# Patent

## Title
Compositions and methods for inhibiting expression of XBP-1 gene

## Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting X-Box Protein 1 (XBP-1), and methods of using the dsRNA to inhibit expression of XBP-1.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority to U.S. application Ser. No. 61/045,947, filed Apr. 17, 2008; to U.S. Ser. No. 61/078,302, filed Jul. 3, 2008; to U.S. Ser. No. 61/081,861, filed Jul. 18, 2008. The entire contents of each of these provisional applications are hereby incorporated by reference in the present application.


FIELD OF THE INVENTION
The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting X-Box Protein 1 (XBP-1), and methods of using the dsRNA to inhibit expression of XBP-1.
BACKGROUND OF THE INVENTION
X-box binding protein 1 (XBP-1) is a basic leucine zipper transcription factor that is involved in the cellular unfolded protein response (UPR). XBP-1 is known to be active in the endoplasmic reticulum (ER). The ER consists of a system of folded membranes and tubules in the cytoplasm of cells. Proteins and lipids are manufactured and processed in the ER. When unusual demands are placed on the ER, “ER stress” occurs. ER stress can be triggered by a viral infection, gene mutations, exposure to toxins, aggregation of improperly folded proteins or a shortage of intracellular nutrients. The result can be Type II diabetes, metabolic syndrome, a neurological disorder or cancer.
Two XBP-1 isoforms are known to exist in cells: spliced XBP-1S and unspliced XBP-1U. Both isoforms of XBP-1 bind to the 21-bp Tax-responsive element of the human T-lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR) in vitro and transactivate HTLV-1 transcription. HTLV-1 is associated with a rare form of blood dyscrasia known as Adult T-cell Leukemia/lymphoma (ATLL) and a myelopathy, tropical spastic paresis.
Double-stranded RNA molecules (dsRNA) have been shown to block gene expression in a highly conserved regulatory mechanism known as RNA interference (RNAi). WO 99/32619 (Fire et al.) disclosed the use of a dsRNA of at least 25 nucleotides in length to inhibit the expression of genes in C. elegans. dsRNA has also been shown to degrade target RNA in other organisms, including plants (see, e.g., WO 99/53050, Waterhouse et al.; and WO 99/61631, Heifetz et al.), Drosophila (see, e.g., Yang, D., et al., Curr. Biol. (2000) 10:1191-1200), and mammals (see WO 00/44895, Limmer; and DE 101 00 586.5, Kreutzer et al.).
SUMMARY OF THE INVENTION
The invention provides compositions containing double-stranded ribonucleic acid (dsRNA) and methods for inhibiting the expression of an XBP-1 gene in a cell or mammal. The invention also provides compositions and methods for treating pathological conditions and diseases caused by the expression of XBP-1 gene, such as metabolic disorders (e.g., diabetes or metabolic syndrome), cardiovascular disease, protein folding diseases or cancer. The dsRNAs included in the compositions featured herein include a dsRNA having an RNA strand (the antisense strand) having a region which is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and is substantially complementary to at least part of an mRNA transcript of the XBP-1 gene.
In one aspect, a dsRNA for inhibiting expression of an XBP-1 gene includes at least two sequences that are complementary to each other. The dsRNA includes a sense strand having a first sequence and an antisense strand having a second sequence. The antisense strand includes a nucleotide sequence that is substantially complementary to at least part of an mRNA encoding XBP-1, and the region of complementarity is less than 30 nucleotides in length, and at least 15 nucleotides in length. Generally, the dsRNA is 19 to 24, e.g., 19 to 21 nucleotides in length. In some embodiments the dsRNA is from about 10 to about 15 nucleotides in length, and in other embodiments the dsRNA is from about 25 to about 30 nucleotides in length. The dsRNA, upon contacting with a cell expressing XBP-1, inhibits the expression of an XBP-1 gene by at least 20%, at least 25%, at least 30%, at least 35% or at least 40%, such as when assayed by a method as described herein. In one embodiment, the Factor VII dsRNA is formulated in a stable nucleic acid particle (SNALP).
For example, the dsRNA molecules featured herein can include a first sequence of the dsRNA that is selected from the group consisting of the sense sequences of Tables 2, 4, 8, 9, 11 and 12 and a second sequence that is selected from the group consisting of the antisense sequences of Tables 2, 4, 8, 9, 11 and 12. The dsRNA molecules featured herein can include naturally occurring nucleotides or can include at least one modified nucleotide, such as a 2′-O-methyl modified nucleotide, a nucleotide having a 5′-phosphorothioate group, and a terminal nucleotide linked to a conjugate group, such as to a cholesteryl derivative, to vitamin E, or to a dodecanoic acid bisdecylamide group. Alternatively, the modified nucleotide may be chosen from the group of: a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide. Generally, such modified sequence will be based on a first sequence of said dsRNA selected from the group consisting of the sense sequences of Tables 2, 4, 8, 9, 11 and 12 and a second sequence selected from the group consisting of the antisense sequences of Tables 2, 4, 8, 9, 11 and 12.
