
B CUUCACCUGACAGAUCCAATT B
4100


R-008398449-000P
1370
1087
CUUCACCUGACAGAUCCAA
UUGGAUCUGUCAGGUGAAGUU
4101


R-008398452-000W
1429
1088
UCUUUCAGAUGCUGCAACU
B UCUUUCAGAUGCUGCAACUTT B
4102


R-008398452-000W
1429
1088
UCUUUCAGAUGCUGCAACU
AGUUGCAGCAUCUGAAAGAUU
4103


R-008398455-000X
3173
1089
UGUAACCUGCUGUGAUACG
B UGUAACCUGCUGUGAUACGTT B
4104


R-008398455-000X
3173
1089
UGUAACCUGCUGUGAUACG
CGUAUCACAGCAGGUUACAUU
4105


R-008398458-000Y
444
1090
CCUCCCAAGUCCUGUAUGA
B CCUCCCAAGUCCUGUAUGATT B
4106


R-008398458-000Y
444
1090
CCUCCCAAGUCCUGUAUGA
UCAUACAGGACUUGGGAGGUU
4107


R-008398461-000E
1081
1091
GGCAGUGCGUUUAGCUGGU
B GGCAGUGCGUUUAGCUGGUTT B
4108


R-008398461-000E
1081
1091
GGCAGUGCGUUUAGCUGGU
ACCAGCUAAACGCACUGCCUU
4109


R-008398464-000F
1318
1092
CUCUAGUAAUAAGCCGGCU
AGCCGGCUUAUUACUAGAGUU
4111


R-008398464-000F
1318
1092
CUCUAGUAAUAAGCCGGCU
B CUCUAGUAAUAAGCCGGCUTT B
4110


R-008398467-000G
329
1093
GCUGUUAGUCACUGGCAGC
B GCUGUUAGUCACUGGCAGCTT B
4112


R-008398467-000G
329
1093
GCUGUUAGUCACUGGCAGC
GCUGCCAGUGACUAACAGCUU
4113


R-008398470-000N
1389
1094
GUCAACGUCUUGUUCAGAA
UUCUGAACAAGACGUUGACUU
4115


R-008398470-000N
1389
1094
GUCAACGUCUUGUUCAGAA
B GUCAACGUCUUGUUCAGAATT B
4114


R-008398473-000P
428
1095
GAAGAGGAUGUGGAUACCU
AGGUAUCCACAUCCUCUUCUU
4117


R-008398473-000P
428
1095
GAAGAGGAUGUGGAUACCU
B GAAGAGGAUGUGGAUACCUTT B
4116


R-008398476-000R
3175
1096
UAACCUGCUGUGAUACGAU
AUCGUAUCACAGCAGGUUAUU
4119


R-008398476-000R
3175
1096
UAACCUGCUGUGAUACGAU
B UAACCUGCUGUGAUACGAUTT B
4118


R-008398479-000S
1422
114
UCAGGAAUCUUUCAGAUGC
B UCAGGAAUCUUUCAGAUGCTT B
4120


R-008398479-000S
1422
114
UCAGGAAUCUUUCAGAUGC
GCAUCUGAAAGAUUCCUGAUU
4121


R-008398482-000Y
1500
97
CAGAUGAUAUAAAUGUGGU
ACCACAUUUAUAUCAUCUGUU
4123


R-008398482-000Y
1500
97
CAGAUGAUAUAAAUGUGGU
B CAGAUGAUAUAAAUGUGGUTT B
4122


R-008398485-000Z
3117
1097
GUUAUUUGGAACCUUGUUU
B GUUAUUUGGAACCUUGUUUTT B
4124


R-008398485-000Z
3117
1097
GUUAUUUGGAACCUUGUUU
AAACAAGGUUCCAAAUAACUU
4125


R-008398488-000A
2020
1098
UCACAACCGAAUUGUUAUC
B UCACAACCGAAUUGUUAUCTT B
4126


R-008398488-000A
2020
1098
UCACAACCGAAUUGUUAUC
GAUAACAAUUCGGUUGUGAUU
4127


R-008398491-000G
1625
1099
CGGGCUGGUGACAGGGAAG
B CGGGCUGGUGACAGGGAAGTT B
4128


R-008398491-000G
1625
1099
CGGGCUGGUGACAGGGAAG
CUUCCCUGUCACCAGCCCGUU
4129


R-008398494-000H
2022
1100
ACAACCGAAUUGUUAUCAG
B ACAACCGAAUUGUUAUCAGTT B
4130


R-008398494-000H
2022
1100
ACAACCGAAUUGUUAUCAG
CUGAUAACAAUUCGGUUGUUU
4131


R-008398497-000J
624
1101
CCACUAAUGUCCAGCGUUU
B CCACUAAUGUCCAGCGUUUTT B
4132


R-008398497-000J
624
1101
CCACUAAUGUCCAGCGUUU
AAACGCUGGACAUUAGUGGUU
4133


R-008398500-000B 
1648
1102
CACUGAGCCUGCCAUCUGU
ACAGAUGGCAGGCUCAGUGUU
4135


R-008398500-000B 
1648
1102
CACUGAGCCUGCCAUCUGU
B CACUGAGCCUGCCAUCUGUTT B
4134


R-008398503-000C
790
1103
GGUCCAUCAGCUUUCUAAA
B GGUCCAUCAGCUUUCUAAATT B
4136


R-008398503-000C
790
1103
GGUCCAUCAGCUUUCUAAA
UUUAGAAAGCUGAUGGACCUU
4137


R-008398506-000D
2122
59
CUGUGAACUUGCUCAGGAC
B CUGUGAACUUGCUCAGGACTT B
4138


R-008398506-000D
2122
59
CUGUGAACUUGCUCAGGAC
GUCCUGAGCAAGUUCACAGUU
4139


R-008398509-000E
3160
1104
AUCCCAAAGUUGUUGUAAC
B AUCCCAAAGUUGUUGUAACTT B
4140


R-008398509-000E
3160
1104
AUCCCAAAGUUGUUGUAAC
GUUACAACAACUUUGGGAUUU
4141


R-008398512-000L
1251
1105
UGAGGACCUAUACUUACGA
B UGAGGACCUAUACUUACGATT B
4142


R-008398512-000L
1251
1105
UGAGGACCUAUACUUACGA
UCGUAAGUAUAGGUCCUCAUU
4143


R-008398518-000N
2253
1106
UGUCUGAGGACAAGCCACA
UGUGGCUUGUCCUCAGACAUU
4145


R-008398518-000N
2253
1106
UGUCUGAGGACAAGCCACA
B UGUCUGAGGACAAGCCACATT B
4144


R-008398521-000V
2515
1107
AGUUGAUGGGCUGCCAGAU
B AGUUGAUGGGCUGCCAGAUTT B
4146


R-008398521-000V
2515
1107
AGUUGAUGGGCUGCCAGAU
AUCUGGCAGCCCAUCAACUUU
4147


R-008398524-000W
1680
1108
UGACCAGCCGACACCAAGA
B UGACCAGCCGACACCAAGATT B
4148


R-008398524-000W
1680
1108
UGACCAGCCGACACCAAGA
UCUUGGUGUCGGCUGGUCAUU
4149


R-008398527-000X
2169
1109
AGGGAGCCACAGCUCCUCU
B AGGGAGCCACAGCUCCUCUTT B
4150


R-008398527-000X
2169
1109
AGGGAGCCACAGCUCCUCU
AGAGGAGCUGUGGCUCCCUUU
4151


R-008398530-000D
3165
1110
AAAGUUGUUGUAACCUGCU
AGCAGGUUACAACAACUUUUU
4153


R-008398530-000D
3165
1110
AAAGUUGUUGUAACCUGCU
B AAAGUUGUUGUAACCUGCUTT B
4152


R-008398533-000E
780
1111
CUGCAGUUAUGGUCCAUCA
UGAUGGACCAUAACUGCAGUU
4155


R-008398533-000E
780
1111
CUGCAGUUAUGGUCCAUCA
B CUGCAGUUAUGGUCCAUCATT B
4154


R-008398536-000F
1978
1112
UGAAGGUUGUACCGGAGCC
B UGAAGGUUGUACCGGAGCCTT B
4156


R-008398536-000F
1978
1112
UGAAGGUUGUACCGGAGCC
GGCUCCGGUACAACCUUCAUU
4157


R-008398539-000G
661
122
GCUGAAACAUGCAGUUGUA
B GCUGAAACAUGCAGUUGUATT B
4158


R-008398539-000G
661
122
GCUGAAACAUGCAGUUGUA
UACAACUGCAUGUUUCAGCUU
4159


R-008398542-000N
1354
181
AAUGCAAGCUUUAGGACUU
B AAUGCAAGCUUUAGGACUUTT B
4160


R-008398542-000N
1354
181
AAUGCAAGCUUUAGGACUU
AAGUCCUAAAGCUUGCAUUUU
4161


R-008398545-000P
563
1113
UUCCCUGAGACAUUAGAUG
B UUCCCUGAGACAUUAGAUGTT B
4162


R-008398545-000P
563
1113
UUCCCUGAGACAUUAGAUG
CAUCUAAUGUCUCAGGGAAUU
4163


R-008398548-000R
1622
1114
CUUCGGGCUGGUGACAGGG
B CUUCGGGCUGGUGACAGGGTT B
4164


R-008398548-000R
1622
1114
CUUCGGGCUGGUGACAGGG
CCCUGUCACCAGCCCGAAGUU
4165


R-008398551-000X
2295
1115
UUGAGCUGACCAGCUCUCU
AGAGAGCUGGUCAGCUCAAUU
4167


R-008398551-000X
2295
1115
UUGAGCUGACCAGCUCUCU
B UUGAGCUGACCAGCUCUCUTT B
4166


R-008398554-000Y
2126
1116
GAACUUGCUCAGGACAAGG
CCUUGUCCUGAGCAAGUUCUU
4169


R-008398554-000Y
2126
1116
GAACUUGCUCAGGACAAGG
B GAACUUGCUCAGGACAAGGTT B
4168


R-008398557-000Z
1683
1117
CCAGCCGACACCAAGAAGC
GCUUCUUGGUGUCGGCUGGUU
4171


R-008398557-000Z
1683
1117
CCAGCCGACACCAAGAAGC
B CCAGCCGACACCAAGAAGCTT B
4170


R-008398560-000F
1857
1118
AGGGUGCCAUUCCACGACU
AGUCGUGGAAUGGCACCCUUU
4173


R-008398560-000F
1857
1118
AGGGUGCCAUUCCACGACU
B AGGGUGCCAUUCCACGACUTT B
4172


R-008398563-000G
2064
1119
UUGUGCAGCUGCUUUAUUC
GAAUAAAGCAGCUGCACAAUU
4175


R-008398563-000G
2064
1119
UUGUGCAGCUGCUUUAUUC
B UUGUGCAGCUGCUUUAUUCTT B
4174


R-008398566-000H
1245
31
AUAUAAUGAGGACCUAUAC
GUAUAGGUCCUCAUUAUAUUU
4177


R-008398566-000H
1245
31
AUAUAAUGAGGACCUAUAC
B AUAUAAUGAGGACCUAUACTT B
4176


R-008398569-000J
489
1120
UCACUCAAGAACAAGUAGC
B UCACUCAAGAACAAGUAGCTT B
4178


R-008398569-000J
489
1120
UCACUCAAGAACAAGUAGC
GCUACUUGUUCUUGAGUGAUU
4179


R-008398572-000R
1346
1121
GCUGGUGGAAUGCAAGCUU
B GCUGGUGGAAUGCAAGCUUTT B
4180


R-008398572-000R
1346
1121
GCUGGUGGAAUGCAAGCUU
AAGCUUGCAUUCCACCAGCUU
4181


R-008398575-000S
1442
1122
GCAACUAAACAGGAAGGGA
UCCCUUCCUGUUUAGUUGCUU
4183


R-008398575-000S
1442
1122
GCAACUAAACAGGAAGGGA
B GCAACUAAACAGGAAGGGATT B
4182


R-008398578-000T
1981
1123
AGGUUGUACCGGAGCCCUU
B AGGUUGUACCGGAGCCCUUTT B
4184


R-008398578-000T
1981
1123
AGGUUGUACCGGAGCCCUU
AAGGGCUCCGGUACAACCUUU
4185


R-008398581-000Z
777
1124
AGGCUGCAGUUAUGGUCCA
UGGACCAUAACUGCAGCCUUU
4187


R-008398581-000Z
777
1124
AGGCUGCAGUUAUGGUCCA
B AGGCUGCAGUUAUGGUCCATT B
4186


R-008398584-000A
589
1125
GCAGAUCCCAUCUACACAG
CUGUGUAGAUGGGAUCUGCUU
4189


R-008398584-000A
589
1125
GCAGAUCCCAUCUACACAG
B GCAGAUCCCAUCUACACAGTT B
4188


R-008398587-000B
2205
1126
CUAGGAAUGAAGGUGUGGC
GCCACACCUUCAUUCCUAGUU
4191


R-008398587-000B
2205
1126
CUAGGAAUGAAGGUGUGGC
B CUAGGAAUGAAGGUGUGGCTT B
4190


R-008398590-000H
394
1127
AGCUCCUUCUCUGAGUGGU
B AGCUCCUUCUCUGAGUGGUTT B
4192


R-008398590-000H
394
1127
AGCUCCUUCUCUGAGUGGU
AC CACUCAGAGAAGGAGCUUU
4193


R-008398593-000J
1035
1128
UUACAACUCUCCACAACCU
B UUACAACUCUCCACAACCUTT B
4194


R-008398593-000J
1035
1128
UUACAACUCUCCACAACCU
AGGUUGUGGAGAGUUGUAAUU
4195


R-008398605-000E
410
1129
GGUAAAGGCAAUCCUGAGG
B GGUAAAGGCAAUCCUGAGGTT B
4196


R-008398605-000E
410
1129
GGUAAAGGCAAUCCUGAGG
CCUCAGGAUUGCCUUUACCUU
4197


R-008398608-000F
1721
1130
GUUCGCCUUCACUAUGGAC
GUCCAUAGUGAAGGCGAACUU
4199


R-008398608-000F
1721
1130
GUUCGCCUUCACUAUGGAC
B GUUCGCCUUCACUAUGGACTT B
4198


R-008398611-000M
1134
1131
CAAAUGUUAAAUUCUUGGC
GCCAAGAAUUUAACAUUUGUU
4201


R-008398611-000M
1134
1131
CAAAUGUUAAAUUCUUGGC
B CAAAUGUUAAAUUCUUGGCTT B
4200


R-008398614-000N
3182
1132
CUGUGAUACGAUGCUUCAA
B CUGUGAUACGAUGCUUCAATT B
4202


R-008398614-000N
3182
1132
CUGUGAUACGAUGCUUCAA
UUGAAGCAUCGUAUCACAGUU
4203


R-008398617-000P
881
1133
ACAAAUGAUGUAGAAACAG
B ACAAAUGAUGUAGAAACAGTT B
4204


R-008398617-000P
881
1133
ACAAAUGAUGUAGAAACAG
CUGUUUCUACAUCAUUUGUUU
4205


R-008398620-000W
547
1134
GGUACGAGCUGCUAUGUUC
GAACAUAGCAGCUCGUACCUU
4207


R-008398620-000W
547
1134
GGUACGAGCUGCUAUGUUC
B GGUACGAGCUGCUAUGUUCTT B
4206


R-008398623-000X
2028
1135
GAAUUGUUAUCAGAGGACU
AGUCCUCUGAUAACAAUUCUU
4209


R-008398623-000X
2028
1135
GAAUUGUUAUCAGAGGACU
B GAAUUGUUAUCAGAGGACUTT B
4208


R-008398629-000Z
2023
1136
CAACCGAAUUGUUAUCAGA
B CAACCGAAUUGUUAUCAGATT B
4210


R-008398629-000Z
2023
1136
CAACCGAAUUGUUAUCAGA
UCUGAUAACAAUUCGGUUGUU
4211


R-008398632-000F
3184
1137
GUGAUACGAUGCUUCAAGA
B GUGAUACGAUGCUUCAAGATT B
4212


R-008398632-000F
3184
1137
GUGAUACGAUGCUUCAAGA
UCUUGAAGCAUCGUAUCACUU
4213


R-008398635-000G
413
1138
AAAGGCAAUCCUGAGGAAG
CUUCCUCAGGAUUGCCUUUUU
4215


R-008398635-000G
413
1138
AAAGGCAAUCCUGAGGAAG
B AAAGGCAAUCCUGAGGAAGTT B
4214


R-008398638-000H
2178
1139
CAGCUCCUCUGACAGAGUU
B CAGCUCCUCUGACAGAGUUTT B
4216


R-008398638-000H
2178
1139
CAGCUCCUCUGACAGAGUU
AACUCUGUCAGAGGAGCUGUU
4217


R-008398641-000P
618
143
CUCAUCCCACUAAUGUCCA
B CUCAUCCCACUAAUGUCCATT B
4218


R-008398641-000P
618
143
CUCAUCCCACUAAUGUCCA
UGGACAUUAGUGGGAUGAGUU
4219


R-008398644-000R
1577
1140
AUGGUCUGCCAAGUGGGUG
B AUGGUCUGCCAAGUGGGUGTT B
4220


R-008398644-000R
1577
1140
AUGGUCUGCCAAGUGGGUG
CACCCACUUGGCAGACCAUUU
4221


R-008398647-000S
1793
1141
GCUACUGUUGGAUUGAUUC
GAAUCAAUCCAACAGUAGCUU
4223


R-008398647-000S
1793
1141
GCUACUGUUGGAUUGAUUC
B GCUACUGUUGGAUUGAUUCTT B
4222


R-008398650-000Y
526
1142
UGCAAUGACUCGAGCUCAG
B UGCAAUGACUCGAGCUCAGTT B
4224


R-008398650-000Y
526
1142
UGCAAUGACUCGAGCUCAG
CUGAGCUCGAGUCAUUGCAUU
4225


R-008398653-000Z
2358
1143
GACUUGAUAUUGGUGCCCA
UGGGCACCAAUAUCAAGUCUU
4227


R-008398653-000Z
2358
1143
GACUUGAUAUUGGUGCCCA
B GACUUGAUAUUGGUGCCCATT B
4226


R-008398656-000A
852
11
UGUCUGCUAUUGUACGUAC
B UGUCUGCUAUUGUACGUACTT B
4228


R-008398656-000A
852
11
UGUCUGCUAUUGUACGUAC
GUACGUACAAUAGCAGACAUU
4229


R-008398659-000B
1403
1144
CAGAACUGUCUUUGGACUC
GAGUCCAAAGACAGUUCUGUU
4231


R-008398659-000B
1403
1144
CAGAACUGUCUUUGGACUC
B CAGAACUGUCUUUGGACUCTT B
4230


R-008398662-000H
1875
1145
UAGUUCAGUUGCUUGUUCG
CGAACAAGCAACUGAACUAUU
4233


R-008398662-000H
1875
1145
UAGUUCAGUUGCUUGUUCG
B UAGUUCAGUUGCUUGUUCGTT B
4232


R-008398665-000J
1160
1146
ACAGACUGCCUUCAAAUUU
B ACAGACUGCCUUCAAAUUUTT B
4234


R-008398665-000J
1160
1146
ACAGACUGCCUUCAAAUUU
AAAUUUGAAGGCAGUCUGUUU
4235


R-008398668-000K
1591
1147
GGGUGGUAUAGAGGCUCUU
AAGAGCCUCUAUACCACCCUU
4237


R-008398668-000K
1591
1147
GGGUGGUAUAGAGGCUCUU
B GGGUGGUAUAGAGGCUCUUTT B
4236


R-008398671-000S
1734
1148
AUGGACUACCAGUUGUGGU
B AUGGACUACCAGUUGUGGUTT B
4238


R-008398671-000S
1734
1148
AUGGACUACCAGUUGUGGU
ACCACAACUGGUAGUCCAUUU
4239


R-008398674-000T
2030
1149
AUUGUUAUCAGAGGACUAA
UUAGUCCUCUGAUAACAAUUU
4241


R-008398674-000T
2030
1149
AUUGUUAUCAGAGGACUAA
B AUUGUUAUCAGAGGACUAATT B
4240


R-008398677-000U
775
1150
UAAGGCUGCAGUUAUGGUC
GACCAUAACUGCAGCCUUAUU
4243


R-008398677-000U
775
1150
UAAGGCUGCAGUUAUGGUC
B UAAGGCUGCAGUUAUGGUCTT B
4242


R-008398680-000A
1813
1151
AAAUCUUGCCCUUUGUCCC
GGGACAAAGGGCAAGAUUUUU
4245


R-008398680-000A
1813
1151
AAAUCUUGCCCUUUGUCCC
B AAAUCUUGCCCUUUGUCCCTT B
4244


R-008398683-000B
1938
1152
AGCAGCAAUUUGUGGAGGG
B AGCAGCAAUUUGUGGAGGGTT B
4246


R-008398683-000B
1938
1152
AGCAGCAAUUUGUGGAGGG
CCCUCCACAAAUUGCUGCUUU
4247


R-008398686-000C
2039
1153
AGAGGACUAAAUACCAUUC
B AGAGGACUAAAUACCAUUCTT B
4248


R-008398686-000C
2039
1153
AGAGGACUAAAUACCAUUC
GAAUGGUAUUUAGUCCUCUUU
4249


R-008398689-000D
1297
1154
GCUGAAGGUGCUAUCUGUC
B GCUGAAGGUGCUAUCUGUCTT B
4250


R-008398689-000D
1297
1154
GCUGAAGGUGCUAUCUGUC
GACAGAUAGCACCUUCAGCUU
4251


R-008398692-000K
456
1155
UGUAUGAGUGGGAACAGGG
CCCUGUUCCCACUCAUACAUU
4253


R-008398692-000K
456
1155
UGUAUGAGUGGGAACAGGG
B UGUAUGAGUGGGAACAGGGTT B
4252


R-008398695-000L
869
51
ACCAUGCAGAAUACAAAUG
B ACCAUGCAGAAUACAAAUGTT B
4254


R-008398695-000L
869
51
ACCAUGCAGAAUACAAAUG
CAUUUGUAUUCUGCAUGGUUU
4255


R-008398698-000M
590
1156
CAGAUCCCAUCUACACAGU
B CAGAUCCCAUCUACACAGUTT B
4256


R-008398698-000M
590
1156
CAGAUCCCAUCUACACAGU
ACUGUGUAGAUGGGAUCUGUU
4257


R-008398701-000E
1933
1157
GACACAGCAGCAAUUUGUG
B GACACAGCAGCAAUUUGUGTT B
4258


R-008398701-000E
1933
1157
GACACAGCAGCAAUUUGUG
CACAAAUUGCUGCUGUGUCUU
4259


R-008398704-000F
583
1158
GGGCAUGCAGAUCCCAUCU
AGAUGGGAUCUGCAUGCCCUU
4261


R-008398704-000F
583
1158
GGGCAUGCAGAUCCCAUCU
B GGGCAUGCAGAUCCCAUCUTT B
4260


R-008398707-000G
2540
1159
CAUGCCCAGGACCUCAUGG
B CAUGCCCAGGACCUCAUGGTT B
4262


R-008398707-000G
2540
1159
CAUGCCCAGGACCUCAUGG
CCAUGAGGUCCUGGGCAUGUU
4263


R-008398710-000N
2162
1160
GAAGCUGAGGGAGCCACAG
B GAAGCUGAGGGAGCCACAGTT B
4264


R-008398710-000N
2162
1160
GAAGCUGAGGGAGCCACAG
CUGUGGCUCCCUCAGCUUCUU
4265


R-008398713-000P
330
1161
CUGUUAGUCACUGGCAGCA
B CUGUUAGUCACUGGCAGCATT B
4266


R-008398713-000P
330
1161
CUGUUAGUCACUGGCAGCA
UGCUGCCAGUGACUAACAGUU
4267


R-008398716-000R
1481
1162
CUUGUUCAGCUUCUGGGUU
B CUUGUUCAGCUUCUGGGUUTT B
4268


R-008398716-000R
1481
1162
CUUGUUCAGCUUCUGGGUU
AACCCAGAAGCUGAACAAGUU
4269


R-008398719-000S
1612
22
GCGUACUGUCCUUCGGGCU
AGCCCGAAGGACAGUACGCUU
4271


R-008398719-000S
1612
22
GCGUACUGUCCUUCGGGCU
B GCGUACUGUCCUUCGGGCUTT B
4270


R-008398722-000Y
1709
3
GCCCAGAAUGCAGUUCGCC
GGCGAACUGCAUUCUGGGCUU
4273


R-008398722-000Y
1709
3
GCCCAGAAUGCAGUUCGCC
B GCCCAGAAUGCAGUUCGCCTT B
4272


R-008398725-000Z
1344
1163
AAGCUGGUGGAAUGCAAGC
GCUUGCAUUCCACCAGCUUUU
4275


R-008398725-000Z
1344
1163
AAGCUGGUGGAAUGCAAGC
B AAGCUGGUGGAAUGCAAGCTT B
4274


R-008398728-000A
431
1164
GAGGAUGUGGAUACCUCCC
GGGAGGUAUCCACAUCCUCUU
4277


R-008398728-000A
431
1164
GAGGAUGUGGAUACCUCCC
B GAGGAUGUGGAUACCUCCCTT B
4276


R-008398731-000G
1508
1165
AUAAAUGUGGUCACCUGUG
CACAGGUGACCACAUUUAUUU
4279


R-008398731-000G
1508
1165
AUAAAUGUGGUCACCUGUG
B AUAAAUGUGGUCACCUGUGTT B
4278


R-008398734-000H
1918
1166
UACGUCCAUGGGUGGGACA
B UACGUCCAUGGGUGGGACATT B
4280


R-008398734-000H
1918
1166
UACGUCCAUGGGUGGGACA
UGUCCCACCCAUGGACGUAUU
4281


R-008398737-000J
289
1167
GAUGGAGUUGGACAUGGCC
GGCCAUGUCCAACUCCAUCUU
4283


R-008398737-000J
289
1167
GAUGGAGUUGGACAUGGCC
B GAUGGAGUUGGACAUGGCCTT B
4282


R-008398740-000R
631
1168
UGUCCAGCGUUUGGCUGAA
B UGUCCAGCGUUUGGCUGAATT B
4284


R-008398740-000R
631
1168
UGUCCAGCGUUUGGCUGAA
UUCAGCCAAACGCUGGACAUU
4285


R-008398743-000S
1642
60
AGACAUCACUGAGCCUGCC
B AGACAUCACUGAGCCUGCCTT B
4286


R-008398743-000S
1642
60
AGACAUCACUGAGCCUGCC
GGCAGGCUCAGUGAUGUCUUU
4287


R-008398746-000T
1853
1169
GAGCAGGGUGCCAUUCCAC
B GAGCAGGGUGCCAUUCCACTT B
4288


R-008398746-000T
1853
1169
GAGCAGGGUGCCAUUCCAC
GUGGAAUGGCACCCUGCUCUU
4289


R-008398749-000U
1243
1170
AAAUAUAAUGAGGACCUAU
AUAGGUCCUCAUUAUAUUUUU
4291


R-008398749-000U
1243
1170
AAAUAUAAUGAGGACCUAU
B AAAUAUAAUGAGGACCUAUTT B
4290


R-008398752-000A
1212
1171
UACUGGCUAGUGGUGGACC
GGUCCACCACUAGCCAGUAUU
4293


R-008398752-000A
1212
1171
UACUGGCUAGUGGUGGACC
B UACUGGCUAGUGGUGGACCTT B
4292


R-008398755-000B
996
1172
UGCUUGGUUCACCAGUGGA
UCCACUGGUGAACCAAGCAUU
4295


R-008398755-000B
996
1172
UGCUUGGUUCACCAGUGGA
B UGCUUGGUUCACCAGUGGATT B
4294


R-008398758-000C
2256
1173
CUGAGGACAAGCCACAAGA
B CUGAGGACAAGCCACAAGATT B
4296


R-008398758-000C
2256
1173
CUGAGGACAAGCCACAAGA
UCUUGUGGCUUGUCCUCAGUU
4297


R-008398761-000J
1607
1174
CUUGUGCGUACUGUCCUUC
GAAGGACAGUACGCACAAGUU
4299


R-008398761-000J
1607
1174
CUUGUGCGUACUGUCCUUC
B CUUGUGCGUACUGUCCUUCTT B
4298


R-008398764-000K
3116
1175
UGUUAUUUGGAACCUUGUU
B UGUUAUUUGGAACCUUGUUTT B
4300


R-008398764-000K
3116
1175
UGUUAUUUGGAACCUUGUU
AACAAGGUUCCAAAUAACAUU
4301


R-008398767-000L
1179
1176
UAGCUUAUGGCAACCAAGA
UCUUGGUUGCCAUAAGCUAUU
4303


R-008398767-000L
1179
1176
UAGCUUAUGGCAACCAAGA
B UAGCUUAUGGCAACCAAGATT B
4302


R-008398770-000T
3185
1177
UGAUACGAUGCUUCAAGAG
CUCUUGAAGCAUCGUAUCAUU
4305


R-008398770-000T
3185
1177
UGAUACGAUGCUUCAAGAG
B UGAUACGAUGCUUCAAGAGTT B
4304


R-008398773-000U
1594
1178
UGGUAUAGAGGCUCUUGUG
CACAAGAGCCUCUAUACCAUU
4307


R-008398773-000U
1594
1178
UGGUAUAGAGGCUCUUGUG
B UGGUAUAGAGGCUCUUGUGTT B
4306


R-008398776-000V
887
1179
GAUGUAGAAACAGCUCGUU
B GAUGUAGAAACAGCUCGUUTT B
4308


R-008398776-000V
887
1179
GAUGUAGAAACAGCUCGUU
AACGAGCUGUUUCUACAUCUU
4309


R-008398779-000W
928
1180
CCUUUCCCAUCAUCGUGAG
B CCUUUCCCAUCAUCGUGAGTT B
4310


R-008398779-000W
928
1180
CCUUUCCCAUCAUCGUGAG
CUCACGAUGAUGGGAAAGGUU
4311


R-008398782-000C
835
1181
GCGUUCUCCUCAGAUGGUG