In one aspect, the invention provides a cell containing at least one of the dsRNAs featured in the invention. The cell is generally a mammalian cell, such as a human cell.
In another aspect, the invention provides a pharmaceutical composition for inhibiting the expression of an XBP-1 gene in an organism, generally a human subject. The composition typically includes one or more of the dsRNAs described herein and a pharmaceutically acceptable carrier or delivery vehicle. In one embodiment, the composition is used for treating cancer, e.g., a cancer of the liver.
In another aspect, the invention provides a method for inhibiting the expression of an XBP-1 gene in a cell by performing the following steps:

    
    
        (a) introducing into the cell a double-stranded ribonucleic acid (dsRNA), wherein the dsRNA includes at least two sequences that are complementary to each other. The dsRNA has a sense strand comprising a first sequence and an antisense strand having a second sequence; the antisense strand has a region of complementarity that is substantially complementary to at least a part of a mRNA encoding XBP-1, and where the region of complementarity is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and where the dsRNA, upon contact with a cell expressing the XBP-1, inhibits expression of the XBP-1 gene by at least 20%, at least 30%, or at least 40%; and
        (b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of XBP-1 gene, thereby inhibiting expression of the XBP-1 gene in the cell.
    
    


In one embodiment, the method is for inhibiting gene expression in a cell infected with HTLV-1, such as a tumor cell.
In another aspect, the invention provides methods for treating, preventing or managing pathological processes mediated by XBP-1 expression, e.g., a metabolic disease such as diabetes (e.g., Type II diabetes or metabolic syndrome), or cardiovascular disease. The method can include administering to a patient in need of such treatment, prevention or management a therapeutically or prophylactically effective amount of one or more of the dsRNAs featured in the invention. In one embodiment the patient has metabolic syndrome. For example, a patient with metabolic syndrome can have one of more of high cholesterol, obesity, and/or insulin insensitivity. In some embodiments, a patient with metabolic syndrome will also have heart disease. In another embodiment, the patient has a dyslipidemia or a disorder associated with a dyslipidemia. For example, in one embodiment the patient has atherosclerosis, which is often associated with hypercholesterolemia. In another embodiment, the patient has cancer or a neurological disorder. In yet another embodiment, the patient (e.g., a human patient) is infected with a retrovirus, such as HTLV-1. In another embodiment, the patient has a disorder or condition caused by the HTVL-1, such as a myelopathy, e.g., tropical spastic paresis. In one embodiment, administration of the dsRNA targeting XBP-1 alleviates or relieves the severity of at least one symptom of the XBP-1 mediated disorder in the patient.
In another embodiment, the invention provides a vector for inhibiting the expression of an XBP-1 gene in a cell. In one embodiment, the vector includes at least one regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of one of a dsRNA featured in the invention.
In another embodiment, the invention provides a cell containing a vector for inhibiting the expression of an XBP-1 gene in a cell. The vector includes a regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of one of the dsRNA featured in the invention.
In a further embodiment, the invention provides a composition containing an XBP-1 dsRNA, in combination with a second dsRNA targeting a second gene involved in a pathological disease, and useful for treating the disease, e.g., diabetes or cardiovascular disease.



BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A and 1B represent the sequence of the XBP-1 5′ RACE product around the target sequence of the siRNA AD18038. The intended cleavage site of the siRNA is indicated by a vertical arrow above the sequence. The cleavage sites due to degradation of the 5′ RACE product in mice are indicated by arrowheads above the sequence. “0/22” is the number of cleavage events what were observed at the expected XBP-1 siRNA cleavage site in the sample group of negative control mice, which were treated with siRNA LNP01-1955 or PBS (FIG. 1A; SEQ ID NO:4329). “26/34” is the number of cleavage events that were observed at the expected siRNA cleavage site in the sample group of mice treated with the XBP-1 siRNA AD18038 (FIG. 1B; SEQ ID NO:4330). The underlined sequence is the target of the XBP-1 siRNA AD18038.
FIG. 2 is the sequence of human XBP-1 mRNA as recorded at RefSeq No. NM—005080.2 (GI Ref. No. 14110394) (SEQ ID NO:4331).