CACCAUCUGAGGAGAACGCUU
4313


R-008398782-000C
835
1181
GCGUUCUCCUCAGAUGGUG
B GCGUUCUCCUCAGAUGGUGTT B
4312


R-008398785-000D
1900
1182
UCAGGAUACCCAGCGCCGU
B UCAGGAUACCCAGCGCCGUTT B
4314


R-008398785-000D
1900
1182
UCAGGAUACCCAGCGCCGU
ACGGCGCUGGGUAUCCUGAUU
4315


R-008398788-000E
2284
1183
ACGGCUUUCAGUUGAGCUG
B ACGGCUUUCAGUUGAGCUGTT B
4316


R-008398788-000E
2284
1183
ACGGCUUUCAGUUGAGCUG
CAGCUCAACUGAAAGCCGUUU
4317


R-008398791-000L
1976
1184
GUUGAAGGUUGUACCGGAG
CUCCGGUACAACCUUCAACUU
4319


R-008398791-000L
1976
1184
GUUGAAGGUUGUACCGGAG
B GUUGAAGGUUGUACCGGAGTT B
4318


R-008398794-000M
2393
1185
UAUCGCCAGGAUGAUCCUA
B UAUCGCCAGGAUGAUCCUATT B
4320


R-008398794-000M
2393
1185
UAUCGCCAGGAUGAUCCUA
UAGGAUCAUCCUGGCGAUAUU
4321


R-008398797-000N
1295
1186
GUGCUGAAGGUGCUAUCUG
B GUGCUGAAGGUGCUAUCUGTT B
4322


R-008398797-000N
1295
1186
GUGCUGAAGGUGCUAUCUG
CAGAUAGCACCUUCAGCACUU
4323


R-008398800-000F
1410
1187
GUCUUUGGACUCUCAGGAA
UUCCUGAGAGUCCAAAGACUU
4325


R-008398800-000F
1410
1187
GUCUUUGGACUCUCAGGAA
B GUCUUUGGACUCUCAGGAATT B
4324


R-008398803-000G
1457
1188
GGGAUGGAAGGUCUCCUUG
B GGGAUGGAAGGUCUCCUUGTT B
4326


R-008398803-000G
1457
1188
GGGAUGGAAGGUCUCCUUG
CAAGGAGACCUUCCAUCCCUU
4327


R-008398806-000H
2296
1189
UGAGCUGACCAGCUCUCUC
B UGAGCUGACCAGCUCUCUCTT B
4328


R-008398806-000H
2296
1189
UGAGCUGACCAGCUCUCUC
GAGAGAGCUGGUCAGCUCAUU
4329


R-008398809-000J
929
1190
CUUUCCCAUCAUCGUGAGG
CCUCACGAUGAUGGGAAAGUU
4331


R-008398809-000J
929
1190
CUUUCCCAUCAUCGUGAGG
B CUUUCCCAUCAUCGUGAGGTT B
4330


R-008398812-000R
1359
1191
AAGCUUUAGGACUUCACCU
B AAGCUUUAGGACUUCACCUTT B
4332


R-008398812-000R
1359
1191
AAGCUUUAGGACUUCACCU
AGGUGAAGUCCUAAAGCUUUU
4333


R-008398815-000S
1351
1192
UGGAAUGCAAGCUUUAGGA
B UGGAAUGCAAGCUUUAGGATT B
4334


R-008398815-000S
1351
1192
UGGAAUGCAAGCUUUAGGA
UCCUAAAGCUUGCAUUCCAUU
4335


R-008398818-000T
969
1193
CUGGAGGCAUUCCUGCCCU
B CUGGAGGCAUUCCUGCCCUTT B
4336


R-008398818-000T
969
1193
CUGGAGGCAUUCCUGCCCU
AGGGCAGGAAUGCCUCCAGUU
4337


R-008398821-000Z
1876
1194
AGUUCAGUUGCUUGUUCGU
ACGAACAAGCAACUGAACUUU
4339


R-008398821-000Z
1876
1194
AGUUCAGUUGCUUGUUCGU
B AGUUCAGUUGCUUGUUCGUTT B
4338


R-008398824-000A
552
1195
GAGCUGCUAUGUUCCCUGA
B GAGCUGCUAUGUUCCCUGATT B
4340


R-008398824-000A
552
1195
GAGCUGCUAUGUUCCCUGA
UCAGGGAACAUAGCAGCUCUU
4341


R-008398827-000B
2441
1196
GGCCAGGAUGCCUUGGGUA
B GGCCAGGAUGCCUUGGGUATT B
4342


R-008398827-000B
2441
1196
GGCCAGGAUGCCUUGGGUA
UACCCAAGGCAUCCUGGCCUU
4343


R-008398830-000H
2402
1197
GAUGAUCCUAGCUAUCGUU
B GAUGAUCCUAGCUAUCGUUTT B
4344


R-008398830-000H
2402
1197
GAUGAUCCUAGCUAUCGUU
AACGAUAGCUAGGAUCAUCUU
4345


R-008398833-000J
1803
1198
GAUUGAUUCGAAAUCUUGC
GCAAGAUUUCGAAUCAAUCUU
4347


R-008398833-000J
1803
1198
GAUUGAUUCGAAAUCUUGC
B GAUUGAUUCGAAAUCUUGCTT B
4346


R-008398836-000K
1701
1199
CAGAGAUGGCCCAGAAUGC
B CAGAGAUGGCCCAGAAUGCTT B
4348


R-008398836-000K
1701
1199
CAGAGAUGGCCCAGAAUGC
GCAUUCUGGGCCAUCUCUGUU
4349


R-008398839-000L
1910
1200
CAGCGCCGUACGUCCAUGG
CCAUGGACGUACGGCGCUGUU
4351


R-008398839-000L
1910
1200
CAGCGCCGUACGUCCAUGG
B CAGCGCCGUACGUCCAUGGTT B
4350


R-008398842-000T
888
1201
AUGUAGAAACAGCUCGUUG
CAACGAGCUGUUUCUACAUUU
4353


R-008398842-000T
888
1201
AUGUAGAAACAGCUCGUUG
B AUGUAGAAACAGCUCGUUGTT B
4352


R-008398845-000U
1294
1202
AGUGCUGAAGGUGCUAUCU
AGAUAGCACCUUCAGCACUUU
4355


R-008398845-000U
1294
1202
AGUGCUGAAGGUGCUAUCU
B AGUGCUGAAGGUGCUAUCUTT B
4354


R-008398848-000V
1737
1203
GACUACCAGUUGUGGUUAA
UUAACCACAACUGGUAGUCUU
4357


R-008398848-000V
1737
1203
GACUACCAGUUGUGGUUAA
B GACUACCAGUUGUGGUUAATT B
4356


R-008398851-000B
1450
1204
ACAGGAAGGGAUGGAAGGU
B ACAGGAAGGGAUGGAAGGUTT B
4358


R-008398851-000B
1450
1204
ACAGGAAGGGAUGGAAGGU
ACCUUCCAUCCCUUCCUGUUU
4359


R-008398854-000C
761
1205
CAGGUGGUGGUUAAUAAGG
C CUUAUUAACCACCACCUGUU
4361


R-008398854-000C
761
1205
CAGGUGGUGGUUAAUAAGG
B CAGGUGGUGGUUAAUAAGGTT B
4360


R-008398857-000D
776
1206
AAGGCUGCAGUUAUGGUCC
B AAGGCUGCAGUUAUGGUCCTT B
4362


R-008398857-000D
776
1206
AAGGCUGCAGUUAUGGUCC
GGACCAUAACUGCAGCCUUUU
4363


R-008398860-000K
1509
1207
UAAAUGUGGUCACCUGUGC
GCACAGGUGACCACAUUUAUU
4365


R-008398860-000K
1509
1207
UAAAUGUGGUCACCUGUGC
B UAAAUGUGGUCACCUGUGCTT B
4364


R-008398863-000L
1788
1208
UAAAGGCUACUGUUGGAUU
B UAAAGGCUACUGUUGGAUUTT B
4366


R-008398863-000L
1788
1208
UAAAGGCUACUGUUGGAUU
AAUCCAACAGUAGCCUUUAUU
4367


R-008398866-000M
515
1209
GAUGGACAGUAUGCAAUGA
UCAUUGCAUACUGUCCAUCUU
4369


R-008398866-000M
515
1209
GAUGGACAGUAUGCAAUGA
B GAUGGACAGUAUGCAAUGATT B
4368


R-008398869-000N
1491
1210
UUCUGGGUUCAGAUGAUAU
B UUCUGGGUUCAGAUGAUAUTT B
4370


R-008398869-000N
1491
1210
UUCUGGGUUCAGAUGAUAU
AUAUCAUCUGAACCCAGAAUU
4371


R-008398872-000V
1614
1211
GUACUGUCCUUCGGGCUGG
B GUACUGUCCUUCGGGCUGGTT B
4372


R-008398872-000V
1614
1211
GUACUGUCCUUCGGGCUGG
CCAGCCCGAAGGACAGUACUU
4373


R-008398875-000W
998
1212
CUUGGUUCACCAGUGGAUU
B CUUGGUUCACCAGUGGAUUTT B
4374


R-008398875-000W
998
1212
CUUGGUUCACCAGUGGAUU
AAUCCACUGGUGAACCAAGUU
4375


R-008398878-000X
2158
1213
UAUUGAAGCUGAGGGAGCC
B UAUUGAAGCUGAGGGAGCCTT B
4376


R-008398878-000X
2158
1213
UAUUGAAGCUGAGGGAGCC
GGCUCCCUCAGCUUCAAUAUU
4377


R-008398881-000D
3168
1214
GUUGUUGUAACCUGCUGUG
B GUUGUUGUAACCUGCUGUGTT B
4378


R-008398881-000D
3168
1214
GUUGUUGUAACCUGCUGUG
CACAGCAGGUUACAACAACUU
4379


R-008398884-000E
1854
1215
AGCAGGGUGCCAUUCCACG
B AGCAGGGUGCCAUUCCACGTT B
4380


R-008398884-000E
1854
1215
AGCAGGGUGCCAUUCCACG
CGUGGAAUGGCACCCUGCUUU
4381


R-008398887-000F
2117
1216
GUCCUCUGUGAACUUGCUC
GAGCAAGUUCACAGAGGACUU
4383


R-008398887-000F
2117
1216
GUCCUCUGUGAACUUGCUC
B GUCCUCUGUGAACUUGCUCTT B
4382


R-008398890-000M
1678
1217
UCUGACCAGCCGACACCAA
UUGGUGUCGGCUGGUCAGAUU
4385


R-008398890-000M
1678
1217
UCUGACCAGCCGACACCAA
B UCUGACCAGCCGACACCAATT B
4384


R-008398893-000N
2159
63
AUUGAAGCUGAGGGAGCCA
B AUUGAAGCUGAGGGAGCCATT B
4386


R-008398893-000N
2159
63
AUUGAAGCUGAGGGAGCCA
UGGCUCCCUCAGCUUCAAUUU
4387


R-008398896-000P
305
1218
GCCAUGGAACCAGACAGAA
UUCUGUCUGGUUCCAUGGCUU
4389


R-008398896-000P
305
1218
GCCAUGGAACCAGACAGAA
B GCCAUGGAACCAGACAGAATT B
4388


R-008398899-000R
2154
1219
AAGCUAUUGAAGCUGAGGG
B AAGCUAUUGAAGCUGAGGGTT B
4390


R-008398899-000R
2154
1219
AAGCUAUUGAAGCUGAGGG
CCCUCAGCUUCAAUAGCUUUU
4391


R-008398902-000H
1807
1220
GAUUCGAAAUCUUGCCCUU
B GAUUCGAAAUCUUGCCCUUTT B
4392


R-008398902-000H
1807
1220
GAUUCGAAAUCUUGCCCUU
AAGGGCAAGAUUUCGAAUCUU
4393


R-008398905-000J
1881
1221
AGUUGCUUGUUCGUGCACA
B AGUUGCUUGUUCGUGCACATT B
4394


R-008398905-000J
1881
1221
AGUUGCUUGUUCGUGCACA
UGUGCACGAACAAGCAACUUU
4395


R-008398908-000K
1565
1222
AAGAACAAGAUGAUGGUCU
B AAGAACAAGAUGAUGGUCUTT B
4396


R-008398908-000K
1565
1222
AAGAACAAGAUGAUGGUCU
AGACCAUCAUCUUGUUCUUUU
4397


R-008398911-000S
407
1223
AGUGGUAAAGGCAAUCCUG
B AGUGGUAAAGGCAAUCCUGTT B
4398


R-008398911-000S
407
1223
AGUGGUAAAGGCAAUCCUG
CAGGAUUGCCUUUACCACUUU
4399


R-008398914-000T
1434
1224
CAGAUGCUGCAACUAAACA
UGUUUAGUUGCAGCAUCUGUU
4401


R-008398914-000T
1434
1224
CAGAUGCUGCAACUAAACA
B CAGAUGCUGCAACUAAACATT B
4400


R-008398917-000U
566
1225
CCUGAGACAUUAGAUGAGG
B CCUGAGACAUUAGAUGAGGTT B
4402


R-008398917-000U
566
1225
CCUGAGACAUUAGAUGAGG
CCUCAUCUAAUGUCUCAGGUU
4403


R-008398920-000A 
3161
1226
UCCCAAAGUUGUUGUAACC
GGUUACAACAACUUUGGGAUU
4405


R-008398920-000A 
3161
1226
UCCCAAAGUUGUUGUAACC
B UCCCAAAGUUGUUGUAACCTT B
4404


R-008398923-000B
666
117
AACAUGCAGUUGUAAACUU
AAGUUUACAACUGCAUGUUUU
4407


R-008398923-000B
666
117
AACAUGCAGUUGUAAACUU
B AACAUGCAGUUGUAAACUUTT B
4406


R-008398926-000C
848
98
AUGGUGUCUGCUAUUGUAC
GUACAAUAGCAGACACCAUUU
4409


R-008398926-000C
848
98
AUGGUGUCUGCUAUUGUAC
B AUGGUGUCUGCUAUUGUACTT B
4408


R-008398929-000D
1679
1227
CUGACCAGCCGACACCAAG
B CUGACCAGCCGACACCAAGTT B
4410


R-008398929-000D
1679
1227
CUGACCAGCCGACACCAAG
CUUGGUGUCGGCUGGUCAGUU
4411


R-008398932-000K 
2096
1228
AUCCAAAGAGUAGCUGCAG
B AUCCAAAGAGUAGCUGCAGTT B
4412


R-008398932-000K 
2096
1228
AUCCAAAGAGUAGCUGCAG
CUGCAGCUACUCUUUGGAUUU
4413


R-008398935-000L
630
1229
AUGUCCAGCGUUUGGCUGA
B AUGUCCAGCGUUUGGCUGATT B
4414


R-008398935-000L
630
1229
AUGUCCAGCGUUUGGCUGA
UCAGCCAAACGCUGGACAUUU
4415


R-008398938-000M 
1606
1230
UCUUGUGCGUACUGUCCUU
AAGGACAGUACGCACAAGAUU
4417


R-008398938-000M 
1606
1230
UCUUGUGCGUACUGUCCUU
B UCUUGUGCGUACUGUCCUUTT B
4416


R-008398941-000U
432
1231
AGGAUGUGGAUACCUCCCA
UGGGAGGUAUCCACAUCCUUU
4419


R-008398941-000U
432
1231
AGGAUGUGGAUACCUCCCA
B AGGAUGUGGAUACCUCCCATT B
4418


R-008398944-000V
778
1232
GGCUGCAGUUAUGGUCCAU
B GGCUGCAGUUAUGGUCCAUTT B
4420


R-008398944-000V
778
1232
GGCUGCAGUUAUGGUCCAU
AUGGACCAUAACUGCAGCCUU
4421


R-008398947-000W 
1999
1233
UCACAUCCUAGCUCGGGAU
B UCACAUCCUAGCUCGGGAUTT B
4422


R-008398947-000W
1999
1233
UCACAUCCUAGCUCGGGAU
AUCCCGAGCUAGGAUGUGAUU
4423


R-008398950-000C 
1692
1234
ACCAAGAAGCAGAGAUGGC
GCCAUCUCUGCUUCUUGGUUU
4425


R-008398950-000C 
1692
1234
ACCAAGAAGCAGAGAUGGC
B ACCAAGAAGCAGAGAUGGCTT B
4424


R-008398953-000D
2490
1235
GCCACCACCCUGGUGCUGA
B GCCACCACCCUGGUGCUGATT B
4426


R-008398953-000D
2490
1235
GCCACCACCCUGGUGCUGA
UCAGCACCAGGGUGGUGGCUU
4427


R-008398956-000E
623
1236
CCCACUAAUGUCCAGCGUU
AACGCUGGACAUUAGUGGGUU
4429


R-008398956-000E
623
1236
CCCACUAAUGUCCAGCGUU
B CCCACUAAUGUCCAGCGUUTT B
4428


R-008398959-000F
339
1237
ACUGGCAGCAACAGUCUUA
B ACUGGCAGCAACAGUCUUATT B
4430


R-008398959-000F
339
1237
ACUGGCAGCAACAGUCUUA
UAAGACUGUUGCUGCCAGUUU
4431


R-008398962-000M 
2471
166
AUGGAACAUGAGAUGGGUG
CACCCAUCUCAUGUUCCAUUU
4433


R-008398962-000M 
2471
166
AUGGAACAUGAGAUGGGUG
B AUGGAACAUGAGAUGGGUGTT B
4432


R-008398965-000N 
2037
164
UCAGAGGACUAAAUACCAU
AUGGUAUUUAGUCCUCUGAUU
4435


R-008398965-000N 
2037
164
UCAGAGGACUAAAUACCAU
B UCAGAGGACUAAAUACCAUTT B
4434


R-008398968-000P
912
179
CUGGGACCUUGCAUAACCU
AGGUUAUGCAAGGUCCCAGUU
4437


R-008398968-000P
912
179
CUGGGACCUUGCAUAACCU
B CUGGGACCUUGCAUAACCUTT B
4436


R-008398971-000W
2946
1238
AUCUGAAUAAAGUGUAACA
B AUCUGAAUAAAGUGUAACATT B
4438


R-008398971-000W
2946
1238
AUCUGAAUAAAGUGUAACA
UGUUACACUUUAUUCAGAUUU
4439


R-008398974-000X
1654
1239
GCCUGCCAUCUGUGCUCUU
AAGAGCACAGAUGGCAGGCUU
4441


R-008398974-000X
1654
1239
GCCUGCCAUCUGUGCUCUU
B GCCUGCCAUCUGUGCUCUUTT B
4440


R-008398977-000Y
1033
1240
CAUUACAACUCUCCACAAC
B CAUUACAACUCUCCACAACTT B
4442


R-008398977-000Y
1033
1240
CAUUACAACUCUCCACAAC
GUUGUGGAGAGUUGUAAUGUU
4443


R-008398980-000E
840
1241
CUCCUCAGAUGGUGUCUGC
GCAGACACCAUCUGAGGAGUU
4445


R-008398980-000E
840
1241
CUCCUCAGAUGGUGUCUGC
B CUCCUCAGAUGGUGUCUGCTT B
4444


R-008398983-000F
1880
1242
CAGUUGCUUGUUCGUGCAC
GUGCACGAACAAGCAACUGUU
4447


R-008398983-000F
1880
1242
CAGUUGCUUGUUCGUGCAC
B CAGUUGCUUGUUCGUGCACTT B
4446


R-008398986-000G
420
1243
AUCCUGAGGAAGAGGAUGU
B AUCCUGAGGAAGAGGAUGUTT B
4448


R-008398986-000G
420
1243
AUCCUGAGGAAGAGGAUGU
ACAUCCUCUUCCUCAGGAUUU
4449


R-008398989-000H
1005
1244
CACCAGUGGAUUCUGUGUU
B CACCAGUGGAUUCUGUGUUTT B
4450


R-008398989-000H
1005
1244
CACCAGUGGAUUCUGUGUU
AACACAGAAUCCACUGGUGUU
4451


R-008398992-000P
1193
1245
CAAGAAAGCAAGCUCAUCA
B CAAGAAAGCAAGCUCAUCATT B
4452


R-008398992-000P
1193
1245
CAAGAAAGCAAGCUCAUCA
UGAUGAGCUUGCUUUCUUGUU
4453


R-008398995-000R
919
1246
CUUGCAUAACCUUUCCCAU
AUGGGAAAGGUUAUGCAAGUU
4455


R-008398995-000R
919
1246
CUUGCAUAACCUUUCCCAU
B CUUGCAUAACCUUUCCCAUTT B
4454


R-008399001-000F
1727
1247
CUUCACUAUGGACUACCAG
CUGGUAGUCCAUAGUGAAGUU
4457


R-008399001-000F
1727
1247
CUUCACUAUGGACUACCAG
B CUUCACUAUGGACUACCAGTT B
4456


R-008399004-000G
1883
1248
UUGCUUGUUCGUGCACAUC
B UUGCUUGUUCGUGCACAUCTT B
4458


R-008399004-000G
1883
1248
UUGCUUGUUCGUGCACAUC
GAUGUGCACGAACAAGCAAUU
4459


R-008399007-000H
859
1249
UAUUGUACGUACCAUGCAG
B UAUUGUACGUACCAUGCAGTT B
4460


R-008399007-000H
859
1249
UAUUGUACGUACCAUGCAG
CUGCAUGGUACGUACAAUAUU
4461


R-008399010-000P
870
57
CCAUGCAGAAUACAAAUGA
B CCAUGCAGAAUACAAAUGATT B
4462


R-008399010-000P
870
57
CCAUGCAGAAUACAAAUGA
UCAUUUGUAUUCUGCAUGGUU
4463


R-008399013-000R
1812
1250
GAAAUCUUGCCCUUUGUCC
GGACAAAGGGCAAGAUUUCUU
4465


R-008399013-000R
1812
1250
GAAAUCUUGCCCUUUGUCC
B GAAAUCUUGCCCUUUGUCCTT B
4464


R-008399016-000S
1605
1251
CUCUUGUGCGUACUGUCCU
AGGACAGUACGCACAAGAGUU
4467


R-008399016-000S
1605
1251
CUCUUGUGCGUACUGUCCU
B CUCUUGUGCGUACUGUCCUTT B
4466


R-008399019-000T
2021
1252
CACAACCGAAUUGUUAUCA
UGAUAACAAUUCGGUUGUGUU
4469


R-008399019-000T
2021
1252
CACAACCGAAUUGUUAUCA
B CACAACCGAAUUGUUAUCATT B
4468


R-008399022-000Z
2180
1253
GCUCCUCUGACAGAGUUAC
GUAACUCUGUCAGAGGAGCUU
4471


R-008399022-000Z
2180
1253
GCUCCUCUGACAGAGUUAC
B GCUCCUCUGACAGAGUUACTT B
4470


R-008399025-000A
636
1254
AGCGUUUGGCUGAACCAUC
B AGCGUUUGGCUGAACCAUCTT B
4472


R-008399025-000A
636
1254
AGCGUUUGGCUGAACCAUC
GAUGGUUCAGCCAAACGCUUU
4473


R-008399031-000H
871
48
CAUGCAGAAUACAAAUGAU
B CAUGCAGAAUACAAAUGAUTT B
4474


R-008399031-000H
871
48
CAUGCAGAAUACAAAUGAU
AUCAUUUGUAUUCUGCAUGUU
4475


R-008399034-000J
1801
96
UGGAUUGAUUCGAAAUCUU
B UGGAUUGAUUCGAAAUCUUTT B
4476


R-008399034-000J
1801
96
UGGAUUGAUUCGAAAUCUU
AAGAUUUCGAAUCAAUCCAUU
4477


R-008399037-000K
2282
1255
AAACGGCUUUCAGUUGAGC
GCUCAACUGAAAGCCGUUUUU
4479


R-008399037-000K
2282
1255
AAACGGCUUUCAGUUGAGC
B AAACGGCUUUCAGUUGAGCTT B
4478


R-008399040-000S
1824
1256
UUUGUCCCGCAAAUCAUGC
GCAUGAUUUGCGGGACAAAUU
4481


R-008399040-000S
1824
1256
UUUGUCCCGCAAAUCAUGC
B UUUGUCCCGCAAAUCAUGCTT B
4480


R-008399043-000T
2204
1257
UCUAGGAAUGAAGGUGUGG
CCACACCUUCAUUCCUAGAUU
4483


R-008399043-000T
2204
1257
UCUAGGAAUGAAGGUGUGG
B UCUAGGAAUGAAGGUGUGGTT B
4482


R-008399046-000U
450
1258
AAGUCCUGUAUGAGUGGGA
B AAGUCCUGUAUGAGUGGGATT B
4484


R-008399046-000U
450
1258
AAGUCCUGUAUGAGUGGGA
UCCCACUCAUACAGGACUUUU
4485


R-008399049-000V
1001
1259
GGUUCACCAGUGGAUUCUG
B GGUUCACCAGUGGAUUCUGTT B
4486


R-008399049-000V
1001
1259
GGUUCACCAGUGGAUUCUG
CAGAAUCCACUGGUGAACCUU
4487


R-008399052-000B
1579
1260
GGUCUGCCAAGUGGGUGGU
ACCACCCACUUGGCAGACCUU 
4489


R-008399052-000B
1579
1260
GGUCUGCCAAGUGGGUGGU
B GGUCUGCCAAGUGGGUGGUTT B
4488


R-008399055-000C
2179
1261
AGCUCCUCUGACAGAGUUA
UAACUCUGUCAGAGGAGCUUU
4491


R-008399055-000C
2179
1261
AGCUCCUCUGACAGAGUUA
B AGCUCCUCUGACAGAGUUATT B
4490


R-008399058-000D
376
1262
UUCUGGUGCCACUACCACA
B UUCUGGUGCCACUACCACATT B
4492


R-008399058-000D
376
1262
UUCUGGUGCCACUACCACA
UGUGGUAGUGGCACCAGAAUU
4493


R-008399061-000K
556
1263
UGCUAUGUUCCCUGAGACA
B UGCUAUGUUCCCUGAGACATT B
4494


R-008399061-000K
556
1263
UGCUAUGUUCCCUGAGACA
UGUCUCAGGGAACAUAGCAUU
4495


R-008399064-000L
1804
1264
AUUGAUUCGAAAUCUUGCC
B AUUGAUUCGAAAUCUUGCCTT B
4496


R-008399064-000L
1804
1264
AUUGAUUCGAAAUCUUGCC
GGCAAGAUUUCGAAUCAAUUU
4497


R-008399067-000M
2552
1265
CUCAUGGAUGGGCUGCCUC
B CUCAUGGAUGGGCUGCCUCTT B
4498


R-008399067-000M
2552
1265
CUCAUGGAUGGGCUGCCUC
GAGGCAGCCCAUCCAUGAGUU
4499


R-008399070-000U
2071
1266
GCUGCUUUAUUCUCCCAUU
B GCUGCUUUAUUCUCCCAUUTT B
4500


R-008399070-000U
2071
1266
GCUGCUUUAUUCUCCCAUU
AAUGGGAGAAUAAAGCAGCUU
4501


R-008399073-000V
1145
16
UUCUUGGCUAUUACGACAG
B UUCUUGGCUAUUACGACAGTT B
4502


R-008399073-000V
1145
16
UUCUUGGCUAUUACGACAG
CUGUCGUAAUAGCCAAGAAUU
4503


R-008399076-000W
1836
1267
AUCAUGCACCUUUGCGUGA
UCACGCAAAGGUGCAUGAUUU
4505


R-008399076-000W
1836
1267
AUCAUGCACCUUUGCGUGA
B AUCAUGCACCUUUGCGUGATT B
4504


R-008399079-000X
336
1268
GUCACUGGCAGCAACAGUC
B GUCACUGGCAGCAACAGUCTT B
4506


R-008399079-000X
336
1268
GUCACUGGCAGCAACAGUC
GACUGUUGCUGCCAGUGACUU
4507


R-008399082-000D
460
1269
UGAGUGGGAACAGGGAUUU
AAAUCCCUGUUCCCACUCAUU
4509


R-008399082-000D
460
1269
UGAGUGGGAACAGGGAUUU
B UGAGUGGGAACAGGGAUUUTT B
4508


R-008399085-000E
1559
1270
AAUUAUAAGAACAAGAUGA
B AAUUAUAAGAACAAGAUGATT B
4510


R-008399085-000E
1559
1270
AAUUAUAAGAACAAGAUGA
UCAUCUUGUUCUUAUAAUUUU
4511


R-008399091-000M
3136
1271
UGGACAGUUUACCAGUUGC
B UGGACAGUUUACCAGUUGCTT B
4512


R-008399091-000M
3136
1271
UGGACAGUUUACCAGUUGC
GCAACUGGUAAACUGUCCAUU
4513


R-008399097-000P
1250
1272
AUGAGGACCUAUACUUACG
B AUGAGGACCUAUACUUACGTT B
4514


R-008399097-000P
1250
1272
AUGAGGACCUAUACUUACG
CGUAAGUAUAGGUCCUCAUUU
4515


R-008399100-000G
1462
1273
GGAAGGUCUCCUUGGGACU
B GGAAGGUCUCCUUGGGACUTT B
4516


R-008399100-000G
1462
1273
GGAAGGUCUCCUUGGGACU
AGUCCCAAGGAGACCUUCCUU
4517


R-008399103-000H
1965
1274
UGGAAGAAAUAGUUGAAGG
B UGGAAGAAAUAGUUGAAGGTT B
4518


R-008399103-000H
1965
1274
UGGAAGAAAUAGUUGAAGG
CCUUCAACUAUUUCUUCCAUU
4519


R-008399109-000K
3114
1275
GGUGUUAUUUGGAACCUUG
CAAGGUUCCAAAUAACACCUU
4521


R-008399109-000K
3114
1275
GGUGUUAUUUGGAACCUUG
B GGUGUUAUUUGGAACCUUGTT B
4520


R-008399112-000S
1665
1276
GUGCUCUUCGUCAUCUGAC
B GUGCUCUUCGUCAUCUGACTT B
4522


R-008399112-000S
1665
1276
GUGCUCUUCGUCAUCUGAC
GUCAGAUGACGAAGAGCACUU
4523


R-008399115-000T