FIG. 3 is the sequence of mouse XBP-1 mRNA as recorded at RefSeq No. NM—013842.2 (GI Ref. No. 13775155) (SEQ ID NO:4332). The underlined sequence is the target of siRNA AD18038.
FIG. 4 is the sequence of rat XBP-1 mRNA as recorded at RefSeq No. NM—001004210.1 (GI Ref. No. 51948391) (SEQ ID NO:4333).
FIG. 5 is the sequence of rhesus XBP-1 as recorded at RefSeq No. XM—001103095.1 (GI Ref. No. 109093732) (SEQ ID NO:4334).
FIG. 6 illustrates mXBP-1 and cholesterol levels after XBP-1 siRNA injection in C57BL/6 mice.



DETAILED DESCRIPTION OF THE INVENTION
The invention provides dsRNAs and methods of using the dsRNAs for inhibiting the expression of an XBP-1 gene in a cell or a mammal where the dsRNA targets the XBP-1 gene. The invention also provides compositions and methods for treating pathological conditions and diseases, such as a metabolic disease or a cardiovascular disease, in a mammal caused by the expression of the XBP-1 gene. dsRNA directs the sequence-specific degradation of mRNA through a process known as RNA interference (RNAi).
The dsRNAs of the compositions featured herein include an RNA strand (the antisense strand) having a region which is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and is substantially complementary to at least part of an mRNA transcript of the XBP-1 gene. The use of these dsRNAs enables the targeted degradation of mRNAs of genes that are implicated in replication and or maintenance of cancer cells in mammals. Very low dosages of XBP-1 dsRNAs in particular can specifically and efficiently mediate RNAi, resulting in significant inhibition of expression of the XBP-1 gene. The methods and compositions containing the XBP-1 dsRNA are useful for treating pathological processes mediated by XBP-1 expression, e.g., a metabolic disease or cardiovascular disease.
The following detailed description discloses how to make and use the compositions containing dsRNAs to inhibit the expression of the XBP-1 gene, as well as compositions and methods for treating diseases and disorders caused by the expression of these genes, such as leukemia. The pharmaceutical compositions featured in the invention include a dsRNA having an antisense strand comprising a region of complementarity which is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and is substantially complementary to at least part of an RNA transcript of the XBP-1 gene, together with a pharmaceutically acceptable carrier. The compositions featured in the invention also include a dsRNA having an antisense strand having a region of complementarity which is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and is substantially complementary to at least part of an RNA transcript of the XBP-1 gene.
Accordingly, in some aspects, pharmaceutical compositions containing the XBP-1 dsRNA and a pharmaceutically acceptable carrier, methods of using the compositions to inhibit expression of the XBP-1 gene, and methods of using the pharmaceutical compositions to treat diseases caused by expression of the XBP-1 gene are featured in the invention.
I. Definitions
For convenience, the meaning of certain terms and phrases used in the specification, examples, and appended claims, are provided below. If there is an apparent discrepancy between the usage of a term in other parts of this specification and its definition provided in this section, the definition in this section shall prevail.
“G,” “C,” “A,” “T” and “U” each generally stand for a nucleotide that contains guanine, cytosine, adenine, thymidine and uracil as a base, respectively. However, it will be understood that the term “ribonucleotide” or “nucleotide” can also refer to a modified nucleotide, as further detailed below, or a surrogate replacement moiety. The skilled person is well aware that guanine, cytosine, adenine, thymidine and uracil may be replaced by other moieties without substantially altering the base pairing properties of an oligonucleotide comprising a nucleotide bearing such replacement moiety. For example, without limitation, a nucleotide comprising inosine as its base may base pair with nucleotides containing adenine, cytosine, or uracil. Hence, nucleotides containing uracil, guanine, or adenine may be replaced in the nucleotide sequences of dsRNA featured in the invention by a nucleotide containing, for example, inosine. In another example, adenine and cytosine anywhere in the oligonucleotide can be replaced with guanine and uracil, respectively to form G:U Wobble base pairing with the target mRNA. Sequences containing such replacement moieties are suitable for the compositions and methods featured the invention.
As used herein, “XBP-1” refers to X-Box Protein 1, which is also known as Tax-responsive element-binding protein 5, TREB5, and XBP2. XBP-1 sequence can be found as NCBI GeneID:7494 and RefSeq ID number:NM—005080 (human) (FIG. 1) and NM—013842 (mouse, FIG. 2). A dsRNA featured in the invention can target a specific XBP-1 isoform, e.g., the spliced form (XBP-1S) or the unspliced form (XBP-1U), or a dsRNA featured in the invention can target both isoforms by binding to a common region of the mRNA transcript.