304
1277
GGCCAUGGAACCAGACAGA
UCUGUCUGGUUCCAUGGCCUU
4525


R-008399115-000T
304
1277
GGCCAUGGAACCAGACAGA
B GGCCAUGGAACCAGACAGATT B
4524


R-008399118-000U
327
1278
CGGCUGUUAGUCACUGGCA
UGCCAGUGACUAACAGCCGUU
4527


R-008399118-000U
327
1278
CGGCUGUUAGUCACUGGCA
B CGGCUGUUAGUCACUGGCATT B
4526


R-008399121-000A
1866
1279
UUCCACGACUAGUUCAGUU
B UUCCACGACUAGUUCAGUUTT B
4528


R-008399121-000A
1866
1279
UUCCACGACUAGUUCAGUU
AACUGAACUAGUCGUGGAAUU
4529


R-008399124-000B
1699
1280
AGCAGAGAUGGCCCAGAAU
AUUCUGGGCCAUCUCUGCUUU
4531


R-008399124-000B
1699
1280
AGCAGAGAUGGCCCAGAAU
B AGCAGAGAUGGCCCAGAAUTT B
4530


R-008399127-000C
2397
1281
GCCAGGAUGAUCCUAGCUA
UAGCUAGGAUCAUCCUGGCUU
4533


R-008399127-000C
2397
1281
GCCAGGAUGAUCCUAGCUA
B GCCAGGAUGAUCCUAGCUATT B
4532


R-008399130-000J
1658
1282
GCCAUCUGUGCUCUUCGUC
B GCCAUCUGUGCUCUUCGUCTT B
4534


R-008399130-000J
1658
1282
GCCAUCUGUGCUCUUCGUC
GACGAAGAGCACAGAUGGCUU
4535


R-008399133-000K
891
1283
UAGAAACAGCUCGUUGUAC
GUACAACGAGCUGUUUCUAUU
4537


R-008399133-000K
891
1283
UAGAAACAGCUCGUUGUAC
B UAGAAACAGCUCGUUGUACTT B
4536


R-008399136-000L
1572
1284
AGAUGAUGGUCUGCCAAGU
B AGAUGAUGGUCUGCCAAGUTT B
4538


R-008399136-000L
1572
1284
AGAUGAUGGUCUGCCAAGU
ACUUGGCAGACCAUCAUCUUU
4539


R-008399139-000M
927
1285
ACCUUUCCCAUCAUCGUGA
B ACCUUUCCCAUCAUCGUGATT B
4540


R-008399139-000M
927
1285
ACCUUUCCCAUCAUCGUGA
UCACGAUGAUGGGAAAGGUUU
4541


R-008399142-000U
290
1286
AUGGAGUUGGACAUGGCCA
UGGCCAUGUCCAACUCCAUUU
4543


R-008399142-000U
290
1286
AUGGAGUUGGACAUGGCCA
B AUGGAGUUGGACAUGGCCATT B
4542


R-008399145-000V
1663
1287
CUGUGCUCUUCGUCAUCUG
CAGAUGACGAAGAGCACAGUU
4545


R-008399145-000V
1663
1287
CUGUGCUCUUCGUCAUCUG
B CUGUGCUCUUCGUCAUCUGTT B
4544


R-008399148-000W
1562
1288
UAUAAGAACAAGAUGAUGG
B UAUAAGAACAAGAUGAUGGTT B
4546


R-008399148-000W
1562
1288
UAUAAGAACAAGAUGAUGG
CCAUCAUCUUGUUCUUAUAUU
4547


R-008399154-000D
2947
1289
UCUGAAUAAAGUGUAACAA
UUGUUACACUUUAUUCAGAUU
4549


R-008399154-000D
2947
1289
UCUGAAUAAAGUGUAACAA
B UCUGAAUAAAGUGUAACAATT B
4548


R-008399157-000E
1711
1290
CCAGAAUGCAGUUCGCCUU
AAGGCGAACUGCAUUCUGGUU
4551


R-008399157-000E
1711
1290
CCAGAAUGCAGUUCGCCUU
B CCAGAAUGCAGUUCGCCUUTT B
4550


R-008399160-000L
1566
1291
AGAACAAGAUGAUGGUCUG
B AGAACAAGAUGAUGGUCUGTT B
4552


R-008399160-000L
1566
1291
AGAACAAGAUGAUGGUCUG
CAGACCAUCAUCUUGUUCUUU
4553


R-008399163-000M
1815
1292
AUCUUGCCCUUUGUCCCGC
GCGGGACAAAGGGCAAGAUUU
4555


R-008399163-000M
1815
1292
AUCUUGCCCUUUGUCCCGC
B AUCUUGCCCUUUGUCCCGCTT B
4554


R-008399166-000N
1087
1293
GCGUUUAGCUGGUGGGCUG
CAGCCCACCAGCUAAACGCUU
4557


R-008399166-000N
1087
1293
GCGUUUAGCUGGUGGGCUG
B GCGUUUAGCUGGUGGGCUGTT B
4556


R-008399169-000P
1495
1294
GGGUUCAGAUGAUAUAAAU
B GGGUUCAGAUGAUAUAAAUTT B
4558


R-008399169-000P
1495
1294
GGGUUCAGAUGAUAUAAAU
AUUUAUAUCAUCUGAACCCUU
4559


R-008399172-000W
1363
1295
UUUAGGACUUCACCUGACA
B UUUAGGACUUCACCUGACATT B
4560


R-008399172-000W
1363
1295
UUUAGGACUUCACCUGACA
UGUCAGGUGAAGUCCUAAAUU
4561


R-008399175-000X
391
1296
CACAGCUCCUUCUCUGAGU
ACUCAGAGAAGGAGCUGUGUU
4563


R-008399175-000X
391
1296
CACAGCUCCUUCUCUGAGU
B CACAGCUCCUUCUCUGAGUTT B
4562


R-008399178-000Y
1392
1297
AACGUCUUGUUCAGAACUG
CAGUUCUGAACAAGACGUUUU
4565


R-008399178-000Y
1392
1297
AACGUCUUGUUCAGAACUG
B AACGUCUUGUUCAGAACUGTT B
4564


R-008399181-000E
1935
1298
CACAGCAGCAAUUUGUGGA
B CACAGCAGCAAUUUGUGGATT B
4566


R-008399181-000E
1935
1298
CACAGCAGCAAUUUGUGGA
UCCACAAAUUGCUGCUGUGUU
4567


R-008399184-000F
1872
1299
GACUAGUUCAGUUGCUUGU
B GACUAGUUCAGUUGCUUGUTT B
4568


R-008399184-000F
1872
1299
GACUAGUUCAGUUGCUUGU
ACAAGCAACUGAACUAGUCUU
4569


R-008399187-000G
1159
1300
GACAGACUGCCUUCAAAUU
AAUUUGAAGGCAGUCUGUCUU
4571


R-008399187-000G
1159
1300
GACAGACUGCCUUCAAAUU
B GACAGACUGCCUUCAAAUUTT B
4570


R-008399190-000N
2308
1301
CUCUCUCUUCAGAACAGAG
CUCUGUUCUGAAGAGAGAGUU
4573


R-008399190-000N
2308
1301
CUCUCUCUUCAGAACAGAG
B CUCUCUCUUCAGAACAGAGTT B
4572


R-008399193-000P
632
1302
GUCCAGCGUUUGGCUGAAC
GUUCAGCCAAACGCUGGACUU
4575


R-008399193-000P
632
1302
GUCCAGCGUUUGGCUGAAC
B GUCCAGCGUUUGGCUGAACTT B
4574


R-008399196-000R
580
173
UGAGGGCAUGCAGAUCCCA
B UGAGGGCAUGCAGAUCCCATT B
4576


R-008399196-000R
580
173
UGAGGGCAUGCAGAUCCCA
UGGGAUCUGCAUGCCCUCAUU
4577


R-008399199-000S
1564
1303
UAAGAACAAGAUGAUGGUC
B UAAGAACAAGAUGAUGGUCTT B
4578


R-008399199-000S
1564
1303
UAAGAACAAGAUGAUGGUC
GACCAUCAUCUUGUUCUUAUU
4579


R-008399202-000J
1384
1304
UCCAAGUCAACGUCUUGUU
B UCCAAGUCAACGUCUUGUUTT B
4580


R-008399202-000J
1384
1304
UCCAAGUCAACGUCUUGUU
AACAAGACGUUGACUUGGAUU
4581


R-008399205-000K
1690
1305
ACACCAAGAAGCAGAGAUG
B ACACCAAGAAGCAGAGAUGTT B
4582


R-008399205-000K
1690
1305
ACACCAAGAAGCAGAGAUG
CAUCUCUGCUUCUUGGUGUUU
4583


R-008399208-000L
1421
1306
CUCAGGAAUCUUUCAGAUG
B CUCAGGAAUCUUUCAGAUGTT B
4584


R-008399208-000L
1421
1306
CUCAGGAAUCUUUCAGAUG
CAUCUGAAAGAUUCCUGAGUU
4585


R-008399211-000T
1141
1307
UAAAUUCUUGGCUAUUACG
B UAAAUUCUUGGCUAUUACGTT B
4586


R-008399211-000T
1141
1307
UAAAUUCUUGGCUAUUACG
CGUAAUAGCCAAGAAUUUAUU
4587


R-008399214-000U
1732
1308
CUAUGGACUACCAGUUGUG
B CUAUGGACUACCAGUUGUGTT B
4588


R-008399214-000U
1732
1308
CUAUGGACUACCAGUUGUG
CACAACUGGUAGUCCAUAGUU
4589


R-008399217-000V
634
1309
CCAGCGUUUGGCUGAACCA
B CCAGCGUUUGGCUGAACCATT B
4590


R-008399217-000V
634
1309
CCAGCGUUUGGCUGAACCA
UGGUUCAGCCAAACGCUGGUU
4591


R-008399220-000B
932
1310
UCCCAUCAUCGUGAGGGCU
B UCCCAUCAUCGUGAGGGCUTT B
4592


R-008399220-000B
932
1310
UCCCAUCAUCGUGAGGGCU
AGCCCUCACGAUGAUGGGAUU
4593


R-008399223-000C
579
171
AUGAGGGCAUGCAGAUCCC
GGGAUCUGCAUGCCCUCAUUU
4595


R-008399223-000C
579
171
AUGAGGGCAUGCAGAUCCC
B AUGAGGGCAUGCAGAUCCCTT B
4594


R-008399226-000D
1366
1311
AGGACUUCACCUGACAGAU
AUCUGUCAGGUGAAGUCCUUU
4597


R-008399226-000D
1366
1311
AGGACUUCACCUGACAGAU
B AGGACUUCACCUGACAGAUTT B
4596


R-008399229-000E
1608
1312
UUGUGCGUACUGUCCUUCG
B UUGUGCGUACUGUCCUUCGTT B
4598


R-008399229-000E
1608
1312
UUGUGCGUACUGUCCUUCG
CGAAGGACAGUACGCACAAUU
4599


R-008399232-000L
814
10
AGCUUCCAGACACGCUAUC
GAUAGCGUGUCUGGAAGCUUU
4601


R-008399232-000L
814
10
AGCUUCCAGACACGCUAUC
B AGCUUCCAGACACGCUAUCTT B
4600


R-008399235-000M
1923
1313
CCAUGGGUGGGACACAGCA
B CCAUGGGUGGGACACAGCATT B
4602


R-008399235-000M
1923
1313
CCAUGGGUGGGACACAGCA
UGCUGUGUCCCACCCAUGGUU
4603


R-008399238-000N
1458
1314
GGAUGGAAGGUCUCCUUGG
CCAAGGAGACCUUCCAUCCUU
4605


R-008399238-000N
1458
1314
GGAUGGAAGGUCUCCUUGG
B GGAUGGAAGGUCUCCUUGGTT B
4604


R-008399241-000V
1908
1315
CCCAGCGCCGUACGUCCAU
B CCCAGCGCCGUACGUCCAUTT B
4606


R-008399241-000V
1908
1315
CCCAGCGCCGUACGUCCAU
AUGGACGUACGGCGCUGGGUU
4607


R-008399244-000W
539
1316
GCUCAGAGGGUACGAGCUG
CAGCUCGUACCCUCUGAGCUU
4609


R-008399244-000W
539
1316
GCUCAGAGGGUACGAGCUG
B GCUCAGAGGGUACGAGCUGTT B
4608


R-008399247-000X
2016
1317
AUGUUCACAACCGAAUUGU
ACAAUUCGGUUGUGAACAUUU
4611


R-008399247-000X
2016
1317
AUGUUCACAACCGAAUUGU
B AUGUUCACAACCGAAUUGUTT B
4610


R-008399250-000D
1884
1318
UGCUUGUUCGUGCACAUCA
B UGCUUGUUCGUGCACAUCATT B
4612


R-008399250-000D
1884
1318
UGCUUGUUCGUGCACAUCA
UGAUGUGCACGAACAAGCAUU
4613


R-008399253-000E
560
1319
AUGUUCCCUGAGACAUUAG
B AUGUUCCCUGAGACAUUAGTT B
4614


R-008399253-000E
560
1319
AUGUUCCCUGAGACAUUAG
CUAAUGUCUCAGGGAACAUUU
4615


R-008399256-000F
411
1320
GUAAAGGCAAUCCUGAGGA
UCCUCAGGAUUGCCUUUACUU
4617


R-008399256-000F
411
1320
GUAAAGGCAAUCCUGAGGA
B GUAAAGGCAAUCCUGAGGATT B
4616


R-008399259-000G
338
1321
CACUGGCAGCAACAGUCUU
AAGACUGUUGCUGCCAGUGUU
4619


R-008399259-000G
338
1321
CACUGGCAGCAACAGUCUU
B CACUGGCAGCAACAGUCUUTT B
4618


R-008399262-000N
830
1322
AUCAUGCGUUCUCCUCAGA
UCUGAGGAGAACGCAUGAUUU
4621


R-008399262-000N
830
1322
AUCAUGCGUUCUCCUCAGA
B AUCAUGCGUUCUCCUCAGATT B
4620


R-008399265-000P
3086
1323
UAUGUAUGGGUAGGGUAAA
B UAUGUAUGGGUAGGGUAAATT B
4622


R-008399265-000P
3086
1323
UAUGUAUGGGUAGGGUAAA
UUUACCCUACCCAUACAUAUU
4623


R-008399268-000R
3115
1324
GUGUUAUUUGGAACCUUGU
ACAAGGUUCCAAAUAACACUU
4625


R-008399268-000R
3115
1324
GUGUUAUUUGGAACCUUGU
B GUGUUAUUUGGAACCUUGUTT B
4624


R-008399271-000X
2177
1325
ACAGCUCCUCUGACAGAGU
B ACAGCUCCUCUGACAGAGUTT B
4626


R-008399271-000X
2177
1325
ACAGCUCCUCUGACAGAGU
ACUCUGUCAGAGGAGCUGUUU
4627


R-008399274-000Y
1733
1326
UAUGGACUACCAGUUGUGG
B UAUGGACUACCAGUUGUGGTT B
4628


R-008399274-000Y
1733
1326
UAUGGACUACCAGUUGUGG
CCACAACUGGUAGUCCAUAUU
4629


R-008399277-000Z
375
1327
AUUCUGGUGCCACUACCAC
GUGGUAGUGGCACCAGAAUUU
4631


R-008399277-000Z
375
1327
AUUCUGGUGCCACUACCAC
B AUUCUGGUGCCACUACCACTT B
4630


R-008399280-000F
2565
1328
UGCCUCCAGGUGACAGCAA
B UGCCUCCAGGUGACAGCAATT B
4632


R-008399280-000F
2565
1328
UGCCUCCAGGUGACAGCAA
UUGCUGUCACCUGGAGGCAUU
4633


R-008399283-000G
442
1329
UACCUCCCAAGUCCUGUAU
AUACAGGACUUGGGAGGUAUU
4635


R-008399283-000G
442
1329
UACCUCCCAAGUCCUGUAU
B UACCUCCCAAGUCCUGUAUTT B
4634


R-008399286-000H
819
1330
CCAGACACGCUAUCAUGCG
CGCAUGAUAGCGUGUCUGGUU
4637


R-008399286-000H
819
1330
CCAGACACGCUAUCAUGCG
B CCAGACACGCUAUCAUGCGTT B
4636


R-008399289-000J
700
1331
UGAUGCAGAACUUGCCACA
B UGAUGCAGAACUUGCCACATT B
4638


R-008399289-000J
700
1331
UGAUGCAGAACUUGCCACA
UGUGGCAAGUUCUGCAUCAUU
4639


R-008399292-000R
1089
1332
GUUUAGCUGGUGGGCUGCA
B GUUUAGCUGGUGGGCUGCATT B
4640


R-008399292-000R
1089
1332
GUUUAGCUGGUGGGCUGCA
UGCAGCCCACCAGCUAAACUU
4641


R-008399295-000S
1580
1333
GUCUGCCAAGUGGGUGGUA
UACCACCCACUUGGCAGACUU
4643


R-008399295-000S
1580
1333
GUCUGCCAAGUGGGUGGUA
B GUCUGCCAAGUGGGUGGUATT B
4642


R-008399298-000T
1982
1334
GGUUGUACCGGAGCCCUUC
GAAGGGCUCCGGUACAACCUU
4645


R-008399298-000T
1982
1334
GGUUGUACCGGAGCCCUUC
B GGUUGUACCGGAGCCCUUCTT B
4644


R-008399301-000K
1986
1335
GUACCGGAGCCCUUCACAU
B GUACCGGAGCCCUUCACAUTT B
4646


R-008399301-000K
1986
1335
GUACCGGAGCCCUUCACAU
AUGUGAAGGGCUCCGGUACUU
4647


R-008399304-000L
418
1336
CAAUCCUGAGGAAGAGGAU
AUCCUCUUCCUCAGGAUUGUU
4649


R-008399304-000L
418
1336
CAAUCCUGAGGAAGAGGAU
B CAAUCCUGAGGAAGAGGAUTT B
4648


R-008399307-000M
1306
1337
GCUAUCUGUCUGCUCUAGU
ACUAGAGCAGACAGAUAGCUU
4651


R-008399307-000M
1306
1337
GCUAUCUGUCUGCUCUAGU
B GCUAUCUGUCUGCUCUAGUTT B
4650


R-008399310-000U
1377
1338
UGACAGAUCCAAGUCAACG
CGUUGACUUGGAUCUGUCAUU
4653


R-008399310-000U
1377
1338
UGACAGAUCCAAGUCAACG
B UGACAGAUCCAAGUCAACGTT B
4652


R-008399313-000V
2467
1339
CAUGAUGGAACAUGAGAUG
CAUCUCAUGUUCCAUCAUGUU
4655


R-008399313-000V
2467
1339
CAUGAUGGAACAUGAGAUG
B CAUGAUGGAACAUGAGAUGTT B
4654


R-008399316-000W
1414
1340
UUGGACUCUCAGGAAUCUU
B UUGGACUCUCAGGAAUCUUTT B
4656


R-008399316-000W
1414
1340
UUGGACUCUCAGGAAUCUU
AAGAUUCCUGAGAGUCCAAUU
4657


R-008399319-000X
1668
1341
CUCUUCGUCAUCUGACCAG
B CUCUUCGUCAUCUGACCAGTT B
4658


R-008399319-000X
1668
1341
CUCUUCGUCAUCUGACCAG
CUGGUCAGAUGACGAAGAGUU
4659


R-008399322-000D
1818
1342
UUGCCCUUUGUCCCGCAAA
B UUGCCCUUUGUCCCGCAAATT B
4660


R-008399322-000D
1818
1342
UUGCCCUUUGUCCCGCAAA
UUUGCGGGACAAAGGGCAAUU
4661


R-008399325-000E
1697
1343
GAAGCAGAGAUGGCCCAGA
B GAAGCAGAGAUGGCCCAGATT B
4662


R-008399325-000E
1697
1343
GAAGCAGAGAUGGCCCAGA
UCUGGGCCAUCUCUGCUUCUU
4663


R-008399328-000F
918
1344
CCUUGCAUAACCUUUCCCA
B CCUUGCAUAACCUUUCCCATT B
4664


R-008399328-000F
918
1344
CCUUGCAUAACCUUUCCCA 
UGGGAAAGGUUAUGCAAGGUU
4665


R-008399331-000M
605
1345
CAGUUUGAUGCUGCUCAUC
GAUGAGCAGCAUCAAACUGUU
4667


R-008399331-000M
605
1345
CAGUUUGAUGCUGCUCAUC
B CAGUUUGAUGCUGCUCAUCTT B
4666


R-008399334-000N
1374
1346
ACCUGACAGAUCCAAGUCA
B ACCUGACAGAUCCAAGUCATT B
4668


R-008399334-000N
1374
1346
ACCUGACAGAUCCAAGUCA
UGACUUGGAUCUGUCAGGUUU
4669


R-008399337-000P
1430
1347
CUUUCAGAUGCUGCAACUA
UAGUUGCAGCAUCUGAAAGUU
4671


R-008399337-000P
1430
1347
CUUUCAGAUGCUGCAACUA
B CUUUCAGAUGCUGCAACUATT B
4670


R-008399340-000W
3186
1348
GAUACGAUGCUUCAAGAGA
UCUCUUGAAGCAUCGUAUCUU
4673


R-008399340-000W
3186
1348
GAUACGAUGCUUCAAGAGA
B GAUACGAUGCUUCAAGAGATT B
4672


R-008399343-000X 
1355
1349
AUGCAAGCUUUAGGACUUC
B AUGCAAGCUUUAGGACUUCTT B
4674


R-008399343-000X 
1355
1349
AUGCAAGCUUUAGGACUUC
GAAGUCCUAAAGCUUGCAUUU
4675


R-008399346-000Y
433
1350
GGAUGUGGAUACCUCCCAA
UUGGGAGGUAUCCACAUCCUU
4677


R-008399346-000Y
433
1350
GGAUGUGGAUACCUCCCAA
B GGAUGUGGAUACCUCCCAATT B
4676


R-008399349-000Z
1901
13
CAGGAUACCCAGCGCCGUA
B CAGGAUACCCAGCGCCGUATT B
4678


R-008399349-000Z
1901
13
CAGGAUACCCAGCGCCGUA
UACGGCGCUGGGUAUCCUGUU
4679


R-008399352-000F
1713
1351
AGAAUGCAGUUCGCCUUCA
UGAAGGCGAACUGCAUUCUUU
4681


R-008399352-000F
1713
1351
AGAAUGCAGUUCGCCUUCA
B AGAAUGCAGUUCGCCUUCATT B
4680


R-008399355-000G
823
17
ACACGCUAUCAUGCGUUCU
AGAACGCAUGAUAGCGUGUUU
4683


R-008399355-000G
823
17
ACACGCUAUCAUGCGUUCU
B ACACGCUAUCAUGCGUUCUTT B
4682


R-008399358-000H
1811
1352
CGAAAUCUUGCCCUUUGUC
B CGAAAUCUUGCCCUUUGUCTT B
4684


R-008399358-000H
1811
1352
CGAAAUCUUGCCCUUUGUC
GACAAAGGGCAAGAUUUCGUU
4685


R-008399361-000P
491
1353
ACUCAAGAACAAGUAGCUG
B ACUCAAGAACAAGUAGCUGTT B
4686


R-008399361-000P
491
1353
ACUCAAGAACAAGUAGCUG
CAGCUACUUGUUCUUGAGUUU
4687


R-008399364-000R
2209
1354
GAAUGAAGGUGUGGCGACA
UGUCGCCACACCUUCAUUCUU
4689


R-008399364-000R
2209
1354
GAAUGAAGGUGUGGCGACA
B GAAUGAAGGUGUGGCGACATT B
4688


R-008399367-000S
1840
1355
UGCACCUUUGCGUGAGCAG
B UGCACCUUUGCGUGAGCAGTT B
4690


R-008399367-000S
1840
1355
UGCACCUUUGCGUGAGCAG
CUGCUCACGCAAAGGUGCAUU
4691


R-008399370-000Y
550
1356
ACGAGCUGCUAUGUUCCCU
AGGGAACAUAGCAGCUCGUUU
4693


R-008399370-000Y
550
1356
ACGAGCUGCUAUGUUCCCU
B ACGAGCUGCUAUGUUCCCUTT B
4692


R-008399373-000Z
429
1357
AAGAGGAUGUGGAUACCUC
GAGGUAUCCACAUCCUCUUUU
4695


R-008399373-000Z
429
1357
AAGAGGAUGUGGAUACCUC
B AAGAGGAUGUGGAUACCUCTT B
4694


R-008399376-000A
2436
1358
GAUAUGGCCAGGAUGCCUU
AAGGCAUCCUGGCCAUAUCUU
4697


R-008399376-000A
2436
1358
GAUAUGGCCAGGAUGCCUU
B GAUAUGGCCAGGAUGCCUUTT B
4696


R-008399379-000B
1597
1359
UAUAGAGGCUCUUGUGCGU
B UAUAGAGGCUCUUGUGCGUTT B
4698


R-008399379-000B
1597
1359
UAUAGAGGCUCUUGUGCGU
ACGCACAAGAGCCUCUAUAUU
4699


R-008399382-000H
1496
1360
GGUUCAGAUGAUAUAAAUG
B GGUUCAGAUGAUAUAAAUGTT B
4700


R-008399382-000H
1496
1360
GGUUCAGAUGAUAUAAAUG
CAUUUAUAUCAUCUGAACCUU
4701


R-008399385-000J
1456
1361
AGGGAUGGAAGGUCUCCUU
AAGGAGACCUUCCAUCCCUUU
4703


R-008399385-000J
1456
1361
AGGGAUGGAAGGUCUCCUU
B AGGGAUGGAAGGUCUCCUUTT B
4702


R-008399388-000K
3159
1362
UAUCCCAAAGUUGUUGUAA
UUACAACAACUUUGGGAUAUU
4705


R-008399388-000K
3159
1362
UAUCCCAAAGUUGUUGUAA
B UAUCCCAAAGUUGUUGUAATT B
4704


R-008399391-000S
2309
1363
UCUCUCUUCAGAACAGAGC
B UCUCUCUUCAGAACAGAGCTT B
4706


R-008399391-000S
2309
1363
UCUCUCUUCAGAACAGAGC
GCUCUGUUCUGAAGAGAGAUU
4707


R-008399394-000T
2300
1364
CUGACCAGCUCUCUCUUCA
B CUGACCAGCUCUCUCUUCATT B
4708


R-008399394-000T
2300
1364
CUGACCAGCUCUCUCUUCA
UGAAGAGAGAGCUGGUCAGUU
4709


R-008399397-000U
3177
1365
ACCUGCUGUGAUACGAUGC
B ACCUGCUGUGAUACGAUGCTT B
4710


R-008399397-000U
3177
1365
ACCUGCUGUGAUACGAUGC
GCAUCGUAUCACAGCAGGUUU
4711


R-008399400-000L
1079
1366
AUGGCAGUGCGUUUAGCUG
B AUGGCAGUGCGUUUAGCUGTT B
4712


R-008399400-000L
1079
1366
AUGGCAGUGCGUUUAGCUG
CAGCUAAACGCACUGCCAUUU
4713


R-008399403-000M
1383
1367
AUCCAAGUCAACGUCUUGU
ACAAGACGUUGACUUGGAUUU
4715


R-008399403-000M
1383
1367
AUCCAAGUCAACGUCUUGU
B AUCCAAGUCAACGUCUUGUTT B
4714


R-008399406-000N
2563
1368
GCUGCCUCCAGGUGACAGC
GCUGUCACCUGGAGGCAGCUU
4717


R-008399406-000N
2563
1368
GCUGCCUCCAGGUGACAGC
B GCUGCCUCCAGGUGACAGCTT B
4716


R-008399409-000P
1084
1369
AGUGCGUUUAGCUGGUGGG
B AGUGCGUUUAGCUGGUGGGTT B
4718


R-008399409-000P
1084
1369
AGUGCGUUUAGCUGGUGGG
CCCACCAGCUAAACGCACUUU
4719


R-008399412-000W
1329
1370
AGCCGGCUAUUGUAGAAGC
B AGCCGGCUAUUGUAGAAGCTT B
4720


R-008399412-000W
1329
1370
AGCCGGCUAUUGUAGAAGC
GCUUCUACAAUAGCCGGCUUU
4721


R-008399415-000X
1662
169
UCUGUGCUCUUCGUCAUCU
AGAUGACGAAGAGCACAGAUU
4723


R-008399415-000X
1662
169
UCUGUGCUCUUCGUCAUCU
B UCUGUGCUCUUCGUCAUCUTT B
4722


R-008399418-000Y
2268
99
CACAAGAUUACAAGAAACG
CGUUUCUUGUAAUCUUGUGUU
4725


R-008399418-000Y
2268
99
CACAAGAUUACAAGAAACG
B CACAAGAUUACAAGAAACGTT B
4724


R-008399421-000E
2470
108
GAUGGAACAUGAGAUGGGU
B GAUGGAACAUGAGAUGGGUTT B
4726


R-008399421-000E
2470
108
GAUGGAACAUGAGAUGGGU
ACCCAUCUCAUGUUCCAUCUU
4727


R-008399424-000F
573
1371
CAUUAGAUGAGGGCAUGCA
B CAUUAGAUGAGGGCAUGCATT B
4728


R-008399424-000F
573
1371
CAUUAGAUGAGGGCAUGCA
UGCAUGCCCUCAUCUAAUGUU
4729


R-008399427-000G
2213
1372
GAAGGUGUGGCGACAUAUG
B GAAGGUGUGGCGACAUAUGTT B
4730


R-008399427-000G
2213
1372
GAAGGUGUGGCGACAUAUG
CAUAUGUCGCCACACCUUCUU
4731


R-008399430-000N
1587
1373
AAGUGGGUGGUAUAGAGGC
B AAGUGGGUGGUAUAGAGGCTT B
4732


R-008399430-000N
1587
1373
AAGUGGGUGGUAUAGAGGC
GCCUCUAUACCACCCACUUUU
4733


R-008399433-000P
2166
1374
CUGAGGGAGCCACAGCUCC
B CUGAGGGAGCCACAGCUCCTT B
4734


R-008399433-000P
2166
1374
CUGAGGGAGCCACAGCUCC
GGAGCUGUGGCUCCCUCAGUU
4735


R-008399436-000R
637
1375
GCGUUUGGCUGAACCAUCA
UGAUGGUUCAGCCAAACGCUU
4737


R-008399436-000R
637
1375
GCGUUUGGCUGAACCAUCA
B GCGUUUGGCUGAACCAUCATT B
4736


R-008399439-000S
397
1376
UCCUUCUCUGAGUGGUAAA
B UCCUUCUCUGAGUGGUAAATT B
4738


R-008399439-000S
397
1376
UCCUUCUCUGAGUGGUAAA
UUUACCACUCAGAGAAGGAUU
4739


R-008399442-000Y
1718
1377
GCAGUUCGCCUUCACUAUG
B GCAGUUCGCCUUCACUAUGTT B
4740


R-008399442-000Y
1718
1377
GCAGUUCGCCUUCACUAUG
CAUAGUGAAGGCGAACUGCUU
4741


R-008399445-000Z
1415
111
UGGACUCUCAGGAAUCUUU
B UGGACUCUCAGGAAUCUUUTT B
4742


R-008399445-000Z
1415
111
UGGACUCUCAGGAAUCUUU
AAAGAUUCCUGAGAGUCCAUU
4743


R-008399448-000A
1413
162
UUUGGACUCUCAGGAAUCU
B UUUGGACUCUCAGGAAUCUTT B
4744


R-008399448-000A
1413
162
UUUGGACUCUCAGGAAUCU
AGAUUCCUGAGAGUCCAAAUU
4745


R-008399451-000G
2445
160
AGGAUGCCUUGGGUAUGGA
B AGGAUGCCUUGGGUAUGGATT B
4746


R-008399451-000G
2445
160
AGGAUGCCUUGGGUAUGGA
UCCAUACCCAAGGCAUCCUUU
4747


R-008399454-000H
567
157
CUGAGACAUUAGAUGAGGG
B CUGAGACAUUAGAUGAGGGTT B
4748


R-008399454-000H
567
157
CUGAGACAUUAGAUGAGGG
CCCUCAUCUAAUGUCUCAGUU
4749


R-008399457-000J
1498
86
UUCAGAUGAUAUAAAUGUG
CACAUUUAUAUCAUCUGAAUU
4751


R-008399457-000J
1498
86
UUCAGAUGAUAUAAAUGUG
B UUCAGAUGAUAUAAAUGUGTT B
4750


R-008399460-000R
2357
1378
GGACUUGAUAUUGGUGCCC
B GGACUUGAUAUUGGUGCCCTT B
4752


R-008399460-000R
2357
1378
GGACUUGAUAUUGGUGCCC
GGGCACCAAUAUCAAGUCCUU
4753


R-008399463-000S
639
1379
GUUUGGCUGAACCAUCACA
UGUGAUGGUUCAGCCAAACUU
4755


R-008399463-000S
639
1379
GUUUGGCUGAACCAUCACA
B GUUUGGCUGAACCAUCACATT B
4754


R-008399466-000T
585
1380
GCAUGCAGAUCCCAUCUAC
GUAGAUGGGAUCUGCAUGCUU
4757


R-008399466-000T
585
1380
GCAUGCAGAUCCCAUCUAC
B GCAUGCAGAUCCCAUCUACTT B
4756


R-008399469-000U
2519
1381
GAUGGGCUGCCAGAUCUGG
B GAUGGGCUGCCAGAUCUGGTT B
4758


R-008399469-000U
2519
1381
GAUGGGCUGCCAGAUCUGG
CCAGAUCUGGCAGCCCAUCUU
4759


R-008399472-000A
1367
1382
GGACUUCACCUGACAGAUC
B GGACUUCACCUGACAGAUCTT B
4760


R-008399472-000A
1367
1382
GGACUUCACCUGACAGAUC
GAUCUGUCAGGUGAAGUCCUU
4761


R-008399475-000B
1391
1383
CAACGUCUUGUUCAGAACU
B CAACGUCUUGUUCAGAACUTT B
4762


R-008399475-000B
1391
1383
CAACGUCUUGUUCAGAACU
AGUUCUGAACAAGACGUUGUU
4763


R-008399478-000C
509
1384
GAUAUUGAUGGACAGUAUG
B GAUAUUGAUGGACAGUAUGTT B
4764


R-008399478-000C
509
1384
GAUAUUGAUGGACAGUAUG
CAUACUGUCCAUCAAUAUCUU
4765


R-008399481-000J
303
1385
UGGCCAUGGAACCAGACAG
B UGGCCAUGGAACCAGACAGTT B
4766


R-008399481-000J
303
1385
UGGCCAUGGAACCAGACAG
CUGUCUGGUUCCAUGGCCAUU
4767


R-008399484-000K
494
1386
CAAGAACAAGUAGCUGAUA
UAUCAGCUACUUGUUCUUGUU
4769


R-008399484-000K
494
1386
CAAGAACAAGUAGCUGAUA
B CAAGAACAAGUAGCUGAUATT B
4768


R-008399487-000L
328
1387
GGCUGUUAGUCACUGGCAG
CUGCCAGUGACUAACAGCCUU
4771


R-008399487-000L
328
1387
GGCUGUUAGUCACUGGCAG
B GGCUGUUAGUCACUGGCAGTT B
4770


R-008399490-000T
2058
1388
CAUUGUUUGUGCAGCUGCU
AGCAGCUGCACAAACAAUGUU
4773


R-008399490-000T
2058
1388
CAUUGUUUGUGCAGCUGCU
B CAUUGUUUGUGCAGCUGCUTT B
4772


R-008399493-000U
1447
1389
UAAACAGGAAGGGAUGGAA
B UAAACAGGAAGGGAUGGAATT B
4774


R-008399493-000U
1447
1389
UAAACAGGAAGGGAUGGAA
UUCCAUCCCUUCCUGUUUAUU
4775


R-008399496-000V
1563
1390
AUAAGAACAAGAUGAUGGU
ACCAUCAUCUUGUUCUUAUUU
4777


R-008399496-000V
1563
1390
AUAAGAACAAGAUGAUGGU
B AUAAGAACAAGAUGAUGGUTT B
4776


R-008399499-000W
1350
1391
GUGGAAUGCAAGCUUUAGG
CCUAAAGCUUGCAUUCCACUU
4779


R-008399499-000W
1350
1391
GUGGAAUGCAAGCUUUAGG
B GUGGAAUGCAAGCUUUAGGTT B
4778


R-008399502-000N
2208
1392
GGAAUGAAGGUGUGGCGAC
GUCGCCACACCUUCAUUCCUU
4781


R-008399502-000N
2208
1392
GGAAUGAAGGUGUGGCGAC
B GGAAUGAAGGUGUGGCGACTT B
4780


R-008399505-000P
1689
1393
GACACCAAGAAGCAGAGAU
AUCUCUGCUUCUUGGUGUCUU
4783


R-008399505-000P
1689
1393
GACACCAAGAAGCAGAGAU
B GACACCAAGAAGCAGAGAUTT B
4782


R-008399508-000R
1407
1394
ACUGUCUUUGGACUCUCAG
B ACUGUCUUUGGACUCUCAGTT B
4784


R-008399508-000R
1407
1394
ACUGUCUUUGGACUCUCAG
CUGAGAGUCCAAAGACAGUUU
4785


R-008399511-000X
2137
1395
GGACAAGGAAGCUGCAGAA
B GGACAAGGAAGCUGCAGAATT B
4786


R-008399511-000X
2137
1395
GGACAAGGAAGCUGCAGAA
UUCUGCAGCUUCCUUGUCCUU
4787


R-008399514-000Y
854
1396
UCUGCUAUUGUACGUACCA
B UCUGCUAUUGUACGUACCATT B
4788


R-008399514-000Y
854
1396
UCUGCUAUUGUACGUACCA
UGGUACGUACAAUAGCAGAUU
4789


R-008399517-000Z 
2070
1397
AGCUGCUUUAUUCUCCCAU
AUGGGAGAAUAAAGCAGCUUU
4791


R-008399517-000Z 
2070
1397
AGCUGCUUUAUUCUCCCAU
B AGCUGCUUUAUUCUCCCAUTT B
4790


R-008399520-000F
545
1398
AGGGUACGAGCUGCUAUGU
ACAUAGCAGCUCGUACCCUUU
4793


R-008399520-000F
545
1398
AGGGUACGAGCUGCUAUGU
B AGGGUACGAGCUGCUAUGUTT B
4792


R-008399523-000G 
1640
1399
GAAGACAUCACUGAGCCUG
B GAAGACAUCACUGAGCCUGTT B
4794


R-008399523-000G 
1640
1399
GAAGACAUCACUGAGCCUG
CAGGCUCAGUGAUGUCUUCUU
4795


R-008399526-000H 
2012
1400
CGGGAUGUUCACAACCGAA
UUCGGUUGUGAACAUCCCGUU
4797


R-008399526-000H 
2012
1400
CGGGAUGUUCACAACCGAA
B CGGGAUGUUCACAACCGAATT B
4796


R-008399529-000J 
1684
1401
CAGCCGACACCAAGAAGCA
B CAGCCGACACCAAGAAGCATT B
4798


R-008399529-000J 
1684
1401
CAGCCGACACCAAGAAGCA
UGCUUCUUGGUGUCGGCUGUU
4799


R-008399535-000S
520
9
ACAGUAUGCAAUGACUCGA
UCGAGUCAUUGCAUACUGUUU
4801


R-008399535-000S
520
9
ACAGUAUGCAAUGACUCGA
B ACAGUAUGCAAUGACUCGATT B
4800


R-008399538-000T 
1969
182
AGAAAUAGUUGAAGGUUGU
B AGAAAUAGUUGAAGGUUGUTT B
4802


R-008399538-000T 
1969
182
AGAAAUAGUUGAAGGUUGU
ACAACCUUCAACUAUUUCUUU
4803


R-008399541-000Z 
2017
1402
UGUUCACAACCGAAUUGUU
B UGUUCACAACCGAAUUGUUTT B 
4804


R-008399541-000Z 
2017
1402
UGUUCACAACCGAAUUGUU
AACAAUUCGGUUGUGAACAUU
4805


R-008399544-000A 
2307
1403
GCUCUCUCUUCAGAACAGA
B GCUCUCUCUUCAGAACAGATT B
4806


R-008399544-000A 
2307
1403
GCUCUCUCUUCAGAACAGA
UCUGUUCUGAAGAGAGAGCUU
4807


R-008399547-000B
844
1404
UCAGAUGGUGUCUGCUAUU
B UCAGAUGGUGUCUGCUAUUTT B 
4808


R-008399547-000B
844
1404
UCAGAUGGUGUCUGCUAUU
AAUAGCAGACACCAUCUGAUU
4809


R-008399550-000H
405
1405
UGAGUGGUAAAGGCAAUCC
GGAUUGCCUUUACCACUCAUU
4811


R-008399550-000H
405
1405
UGAGUGGUAAAGGCAAUCC
B UGAGUGGUAAAGGCAAUCCTT B
4810


R-008399553-000J
379
1406
UGGUGCCACUACCACAGCU
B UGGUGCCACUACCACAGCUTT B 
4812


R-008399553-000J
379
1406
UGGUGCCACUACCACAGCU
AGCUGUGGUAGUGGCACCAUU
4813


R-008399556-000K
1825
1407
UUGUCCCGCAAAUCAUGCA
B UUGUCCCGCAAAUCAUGCATT B
4814


R-008399556-000K
1825
1407
UUGUCCCGCAAAUCAUGCA
UGCAUGAUUUGCGGGACAAUU
4815


R-008399559-000L
2495
1408
CACCCUGGUGCUGACUAUC
GAUAGUCAGCACCAGGGUGUU
4817


R-008399559-000L
2495
1408
CACCCUGGUGCUGACUAUC
B CACCCUGGUGCUGACUAUCTT B 
4816


R-008399562-000T
629
1409
AAUGUCCAGCGUUUGGCUG
B AAUGUCCAGCGUUUGGCUGTT B 
4818


R-008399562-000T
629
1409
AAUGUCCAGCGUUUGGCUG
CAGCCAAACGCUGGACAUUUU
4819


R-008399565-000U
2561
1410
GGGCUGCCUCCAGGUGACA
UGUCACCUGGAGGCAGCCCUU
4821


R-008399565-000U
2561
1410
GGGCUGCCUCCAGGUGACA
B GGGCUGCCUCCAGGUGACATT B
4820


R-008399568-000V
2192
1411
GAGUUACUUCACUCUAGGA
B GAGUUACUUCACUCUAGGATT B
4822


R-008399568-000V
2192
1411
GAGUUACUUCACUCUAGGA
UCCUAGAGUGAAGUAACUCUU
4823


R-008399571-000B
1809
1412
UUCGAAAUCUUGCCCUUUG
B UUCGAAAUCUUGCCCUUUGTT B
4824


R-008399571-000B
1809
1412
UUCGAAAUCUUGCCCUUUG
CAAAGGGCAAGAUUUCGAAUU
4825


R-008399574-000C
1596
1413
GUAUAGAGGCUCUUGUGCG
B GUAUAGAGGCUCUUGUGCGTT B
4826


R-008399574-000C
1596
1413
GUAUAGAGGCUCUUGUGCG
CGCACAAGAGCCUCUAUACUU
4827


R-008399577-000D
2298
1414
AGCUGACCAGCUCUCUCUU
AAGAGAGAGCUGGUCAGCUUU
4829


R-008399577-000D
2298
1414
AGCUGACCAGCUCUCUCUU
B AGCUGACCAGCUCUCUCUUTT B
4828


R-008399580-000K
858
1415
CUAUUGUACGUACCAUGCA
UGCAUGGUACGUACAAUAGUU
4831


R-008399580-000K
858
1415
CUAUUGUACGUACCAUGCA
B CUAUUGUACGUACCAUGCATT B
4830


R-008399583-000L
524
1416
UAUGCAAUGACUCGAGCUC
B UAUGCAAUGACUCGAGCUCTT B
4832


R-008399583-000L
524
1416
UAUGCAAUGACUCGAGCUC
GAGCUCGAGUCAUUGCAUAUU
4833


R-008399586-000M
2542
1417
UGCCCAGGACCUCAUGGAU
B UGCCCAGGACCUCAUGGAUTT B
4834


R-008399586-000M
2542
1417
UGCCCAGGACCUCAUGGAU
AUCCAUGAGGUCCUGGGCAUU
4835


R-008399589-000N
498
1418
AACAAGUAGCUGAUAUUGA
B AACAAGUAGCUGAUAUUGATT B
4836


R-008399589-000N
498
1418
AACAAGUAGCUGAUAUUGA
UCAAUAUCAGCUACUUGUUUU
4837


R-008399592-000V
414
1419
AAGGCAAUCCUGAGGAAGA
UCUUCCUCAGGAUUGCCUUUU
4839


R-008399592-000V
414
1419
AAGGCAAUCCUGAGGAAGA
B AAGGCAAUCCUGAGGAAGATT B
4838


R-008399595-000W
1570
1420
CAAGAUGAUGGUCUGCCAA
B CAAGAUGAUGGUCUGCCAATT B
4840


R-008399595-000W
1570
1420
CAAGAUGAUGGUCUGCCAA
UUGGCAGACCAUCAUCUUGUU
4841


R-008399598-000X
1030
1421
UGCCAUUACAACUCUCCAC
GUGGAGAGUUGUAAUGGCAUU
4843


R-008399598-000X
1030
1421
UGCCAUUACAACUCUCCAC
B UGCCAUUACAACUCUCCACTT B
4842


R-008399601-000P
1380
20
CAGAUCCAAGUCAACGUCU
AGACGUUGACUUGGAUCUGUU
4845


R-008399601-000P
1380
20
CAGAUCCAAGUCAACGUCU
B CAGAUCCAAGUCAACGUCUTT B
4844


R-008399604-000R
3087
1422
AUGUAUGGGUAGGGUAAAU
B AUGUAUGGGUAGGGUAAAUTT B
4846


R-008399604-000R
3087
1422
AUGUAUGGGUAGGGUAAAU
AUUUACCCUACCCAUACAUUU
4847


R-008399607-000S
1664
1423
UGUGCUCUUCGUCAUCUGA
B UGUGCUCUUCGUCAUCUGATT B
4848


R-008399607-000S
1664
1423
UGUGCUCUUCGUCAUCUGA
UCAGAUGACGAAGAGCACAUU
4849


R-008399610-000Y
1790
1424
AAGGCUACUGUUGGAUUGA
B AAGGCUACUGUUGGAUUGATT B
4850


R-008399610-000Y
1790
1424
AAGGCUACUGUUGGAUUGA
UCAAUCCAACAGUAGCCUUUU
4851


R-008399613-000Z
1615
1425
UACUGUCCUUCGGGCUGGU
ACCAGCCCGAAGGACAGUAUU
4853


R-008399613-000Z
1615
1425
UACUGUCCUUCGGGCUGGU
B UACUGUCCUUCGGGCUGGUTT B
4852


R-008399616-000A
774
1426
AUAAGGCUGCAGUUAUGGU
ACCAUAACUGCAGCCUUAUUU
4855


R-008399616-000A
774
1426
AUAAGGCUGCAGUUAUGGU
B AUAAGGCUGCAGUUAUGGUTT B
4854


R-008399619-000B
1672
1427
UCGUCAUCUGACCAGCCGA
UCGGCUGGUCAGAUGACGAUU
4857


R-008399619-000B 
1672
1427
UCGUCAUCUGACCAGCCGA
B UCGUCAUCUGACCAGCCGATT B 
4856


R-008399625-000J 
3171
1428
GUUGUAACCUGCUGUGAUA
UAUCACAGCAGGUUACAACUU
4859


R-008399625-000J 
3171
1428
GUUGUAACCUGCUGUGAUA
B GUUGUAACCUGCUGUGAUATT B
4858


R-008399628-000K 
2271
1429
AAGAUUACAAGAAACGGCU
B AAGAUUACAAGAAACGGCUTT B 
4860


R-008399628-000K 
2271
1429
AAGAUUACAAGAAACGGCU
AGCCGUUUCUUGUAAUCUUUU
4861


R-008399631-000S 
1183
1430
UUAUGGCAACCAAGAAAGC
B UUAUGGCAACCAAGAAAGCTT B
4862


R-008399631-000S 
1183
1430
UUAUGGCAACCAAGAAAGC
GCUUUCUUGGUUGCCAUAAUU
4863


R-008399634-000T 
2512
1431
UCCAGUUGAUGGGCUGCCA
B UCCAGUUGAUGGGCUGCCATT B
4864


R-008399634-000T 
2512
1431
UCCAGUUGAUGGGCUGCCA
UGGCAGCCCAUCAACUGGAUU
4865


R-008399637-000U 
1521
132
CCUGUGCAGCUGGAAUUCU
AGAAUUCCAGCUGCACAGGUU
4867


R-008399637-000U 
1521
132
CCUGUGCAGCUGGAAUUCU
B CCUGUGCAGCUGGAAUUCUTT B 
4866


R-008399640-000A 
1931
1432
GGGACACAGCAGCAAUUUG
CAAAUUGCUGCUGUGUCCCUU
4869


R-008399640-000A 
1931
1432
GGGACACAGCAGCAAUUUG
B GGGACACAGCAGCAAUUUGTT B
4868


R-008399643-000B
2468
1433
AUGAUGGAACAUGAGAUGG
B AUGAUGGAACAUGAGAUGGTT B
4870


R-008399643-000B
2468
1433
AUGAUGGAACAUGAGAUGG
CCAUCUCAUGUUCCAUCAUUU
4871


R-008399646-000C 
3077
1434
UAUUUGGGAUAUGUAUGGG
B UAUUUGGGAUAUGUAUGGGTT B 
4872


R-008399646-000C 
3077
1434
UAUUUGGGAUAUGUAUGGG
CCCAUACAUAUCCCAAAUAUU
4873


R-008399649-000D 
2069
1435
CAGCUGCUUUAUUCUCCCA
UGGGAGAAUAAAGCAGCUGUU
4875


R-008399649-000D 
2069
1435
CAGCUGCUUUAUUCUCCCA
B CAGCUGCUUUAUUCUCCCATT B
4874


R-008399652-000K
272
1436
GCUACUCAAGCUGAUUUGA
B GCUACUCAAGCUGAUUUGATT B 
4876


R-008399652-000K
272
1436
GCUACUCAAGCUGAUUUGA
UCAAAUCAGCUUGAGUAGCUU
4877


R-008399655-000L
564
1437
UCCCUGAGACAUUAGAUGA
UCAUCUAAUGUCUCAGGGAUU
4879


R-008399655-000L
564
1437
UCCCUGAGACAUUAGAUGA
B UCCCUGAGACAUUAGAUGATT B 
4878


R-008399658-000M
437
1438
GUGGAUACCUCCCAAGUCC
GGACUUGGGAGGUAUCCACUU
4881


R-008399658-000M
437
1438
GUGGAUACCUCCCAAGUCC
B GUGGAUACCUCCCAAGUCCTT B
4880


R-008399661-000U
2206
1439
UAGGAAUGAAGGUGUGGCG
B UAGGAAUGAAGGUGUGGCGTT B 
4882


R-008399661-000U
2206
1439
UAGGAAUGAAGGUGUGGCG
CGCCACACCUUCAUUCCUAUU
4883


R-008399664-000V
2187
1440
UGACAGAGUUACUUCACUC
GAGUGAAGUAACUCUGUCAUU
4885


R-008399664-000V
2187
1440
UGACAGAGUUACUUCACUC
B UGACAGAGUUACUUCACUCTT B
4884


R-008399667-000W
325
1441
AGCGGCUGUUAGUCACUGG
CCAGUGACUAACAGCCGCUUU
4887


R-008399667-000W
325
1441
AGCGGCUGUUAGUCACUGG
B AGCGGCUGUUAGUCACUGGTT B 
4886


R-008399670-000C
3222
1442
AUGGUUCAGAAUUAAACUU
B AUGGUUCAGAAUUAAACUUTT B 
4888


R-008399670-000C
3222
1442
AUGGUUCAGAAUUAAACUU
AAGUUUAAUUCUGAACCAUUU
4889


R-008399673-000D
2024
1443
AACCGAAUUGUUAUCAGAG
B AACCGAAUUGUUAUCAGAGTT B
4890


R-008399673-000D
2024
1443
AACCGAAUUGUUAUCAGAG
CUCUGAUAACAAUUCGGUUUU
4891


R-008399676-000E
1858
1444
GGGUGCCAUUCCACGACUA
B GGGUGCCAUUCCACGACUATT B
4892


R-008399676-000E
1858
1444
GGGUGCCAUUCCACGACUA
UAGUCGUGGAAUGGCACCCUU
4893


R-008399679-000F
1574
1445
AUGAUGGUCUGCCAAGUGG
B AUGAUGGUCUGCCAAGUGGTT B
4894


R-008399679-000F
1574
1445
AUGAUGGUCUGCCAAGUGG
CCACUUGGCAGACCAUCAUUU
4895


R-008399682-000M
1638
78
GGGAAGACAUCACUGAGCC
B GGGAAGACAUCACUGAGCCTT B
4896


R-008399682-000M
1638
78
GGGAAGACAUCACUGAGCC
GGCUCAGUGAUGUCUUCCCUU
4897


R-008399685-000N
1896
1446
CACAUCAGGAUACCCAGCG
B CACAUCAGGAUACCCAGCGTT B
4898


R-008399685-000N
1896
1446
CACAUCAGGAUACCCAGCG
CGCUGGGUAUCCUGAUGUGUU
4899


R-008399688-000P
2207
1447
AGGAAUGAAGGUGUGGCGA
B AGGAAUGAAGGUGUGGCGATT B
4900


R-008399688-000P
2207
1447
AGGAAUGAAGGUGUGGCGA
UCGCCACACCUUCAUUCCUUU
4901


R-008399691-000W
1300
1448
GAAGGUGCUAUCUGUCUGC
B GAAGGUGCUAUCUGUCUGCTT B
4902


R-008399691-000W
1300
1448
GAAGGUGCUAUCUGUCUGC
GCAGACAGAUAGCACCUUCUU
4903


R-008399694-000X
1192
1449
CCAAGAAAGCAAGCUCAUC
GAUGAGCUUGCUUUCUUGGUU
4905


R-008399694-000X
1192
1449
CCAAGAAAGCAAGCUCAUC
B CCAAGAAAGCAAGCUCAUCTT B
4904


R-008399697-000Y
551
1450
CGAGCUGCUAUGUUCCCUG
B CGAGCUGCUAUGUUCCCUGTT B 
4906


R-008399697-000Y
551
1450
CGAGCUGCUAUGUUCCCUG
CAGGGAACAUAGCAGCUCGUU
4907


R-008399700-000R
2498
1451
CCUGGUGCUGACUAUCCAG
B CCUGGUGCUGACUAUCCAGTT B 
4908


R-008399700-000R
2498
1451
CCUGGUGCUGACUAUCCAG
CUGGAUAGUCAGCACCAGGUU
4909


R-008399703-000S
1305
1452
UGCUAUCUGUCUGCUCUAG
B UGCUAUCUGUCUGCUCUAGTT B
4910


R-008399703-000S
1305
1452
UGCUAUCUGUCUGCUCUAG
CUAGAGCAGACAGAUAGCAUU
4911


R-008399706-000T
1337
1453
AUUGUAGAAGCUGGUGGAA
B AUUGUAGAAGCUGGUGGAATT B
4912


R-008399706-000T
1337
1453
AUUGUAGAAGCUGGUGGAA
UUCCACCAGCUUCUACAAUUU
4913


R-008472717-000G
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCUAguUCAGUUGCUUUsU B
2147


R-008472717-000G
1870
194
ACGACUAGUUCAGUUGCUU
aaGCAAcUgAAcuagUCGUUsU
6367


R-008472765-000B
1870
194
ACGACUAGUUCAGUUGCUU
aaGCaAcUGAAcuaGUCGUUsU
6368


R-008472765-000B
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCUAguUCAGUUGCUUUsU B
2147


R-008488882-000B
1797
5
CUGUUGGAUUGAUUCGAAA
B CUGUUGGAUUGAUUCGAAAUU B
6370


R-008488882-000B
1797
5
CUGUUGGAUUGAUUCGAAA
uuucGAauCaAUCcAaCaGUU
6369


R-008488887-000V
1870
194
ACGACUAGUUCAGUUGCUU
aaGCAAcUgAaCuagUcGUUU
6371


R-008488887-000V
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCUAguUCAGUUGCUUUU B
6372


R-008488885-000C
1870
194
ACGACUAGUUCAGUUGCUU
aaGCAAcUgAAcuagUCGUUU
6373


R-008488885-000C
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCUAguUCAGUUGCUUUU B
6372


R-008488889-000M
1870
194
ACGACUAGUUCAGUUGCUU
B aCgaCUAguUCAGUUGCUUUU B
6372


R-008488889-000M
1870
194
ACGACUAGUUCAGUUGCUU
aaGCaAcUGAAcuaGUCGUUU
6374





wherein:


A, C, G, and U = ribose A, C, G or U


a, g, c and u = 2'-deoxy-2'-fluoro A, G, C or U


A, U, C and G = 2'-O-methyl (2'-OMe) A, U, C, or G


A, U, C, and G = deoxy A, U, C, or G


B = inverted abasic


T = thymidine


I = inosine


s = phosphorothioate linkage






Further Synthesis Steps for Commercial Preparation

Once analysis indicates that the target product purity has been achieved after the annealing step, the material is transferred to the tangential flow filtration (TFF) system for concentration and desalting, as opposed to doing this prior to the annealing step.
Ultrafiltration: The annealed product solution is concentrated using a TFF system containing an appropriate molecular weight cut-off membrane. Following concentration, the product solution is desalted via diafiltration using Milli-Q water until the conductivity of the filtrate is that of water.
Lyophilization: The concentrated solution is transferred to a bottle, flash frozen and attached to a lyophilizer. The product is then freeze-dried to a powder. The bottle is removed from the lyophilizer and is now ready for use.
Initial Screening Protocol (96-Well Plate Transfections)
Cell Culture Preparation:
Human hepatoma cell line, HepG2, rhesus kidney epithelial cell line, LLC-MK2 Derivative, and the Huh7 cell line, were grown in modified Eagle's medium. All the culture media were supplemented with 10% fetal bovine serum, 100 μg/mL streptomycin, 100 U/mL penicillin, and 1% sodium bicarbonate.
Transfection and Screening