As used herein, “target sequence” refers to a contiguous portion of the nucleotide sequence of an mRNA molecule formed during the transcription of the XBP-1 gene, including mRNA that is a product of RNA processing of a primary transcription product.
As used herein, the term “strand comprising a sequence” refers to an oligonucleotide comprising a chain of nucleotides that is described by the sequence referred to using the standard nucleotide nomenclature.
As used herein, and unless otherwise indicated, the term “complementary,” when used to describe a first nucleotide sequence in relation to a second nucleotide sequence, refers to the ability of an oligonucleotide or polynucleotide comprising the first nucleotide sequence to hybridize and form a duplex structure under certain conditions with an oligonucleotide or polynucleotide comprising the second nucleotide sequence, as will be understood by the skilled person. Such conditions can, for example, be stringent conditions, where stringent conditions may include: 400 mM NaCl, 40 mM PIPES pH 6.4, 1 mM EDTA, 50° C. or 70° C. for 12-16 hours followed by washing. Other conditions, such as physiologically relevant conditions as may be encountered inside an organism, can apply. The skilled person will be able to determine the set of conditions most appropriate for a test of complementarity of two sequences in accordance with the ultimate application of the hybridized nucleotides.
This includes base-pairing of the oligonucleotide or polynucleotide comprising the first nucleotide sequence to the oligonucleotide or polynucleotide comprising the second nucleotide sequence over the entire length of the first and second nucleotide sequence. Such sequences can be referred to as “fully complementary” with respect to each other herein. However, where a first sequence is referred to as “substantially complementary” with respect to a second sequence herein, the two sequences can be fully complementary, or they may form one or more, but generally not more than 4, 3 or 2 mismatched base pairs upon hybridization, while retaining the ability to hybridize under the conditions most relevant to their ultimate application. However, where two oligonucleotides are designed to form, upon hybridization, one or more single stranded overhangs, such overhangs shall not be regarded as mismatches with regard to the determination of complementarity. For example, a dsRNA comprising one oligonucleotide 21 nucleotides in length and another oligonucleotide 23 nucleotides in length, wherein the longer oligonucleotide comprises a sequence of 21 nucleotides that is fully complementary to the shorter oligonucleotide, may yet be referred to as “fully complementary” for the purposes described herein.
“Complementary” sequences, as used herein, may also include, or be formed entirely from, non-Watson-Crick base pairs and/or base pairs formed from non-natural and modified nucleotides, in as far as the above requirements with respect to their ability to hybridize are fulfilled. Such non-Watson-Crick base pairs includes, but not limited to, G:U Wobble or Hoogstein base pairing.
The terms “complementary,” “fully complementary” and “substantially complementary” herein may be used with respect to the base matching between the sense strand and the antisense strand of a dsRNA, or between the antisense strand of a dsRNA and a target sequence, as will be understood from the context of their use.
As used herein, a polynucleotide which is “substantially complementary to at least part of” a messenger RNA (mRNA) refers to a polynucleotide which is substantially complementary to a contiguous portion of the mRNA of interest (e.g., encoding XBP-1). For example, a polynucleotide is complementary to at least a part of an XBP-1 mRNA if the sequence is substantially complementary to a non-interrupted portion of an mRNA encoding XBP-1.
The term “double-stranded RNA” or “dsRNA,” as used herein, refers to a complex of ribonucleic acid molecules, having a duplex structure comprising two anti-parallel and substantially complementary, as defined above, nucleic acid strands. The two strands forming the duplex structure may be different portions of one larger RNA molecule, or they may be separate RNA molecules. Where the two strands are part of one larger molecule, and therefore are connected by an uninterrupted chain of nucleotides between the 3′-end of one strand and the 5′ end of the respective other strand forming the duplex structure, the connecting RNA chain is referred to as a “hairpin loop.” Where the two strands are connected covalently by means other than an uninterrupted chain of nucleotides between the 3′-end of one strand and the 5′ end of the respective other strand forming the duplex structure, the connecting structure is referred to as a “linker.” The RNA strands may have the same or a different number of nucleotides. The maximum number of base pairs is the number of nucleotides in the shortest strand of the dsRNA minus any overhangs that are present in the duplex. In addition to the duplex structure, a dsRNA may comprise one or more nucleotide overhangs. For example, a dsRNA can have a dinucleotide overhang at the 3′ end at one or both of the sense or antisense strands, such as a dTdT (deoxythymidine-deoxythymidine) or a dTsdT (deoxythymidine-(thiophosphate linker)-deoxythymidine) dinucleotide overhang at one or both of the 3′ ends of the sense or antisense strands.