Cells were plated in all wells of tissue-culture treated, 96-well plates at a final count of 3500 (HepG2 and LLC-MK2 Derivative and Huh7) cells/well in 100 μL of the appropriate culture media. The cells were cultured for overnight after plating at 37° C. in the presence of 5% CO2.
On the next day, complexes containing siNA and RNAiMax (Invitrogen) were created as follows. A solution of RNAiMax diluted 33-fold in OPTI-MEM was prepared. In parallel, solutions of the siNAs for testing were prepared to a final concentration of 120 nM in OPTI-MEM. After incubation of RNAiMax/OPTI-MEM solution at room temperature for 5 min, an equal volume of the siNA solution and the RNAiMax solution were added together for each of the siNAs.
Mixing resulted in a solution of siNA/RNAiMax where the concentration of siNA was 60 nM. This solution was incubated at room temperature for 20 minutes. After incubation, 20 μL of the solution was added to each of the relevant wells. The final concentration of siNA in each well was 10 nM and the final volume of RNAiMax in each well was 0.3 ul.
For low concentration screens, siNAs were transfected at 200, 150, 100 or 75 pM per well. For 12-point dose response curve studies, the siNA series are 6-fold serial dilution starting at 30 nM or 4-fold serial dilution starting at 40 nM. All transfections were set up as multiple biological replicates.
The time of incubation with the RNAiMax-siNA complexes was 24 hours and there was no change in media between transfection and harvesting for screening and dose response curve studies. For duration assays, the time of incubation with the RNAiMax-siNA complexes was 24, 72, and 120 hours. There was no change in media between transfection and harvesting for 24- and 72-hour time points. Media was replaced with fresh media 72 hours after transfection for 120-hour time point.
Cells-to-Ct and Reverse Transcription Reactions
The culture medium was aspirated and discarded from the wells of the culture plates at the desired time points. The transfected cells were washed once with 50 uL DPBS solution per well. Fifty microliters per well of the Lysis Solution from the TaqMan® Gene Expression Cells-to-CTTM Kit (Applied Biosystems, Cat#4399002) supplemented with DNase I was added directly to the plates to lyse the cells. Five microliters per well of Stop Solution from the same kit was added to the plates to inactivate DNase 15 minutes later. The lysis plates were incubated for at least 2 minutes at room temperature. The plates can be stored for 2 hours at 4° C., or −80° C. for two months.
Each well of the reverse transcription plate required 10 uL of 2× reverse transcriptase buffer, 1 uL of 20× reverse transcription enzyme and 2 uL of nuclease-free water. The reverse transcription master mix was prepared by mixing 2× reverse transcription buffer, 20× reverse transcription enzyme mix, and nuclease-free water. 13 uL of the reverse transcription master mix was dispensed into each well of the reverse transcription plate (semi-skirted). A separate reverse transcription plate was prepared for each cell plate. A separate reverse transcription plate was prepared for each cell plate. Seven microliters per lysate from the cell lysis procedure described above was added into each well of the reverse transcription plate. The plate was sealed and spun on a centrifuge (1000 rpm for 30 seconds) to settle the contents to the bottom of the reverse transcription plate. The plate was placed in a thermocycler at 37° C. for 60 min, 95° C. for 5 min, and 4° C. until the plate is removed from the thermocycler. Upon removal, if not used immediately, the plate was frozen at −20° C.
For duration assays, a similar protocol was followed, however, the cells were lysed 1, 3, or 5 days after transfection. cDNA was generated using Cells-to-CtTM Kit (Applied Biosystems).
Quantitative RT-PCR (Taqman)
A series of probes and primers were used to detect the various mRNA transcripts of the genes of CTNNB1 and GAPDH. All Taqman probes and primers for the experiments here-in described were supplied as pre-validated sets by Applied Biosystems, Inc. (see Table 2).







TABLE 2







Probes and primers used to carry out Real-Time RT/PCR 


(Taqman) reactions for CTNNB1 mRNA analysis.











Species
Gene
ABI Cat. #







Human
CTNNB1
Hs0035504_ m1



Human
GAPDH
4310884E



Rhesus
GAPDH
Rh02621745_g1



Mouse 
CTNNB1
Mm00483033_m1



Mouse 
GAPDH
4352339E










The assays were performed on an ABI 7900 instrument, according to the manufacturer's instructions. A TaqMan Gene Expression Master Mix (provided in the Cells-to-CTTM Kit, Applied Biosystems, Cat #4399002) was used. The PCR reactions were carried out at 50° C. for 2 min, 95° C. for 10 min followed by 40 cycles at 95° C. for 15 secs and 60° C. for 1 minute.
Within each experiment, the baseline was set in the exponential phase of the amplification curve, and based on the intersection point of the baselines with the amplification curve, a Ct value was assigned by the instrument.
Calculations
The expression level of the gene of interest and % inhibition of gene expression (% KD) was calculated using Comparative Ct method:

ΔCt=CtTarget−CtGAPDH 

ΔΔCt(log 2(fold change))=ΔCt(Target siNA)−ΔCt(NTC) 

Relative expression level=2−ΔΔCt 

% KD=100×(1−2−ΔΔCt)

The non-targeting control siNA was, unless otherwise indicated, chosen as the value against which to calculate the percent inhibition (knockdown) of gene expression, because it is the most relevant control.
Additionally, only normalized data, which reflects the general health of the cell and quality of the RNA extraction, was examined. This was done by looking at the level of two different mRNAs in the treated cells, the first being the target mRNA and the second being the normalizer mRNA. This allowed for elimination of siNAs that might be potentially toxic to cells rather than solely knocking down the gene of interest. This was done by comparing the Ct for GAPDH in each well relative to the GAPDH Ct for the entire plate.
All calculations of IC50s were performed using R.2.9.2 software. The data were analyzed using the sigmoidal dose-response (variable slope) equation for simple ligand binding. In all of the calculations of the percent inhibition (knock-down), the calculation was made relative to the normalized level of expression of the gene of interest in the samples treated with the non-targeting control (Ctrl siNA) unless otherwise indicated.
The level of protein was quantified using the Bio-Rad VersaDoc Imager according to the protocols of that piece of equipment. A pixel count was performed in each lane using an area of identical size. Each sample was then compared to the appropriate control treated sample and converted to a percent of protein remaining compared to control.
The effects of lead siNAs on CTNNB1 protein level were compared to the effects of the universal control using a two tail Student's T-test to obtain a P value. P<0.05 was considered significant.
Results:
The CTNNB1 siNAs were designed and synthesized as described previously. Various siNAs were screened in HepG2, MK2D and Huh7 cells. The log 2(fold change) in CTNNB1 gene expression data upon treatment with various modified CTNNB1 siNAs in human cells is shown in Table 3a. Each screen was performed at 24 hrs. Quantitative RT-PCR was used to assess the level of CTNNB1 mRNA and the data were normalized to the expression level of GAPDH (an ubiquitously expressed ‘house-keeping’ gene). Each treatment was then normalized against the non-CTNNB1 targeting control.







TABLE 3a







Primary screening data in HepG2 Cells, MK2D Cells and Huh7 


Cells (n = 2), recorded as log 2(fold change) in CTNNB1 gene expression.














HEPG2
HEPG2
MK2D
MK2D
Huh7
Huh7



Mean
SD
Mean
SD
Mean
SD


siNA Duplex ID
ΔΔCt
ΔΔCt
ΔΔCt
ΔΔCt
ΔΔCt
ΔΔCt
















R-008362875-000L
5.06
0.28
5.05
0.05
4.10
0.12


R-008362785-000U
4.92
0.24
4.98
0.05
4.05
0.14


R-008362959-000W
4.76
0.11
4.90
0.14
3.99
0.05


R-008363073-000K
4.54
0.16
5.15
0.14
3.98
0.60


R-008308997-000F
4.27
0.32
4.86
0.17
3.97
0.16


R-008362932-000A
4.57
0.50
5.13
0.13
3.97
0.11


R-008362713-000E
4.52
0.02 
4.56
0.00
3.96
0.20


R-008362791-000B
5.14
0.21 
5.96
0.04
3.94
0.06


R-008362689-000U
5.16
0.20 
5.24
0.04
3.94
0.08


R-008362692-000A
0.84
0.06 
4.30
0.09
3.94
0.00


R-008363055-000T
4.87
0.16 
5.19
0.11 
3.86
0.13


R-008309033-000Y
4.39
0.08 
5.35
0.15
3.83
0.04


R-008363058-000U
4.20
0.23 
4.68
0.22
3.83
0.43


R-008362755-000S
4.18
0.21 
4.37
0.08 
3.83
0.10


R-008362821-000P
4.29
0.53 
4.95
0.11 
3.83
0.09


R-008362722-000N
5.37
0.36 
5.27
0.19
3.82
0.25


R-008362824-000R
4.36
0.23 
4.92
0.06 
3.80
0.05


R-008363070-000J
4.51
0.03 
4.54
0.01 
3.79
0.14


R-008362686-000T
4.84
0.26 
5.03
0.08 
3.79
0.34


R-008362947-000L
4.45
0.25 
4.74
0.04 
3.79
0.44


R-008362728-000R
4.66
0.15 
4.47
0.12 
3.77
0.15


R-008363019-000H
4.75
0.08 
5.06
0.05 
3.77
0.21


R-008362833-000Z
4.26
0.11 
4.61
0.15 
3.75
0.09


R-008362812-000F
4.79
0.14 
4.93
0.17 
3.75
0.37


R-008363064-000B
4.54
0.11 
4.87
0.16 
3.75
0.49


R-008362980-000V
1.07
0.02 
4.48
0.13 
3.73
0.09


R-008362992-000E
0.35
0.09 
4.24
0.04 
3.72
0.00


R-008362872-000K
4.28
0.26 
4.77
0.11 
3.70
0.02


R-008362677-000J
4.37
0.06 
4.60
0.01 
3.68
0.08


R-008362878-000M
3.85
0.09 
4.54
0.06
3.67
0.01


R-008363031-000Y
4.82
0.26 
5.19
0.14 
3.65
0.00


R-008363043-000H
4.89
0.27 
5.61
0.03 
3.65
0.04


R-008362797-000D
4.77
0.03 
4.31
0.09 
3.63
0.09


R-008362842-000H
3.92
0.00 
4.71
0.09 
3.63
0.26


R-008362704-000W
4.11
0.16 
4.38
0.12 
3.60
0.17


R-008362740-000F
0.66
0.11 
4.74
0.10 
3.60
0.00


R-008362839-000B
4.10
0.22 
4.43
0.16 
3.57
0.40


R-008362950-000T
4.73
0.08 
4.80
0.21 
3.55
0.03


R-008363010-000E
4.28
0.12 
4.44
0.09 
3.51
0.40


R-008362752-000R
3.42
0.03 
2.93
0.04 
3.50
0.33


R-008362854-000T
0.72
0.26
3.93
0.09 
3.49
0.00


R-008362830-000Y
4.59
0.12 
4.90
0.04 
3.48
0.03


R-008363016-000G
4.14
0.09 
4.35
0.02
3.45
0.05


R-008362998-000G
4.29
0.18 
4.05
0.12 
3.45
0.01


R-008362674-000H
4.55
0.14 
4.55
0.01
3.45
0.32


R-008362938-000C
4.27
0.10 
5.01
0.22
3.44
0.27


R-008362788-000V
4.11
0.21 
4.48
0.09
3.44
0.11


R-008362884-000V
4.11
0.08 
4.90
0.13
3.44
0.11


R-008362896-000E
3.91
0.18
3.86
0.06
3.44
0.29


R-008363061-000A
3.84
0.17 
4.34
0.01
3.43
0.14


R-008362782-000T
3.73
0.60 
5.27
0.13
3.43
0.43


R-008362776-000K
4.08
0.15
4.33
0.15
3.43
0.12


R-008362764-000A
1.00
0.02
4.82
0.14
3.40
0.31


R-008362683-000S
0.85
0.00
4.80 
0.12
3.39
0.32


R-008362869-000D
4.65
0.02
4.57
0.06
3.36
0.24


R-008309054-000S
0.88
0.01
4.27 
0.08
3.36
0.12


R-008362746-000H
4.22
0.08
4.85
0.07
3.35
0.47


R-008362935-000B
4.51
0.01
5.00
0.14
3.33
0.15


R-008362995-000F
3.52
0.02
4.80
0.02
3.31
0.25


R-008362923-000S
4.16
0.16
4.15
0.08
3.31
0.09


R-008309099-000E
3.72
0.38
4.49
0.03
3.30
0.23


R-008362794-000C
3.97
0.05
3.81
0.05
3.30
0.12


R-008308556-000N
4.54
0.04
4.69
0.19
3.29
0.13


R-008309087-000V
4.04
0.06
4.19
0.14
3.28
0.01


R-008362893-000D
0.66
0.15
4.31
0.05
3.27
0.20


R-008362725-000P
4.20
0.22
4.54 
0.23
3.26
0.05


R-008362863-000B
1.04
0.13
4.27 
0.09
3.26
0.20


R-008362941-000J
3.93
0.42
4.38 
0.16
3.24
0.34


R-008362929-000U
1.45
0.05
3.98
0.08
3.23
0.04


R-008363052-000S
0.43
0.13
4.30 
0.07
3.23
0.03


R-008362857-000U
1.73
0.12
3.70
0.08
3.23
0.37


R-008362758-000T
0.70
0.16
4.19
0.10
3.22
0.41


R-008309048-000J
4.21
0.15
4.23 
0.09
3.21
0.14


R-008363004-000X
3.76
0.12
4.55 
0.07
3.20
0.43


R-008362719-000G
3.88
0.16
4.61
0.31
3.20
0.09


R-008362671-000G
4.56
0.19
4.71
0.19
3.20
0.06


R-008363049-000K
3.40
0.08
3.01
0.01
3.19
0.22


R-008362902-000Y
3.79
0.29
3.92
0.12
3.19
0.07


R-008363022-000P
4.32
0.21
4.06 
0.12
3.14
0.43


R-008362848-000K
3.83
0.04
4.04
0.18
3.09
0.08


R-008362743-000G
4.46
0.16
5.28
0.10
3.09
0.69


R-008362737-000Z
4.41
0.09
4.88 
0.24
3.09
0.19


R-008362881-000U
0.77
0.02
4.08
0.10
3.09
0.05


R-008308601-000T
4.21
0.54
4.56 
0.02
3.08
0.17


R-008362983-000W
4.09
0.03
4.38
0.00
3.04
0.12


R-008362800-000W
4.42
0.15
4.69
0.06
3.02
0.38


R-008362971-000L
4.10
0.14
4.48 
0.05
3.02
0.01


R-008308661-000X
3.68
0.27
4.68 
0.21
3.00
0.09


R-008362956-000V
3.89
0.10
3.97 
0.19
3.00
0.05


R-008363001-000W
3.97
0.05
4.25
0.06 
2.99
0.02


R-008362680-000R
4.22
0.16
4.33 
0.12 
2.99
0.31


R-008309081-000T
3.97
0.11
4.21 
0.01 
2.99
0.35


R-008362860-000A
3.39
0.49
3.39
0.01 
2.98
0.19


R-008362716-000F
3.87
0.10
4.27 
0.19 
2.96
0.20


R-008362809-000Z
0.82
0.00
3.79 
0.06 
2.95
0.18


R-008308562-000W
3.85
0.14
4.09
0.09 
2.94
0.01


R-008362989-000Y
4.11
0.07
4.27
0.01 
2.94
0.01


R-008309102-000X
3.95
0.05
3.89
0.20 
2.90
0.11


R-008362773-000J
3.92
0.23
3.99 
0.02 
2.89
0.06


R-008362779-000L
4.30
0.20
4.46 
0.02 
2.85
0.86


R-008362962-000C
3.67
0.08
3.59 
0.09 
2.82
0.00


R-008362905-000Z
3.33
0.22
3.81 
0.08 
2.78
0.14


R-008362707-000X
3.53
0.49
4.13 
0.15 
2.78
0.03


R-008362977-000N
3.29
0.34
4.18 
0.01 
2.76
0.27


R-008362944-000K
3.56
0.19
3.31 
0.13 
2.75
0.19


R-008309018-000G
3.53
0.13
4.22 
0.07 
2.72
0.16


R-008362770-000H
3.92
0.15
3.97 
0.01 
2.72
0.12


R-008362749-000J
3.29
0.13
3.60 
0.02 
2.68
0.09


R-008308496-000Y
3.83
0.21
4.49
0.11 
2.67
0.41


R-008362836-000A
0.49
0.02
3.94
0.05 
2.67
0.81


R-008308667-000Z
4.42
0.01
4.60 
0.03 
2.65
0.45


R-008362926-000T
4.22
0.08
5.81 
0.12 
2.60
0.18


R-008362851-000S
4.01
0.80
4.57 
0.01 
2.53
0.95


R-008363007-000Y
3.23
0.05
2.93 
0.15 
2.51
0.19


R-008362701-000V
3.94
0.09
4.32 
0.13 
2.51
0.48


R-008362698-000C
4.10
0.03
4.15 
0.13 
2.50
0.24


R-008308625-000M
3.77
0.09
3.42
0.24 
2.46
0.03


R-008362815-000G
4.27
0.20
4.14
0.09 
2.46
0.51


R-008363067-000C
4.14
0.27
5.42
0.16 
2.46
0.06


R-008362914-000H
3.78
0.03
3.66
0.06 
2.41
0.25


R-008363028-000S
0.86
0.01
4.10 
0.07 
2.39
0.09


R-008362866-000C
3.42
0.03
3.68
0.01 
2.38
0.07


R-008362695-000B
3.06
0.18
2.78
0.06 
2.37
0.27


R-008363013-000F
3.56
0.24
3.93 
0.11 
2.37
0.16


R-008362908-000A
3.20
0.11
2.63
0.01 
2.35
0.09


R-008362917-000J
3.01
0.04
3.23 
0.05 
2.34
0.15


R-008308508-000U
4.18
0.04
4.17
0.02 
2.29
0.58


R-008308526-000L
0.59
0.04
3.87 
0.09 
2.27
0.15


R-008363034-000Z
0.78
0.17
3.95 
0.02 
2.27
0.30


R-008362827-000S
3.74
0.00
3.12 
0.05 
2.25
0.09


R-008362968-000E
4.00
0.02
3.46 
0.12 
2.24
0.62


R-008309006-000X
2.95
0.26
2.59 
0.04 
2.24
0.07


R-008362734-000Y
4.06
0.02
4.33 
0.15 
2.21
0.41


R-008362767-000B
4.22
0.05
4.19 
0.13 
2.13
0.41


R-008362806-000Y
0.73
0.04
2.89 
0.02 
2.08
0.56


R-008308724-000N
3.34
0.05
3.55 
0.01 
2.06
0.04


R-008362818-000H
1.49
0.14
3.44 
0.05 
2.05
0.18


R-008309051-000R
2.38
0.12
2.71 
0.06 
2.04
0.30


R-008362920-000R
2.82
0.31
3.00 
0.13 
1.98
0.03


R-008362965-000D
1.24
0.07
2.76 
0.00 
1.98
0.05


R-008308544-000D
0.53
0.03
3.67 
0.07 
1.97
0.04


R-008308523-000K
3.15
0.01
3.69 
0.12
1.94
0.17


R-008362986-000X
3.24
0.08
3.50 
0.13
1.92
0.01


R-008362731-000X
3.62
0.04
2.96 
0.09
1.77 
1.24


R-008363046-000J
2.67
0.02
3.94 
0.05
1.75
0.07


R-008308733-000X
3.32
0.16
2.63 
0.08
1.74
0.15


R-008362911-000G
0.75
0.04
2.74 
0.10
1.73
0.26


R-008308706-000W
3.31
0.01
4.09
0.17
1.61
0.09


R-008308709-000X
3.29
0.13
3.95
0.00
1.54
0.30


R-008362890-000C
0.90
0.03
1.03
0.22
1.35
0.34


R-008363025-000R
2.95
0.06
3.05
0.08
1.32
0.81


R-008362953-000U
2.33
0.03
2.67
0.10
1.24
0.10


R-008362899-000F
1.50
0.17
2.77 
0.03
1.24
0.13


R-008308697-000B
2.18
0.11
2.19
0.04
1.17
0.02


R-008308589-000S
2.17
0.22
3.42 
0.03
1.12
0.08


R-008308634-000W
2.41
0.11
2.66
0.01
1.09
0.11


R-008362710-000D
0.71
0.10
2.17
0.11
1.06
0.18


R-008308493-000X
0.55
0.03
2.12
0.24
1.00
0.05


R-008308703-000V
0.87
0.02
1.69
0.02
0.95
0.13


R-008308568-000Y
2.84
0.14
2.85
0.23
0.63
0.41


R-008362887-000W
0.83
0.14
0.93 
0.09
0.33
0.07


R-008362974-000M
0.80
0.07
0.96 
0.02
0.23
0.02


R-008363037-000A
0.69
0.09
0.85 
0.05
0.12
0.03


R-008363040-000G
−0.07
0.02
−0.22
0.05 
−0.19
0.09


R-008362845-000J
−4.37 
0.21
−1.50
0.07 
−1.25
0.33


R-008362761-000Z
−2.03
0.11
−3.54
0.05 
−1.88
0.24


R-008308586-000R
−1.64
0.18
−1.83
0.01 
−2.27
0.31


R-008362803-000X
−4.04
0.51
−4.61
0.01 
−4.03
0.44









A subset of siNAs from Table 3a having a large log 2(fold change) in the primary screen were rescreened in Huh7 cells. The results are shown in Table 3b.







TABLE 3b







Primary screening data in Huh7 Cells (n = 2), recorded 


as log 2(fold change) in CTNNB1 gene expression.










Huh7
Huh7



Mean
SD


siNA Duplex ID
ΔΔCt
ΔΔCt





R-008362791-000B
4.24
0.05


R-008362812-000F
4.17
0.02


R-008362689-000U
4.17
0.01


R-008362722-000N
4.17
0.04


R-008362932-000A
4.07
0.17


R-008363043-000H
4.05
0.02


R-008362875-000L
4.03
0.12


R-008308997-000F
3.99
0.35


R-008362947-000L
3.99
0.18


R-008362821-000P
3.95
0.11


R-008362686-000T
3.94
0.13


R-008363070-000J
3.91
0.08


R-008362824-000R
3.91
0.16


R-008362785-000U
3.88
0.06


R-008363031-000Y
3.88
0.10


R-008363073-000K
3.87
0.19


R-008362782-000T
3.86
0.04


R-008309033-000Y
3.85
0.00


R-008363064-000B
3.84
0.08


R-008362950-000T
3.84
0.05


R-008362959-000W
3.83
0.28


R-008363019-000H
3.82
0.02


R-008362842-000H
3.82
0.14


R-008363058-000U
3.75
0.11


R-008362713-000E
3.73
0.08


R-008362938-000C
3.72
0.05


R-008362755-000S
3.71
0.16


R-008362746-000H
3.59
0.22


R-008362830-000Y
3.56
0.16


R-008362704-000W
3.55
0.11


R-008362839-000B
3.48
0.23


R-008362992-000E
3.45
0.04


R-008363055-000T
3.44
0.26


R-008363061-000A
3.38
0.07


R-008362995-000F
3.35
0.01









The CTNNB1 siNAs were designed and synthesized as described previously. Various siNAs were screened in MK2D cells. The log 2(fold change) in CTNNB1 gene expression data upon treatment with various modified CTNNB1 siNAs in human cells is shown in Table 3c. Each screen was performed at 24 hrs. Quantitative RT-PCR was used to assess the level of CTNNB1 mRNA and the data were normalized to the expression level of GAPDH (a ubiquitously expressed ‘house-keeping’ gene). Each treatment was then normalized against the non-CTNNB1 targeting control.







TABLE 3c







Primary screening data in MK2D Cells (n =2), 


recorded as log 2(fold change) in 


CTNNB1 gene expression.












MK2D
MK2D




MEAN
SD



siNA Duplex ID
ΔΔCT
ΔΔCT















R-008395722-000P
4.06
0.06



R-008395725-000R
3.78
0.08



R-008395749-000K
4.20
0.02



R-008395752-000S
5.53
0.06



R-008395758-000U
2.41
0.01



R-008395761-000A
5.61
0.08



R-008395767-000C
3.00
0.00



R-008395770-000J
5.53
0.18



R-008395779-000M
4.93
0.16



R-008395785-000V
2.56
0.19



R-008395791-000C
6.76
0.23



R-008395800-000X
2.87
0.07



R-008395827-000T
2.89
0.14



R-008395863-000C
1.65
0.22



R-008395881-000V
3.94
0.05



R-008395887-000X
4.54
0.24



R-008395977-000P
5.63
0.47



R-008395980-000W
4.31
0.27



R-008395995-000G
4.83
0.12



R-008396004-000Y
3.16
0.01



R-008396022-000R
4.83
0.13



R-008396052-000T
4.08
0.08



R-008396061-000B
−0.99
0.08



R-008396067-000D
3.52
0.39



R-008396070-000K
4.84
0.03



R-008396079-000N
4.32
0.04



R-008396103-000Z
3.67
0.07



R-008396106-000A
5.34
0.03



R-008396109-000B
−1.10
0.03



R-008396112-000H
5.19
0.26



R-008396118-000K
3.23
0.01



R-008396136-000C
−2.56




R-008396142-000K
−0.95
0.10



R-008396148-000M
3.84
0.24



R-008396151-000U
4.60
0.08



R-008396154-000V
4.77
0.07



R-008396172-000M
6.28
0.06



R-008396214-000K
2.82
0.29



R-008396220-000T
5.40
0.05



R-008396223-000U
4.57
0.06



R-008396226-000V
2.27
0.12



R-008396247-000N
3.32
0.08



R-008396250-000V
3.79
1.00



R-008396253-000W
6.42
0.03



R-008396259-000Y
2.14
0.03



R-008396274-000P
5.39
0.18



R-008396292-000G
3.85
0.05



R-008396295-000H
2.57
0.08



R-008396298-000J
3.00
0.22



R-008396301-000B
2.10
0.24



R-008396304-000C
3.24
0.04



R-008396343-000N
2.49
0.07



R-008396349-000R
4.00
0.08



R-008396379-000T
4.29
0.22



R-008396382-000Z
−0.44
0.02



R-008396388-000B
3.90
0.18



R-008396391-000H
2.23
0.05



R-008396409-000F
3.96
0.26



R-008396415-000N
4.72
0.00



R-008396418-000P
4.48
0.20



R-008396421-000W
3.78
0.14



R-008396457-000A
3.89
0.01



R-008396478-000U
4.62
0.03



R-008396481-000A
4.29
0.14



R-008396529-000A
4.69
0.10



R-008396532-000G
4.46
0.05



R-008396538-000J
5.59
0.05



R-008396544-000S
5.04
0.20



R-008396550-000Z
3.79
0.18



R-008396553-000A
2.32
0.01



R-008396556-000B
2.85
0.07



R-008396559-000C
5.20
0.12



R-008396613-000R
4.92
0.10



R-008396616-000S
2.90
0.01



R-008396619-000T
4.67
0.37



R-008396622-000Z
4.09
0.08



R-008396631-000H
4.28
0.13



R-008396685-000E
4.01
0.10



R-008396694-000N
4.73
0.12



R-008396697-000P
1.56
0.16



R-008396730-000J
2.19
0.02



R-008396730-000J
3.24
0.03



R-008396733-000K
1.43
0.10



R-008396736-000L
5.14
0.04



R-008396742-000U
0.78
0.28



R-008396751-000C
3.62
0.13



R-008396754-000D
4.17
0.05



R-008396793-000P
2.68
0.01



R-008396796-000R
4.94
0.03



R-008396820-000B
4.70
0.08



R-008396826-000D
4.73
0.20



R-008396832-000L
3.63
0.10



R-008396835-000M
2.84
0.85



R-008396838-000N
3.40
0.20



R-008396868-000R
3.99
0.14



R-008396871-000X
4.62
0.12



R-008396874-000Y
4.01
0.02



R-008396898-000T
3.11
0.32



R-008396904-000L
2.46
0.06



R-008396910-000U
2.30
0.03



R-008396919-000X
4.06
0.23



R-008396934-000N
3.37
0.18



R-008396943-000X
3.77
0.01



R-008396949-000Z
3.40
0.07



R-008396958-000H
5.29
0.05



R-008396985-000J
5.25
0.09



R-008396994-000T
3.08
0.40



R-008397015-000U
4.41
0.08



R-008397018-000V
1.73
0.03



R-008397021-000B
5.50
0.05



R-008397024-000C
3.45
0.27



R-008397039-000N
4.21
0.04



R-008397060-000M
1.76
0.08



R-008397069-000R
3.16
0.14



R-008397072-000X
3.94
0.17



R-008397081-000F
3.02
0.02



R-008397108-000M
5.62
0.08



R-008397111-000U
4.08
0.10



R-008397114-000V
3.50
0.03



R-008397132-000M
3.97
0.16



R-008397138-000P
6.60
0.17



R-008397141-000W
4.58
0.02



R-008397147-000Y
3.73
0.00



R-008397150-000E
6.44
0.11



R-008397153-000F
2.43
0.03



R-008397156-000G
4.04
0.31



R-008397165-000R
3.44
0.01



R-008397168-000S
3.29
0.15



R-008397180-000G
4.46
0.02



R-008397186-000J
5.22
0.06



R-008397237-000R
2.77
0.04



R-008397243-000Y
3.31
0.23



R-008397246-000Z
3.21
0.21



R-008397255-000H
3.77
0.05



R-008397258-000J
1.91
0.02



R-008397306-000P
3.04
0.05



R-008397309-000R
3.16
0.05



R-008397312-000X
5.97
0.13



R-008397315-000Y
4.19
0.33



R-008397342-000Z
3.04
0.06



R-008397345-000A
4.87
0.03



R-008397348-000B
3.62
0.04



R-008397351-000H
2.29
0.15



R-008397354-000J
4.81
0.09



R-008397372-000B
4.40
0.10



R-008397381-000K
3.38
0.08



R-008397384-000L
3.95
0.14



R-008397387-000M
6.11
0.04



R-008397390-000U
3.84
0.16



R-008397396-000W
6.69
0.24



R-008397408-000S
5.61
0.05



R-008397417-000A
3.92
0.49



R-008397420-000G
4.53
0.02



R-008397429-000K
2.91
0.05



R-008397450-000J
2.53
0.05



R-008397459-000M
4.75
0.00



R-008397462-000U
5.28
0.17



R-008397465-000V
4.45
0.18



R-008397468-000W
4.05
0.09



R-008397471-000C
3.22
0.12



R-008397474-000D
4.06
0.21



R-008397519-000C
3.67
0.03



R-008397531-000T
5.94
0.10



R-008397537-000V
4.20
0.07



R-008397540-000B
5.04
0.12



R-008397564-000W
5.95
0.12



R-008397576-000F
3.39
0.05



R-008397579-000G
2.94
0.02



R-008397582-000N
3.95
0.12



R-008397588-000R
4.25
0.07



R-008397591-000X
5.25
0.06



R-008397594-000Y
3.81
0.00



R-008397618-000D
4.58
0.03



R-008397630-000U
3.46
0.15



R-008397645-000E
3.71
0.07



R-008397657-000P
−1.50
0.14



R-008397660-000W
4.85
0.04



R-008397663-000X
2.62
0.03



R-008397666-000Y
3.68
0.09



R-008397669-000Z
2.80
0.78



R-008397702-000U
2.34
0.78



R-008397705-000V
5.13
0.20



R-008397732-000W
3.27
0.01



R-008397735-000X
2.92
0.03



R-008397738-000Y
3.97
0.06



R-008397768-000A
1.62
0.05



R-008397771-000G
4.45
0.17



R-008397774-000H
−1.15
0.02



R-008397777-000J
−1.16
0.09



R-008397783-000S
−1.16
0.03



R-008397807-000X
2.52
0.05



R-008397828-000R
4.36
0.27



R-008397855-000S
1.94
0.01



R-008397858-000T
4.43
0.17



R-008397882-000T
5.26
0.10



R-008397885-000U
2.53
0.01



R-008397888-000V
3.55
0.03



R-008397933-000Z
4.19
0.22



R-008397966-000C
5.19
0.17



R-008397969-000D
3.35
0.11



R-008397987-000W
4.95
0.16



R-008397990-000C
4.69
0.09



R-008397993-000D
2.17
0.01



R-008397996-000E
−1.14
0.02



R-008398002-000V
3.74
0.10



R-008398020-000M
3.51
0.06



R-008398026-000P
5.64
0.06



R-008398050-000P
3.57
0.10



R-008398056-000S
4.46
0.13



R-008398086-000U
3.65
0.18



R-008398098-000D
3.93
0.04



R-008398119-000H
2.68
0.25



R-008398137-000A
5.16
0.02



R-008398140-000G
3.87
0.14



R-008398140-000G
4.86
0.03



R-008398143-000H
1.74
0.05



R-008398146-000J
3.95
0.12



R-008398149-000K
4.45
0.03



R-008398155-000T
4.37
0.25



R-008398161-000A
3.82
0.05



R-008398176-000L
3.83
0.14



R-008398182-000U
4.52
0.06



R-008398227-000T
6.28
0.06



R-008398239-000C
2.48
0.02



R-008398242-000J
3.81
0.03



R-008398245-000K
5.34
0.23



R-008398275-000M
1.53
0.08



R-008398278-000N
2.71
0.07



R-008398281-000V
4.31
0.14



R-008398326-000U
5.66
0.09



R-008398329-000V
3.83
0.26



R-008398332-000B
4.63
0.02



R-008398362-000D
2.98
0.17



R-008398365-000E
5.06
0.06



R-008398368-000F
4.37
0.03



R-008398374-000N
3.66
0.03



R-008398377-000P
−1.12
0.02



R-008398401-000A
4.57
0.18



R-008398413-000K
3.23
0.07



R-008398419-000M
3.78
0.10



R-008398422-000U
2.63
0.05



R-008398425-000V
3.31
0.02



R-008398428-000W
4.20
0.05



R-008398431-000C
4.82
0.02



R-008398434-000D
2.54
0.06



R-008398437-000E
5.38
0.09



R-008398479-000S
5.16
0.41



R-008398482-000Y
1.55
0.01



R-008398533-000E
3.60
0.01



R-008398539-000G
4.85
0.07



R-008398542-000N
3.64
0.01



R-008398563-000G
5.22
0.27



R-008398566-000H
2.69
0.13



R-008398575-000S
4.79
0.03



R-008398584-000A
2.92
0.04



R-008398590-000H
4.97
0.13



R-008398593-000J
4.52
0.03



R-008398617-000P
3.50
0.01



R-008398647-000S
4.34
0.23



R-008398650-000Y
4.26
0.01



R-008398653-000Z
3.27
0.22



R-008398656-000A
5.36
0.15



R-008398662-000H
5.03
0.42



R-008398665-000J
3.28
0.08



R-008398668-000K
5.53
0.41



R-008398677-000U
4.94
0.03



R-008398686-000C
1.43
0.14



R-008398701-000E
4.38
0.10



R-008398740-000R
3.54
0.04



R-008398749-000U
2.72
0.18



R-008398782-000C
2.87
0.02



R-008398785-000D
−1.10
0.05



R-008398788-000E
5.61
0.09



R-008398815-000S
3.68
0.14



R-008398821-000Z
5.75
0.00



R-008398830-000H
4.45
0.21



R-008398833-000J
4.61
0.05



R-008398836-000K
3.83
0.01



R-008398863-000L
−1.22
0.03



R-008398866-000M
3.99
0.02



R-008398869-000N
4.06
0.32



R-008398872-000V
4.32
0.18



R-008398875-000W
3.28
0.08



R-008398902-000H
5.58
0.03



R-008398917-000U
2.05
0.13



R-008398923-000B
5.33
0.13



R-008398926-000C
2.22
0.07



R-008398956-000E
3.78
0.15



R-008398962-000M
1.67
0.04



R-008398965-000N
4.87
0.13



R-008398968-000P
3.76
0.21



R-008399031-000H
4.84
0.16



R-008399034-000J
5.71
0.05



R-008399037-000K
2.86
0.08



R-008399049-000V
3.77
0.01



R-008399058-000D
3.88
0.26



R-008399070-000U
5.31
0.00



R-008399091-000M
4.67
0.01



R-008399103-000H
3.75
0.18



R-008399109-000K
5.39
0.14



R-008399133-000K
3.73
0.05



R-008399145-000V
4.27
0.01



R-008399172-000W
3.39
0.07



R-008399175-000X
3.44
0.11



R-008399181-000E
3.37
0.06



R-008399184-000F
6.50
0.11



R-008399187-000G
4.29
0.10



R-008399202-000J
4.09
0.44



R-008399205-000K
2.85
0.21



R-008399208-000L
4.45
0.00



R-008399211-000T
4.08
0.08



R-008399214-000U
4.54
0.01



R-008399226-000D
2.02
0.05



R-008399262-000N
4.13
0.06



R-008399265-000P
3.87
0.03



R-008399268-000R
5.89
0.30



R-008399271-000X
4.44
0.18



R-008399274-000Y
1.24
0.07



R-008399334-000N
2.96
0.22



R-008399343-000X
3.86
0.02



R-008399370-000Y
1.45
0.92



R-008399373-000Z
3.64
0.17



R-008399376-000A
4.79
0.22



R-008399382-000H
4.33
0.06



R-008399394-000T
4.40
0.09



R-008399415-000X
3.21
0.15



R-008399418-000Y
3.33
0.13



R-008399421-000E
3.57
0.21



R-008399436-000R
−1.18
0.08



R-008399439-000S
3.23
0.13



R-008399442-000Y
4.12
0.04



R-008399445-000Z
−0.90
0.12



R-008399451-000G
2.57
0.66



R-008399454-000H
1.55
0.01



R-008399457-000J
2.95
0.00



R-008399481-000J
2.30
0.08



R-008399487-000L
2.81
0.26



R-008399526-000H
5.38
0.35



R-008399535-000S
3.24
0.04



R-008399538-000T
4.18
0.28



R-008399568-000V
3.85
0.13



R-008399571-000B
4.51
0.28



R-008399589-000N
2.43
0.07



R-008399592-000V
5.11
0.02



R-008399604-000R
−1.15
0.03



R-008399610-000Y
4.97
0.16



R-008399616-000A
2.18
0.03



R-008399628-000K
4.04
0.00



R-008399634-000T
3.53
0.23



R-008399640-000A
3.90
0.16



R-008399652-000K
4.94
0.03



R-008399655-000L
3.57
0.14



R-008399658-000M
3.74
0.42



R-008399661-000U
3.01
0.06



R-008399664-000V
3.84
0.16



R-008399670-000C
5.25
0.09



R-008399679-000F
3.51
0.29



R-008399682-000M
1.20
0.08










Select high ranking siNAs from Tables 3a & 3b were further analyzed for efficacy and potency in Huh7 cells use dose response curves. The results for these siNAs are shown in Table 4. The potency 50 is the calculated siNA transfection concentration that produces 50% target mRNA knockdown. The 1050 was determined after 24 hour exposure time.







TABLE 4







Dose response data for various siNAs in Huh 7 cells. Calculated 


maximum ΔΔCt is determined from the dose response curve.












Mean 
SD 
POTENCY 
IC50


siNA Duplex ID
ΔΔCt
ΔΔCt
50 (nM)
(nM)





R-008362824-000R
4.18
0.09
0.02
0.02


R-008362821-000P
4.16
0.01
0.02
0.02


R-008363031-000Y
4.10
0.24
0.01
0.01


R-008362785-000U
4.00
0.31
0.03
0.03


R-008362686-000T
3.98
0.18
0.07
0.06


R-008362782-000T
3.95
0.55
0.05
0.04


R-008362875-000L
3.61
0.36
0.02
0.02


R-008308997-000F
3.59
0.14
0.02
0.02


R-008362722-000N
3.58
0.23
0.03
0.02


R-008362791-000B
3.51
0.89
0.02
0.01


R-008362932-000A
3.48
0.46
0.02
0.02


R-008362689-000U
3.39
0.81
0.02
0.02


R-008363043-000H
3.29
0.01
0.02
0.02


R-008363073-000K
3.21
0.45
0.10
0.08


R-008362812-000F
3.07
0.40
0.03
0.03


R-008362947-000L
3.07
0.28
0.02
0.01


R-008363070-000J
2.91
0.10
0.01
0.01









Additional siNAs from Tables 3a & 3b were further analyzed for efficacy and potency in MK2D cells using dose response curves. The results for these siNAs are shown in Table 5. The potency 50 is the calculated siNA transfection concentration that produces 50% target mRNA knockdown. The IC50 was determined after 24 hour exposure time.







TABLE 5







Dose response data for various siNAs in MK2D cells. Calculated 


maximum ΔΔCt is determined from the dose response curve.











Mean
SD 
IC50


siNA Duplex ID
ΔΔCt
ΔΔCt
(nM)





R-008380929-000H002
6.8
0.03
0.004


R-008488882-000B001
5.8
0.01
0.004


R-008488885-000C001
6.1
0.03
0.007


R-008488887-000V001
6.6
0.02
0.004


R-008488889-000M001
6.4
0.23
0.005









Example 2
Determining In Vitro Serum Stability of siNAs
siNAs are reconstituted as 50 μM to 100 μM stock solution with H2O and added to human serum pre-warmed to 37° C. to a final concentration of 20 μg/mL. The mixture is then incubated at 37° C. for 0, 1 and 2 hours. At the end of each time point, the reactions are stopped by mixing with equal volume of Phenomenex Lysis-Loading Buffer. Oligonucleotides are purified in 96-well format by Phenomenex Solid Phase Extraction and lyophilized until dry with Labconco Triad Lyo-00417. The lyophilized samples are reconstituted in 150 μL of 1 mM EDTA prepared with RNase-free H2O. The sample solutions are then diluted 5 fold with 1 mM EDTA for liquid chromatography/mass spectrometry (LC/MS) analysis on ThermoFisher Orbitrap. Serum metabolites of the siNAs were determined based on the measured molecular weights.
Example 3
Testing of Cytokine Induction
To assess immunostimulative effects of various siNAs of the invention loaded in lipid nanoparticles (DLinDMA/Cholesterol/S-PEG-C-DMA/DSPC in a 40/48/2/10 ratio), C57Bl/6 mice are dosed with a single 3 mpk dose of LNP formulated siNAs through tail vein injection. Serum or plasma samples are collected at 3 and 24 hours post-dose. The cytokine and chemokine levels in these samples is measured with the SearchLight IR Cytokine Array from Aushon Biosciences according to the manufacturer's instruction. The cytokines and chemokines measured are IL-1α, IL-1β, IL-6, KC, IL-10, IFNγ, TNF, GMCSF, MIP-1β, MCP-1/JE, and RANTES.
Example 4
Efficacy Studies in Mouse
Mice are dosed IV via tail vein injections with LNP encapsulated siNAs or vehicle control using 2 different 3-week dosing schemes: one 1 mg/kg dose for 3 consecutive days or a single 6 mg/kg does per week. In some experiments, the mice are co-dosed with sorafenib at a dose of 100 mg/kg BID every day for 3 weeks. Total tumor burden is measured by micro-CT scan imaging. The animals are sacrificed 5 days after the last siNA dose (Day 23), and normal liver and tumor tissues from each animal is collected for RNA purification. Total RNA is purified using RNeasy 96 kit (Qiagen, Cat#74182). cDNA is generated from total RNA using High Capacity cDNA Reverse Transcription Kit (Cat#: 4368813). Quantitative PCR reactions are performed with TaqMan Universal PCR Master Mix (Cat#: 4304437). Human CTNNB1 TaqMan Gene Expression Assay (Hs00355045_m1) and human GAPDH TaqMan Gene Expression Assay is used to monitor the mRNA level of both transcripts in tumor tissue. Mouse CTNNB1 TaqMan Gene Expression Assay (Mm00483033_m1) and mouse GAPDH TaqMan Gene Expression Assay is used to monitor the mRNA level of both transcripts in liver tissue. The expression level of CTNNB1 is normalized against GAPDH to minimize technical variations.
Example 5
Pharmacodynamic Study in Non-Human Primates
Rhesus macaque monkeys are dosed with a single 2.5 mpk dose of siNA loaded lipid nanoparticles through intravenous infusion. To monitor target mRNA knockdown, liver biopsies are performed at various time points pre- and post-dose with 16T gauge Menghini needles for about 20 mg tissue per animal. Whole blood and serum/plasma is also collected at different time points pre- and post-dose to monitor potential toxicity associated with the treatments. All procedures adhere to the regulations outlined in the USDA Animal Welfare Act (9 CFR, Parts 1, 2 and 3) and the conditions specified in The Guide for Care and Use of Laboratory Animals (ILAR publication, 1996, National Academy Press). Total RNA from the liver biopsy tissue was purified using RNeasy 96 kit (Qiagen, Cat#74182). cDNA was generated from total RNA using High Capacity cDNA Reverse Transcription Kit (Cat#: 4368813). Quantitative PCR reactions were performed with TaqMan Universal PCR Master Mix (Cat#: 4304437). Human CTNNB1 TaqMan Gene Expression Assay (Hs00355045_m1) and rhesus GAPDH TaqMan Gene Expression Assay (Rh02621745_g1) is used to monitor the mRNA level of both transcripts in liver biopsy tissue. The expression level of CTNNB1 is normalized against GAPDH to minimize technical variations.
LNP formulations (DLinDMA/Cholesterol/S-PEG-C-DMA/DSPC in a 40/48/2/10 ratio) comprising the siNA are tested. Log 2(fold change) in CTNNB1 gene expression is determined on days 3, 7, 14, and 28 days post-dosing. Pre-dose CTNNB1 expression levels for the monkey is measured 7 days before the first dosing.
Example 6
Pharmacodynamic Studies in Mouse
Mice were dosed IV via tail vein injections with LNP encapsulated siNAs or vehicle control using a single 0.33 mg/kg. Five animals which received each treatment were sacrificed 2, 7, 14 and 21 days after the siNA dose, and liver tissues from each animal was collected for RNA purification. Total RNA was purified using RNeasy 96 kit (Qiagen, Cat#74182). cDNA was generated from total RNA using High Capacity cDNA Reverse Transcription Kit (Cat#: 4368813). Quantitative PCR reactions were performed with TaqMan Universal PCR Master Mix (Cat#: 4304437). Mouse CTNNB1 TaqMan Gene Expression Assay (Mm00483033_m1) and mouse GAPDH TaqMan Gene Expression Assay was used to monitor the mRNA level of both transcripts. The expression level of CTNNB1 was normalized against GAPDH to minimize technical variations. Data is shown in Table 6.