As used herein, a “nucleotide overhang” refers to the unpaired nucleotide or nucleotides that protrude from the duplex structure of a dsRNA when a 3′-end of one strand of the dsRNA extends beyond the 5′-end of the other strand, or vice versa. “Blunt” or “blunt end” means that there are no unpaired nucleotides at that end of the dsRNA, i.e., no nucleotide overhang. A “blunt ended” dsRNA is a dsRNA that is double-stranded over its entire length, i.e., no nucleotide overhang at either end of the molecule.
The term “antisense strand” refers to the strand of a dsRNA which includes a region that is substantially complementary to a target sequence. As used herein, the term “region of complementarity” refers to the region on the antisense strand that is substantially complementary to a sequence, for example a target sequence, as defined herein. Where the region of complementarity is not fully complementary to the target sequence, the mismatches may be in the internal or terminal regions of the molecule. Generally, the most tolerated mismatches are in the terminal regions, e.g., within 6, 5, 4, 3, or 2 nucleotides of the 5′ and/or 3′ terminus.
The term “sense strand,” as used herein, refers to the strand of a dsRNA that includes a region that is substantially complementary to a region of the antisense strand.
The term “identity” is the relationship between two or more polynucleotide sequences, as determined by comparing the sequences. Identity also means the degree of sequence relatedness between polynucleotide sequences, as determined by the match between strings of such sequences. While there exist a number of methods to measure identity between two polynucleotide sequences, the term is well known to skilled artisans (see, e.g., Sequence Analysis in Molecular Biology, von Heinje, G., Academic Press (1987); and Sequence Analysis Primer, Gribskov., M. and Devereux, J., eds., M. Stockton Press, New York (1991)). “Substantially identical,” as used herein, means there is a very high degree of homology (e.g., 100% sequence identity) between the sense strand of the dsRNA and the corresponding part of the target gene. However, dsRNA having greater than 90%, or 95% sequence identity may be used in the present invention, and thus sequence variations that might be expected due to genetic mutation, strain polymorphism, or evolutionary divergence can be tolerated. The dsRNA is typically 100% complementary to the target RNA, but in some embodiments, the dsRNA may contain single or multiple base-pair random mismatches between the RNA and the target gene.
As used herein, the term “SNALP” refers to a stable nucleic acid-lipid particle. A SNALP represents a vesicle of lipids coating a reduced aqueous interior comprising a nucleic acid such as an iRNA agent or a plasmid from which an iRNA agent is transcribed. SNALPs are described, e.g., in U.S. Patent Application Publication Nos. 20060240093, 20070135372, and U.S. Ser. No. 61/045,228 filed Apr. 15, 2008. These applications are hereby incorporated by reference.
“Introducing into a cell,” when referring to a dsRNA, means facilitating uptake or absorption into the cell, as is understood by those skilled in the art. Absorption or uptake of dsRNA can occur through unaided diffusive or active cellular processes, or by auxiliary agents or devices. The meaning of this term is not limited to cells in vitro; a dsRNA may also be “introduced into a cell,” wherein the cell is part of a living organism. In such instance, introduction into the cell will include the delivery to the organism. For example, for in vivo delivery, dsRNA can be injected into a tissue site or administered systemically. In vivo delivery can also be by a beta-glucan delivery system, such as those described in U.S. Pat. Nos. 5,032,401 and 5,607,677, and U.S. Publication No. 2005/0281781. U.S. Pat. Nos. 5,032,401 and 5,607,677, and U.S. Publication No. 2005/0281781 are hereby incorporated by reference in their entirety. In vitro introduction into a cell includes methods known in the art such as electroporation and lipofection.
The terms “silence,” “inhibit the expression of,” “down-regulate the expression of,” “suppress the expression of,” and the like, in as far as they refer to the XBP-1 gene, herein refer to the at least partial suppression of the expression of the XBP-1 gene, as manifested by a reduction of the amount of XBP-1 mRNA which may be isolated from a first cell or group of cells in which the XBP-1 gene is transcribed and which has or have been treated such that the expression of the XBP-1 gene is inhibited, as compared to a second cell or group of cells substantially identical to the first cell or group of cells but which has or have not been so treated (control cells). The degree of inhibition is usually expressed in terms of




  
    
      
        
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Alternatively, the degree of inhibition may be given in terms of a reduction of a parameter that is functionally linked to XBP-1 gene expression, e.g., the amount of protein encoded by the XBP-1 gene which is secreted by a cell, or the number of cells displaying a certain phenotype, e.g., apoptosis. In principle, XBP-1 gene silencing may be determined in any cell expressing XBP-1, either constitutively or by genomic engineering, and by any appropriate assay. However, when a reference is needed in order to determine whether a given dsRNA inhibits the expression of the XBP-1 gene by a certain degree and therefore is encompassed by the instant invention, the assay provided in the Examples below shall serve as such reference.