TABLE 6







In vivo screening data in C57B1/6 mice, recorded as 


log 2(fold change) in CTNNB1 gene expression.












Day 2
Day 7
Day 14
Day 21
















Mouse 
Mouse 
Mouse
Mouse 
Mouse 
Mouse
Mouse
Mouse



Mean
SD
Mean
SD
Mean
SD
Mean
SD



ΔΔCT
ΔΔCT
ΔΔCT
ΔΔCT
ΔΔCT
ΔΔCT
ΔΔCT
ΔΔCT


















PBS
0.00
0.23
0.00
0.21
0.00
0.16
0.00
0.15


R-008380929-000H
2.95
0.27
2.76
0.14
2.33
0.09
1.95
0.33


R-008381104-000W
2.90
0.21
2.43
0.26
1.77
0.30
1.32
0.23


R-008488882-000B
3.21
0.37
2.86
0.33
2.34
0.14
1.93
0.18


R-008488885-000C
2.44
0.13
1.35
0.22
0.59
0.17
0.58
0.31


R-008488887-000V
2.11
0.31
1.76
0.14
0.94
0.42
1.05
0.32


R-008488889-000M
2.31
0.22
1.87
0.35
1.30
0.10
0.86
0.17









Example 7
Pharmacodynamic Study in Non-Human Primates
Rhesus macaque monkeys were dosed with a single 3.34 mg/m2 of body surface area dose of siNA loaded lipid nanoparticles through intravenous infusion. To monitor target mRNA knockdown, liver biopsies were performed at various time points pre- and post-dose with 16T gauge Menghini needles for about 20 mg tissue per animal. Whole blood and serum/plasma is also collected at different time points pre- and post-dose to monitor potential toxicity associated with the treatments. All procedures adhered to the regulations outlined in the USDA Animal Welfare Act (9 CFR, Parts 1, 2 and 3) and the conditions specified in The Guide for Care and Use of Laboratory Animals (ILAR publication, 1996, National Academy Press). Total RNA from the liver biopsy tissue was purified using RNeasy 96 kit (Qiagen, Cat#74182). cDNA was generated from total RNA using High Capacity cDNA Reverse Transcription Kit (Cat#: 4368813). Quantitative PCR reactions were performed with TaqMan Universal PCR Master Mix (Cat#: 4304437). Human CTNNB1 TaqMan Gene Expression Assay (Hs00355045_m1) and rhesus GAPDH TaqMan Gene Expression Assay (Rh02621745_m1) was used to monitor the mRNA level of both transcripts in liver biopsy tissue. The expression level of CTNNB1 was normalized against GAPDH to minimize technical variations. Data is shown in Table 7. LNP formulations (DLinDMA/Cholesterol/S-PEG-C-DMA/DSPC in a 40/48/2/10 ratio) comprising the siNA were tested. Log 2(fold change) in CTNNB1 gene expression was determined on days 2 and 7 days post-dosing. Pre-dose CTNNB1 expression levels for the monkey is measured 6 days before the first dosing.







TABLE 7







In vivo screening data in rhesus, recorded as 


log 2(fold change) in CTNNB1 gene expression.













Day -6
Day 2
Day 7
















Rhesus 
Rhesus 
Rhesus 
Rhesus 
Rhesus 
Rhesus




Mean
SD
Mean
SD
Mean
SD



siNA duplex
ΔΔCT
ΔΔCT
ΔΔCT
ΔΔCT
ΔΔCT
ΔΔCT

















LNP
PBS
0.00
0.37
0.00
0.24
0.00
0.25


LNP-2
R-008488882-000B
−0.11
0.20
1.41
0.35
0.73
0.56


LNP-4
R-008488885-000C
−0.15
0.13
1.79
0.46
1.64
0.59


LNP-1
R-008488889-000M
0.02
0.29
1.59
0.43
1.44
0.60


LNP-3
R-008380929-000H
−0.10
0.25
1.89
0.17
1.60
0.04









Example 8
Short Interfering Nucleic Acid Lipid Nanoparticle (LNP) Formulations
A. General LNP Process Description for LNP Formulations:
The lipid nanoparticles were prepared by an impinging jet process. The particles were formed by mixing lipids dissolved in alcohol with siNA dissolved in a citrate buffer. The lipid solution contained a cationic lipid, a helper lipid (cholesterol), PEG (e.g. PEG-C-DMA, PEG-DMG) lipid, and DSPC at a concentration of 5-15 mg/mL with a target of 9-12 mg/mL in an alcohol (for example ethanol). The ratio of the lipids had a mole percent range of 25-98 for the cationic lipid with a target of 35-65, the helper lipid had a mole percent range from 0-75 with a target of 30-50, the PEG lipid has a mole percent range from 1-15 with a target of 1-6, and the DSPC had a mole percent range of 0-15 with a target of 0-12. The siNA solution contained one or more siNA sequences at a concentration range from 0.3 to 0.6 mg/mL with a target of 0.3-0.9 mg/mL in a sodium citrate buffered salt solution with pH in the range of 3.5-5. The two solutions were heated to a temperature in the range of 15-40° C., targeting 30-40° C., and then mixed in an impinging jet mixer instantly forming the LNP. The teeID had a range from 0.25 to 1.0 mm and a total flow rate from 10-600 mL/minute. The combination of flow rate and tubing ID had the effect of controlling the particle size of the LNPs between 30 and 200 nm. The LNP suspension was then mixed with a buffered solution at a higher pH with a mixing ratio in the range of 1:1 to 1:3 vol:vol, but targeting 1:2 vol:vol. This buffered solution was at a temperature in the range of 15-40° C., targeting 30-40° C. This LNP suspension was further mixed with a buffered solution at a higher pH and with a mixing ratio in the range of 1:1 to 1:3 vol:vol, but targeting 1:2 vol:vol. The buffered solution was at a temperature in the range of 15-40° C., targeting 30-40° C. The mixed LNPs were held from 30 minutes to 2 hrs prior to an anion exchange filtration step. The temperature during incubating was in the range of 15-40° C., targeting 30-40° C. After incubating, the LNP suspension was filtered through a 0.8 um filter containing an anion exchange separation step. This process used tubing IDs ranging from 1 mm ID to 5 mm ID and a flow rate from 10 to 2000 mL/minute The LNPs were concentrated and diafiltered via an ultrafiltration process where the alcohol was removed and the citrate buffer was exchanged for the final buffer solution such as phosphate buffered saline. The ultrafiltration process used a tangential flow filtration format (TFF). This process used a membrane nominal molecular weight cutoff range from 30-500 KD. The membrane format was hollow fiber or flat sheet cassette. The TFF processes with the proper molecular weight cutoff retained the LNP in the retentate and the filtrate or permeate contained the alcohol; citrate buffer; and final buffer wastes. The TFF process is a multiple step process with an initial concentration to a siNA concentration of 1-3 mg/mL. Following concentration, the LNP suspension was diafiltered against the final buffer for 10-20 volumes to remove the alcohol and perform buffer exchange. The material was then concentrated an additional 1-3 fold. The final steps of the LNP process were to sterile filter the concentrated LNP solution and vial the product.
Analytical Procedure:
1) siNA Concentration
The siNA duplex concentrations were determined by Strong Anion-Exchange High-Performance Liquid Chromatography (SAX-HPLC) using Waters 2695 Alliance system (Water Corporation, Milford Mass.) with a 2996 PDA detector. The LNPs, otherwise referred to as RNAi Delivery Vehicles (RDVs), were treated with 0.5% Triton X-100 to free total siNA and analyzed by SAX separation using a Dionex BioLC DNAPac PA 200 (4×250 mm) column with UV detection at 254 nm. Mobile phase was composed of A: 25 mM NaClO4, 10 mM Tris, 20% EtOH, pH 7.0 and B: 250 mM NaClO4, 10 mM Tris, 20% EtOH, pH 7.0 with a liner gradient from 0-15 min and a flow rate of 1 ml/minute. The siNA amount was determined by comparing to the siNA standard curve.
2) Encapsulation Rate
Fluorescence reagent SYBR Gold was employed for RNA quantitation to monitor the encapsulation rate of RDVs. RDVs with or without Triton X-100 were used to determine the free siNA and total siNA amount. The assay is performed using a SpectraMax M5e microplate spectrophotometer from Molecular Devices (Sunnyvale, Calif.). Samples were excited at 485 nm and fluorescence emission was measured at 530 nm. The siNA amount is determined by comparing to an siNA standard curve.

Encapsulation rate=(1−free siNA/total siNA)×100%

3) Particle Size and Polydispersity
RDVs containing 1 μg siNA were diluted to a final volume of 3 ml with 1×PBS. The particle size and polydispersity of the samples was measured by a dynamic light scattering method using ZetaPALS instrument (Brookhaven Instruments Corporation, Holtsville, N.Y.). The scattered intensity was measured with He—Ne laser at 25° C. with a scattering angle of 90°.
4) Zeta Potential Analysis
RDVs containing 1 μg siNA were diluted to a final volume of 2 ml with 1 mM Tris buffer (pH 7.4). Electrophoretic mobility of samples was determined using ZetaPALS instrument (Brookhaven Instruments Corporation, Holtsville, N.Y.) with electrode and He—Ne laser as a light source. The Smoluchowski limit was assumed in the calculation of zeta potentials.
5) Lipid Analysis
Individual lipid concentrations were determined by Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) using Waters 2695 Alliance system (Water Corporation, Milford Mass.) with a Corona charged aerosol detector (CAD) (ESA Biosciences, Inc, Chelmsford, Mass.). Individual lipids in RDVs were analyzed using an Agilent Zorbax SB-C18 (50×4.6 mm, 1.8 μm particle size) column with CAD at 60° C. The mobile phase was composed of A: 0.1% TFA in H2O and B: 0.1% TFA in IPA. The gradient changed from 60% mobile phase A and 40% mobile phase B from time 0 to 40% mobile phase A and 60% mobile phase B at 1.00 min; 40% mobile phase A and 60% mobile phase B from 1.00 to 5.00 min; 40% mobile phase A and 60% mobile phase B from 5.00 min to 25% mobile phase A and 75% mobile phase B at 10.00 min; 25% mobile phase A and 75% mobile phase B from 10.00 min to 5% mobile phase A and 95% mobile phase B at 15.00 min; and 5% mobile phase A and 95% mobile phase B from 15.00 to 60% mobile phase A and 40% mobile phase B at 20.00 min with a flow rate of 1 ml/minute. The individual lipid concentration was determined by comparing to the standard curve with all the lipid components in the RDVs with a quadratic curve fit. The molar percentage of each lipid was calculated based on its molecular weight.
B. General LNP Preparation for Various Formulations in Table 11
siNA nanoparticle suspensions in Table 11 were prepared by dissolving siNAs and/or carrier molecules in 20 mM sodium citrate buffer (pH 5.0) at a concentration of about 0.40 mg/mL. Lipid solutions were prepared by dissolving a mixture of cationic lipid (e.g., (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine, see structure in Table 12), DSPC, Cholesterol, and PEG-DMG (ratios shown in Table 11) in absolute ethanol at a concentration of about 8 mg/mL. The nitrogen to phosphate ratio was approximated to 6:1.
Nearly equal volumes of siNA/carrier and lipid solutions were delivered with two FPLC pumps at the same flow rates to a mixing T connector. A back pressure valve was used to adjust to the desired particle size. The resulting milky mixture was collected in a sterile glass bottle. This mixture was then diluted with an equal volume of citrate buffer, followed by equal volume of PBS (pH 7.4), and filtered through an ion-exchange membrane to remove any free siNA/carrier in the mixture. Ultra filtration against PBS (7.4)) was employed to remove ethanol and to exchange buffer. The final LNP was obtained by concentrating to the desired volume and sterile filtered through a 0.2 μm filter. The obtained LNPs were characterized in term of particle size, Zeta potential, alcohol content, total lipid content, nucleic acid encapsulated, and total nucleic acid concentration.
LNP Manufacture Process
In a non-limiting example, LNPs were prepared in bulk as follows. The process consisted of (1) preparing a lipid solution; (2) preparing an siNA/carrier solution; (3) mixing/particle formation; (4) incubation; (5) dilution; (6) ultrafiltration and concentration.
1. Preparation of Lipid Solution
2 L glass reagent bottles and measuring cylinders were depyrogenated. The lipids were warmed to room temperature. Into the glass reagent bottle was transferred 8.0 g of (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine with a pipette and 1.2 g of DSPC, 3.5 g of Cholesterol, 0.9 g of PEG-DMG were added. To the mixture is added 1 L of ethanol. The reagent bottle was placed in heated water bath, at a temperature not exceeding 50° C. The lipid suspension was stirred with a stir bar. A thermocouple probe was put into the suspension through one neck of the round bottom flask with a sealed adapter. The suspension was heated at 30-40° C. until it became clear. The solution was allowed to cool to room temperature.
2. Preparation of siNA/Carrier Solution
Into a sterile container (Corning storage bottle) was weighed 0.4 g times the water correction factor (approximately 1.2) of siNA powder. The siNA was transferred to a depyrogenated 2 L glass reagent bottle. The weighing container was rinsed 3× with citrate buffer (20 mM, pH 5.0) and the rinses were placed into the 2 L glass bottle, QS with citrate buffer to 1 L. The concentration of the siNA solution was determined with a UV spectrometer using the following procedure. 20 μL was removed from the solution, diluted 50 times to 1000 μL, and the UV reading recorded at A260 nm after blanking with citrate buffer. This was repeated. Note, if the readings for the two samples are consistent, an average can be taken and the concentration calculated based on the extinction coefficients of the siNAs. If the final concentration is out of the range of 0.40±0.01 mg/mL, the concentration can be adjusted by adding more siNA/carrier powder, or adding more citrate buffer. This process can be repeated for the second siNA, if applicable
When the siNA/carrier solution comprised a single siNA duplex instead of a cocktail of two or more siNA duplexes and/or carriers, then the siNA/carrier was dissolved in 20 mM citrate buffer (pH 5.0) to give a final concentration of 0.4 mg/mL.
The lipid and ethanol solutions were then sterile filtered through a Pall Acropak 20 0.8/0.2 μm sterile filter PN 12203 into a depyrogenated glass vessel using a Master Flex Peristaltic Pump Model 7520-40 to provide a sterile starting material for the encapsulation process. The filtration process was run at an 80 mL scale with a membrane area of 20 cm2. The flow rate was 280 mL/minute. This process can be scaled by increasing the tubing diameter and the filtration area.
3. Particle Formation—Mixing Step
Using a two-barrel syringe driven pump (Harvard 33 Twin Syringe), the sterile lipid/ethanol solution and the sterile siNA/carrier or siNA/carrier cocktail/citrate buffer (20 mM citrate buffer, pH 5.0) solutions were mixed in a 0.5 mm ID T-mixer (Mixing Stage I) at equal, or nearly equal, flow rates. The resulting outlet LNP suspension contained 40-50 vol % ethanol. To obtain a 45 vol % ethanol outlet suspension, the sterile lipid/ethanol and the sterile siNA/carrier or siNA/carrier cocktail/citrate buffer solutions were mixed at flow rates of 54 mL/min and 66 mL/min, respectively, such that the total flow rate of the mixing outlet is 120 mL/min.
4. Dilution
The outlet stream of Mixing Stage I was fed directly into a 4 mm ID T-mixer (Mixing Stage II), where it was diluted with a buffered solution at higher pH (20 mM sodium citrate, 300 mM sodium chloride, pH 6.0) at a ratio of 1:1 vol:vol %. This buffered solution was at a temperature in the range of 30-40° C., and was delivered to the 4 mm T-mixer via a peristaltic pump (Cole Parmer MasterFlex L/S 600 RPM) at a flow rate of 120 mL/min.
The outlet stream of Mixing Stage II was fed directly into a 6 mm ID T-mixer (Mixing Stage III), where it was diluted with a buffered solution at higher pH (PBS, pH 7.4) at a ratio of 1:1 vol:vol %. This buffered solution was at a temperature in the range of 15-25° C., and was delivered to the 6 mm T-mixer via peristaltic pump (Cole Parmer MasterFlex L/S 600 RPM) at a flow rate of 240 mL/min.
5. Incubation and Free siNA Removal
The outlet stream of Mixing Stage III was held after mixing for 30 minute incubation. The incubation was conducted at temperature of 35-40° C. and the in-process suspension was protected from light. Following incubation, free (un-encapsulated) siNA was removed via anion exchange with Mustang Q chromatography filters (capsules). Prior to use, the chromatography filters were pre-treated sequentially with flushes of 1N NaOH, 1M NaCl, and a final solution of 12.5 vol % ethanol in PBS. The pH of the final flush was checked to ensure pH <8. The incubated LNP stream was then filtered via Mustang Q filters via peristaltic pump (Cole Parmer MasterFlex L/S 600 RPM) at flow rate of approximately 100 mL/min. The filtered stream was received into a sterile glass container for ultrafiltration and concentration as follows.
6. Ultrafiltration, Concentration and Sterile Filtration
The ultrafiltration process is a timed process and the flow rates must be monitored carefully. This is a two step process; the first is a concentration step taking the diluted material and concentrating approximately 8-fold, to a concentration of approximately 0.3-0.6 mg/mL siNA.
In the first step, a ring-stand with a ultrafiltration membrane 100 kDa PES (Spectrum Labs) installed was attached to a peristaltic pump (Spectrum KrosFloII System). 9.2 L of sterile distilled water was added to the reservoir; 3 L was drained to waste and the remainder was drained through permeate to waste. 5.3 L of 0.25 N sodium hydroxide was added to the reservoir with 1.5 L drained to waste and 3.1 L drained through permeate to waste. The remaining sodium hydroxide was held in the system for sanitization (at least 10 minutes), and then the pump was drained. 9.2 L of 70 (v/v) % isopropyl alcohol was added to the reservoir with 1.5 L drained to waste and the remainder drained through permeate to waste. 6 L of conditioning buffer (12.5% ethanol in phosphate buffered saline) was added with 1.5 L drained to waste and the remainder drained though the permeate until the waste was of neutral pH (7-8). A membrane flux value was recorded, and the pump was then drained.
The diluted LNP solution was placed into the reservoir to the 1.1 L mark. The pump was turned on at 2.3 L/min. After 5 minutes of recirculation, the permeate pump was turned on at 62.5 mL/min and the liquid level was constant at approximately 950 mL in the reservoir. The diluted LNP solution was concentrated from 9.8 L to 1.1 L in 140 minutes, and the pump was paused when all the diluted LNP solution has been transferred to the reservoir.
The second step was a diafiltration step exchanging the ethanol/aqueous buffer to phosphate buffered saline. During this step, approximately 10-20 diafiltration volumes of phosphate buffered saline were used. Following diafiltration, a second concentration was undertaken to concentrate the LNP suspension 3-fold to approximately 1-1.5 mg/mL siRNA. The concentrated suspension was collected into sterile, plastic PETG bottles. The final suspension was then filtered sequentially via Pall 0.45 um PES and Pall 0.2 um PES filters for terminal sterilization prior to vial filling.
The obtained LNPs were characterized in terms of particle size, Zeta potential, alcohol content, total lipid content, nucleic acid encapsulated, and total nucleic acid concentration.
C. Synthesis of Novel Cationic Lipids
Synthesis of the novel cationic lipids is a linear process starting from lipid acid (i). Coupling to N,O-dimethyl hydroxylamine gives the Weinreb amide ii. Grignard addition generates ketone iii. Titanium mediated reductive amination gives final products of type iv.




Synthesis of the single carbon homologated cationic lipids v is a linear process starting from lipid ketone (iii). Conversion of the ketone to the nitrile (iv) is accomplished via treatment with TOSMIC and potassium tert-butoxide. Reduction of the nitrile to the primary amine followed by reductive amination provides final cationic lipids v.




Synthesis of two carbon homologated cationic lipids viii is a linear process starting from lipid ketone (iii). Conversion of the ketone to the α,β-unsaturated amide vi is accomplished under Peterson conditions. Conjugate reduction of the α,β-unsaturation is performed using LS-Selectride to give amide vii. Reduction of the amide with lithium aluminum hydride provides final cationic lipids viii.




Cyclopropyl containing lipids are prepared according to General Scheme 4. Unsaturated Weinreb amides ii are subjected to Simmons-Smith cyclopropanation conditions to give cyclopropyl containing Weinreb amides ix. These are carried on to final products as outlined in General Schemes 1-3.




Synthesis of allylic amine cationic lipids xv is a linear process starting with aldehyde x. Addition of t-butyl acetate generates β-hydroxy ester xi. Conversion of the hydroxyl functionality to a fluoro group followed by acid treatment generates β-fluoro acid xii. Conversion of the acid to the Weinreb amide followed by Grignard addition gives the β-fluoro ketone xiv. Reductive amination results in simultaneous elimination to generate the desired allylic amine xv.




11,14-Eicosadienoic acid, (11Z,14Z)— (50 g, 162 mmol), N,O-Dimethylhydroxylamine hydrochloride (31.6 g, 324 mmol), HOAt (44.1 g, 324 mmol), Et3N (45.2 mL, 324 mmol), and EDC (62.1 g, 324 mmol) were mixed in DCM (810 mL) and stirred overnight at ambient temperature. Reaction was then washed 5×700 mL water, then washed 1×600 mL 1 M NaOH, dried with sodium sulfate, filtered through celite and evaporated to obtain 53.06 g (93%) 11,14-eicosadienamide, N-methoxy-N-methyl-, (11Z,14Z) as a clear golden oil. 1H NMR (400 MHz, CDCl3) δ 5.35 (m, 4H), 3.68 (s, 3H), 3.18 (s, 3H), 2.77 (m, 2H), 2.41 (t, J=7 Hz, 2H), 2.05 (m, 4H), 1.63 (m, 2H), 1.40-1.26 (m, 18H), 0.89 (t, J=7 Hz, 3H).




11,14-eicosadienamide, N-methoxy-N-methyl-, (11Z,14Z)-1 (4 g, 11.38 mmol) was dissolved in dry THF (50.0 ml) in a 250 mL flask then 1 M nonylmagnesium bromide (22.76 ml, 22.76 mmol) was added under nitrogen at ambient temperature. After 10 min, the reaction was slowly quenched with excess sat. aq NH4Cl. The reaction was washed into a separatory funnel with hexane and water, shaken, the lower aqueous layer discarded, the upper layer dried with sodium sulfate, filtered, and evaporated to give crude ketone as a golden oil. To the above crude ketone was added dimethylamine (2 M in THF) (14.22 ml, 28.4 mmol) followed by Ti(O-i-Pr)4 (6.67 ml, 22.76 mmol) and let stir overnight. The next day, added EtOH (50 ml) followed by NaBH4 (0.646 g, 17.07 mmol). After 5 min of stirring, directly injected entire reaction onto a 40 g silica column that was in line with a 330 g silica column. Eluted 10 min 100% DCM, then 30 min 0-15% MeOH/DCM, collected 20,23-nonacosadien-10-amine, N,N-dimethyl-, (20Z,23Z) (1) (2.45 g, 5.47 mmol, 48.1% yield) as a faintly golden oil. 1H NMR (400 MHz, CDCl3) δ 5.35 (m, 4H), 2.78 (m, 2H), 2.23 (m, 1H), 2.21 (s, 6H), 2.05 (m, 4H), 1.45-1.16 (m, 38H), 0.89 (m, 6H). HRMS calcd for C31H61N 448.4877. found 448.4872.
Compounds 2-30 are novel cationic lipids and were prepared according to the General Scheme 1 above.












Com-




pound
Structure
HRMS

















2




calcd C28H56N 406.4407, found 406.4405.


 


3




calcd C27H54N 392.4251, found 392.4250.


 


4




calcd C24H48N 350.3781, found 350.3770.


 


5




calcd C23H46N 336.3625, found 336.3613.


 


6




calcd C25H50N 364.3938, found 364.3941.


 


7




calcd C26H52N 378.4094, found 378.4081.


 


8




calcd C29H58N 420.4564, found 420.4562.


 


9




calcd C26H52N 378.4094, found 378.4089.


 


10




calcd C25H50N 364.3938, found 364.3931.


 


11




calcd C30H60N 434.4720, found 434.4717.


 


12




calcd C29H58N 420.4564, found 420.4561.


 


13




calcd C28H56N 406.4407, found 406.4404.


 


14




calcd C27H54N 392.4251, found 392.4245.


 


15




calcd C33H66N 476.5190, found 476.5196.


 


16




calcd C32H64N 462.5033, found 462.5045.


 


17




calcd C29H59N 422.4720, found 422.4726.


 


18




calcd C28H57N 408.4564, found 408.4570.


 


19




calcd C30H59N 434.4720, found 434.4729.


 


20




calcd C29H61N 424.4877, found 424.4875.


 


21




calcd C32H64N 462.5033, found 462.5023.


 


22




calcd C33H64N 474.5033, found 474.5033.


 


23




calcd C29H60N 422.4720, found 422.4716.


 


24




calcd C29H60N 422.4720, found 422.4718.


 


25




calcd C31H64N 450.5033, found 450.5031.


 


26




calcd C31H64N 450.5033, found 450.5034.


 


27




calcd C35H72N 506.5659, found 506.5635.


 


28




calcd C31H64N 450.5033, found 450.5037.


 


29




calcd C33H68N 478.5346, found 478.5358.


 


30




calcd C27H56N 394.4407, found 394.4407.









(12Z,15Z)—N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine (Compound 31)




A solution of keton iii (4.0 g, 9.55 mmol), TOSMIC (2.4 g, 12.4 mmol) in dimethoxyethane (45 mL) was cooled to 0° C. and treated with potassium tert-butoxide (19.1 mmol, 19.1 mL of a 1M solution in tBuOH). After 90 minutes, the reaction was partitioned between hexanes and water. The organics were washed with water, dried over sodium sulfate, filtered and evaporated in vacuo. This material was purified by flash chromatography (0-5% EtOAc/hexanes) to give desired product (containing  ̃20% of s.m.). This mixture was carried into next step as is. LC/MS (M+H)=430.6.