For example, in certain instances, expression of the XBP-1 gene is suppressed by at least about 20%, 25%, 30%, 35%, 40%, 45%, or 50% by administration of the double-stranded oligonucleotide featured in the invention. In some embodiments, the XBP-1 gene is suppressed by at least about 60%, 70%, or 80% by administration of the double-stranded oligonucleotide featured in the invention. In some embodiments, the XBP-1 gene is suppressed by at least about 85%, 90%, or 95% by administration of the double-stranded oligonucleotide featured in the invention.
As used herein in the context of XBP-1 expression, the terms “treat,” “treatment,” and the like, refer to relief from or alleviation of pathological processes mediated by XBP-1 expression. In the context of the present invention insofar as it relates to any of the other conditions recited herein below (other than pathological processes mediated by XBP-1 expression), the terms “treat,” “treatment,” and the like mean to relieve or alleviate at least one symptom associated with such condition, or to slow or reverse the progression of such condition, such as the slowing and progression of hepatic carcinoma.
As used herein, the phrases “therapeutically effective amount” and “prophylactically effective amount” refer to an amount that provides a therapeutic benefit in the treatment, prevention, or management of pathological processes mediated by XBP-1 expression or an overt symptom of pathological processes mediated by XBP-1 expression. The specific amount that is therapeutically effective can be readily determined by an ordinary medical practitioner, and may vary depending on factors known in the art, such as, e.g., the type of pathological processes mediated by XBP-1 expression, the patient's history and age, the stage of pathological processes mediated by XBP-1 expression, and the administration of other anti-pathological processes mediated by XBP-1 expression agents.
As used herein, a “pharmaceutical composition” comprises a pharmacologically effective amount of a dsRNA and a pharmaceutically acceptable carrier. As used herein, “pharmacologically effective amount,” “therapeutically effective amount” or simply “effective amount” refers to that amount of an RNA effective to produce the intended pharmacological, therapeutic or preventive result. 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 the amount necessary to effect at least a 25% reduction in that parameter.
The term “pharmaceutically acceptable carrier” refers to a carrier for administration of a therapeutic agent. Such carriers include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol, and combinations thereof. The term specifically excludes cell culture medium. For drugs administered orally, pharmaceutically acceptable carriers include, but are not limited to pharmaceutically acceptable excipients such as inert diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservatives. Suitable inert diluents include sodium and calcium carbonate, sodium and calcium phosphate, and lactose, while corn starch and alginic acid are suitable disintegrating agents. Binding agents may include starch and gelatin, while the lubricating agent, if present, will generally be magnesium stearate, stearic acid or talc. If desired, the tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate, to delay absorption in the gastrointestinal tract.
As used herein, a “transformed cell” is a cell into which a vector has been introduced from which a dsRNA molecule may be expressed.
II. Double-Stranded Ribonucleic Acid (dsRNA)
In one embodiment, the invention provides double-stranded ribonucleic acid (dsRNA) molecules for inhibiting the expression of an XBP-1 gene in a cell or mammal, e.g., in a human having a metabolic disease, such as diabetes, or cardiovascular disease, where the dsRNA includes an antisense strand having a region of complementarity which is complementary to at least a part of an mRNA formed in the expression of the XBP-1 gene, and where the region of complementarity is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and where said dsRNA, upon contact with a cell expressing said XBP-1 gene, inhibits the expression of said XBP-1 gene by at least 30% as assayed by, for example, a PCR or branched DNA (bDNA) based method. The dsRNA includes two RNA strands that are sufficiently complementary to hybridize to form a duplex structure. One strand of the dsRNA (the antisense strand) includes a region of complementarity that is substantially complementary, and generally fully complementary, to a target sequence, derived from the sequence of an mRNA formed during the expression of the XBP-1 gene, the other strand (the sense strand) includes a region that is complementary to the antisense strand, such that the two strands hybridize and form a duplex structure when combined under suitable conditions. Generally, the duplex structure is between 15 and 30, more generally between 18 and 25, yet more generally between 19 and 24, and most generally between 19 and 21 base pairs in length. Similarly, the region of complementarity to the target sequence 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 nucleotides in length. In some embodiments, the dsRNA is between 10 and 15 nucleotides in length, and in other embodiments, the dsRNA is between 25 and 30 nucleotides in length. The dsRNA featured in the invention may further include one or more single-stranded nucleotide overhangs.