Lithium aluminum hydride (23.9 mmol, 23.9 mL of a 1M solution in THF) was added directly to nitrile iv (3.42 g, 8 mmol) at ambient temperature and the reaction was stirred for 20 minutes. The reaction was diluted with 100 mL THF, cooled to 0° C. and carefully quenched with sodium sulfate decahydrate solution. The solids were filtered off and washed with THF. The filtrate was evaporated in vacuo and carried directly into next reaction crude. LC/MS (M+H)=434.6.




A solution of primary amine (3.45 g, 6.2 mmol) in dichloroethane (100 mL) was treated with formaldehyde (1.6 mL, 21.7 mmol) followed by sodium triacetoxyborohydride (6.6 g, 31 mmol). After 5 minutes, the reaction was partitioned between dichloromethane and 1N NaOH. The organics were dried over sodium sulfate, filtered and evaporated in vacuo. The crude mixture was purified by reverse phase preparative chromatography (C8 column) to provide (12Z,15Z)—N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine. HRMS calc'd 462.5033. found 462.5026. 1H NMR (400 MHz, CDCl3) δ 5.35 (m, 4H), 2.78 (2H, t, J=5.6 Hz), 2.18 (s, 6H), 2.05 (m, 6H), 1.3 (m, 39H), 0.89 (m, 6H).
(13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine (Compound 32)




The silyl amide Peterson reagent (3.1 g, 16.7 mmol) was dissolved in THF (35 mL) and cooled to −63° C. To this solution was added nBuLi (16.7 mmol, 6.7 mL of a 2.5M solution). The reaction was warmed to ambient temperature for 30 minutes. The ketone (5.0 g, 11.9 mmol) was dissolved in THF (25 mL) in a second flask. The Peterson reagent was transferred to the ketone solution at −60° C. The reaction was warmed to −40° C. for 1 hour, then warmed to 0° C. for 30 minutes. The reaction was quenched with sodium bicarbonate, diluted with additional water and partitioned between water/hexanes. The organics were washed with brine, dried over sodium sulfate, filtered and evaporated in vacuo. Purification by flash chromatography (0-40% MTBE/hexanes) gave α,β-unsaturated amide vi. 1H NMR (400 MHz, CDCl3) δ 5.75 (s, 1H), 5.36 (m, 4H), 3.01 (s, 3H), 2.99 (s, 3H), 2.78 (t, 2H), 2.28 (t, 2H), 2.05 (m, 6H), 1.35 (m, 34H), 0.89 (m, 6H).




α,β-unsaturated amide vi (1 g, 2.1 mmol) and LS-Selectride (4.1 mmol, 4.1 mL of a 1M solution) were combined in a sealed tube and heated to 60° C. for 24 hours. The reaction was cooled to ambient temperature and partitioned between ammonium chloride solution and heptane. The organics were dried over sodium sulfate, filtered and evaporated in vacuo to give amide vii. This intermediate was carried directly into next reaction crude.




To a solution of amide vii (2.85 g, 5.8 mmol) was added lithium aluminum hydride (8.7 mmol, 8.7 mL of a 1M solution). The reaction was stirred at ambient temperature for 10 minutes then quenched by slow addition of sodium sulfate decahydrate solution. The solids were filtered and washed with THF and the filtrate evaporated in vacuo. The crude mixture was purified by reverse phase preparative chromatography (C8 column) to provide (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine (Compound 32) as an oil. HRMS (M+H) calc'd 476.5190. found 476.5189. 1H NMR (400 MHz, CDCl3) δ 5.37 (m, 4H), 2.78 (t, 2H), 2.42 (m, 8H), 2.05 (q, 4H), 1.28 (m, 41H), 0.89 (m, 6H).
N,N-dimethyl-1-(2-octylcyclopropyl)heptadecan-8-amine (Compound 33)




To a solution of oleic acid (1 g, 3.5 mmol) in DCM (500 mL) cooled to 0° C. was added CDI (0.63 g, 3.9 mmol). The reaction was warmed to ambient temperature for 30 minutes before cooling to 0° C. and treating first with triethylamine (0.39 g, 3.9 mmol) and then dimethyl hydroxylamine hydrochloride (0.38 g, 3.9 mmol). After 1 hour the reaction was partitioned between water and heptane. The organics were dried over magnesium sulfate, filtered and evaporate in vacuo to give crude Weinreb amide ii which was carried directly into next reaction.




A solution of diethylzinc (70.3 mmol, 70.3 mL of a 1M solution) in dichloromethane (130 mL) was cooled to −1° C. and treated dropwise with TFA (8.0 g, 70.3 mmol). After 30 minutes, diiodomethane (18.8 g, 70.3 mmol) was added and this was aged for 30 minutes in the ice bath. To this solution was added Weinreb amide ii (7.6 g, 23.4 mmol). The reaction was warmed to ambient temperature and stirred for 1 hour. The reaction was quenched with ammonium chloride solution (100 mL) and organic layer partitioned off, washed with 10% sodium thiosulfate, dried over magnesium sulfate, filtered and evaporated in vacuo. Purification was flash chromatography (0-30% MTBE/heptane) gave desired product ix. 1H NMR (400 MHz, CDCl3) δ 3.72 (s, 3H), 3.22 (s, 3H), 2.48 (t, 2H), 1.65 (m, 2H), 1.39 (m, 22H), 1.18 (m, 2H), 0.91 (t, 3H), 0.68 (m, 2H), 0.59 (m, 1H), −0.32 (m, 1H).




Conversion of Weinreb amide ix to Compound 33 was carried out in a manner analogous to that described for Compound 1 above (nonyl Grignard addition followed by reductive amination). LC/MS (M+H)=436.6. 1H NMR (400 MHz, CDCl3) δ 2.25 (s, 6H), 1.30 (m, 45H), 0.91 (m, 6H), 0.68 (m, 2H), 0.59 (m, 1H), −0.31 (m, 1H).
Compounds 34-43 are novel cationic lipids and were prepared according to General Schemes 1-4 above.












Compound
Structure
HRMS







34




calcd C30H62N 436.4877, found 436.4872.


 


35




calcd C32H66N 464.5190, found 464.5186.


 


36




calcd C34H70N 492.5503, found 492.5496.


 


37




calcd C33H66N 476.5190, found 476.5174.


 


38




calcd C29H60N 422.4720, found 422.4701.


 


39




calcd C30H62N 436.4877, found 436.4880.


 


40




calcd C32H66N 464.5190, found 464.5199.


 


41




calcd C30H62N 436.4877, found 436.4877.


 


42




calcd C30H62N 436.4877, found 436.4875.


 


43




LC/MS (M + H) 408.6.









(11E,20Z,23Z)—N,N-dimethylnonacosa-11,20,23-trien-10-amine (Compound 44)




To a solution of LDA (95 mmol, 47.5 mL of a 2M solution) in THF (127 mL) cooled to −78° C. was added t-butyl acetate. The reaction was stirred for 15 minutes followed by addition of aldehyde x. The reaction was immediately quenched with ammonium chloride solution, warmed to ambient temperature and partitioned between water/pentane. The organics were dried over sodium sulfate, filtered and evaporated in vacuo. LC/MS (M+H-tBu)=325.4.




Hydroxy ketone xi (7 g, 18.4 mmol) was dissolved in dichloromethane (150 mL) and cooled to 0° C. and treated with deoxofluor (7.3 g, 33.1 mmol). The reaction was warmed to ambient temperature with stirring for 16 hours followed by quenching with sodium bicarbonate solution. The reaction was partitioned and the organics dried over sodium sulfate, filtered and evaporate in vacuo. Flash column chromatography (0-5% ethyl acetate/hexanes) gave the -fluoro ester.
Fluoro ester intermediate (6 g, 15.6 mmol) in dichloromethane was treated with hydrogen chloride (157 mmol, 39.2 mL of a 4M solution in dioxane) and the reaction was stirred at ambient temperature for 16 hours. The reaction was evaporated in vacuo to give desired β-fluoro acid xii. LC/MS (M+H)=327.3.




Fluoro carboxylic acid xii (5.1 g, 15.7 mmol), EDC (6.0 g, 31.4 mmol), N,O-dimethylhydroxylamine hydrochloride (3.1 g, 31.4 mmol), trimethylamine (4.0 g, 39.2 mmol), and HOAt (4.3 g, 31.4 mmol) were combined in DCM (78 mL) and stirred at ambient temperature for 16 hours. The reaction was partitioned between water/DCM and the organics were washed with water (3×) and NaOH solution (1×), dried over sodium sulfate, filtered and evaporated in vacuo. Crude material was purified by reverse phase preparative chromatography to give desired Weinreb amide xiii LC/MS (M+H)=370.4.




A solution of Weinreb amide xiii (4.3 g, 11.7 mmol) in THF (50 mL) was treated with nonylmagnesium bromide (23.4 mmol, 23.4 mL of a 1M solution) at ambient temperature. The reaction was quenched with ammonium chloride solution after 1 hour and partitioned between water and pentane. The organics were dried over sodium sulfate, filtered and evaporated in vacuo. This material was carried into next step crude.




Ketone xiv (5.1 g, 11.7 mmol) was treated with dimethylamine (29.3 mmol, 14.7 mL of a 2M solution in THF) and titanium(IV) isopropoxide (6.7 g, 23.5 mmol) and the reaction was stirred at ambient temperature for 16 hours. To the reaction mixture was added ethanol (50 mL) followed by sodium borohydride (0.67 g, 17.6 mmol). The reaction was loaded directly onto a silica column and purified by flash chromatography (0-15% MeOH/DCM). The material required a second purification by preparative reverse phase chromatography to give (11E,20Z,23Z)—N,N-dimethylnonacosa-11,20,23-trien-10-amine. HRMS calc'd 446.4720. found 446.4724. 1H NMR (400 MHz, CDCl3) δ 5.48 (m, 1H), 5.37 (m, 4H), 5.23 (m, 1H), 2.78 (t, 2H), 2.58 (m, 1H), 2.22 (s, 6H), 2.04 (m, 6H), 1.56 (m, 1H), 1.30 (m, 31H), 0.89 (m, 6H).
Compound 45 is DLinKC2DMA as described in Nature Biotechnology, 2010, 28, 172-176, WO 2010/042877 A1, WO 2010/048536 A2, WO 2010/088537 A2, and WO 2009/127060 A1.




Compound 46 is MC3 as described in WO 2010/054401, and WO 2010/144740 A1.




D. Lipid Nanoparticle Compositions

The following lipid nanoparticle compositions (LNPs) of the instant invention are useful for the delivery of oligonucleotides, specifically siNA molecules of the invention:
Cationic Lipid/Cholesterol/PEG-DMG 56.6/38/5.4;
Cationic Lipid/Cholesterol/PEG-DMG 60/38/2;
Cationic Lipid/Cholesterol/PEG-DMG 67.3/29/3.7;
Cationic Lipid/Cholesterol/PEG-DMG 49.3/47/3.7;
Cationic Lipid/Cholesterol/PEG-DMG 50.3/44.3/5.4;
Cationic Lipid/Cholesterol/PEG-C-DMA/DSPC 40/48/2/10;
Cationic Lipid/Cholesterol/PEG-DMG/DSPC 40/48/2/10; and
Cationic Lipid/Cholesterol/PEG-DMG/DSPC 58/30/2/10.
One skilled in the art would readily appreciate that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned, as well as those inherent therein. The methods and compositions described herein, as presently representative of preferred embodiments, are exemplary and are not intended as limitations on the scope of the invention. Changes therein and other uses will occur to those skilled in the art, which are encompassed within the spirit of the invention, are defined by the scope of the claims.







TABLE 8





CTNNB1 Accession Numbers















NM_001098210


Homo sapiens catenin (cadherin-associated protein), beta 1, 88 kDa,


(CTNNB1), transcriptvariant 3, mRNA.


NM_001098210.1 GI:148227671


NM_007614


Mus musculus catenin (cadherin associated protein), beta 1(Ctnnb1),


transcript variant 1, mRNA


NM_007614.2 GI:31560726


XM_001115474


Macaca mulatta catenin (cadherin-associated protein),beta 1, 88 kDa, 


transcript variant (CTNNB1), mRNA.


XM_001115474.1 GI:109041278
















TABLE 9







Non-limiting examples of Stabilization Chemistries for chemically modified


siNA constructs


Non-limiting examples of Stabilization Chemistries for chemically modified siNA constructs












Chemistry
pyrimidine
purine
caps
p = S
Strand





“Stab 00”
Ribo
Ribo
TT at 3′

S/AS





ends




“Stab 1”
Ribo
Ribo
—
5 at 5′-end
S/AS






1 at 3′-end



“Stab 2”
Ribo
Ribo
—
All linkages 
Usually AS


“Stab 3”
2′-fluoro
Ribo
—
4 at 5′-end 
Usually S






4 at 3′-end



“Stab 4”
2′-fluoro
Ribo
5′ and 3′-
—
Usually S





ends




“Stab 5”
2′-fluoro
Ribo
—
1 at 3′-end 
Usually AS


“Stab 6”
2′-O-Methyl 
Ribo
5′ and 3′-
—
Usually S





ends




“Stab 7”
2′-fluoro
2′-deoxy 
5' and 3′-
—
Usually S





ends




“Stab 8”
2′-fluoro
2′-O-
—
1 at 3′-end
S/AS




Methyl





“Stab 9”
Ribo
Ribo
5′ and 3′-
—
Usually S





ends




“Stab 10”
Ribo
Ribo
—
1 at 3′-end 
Usually AS


“Stab 11”
2′-fluoro
2′-deoxy
—
1 at 3′-end 
Usually AS


“Stab 12”
2′-fluoro
LNA
5′ and 3′-

Usually S





ends




“Stab 13”
2′-fluoro
LNA

1 at 3′-end 
Usually AS


“Stab 14”
2′-fluoro
2′-deoxy

2 at 5′-end 
Usually AS






1 at 3′-end



“Stab 15”
2′-deoxy
2′-deoxy

2 at 5′-end 
Usually AS






1 at 3'-end



“Stab 16”
Ribo
2'-O-
5′ and 3′-

Usually S




Methyl
ends




“Stab 17”
2′-O-Methyl
2′-O-
5′ and 3′-

Usually S




Methyl
ends




“Stab 18”
2′-fluoro
2′-O-
5′ and 3′-

Usually S




Methyl
ends




“Stab 19”
2′-fluoro
2′-O-
3′-end

S/AS




Methyl





“Stab 20”
2′-fluoro
2′-deoxy
3′-end

Usually AS


“Stab 21”
2′-fluoro
Ribo
3′ -end

Usually AS


“Stab 22”
Ribo
Ribo
3′ -end

Usually AS


“Stab 23”
2′-fluoro*
2′-deoxy* 
5' and 3′-

Usually S





ends




“Stab 24”
2′-fluoro*
2′-O-
—
1 at 3′-end
S/AS




Methyl*





“Stab 25”
2′-fluoro*
2′-O-
—
1 at 3′-end
S/AS




Methyl*





“Stab 26”
2′-fluoro* 
2′-O-
—

S/AS




Methyl*





“Stab 27”
2′-fluoro* 
2′-O-
3′-end

S/AS




Methyl*





“Stab 28”
2′-fluoro* 
2′-O-
3′-end

S/AS




Methyl*





“Stab 29”
2′-fluoro* 
2′-O-

1 at 3′-end
S/AS




Methyl*





“Stab 30”
2′-fluoro* 
2′-O-


S/AS




Methyl*





“Stab 31”
2′-fluoro* 
2′-O-
3′-end

S/AS




Methyl*





“Stab 32”
2′-fluoro
2′-O-


S/AS




Methyl





“Stab 33”
2′-fluoro 
2′-deoxy*
5′ and 3′-
—
Usually S





ends




“Stab 34”
2′-fluoro
2′-O-
5′ and 3′-

Usually S




Methyl*
ends




“Stab 35”
2′-fluoro*†
2′-O-


Usually AS




Methyl*†





“Stab 36”
2′-fluoro*†
2′-O-


Usually AS




Methyl*†





“Stab04H”
2′-fluoro‡
Ribo‡
5′ and 3′- 
1 at 3′-end 
Ususally S





ends




“Stab06C”
2′-O-Methyl‡
Ribo‡
5′ and 3′-

Ususally S





ends




“Stab07H”
2′-fluoro‡ 
2′-deoxy‡
5' and 3'-
1 at 3'-end
Ususally S





ends




“Stab07mU”
2′-fluoro‡
2′-deoxy‡ 
5' and 3'-

Ususally S





ends




“Stab09H”
Ribo‡
Ribo‡
5′ and 3′- 
1 at 3′-end 
Ususally S





ends




“Stab16C”
Ribo‡
2′-O-
5′ and 3′-

Ususally S




Methyl‡
ends




“Stab16H”
Ribo‡
2′-O-
5′ and 3′- 
1 at 3′-end 
Ususally S




Methyl‡
ends




“Stab18C”
2′-fluoro‡
2′-O-
5′ and 3′-

Ususally S




Methyl‡
ends




“Stab18H”
2′-fluoro‡ 
2′-O-
5′ and 3'- 
1 at 3′-end 
Ususally S




Methyl‡
ends




“Stab52H”
2′-O-Methyl‡
Ribo‡
5′ and 3'- 
1 at 3′-end
Ususally S





ends




“Stab05C”
2′-fluoro‡
Ribo‡


Ususally AS


“Stab05N”
2′-fluoro‡ 
Ribo‡

1 at 3′-end
Ususally AS


“Stab10C”
Ribo‡
Ribo‡


Ususally AS


“Stab10N”
Ribo‡
Ribo‡

1 at 3′-end
Ususally AS


“Stab35G*”
2′-fluoro‡
2′-O-


Ususally AS




Methyl‡





“Stab35N*”
2′-fluoro‡
2′-O-

1 at 3′-end 
Ususally AS




Methyl‡





“Stab35rev”
2′-O-Methyl‡
2′-fluoro‡


Ususally AS


“Stab50”
Ribo‡
2′-O-


Ususally AS




Methyl‡





“Stab53*”
2′-O-Methyl‡
Ribo‡


Ususally AS


“Stab53N*” 
2′-O-Methyl‡
Ribo‡

1 at 3′-end 
Ususally AS


Stab54
Ribo‡
2′-fluoro‡


Ususally AS





CAP = any terminal cap, see for example FIG. 6.


All Stab chemistries can be used in combination with each other for duplexes of the invention (e.g., as combinations of sense and antisense strand chemistries), or alternately can be used in isolation, e.g., for single stranded nucleic acid molecules of the invention.


All Stab chemistries can comprise 3′-overhang nucleotides having 2′-O-alkyl, 2′-deoxy-2′-fluoro, 2′-deoxy, LNA or other modified nucleotides or non-nucleotides.


All Stab chemistries typically comprise about 19-21 nucleotides, but can vary as described herein.


All Stab chemistries can also include a single ribonucleotide in the sense or passenger strand at the 11th base paired position of the double-stranded nucleic acid duplex as determined from the 5′-end of the antisense or guide strand.


All Stab chemistries can also have in place of the Stab designation above a 2′-deoxy-2′-fluoro modification at position 14 from the 5′ end of the antisense strand regardless of whether it is a purine or pyrimidine at that position.


All Stab chemistries of the antisense strand presented above can have a thymidine in place of a 2′-deoxy uridine at position 1, 2, and/or 3 from the 5′ end of the antisense strand.


S = sense strand.


AS = antisense strand


*Stab 23 has a single ribonucleotide adjacent to 3′-CAP.


*Stab 24 and Stab 28 have a single ribonucleotide at 5′-terminus


*Stab 25, Stab 26, Stab 27, Stab 35, Stab 35G*, Stab 35N*, Stab 35rev*, Stab 36, Stab 50*, Stab53*, Stab 53N*, and Stab 54 have three ribonucleotides at 5′-terminus.


*Stab 29, Stab 30, Stab 31, Stab 33, and Stab 34 any purine at first three nucleotide positions from 5′-terminus are ribonucleotides.


p = phosphorothioate linkage.


†Stab 35 has 2′-O-methyl U at 3′-overhangs and three ribonucleotides at 5′-terminus


†Stab 36 has 2′-O-methyl overhangs that are complementary to the target sequence. (naturally occurring overhangs) and three ribonucleotides at 5′-terminus


‡ - Stab 04H, Stab 06C, Stabl07H, Stab07mU, Stab09H, Stab16C, Stab 16H, Stab18C, Stab 18H, Stab 52H, Stab 05C, Stab05N, Stab10C, Stab10N, Stab35G*, Stab35N*, Stab35N*, Stab35rev*, Stab 50*, Stab 53*, Stab 53N*, Stab 54 have two 2′-O-methyl U 3′-overhangs.


Stab35G*, Stab 35N*, Stab35rev*, Stab50*, Stab53*, and Stab53N* do not allow for a 2′-O-methyl modification at position 14 of the guide strand as determined from the 5′-end.













TABLE 10





Exemplary Solid Phase Oligonucleotide Synthsis Conditions







A. 2.5 μmol Synthesis Cycle ABI 394 Instrument















Wait Time*
Wait Time* 2′-O-
Wait


Reagent
Equivalents
Amount
DNA
methyl
Time*RNA



















Phosphorami
6.5
163 
μL
45
sec
2.5
min
7.5
min


dites











S-Ethyl
23.8
238 
μL
45
sec
2.5
min
7.5
min


Tetrazole











Acetic
100
233 
μL
5
sec
5
sec
5
sec


Anhydride











N-
186
233 
μL
5
sec
5
sec
5
sec


CTNNB1hyl











Imidazole











TCA
176
2.3 
mL
21
sec
21
sec
21
sec


Iodine
11.2
1.7 
mL
45
sec
45
sec
45
sec


Beaucage
12.9
645 
μL
100
sec
300
sec
300
sec













Acetonitrile
NA
6.67 
mL
NA
NA
NA










B. 0.2 μmol Synthesis Cycle ABI 394 Instrument















Wait Time*
Wait Time* 2′-O-
Wait


Reagent
Equivalents
Amount
DNA
methyl
Time*RNA



















Phosphorami
15
31 
μL
45
sec
233
sec
465
sec


dites











S-Ethyl
38.7
31 
μL
45
sec
233
min
465
sec


Tetrazole











Acetic
655
124 
μL
5
sec
5
sec
5
sec


Anhydride











N-
1245
124 
μL
5
sec
5
sec
5
sec


CTNNB1hyl











Imidazole











TCA
700
732 
μL
10
sec
10
sec
10
sec


Iodine
20.6
244 
μL
15
sec
15
sec
15
sec


Beaucage
7.7
232 
μL
100
sec
300
sec
300
sec













Acetonitrile
NA
2.64 
mL
NA
NA
NA










C. 0.2 μmol Synthesis Cycle 96 well Instrument













Equivalents
Amount:






DNA/2′-O-
DNA/2′-O-
Wait Time*
Wait Time*
Wait Time*


Reagent
methyl/Ribo
methyl/Ribo
DNA
2′-O-methyl
Ribo



















Phosphorami
22/33/66
40/60/120 
μL
60
sec
180
sec
360
sec


dites











S-Ethyl
70/105/210
40/60/120 
μL
60
sec
180
min
360
sec


Tetrazole











Acetic
265/265/265
50/50/50 
μL
10
sec
10
sec
10
sec


Anhydride











N-
502/502/502
50/50/50 
μL
10
sec
10
sec
10
sec


CTNNB1hyl











Imidazole











TCA
238/475/475
250/500/500 
μL
15
sec
15
sec
15
sec


Iodine
6.8/6.8/6.8
80/80/80 
μL
30
sec
30
sec
30
sec


Beaucage
34/51/51
80/120/120

100
sec
200
sec
200
sec













Acetonitrile
NA
1150/1150/1150
μL
NA
NA
NA





Wait time does not include contact time during delivery.


Tandem synthesis utilizes double coupling of linker molecule













TABLE 11







Composition of Select Lipid Nanoparticle Formulations










LNP
Lipid Components and
siNA



Identifier
Molar Ratios
Duplex
N/P
















LNP-1
Compound
Choles-
DSPC
PEG-
R-008488889-
6



32
terol
(10%)
DMG
000M




(50%)
(30%)

(2%)




LNP-2
Compound
Choles-
DSPC
PEG-
R-008488882-
6



32
terol
(10%)
DMG
000B




(50%)
(30%)

(2%)




LNP-3
Compound
Choles-
DSPC
PEG-
R-008380929-
6



32
terol
(10%)
DMG
000H




(50%)
(30%)

(2%)




LNP-4
Compound
Choles-
DSPC
PEG-
R-008488885-
6



32
terol
(10%)
DMG
000C




(50%)
(30%)

(2%)







N/P ratio = Nitrogen:Phosphorous ratio between cationic lipid and nucleic acid













TABLE 12







Chemical Structures of Lipids in Formulations of Table 11








Lipid
Chemical Structure





Compound 32






 


Cholesterol






 


DSPC






 


PEG-DMG

## Claims

1. A double-stranded short interfering nucleic acid (siNA) molecule that inhibits the expression of CTNNB1, wherein the siNA comprises:
5′-ACGACUAGUUCAGUUGCUU-3′ (SEQ ID NO: 194) and 5′-AAGCAACUGAACUAGUCGU-3′ (SEQ ID NO: 5107).

2. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1, wherein at least one nucleotide is a chemically modified nucleotide.

3. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1 further comprising at least one non-nucleotide.

4. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1, wherein at least one nucleotide comprises a universal base.

5. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1, having at least one phosphorothioate internucleotide linkage.

6. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1, comprising a cap on the 3′-end, 5′-end or both 3′ and 5′ ends of at least one strand.

7. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1, comprising one or more 3′-overhang nucleotides on one or both strands.

8. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1, wherein the 5′ end of the antisense strand is phosphorylated.

9. The double-stranded short interfering nucleic acid (siNA) molecule of claim 7, wherein the 3′-overhang nucleotides on at least one strand are 2′-O-methyl nucleotides.

10. The double-stranded short interfering nucleic acid (siNA) molecule of claim 9, wherein the 2′-O-methyl nucleotides are linked with a phosphorothioate internucleotide linkage.

11. The double-stranded short interfering nucleic acid (siNA) molecule of claim 2, wherein the chemically modified nucleotide is a 2′-deoxy-2′-fluoro nucleotide.

12. The double-stranded short interfering nucleic acid (siNA) molecule of claim 2, wherein the chemically modified nucleotide is a 2′-deoxy nucleotide.

13. The double-stranded short interfering nucleic acid (siNA) molecule of claim 2, wherein the chemically modified nucleotide is a 2′-O-alkyl nucleotide.

14. A double-stranded short interfering nucleic acid (siNA) molecule comprising any of SEQ ID NOS: 6372, 6374, 6370, 6369, 2021, 2068, 6372, 6373, 2147, or 6368.

15. A composition comprising:
(a) a double-stranded short interfering nucleic acid (siNA) having any of SEQ ID NOS: 6372, 6374, 6370, 6369, 2021, 2068, 6372, 6373, 2147, or 6368;
(b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
(c) cholesterol;
(d) DSPC; and
(e) PEG-DMG.

16. The composition according to claim 15, wherein the (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine, cholesterol, DSPC, and PEG-DMG have a molar ratio of 50:30:10:2 respectively.

17. The composition according to claim 15, further comprising sucrose, trehalose, or any combination thereof.