The dsRNA can be synthesized by standard methods known in the art as further discussed below, e.g., by use of an automated DNA synthesizer, such as are commercially available from, for example, Biosearch, Applied Biosystems, Inc. In one embodiment, the XBP-1 gene is the human XBP-1 gene. In specific embodiments, the first sequence is selected from the group consisting of the sense sequences of Tables 2, 4, 8, 9, 11 and 12, and the second sequence is selected from the group consisting of the antisense sequences of Tables 2, 4, 8, 9, 11 and 12. Alternative antisense agents that target elsewhere in the target sequence provided in Tables 2, 4, 8, 9, 11 and 12 can readily be determined using the target sequence and the flanking XBP-1 sequence.
The dsRNA will include at least two nucleotide sequence selected from the groups of sequences provided in Tables 2, 4, 8, 9, 11 and 12. One of the two sequences is complementary to the other of the two sequences, with one of the sequences being substantially complementary to a sequence of an mRNA generated in the expression of the XBP-1 gene. As such, the dsRNA will include two oligonucleotides, where one oligonucleotide is described as the sense strand in Tables 2, 4, 8, 9, 11 and 12 and the second oligonucleotide is described as the antisense strand in Tables 2, 4, 8, 9, 11 and 12.
The skilled person is well aware that dsRNAs comprising a duplex structure of between 20 and 23, but specifically 21, base pairs have been hailed as particularly effective in inducing RNA interference (Elbashir et al., EMBO 2001, 20:6877-6888). However, others have found that shorter or longer dsRNAs can be effective as well. In the embodiments described above, by virtue of the nature of the oligonucleotide sequences provided in Tables 2, 4, 8, 9, 11 and 12, the dsRNAs featured in the invention can include at least one strand of a length of minimally 21 nt. It can be reasonably expected that shorter dsRNAs having one of the sequences of Tables 2, 4, 8, 9, 11 and 12 minus only a few nucleotides on one or both ends may be similarly effective as compared to the dsRNAs described above. Hence, dsRNAs having a partial sequence of at least 15, 16, 17, 18, 19, 20, or more contiguous nucleotides from one of the sequences of Tables 2, 4, 8, 9, 11 and 12, and differing in their ability to inhibit the expression of the XBP-1 gene in a FACS assay as described herein below by not more than 5, 10, 15, 20, 25, or 30% inhibition from a dsRNA comprising the full sequence, are contemplated by the invention. Further, dsRNAs that cleave within a desired XBP-1 target sequence can readily be made using the corresponding XBP-1 antisense sequence and a complementary sense sequence.
In addition, the dsRNAs provided in 2, 4, 8, 9, 11 and 12 identify a site in the XBP-1 mRNA that is susceptible to RNAi based cleavage. As such the present invention further features dsRNAs that target within the sequence targeted by one of the agents of the present invention. As used herein a second dsRNA is said to target within the sequence of a first dsRNA if the second dsRNA cleaves the message anywhere within the mRNA that is complementary to the antisense strand of the first dsRNA. Such a second dsRNA will generally consist of at least 15 contiguous nucleotides from one of the sequences provided in Tables 2, 4, 8, 9, 11 and 12 coupled to additional nucleotide sequences taken from the region contiguous to the selected sequence in the XBP-1 gene. For example, the last 15 nucleotides of SEQ ID NO:1 combined with the next six nucleotides from the target XBP-1 gene produces a single strand agent of 21 nucleotides that is based on one of the sequences provided in Tables 2, 4, 8, 9, 11 and 12.
The dsRNA featured in the invention can contain one or more mismatches to the target sequence. In one embodiment, the dsRNA featured the invention contains no more than 3 mismatches. If the antisense strand of the dsRNA contains mismatches to a target sequence, it the area of mismatch is typically not located in the center of the region of complementarity. If the antisense strand of the dsRNA contains mismatches to the target sequence, the mismatch is typically restricted to 5 nucleotides from either end, for example 5, 4, 3, 2, or 1 nucleotide from either the 5′ or 3′ end of the region of complementarity. For example, for a 23 nucleotide dsRNA strand which is complementary to a region of the XBP-1 gene, the dsRNA generally does not contain any mismatch within the central 13 nucleotides. The methods described within the invention can be used to determine whether a dsRNA containing a mismatch to a target sequence is effective in inhibiting the expression of the XBP-1 gene. Consideration of the efficacy of dsRNAs with mismatches in inhibiting expression of the XBP-1 gene is important, especially if the particular region of complementarity in the XBP-1 gene is known to have polymorphic sequence variation within the population.
In one embodiment, at least one end of the dsRNA has a single-stranded nucleotide overhang of 1 to 4, generally 1 or 2 nucleotides. dsRNAs having at least one nucleotide overhang have unexpectedly superior inhibitory properties than their blunt-ended counterparts. Moreover, the present inventors have discovered that the presence of only one nucleotide overhang strengthens the interference activity of the dsRNA, without affecting its overall stability. dsRNA having only one overhang has proven particularly stable and effective in vivo, as well as in a variety of cells, cell culture mediums, blood, and serum. Generally, the single-stranded overhang is located at the 3′-terminal end of the antisense strand or, alternatively, at the 3′-terminal end of the sense strand. The dsRNA may also have a blunt end, generally located at the 5′-end of the antisense strand. Such dsRNAs have improved stability and inhibitory activity, thus allowing administration at low dosages, i.e., less than 5 mg/kg body weight of the recipient per day. In one embodiment, the antisense strand of the dsRNA has a 1-10 nucleotide overhang at the 3′ end and/or the 5′ end. In one embodiment, the sense strand of the dsRNA has a 1-10 nucleotide overhang at the 3′ end and/or the 5′ end. In another embodiment, one or more of the nucleotides in the overhang is replaced with a nucleoside thiophosphate.
In yet another embodiment, the dsRNA is chemically modified to enhance stability. The nucleic acids featured in the invention may be synthesized and/or modified by methods well established in the art, such as those described in “Current protocols in nucleic acid chemistry,” Beaucage, S. L. et al. (Edrs.), John Wiley & Sons, Inc., New York, N.Y., USA, which is hereby incorporated herein by reference. Specific examples of dsRNA compounds useful in this invention include dsRNAs containing modified backbones or no natural internucleoside linkages. As defined in this specification, dsRNAs having modified backbones include those that retain a phosphorus atom in the backbone and those that do not have a phosphorus atom in the backbone. For the purposes of this specification, and as sometimes referenced in the art, modified dsRNAs that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides.
Modified dsRNA backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates including 3′-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3′-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs of these, and those) having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3′-5′ to 5′-3′ or 2′-5′ to 5′-2′. Various salts, mixed salts and free acid forms are also included.
Representative U.S. patents that teach the preparation of the above phosphorus-containing linkages include, but are not limited to, U.S. Pat. Nos. 3,687,808; 4,469,863; 4,476,301; 5,023,243; 5,177,195; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,316; 5,550,111; 5,563,253; 5,571,799; 5,587,361; and 5,625,050, each of which is herein incorporated by reference
Modified dsRNA backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatoms and alkyl or cycloalkyl internucleoside linkages, or ore or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH2 component parts.
Representative U.S. patents that teach the preparation of the above oligonucleosides include, but are not limited to, U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,64,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; and, 5,677,439, each of which is herein incorporated by reference.
In other suitable dsRNA mimetics, both the sugar and the internucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for hybridization with an appropriate nucleic acid target compound. One such oligomeric compound, an dsRNA mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA compounds, the sugar backbone of an dsRNA is replaced with an amide containing backbone, in particular an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone. Representative U.S. patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Further teaching of PNA compounds can be found in Nielsen et al., Science, 1991, 254, 1497-1500.
Most embodiments featured in the invention include dsRNAs with phosphorothioate backbones and oligonucleosides with heteroatom backbones, and in particular —CH2—NH—CH2—, —CH2—N(CH3)—O—CH2— [known as a methylene (methylimino) or MMI backbone], —CH2—O—N(CH3)—CH2—, —CH2—N(CH3)—N(CH3)—CH2— and —N(CH3)—CH2—CH2— [wherein the native phosphodiester backbone is represented as —O—P—O—CH2—] of the above-referenced U.S. Pat. No. 5,489,677, and the amide backbones of the above-referenced U.S. Pat. No. 5,602,240. In some embodiments, the dsRNAs featured herein have morpholino backbone structures of the above-referenced U.S. Pat. No. 5,034,506.
Modified dsRNAs may also contain one or more substituted sugar moieties. The dsRNAs featured herein can one of the following at the 2′ position: OH; F; O-, S-, or N-alkyl; O-, S-, or N-alkenyl; O-, S- or N-alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted C1 to C10 alkyl or C2 to C10 alkenyl and alkynyl. Typical modifications are O[(CH2)nO]mCH3, O(CH2)nOCH3, O(CH2)nNH2, O(CH2)nCH3, O(CH2)nONH2, and O(CH2)nON[(CH2)nCH3)]2, where n and m are from 1 to about 10. In other embodiments, dsRNAs include one of the following at the 2′ position: C1 to C10 lower alkyl, substituted lower alkyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH, SCH3, OCN, Cl, Br, CN, CF3, OCF3, SOCH3, SO2CH3, ONO2, NO2, N3, NH2, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an dsRNA, or a group for improving the pharmacodynamic properties of an dsRNA, and other substituents having similar properties. In some embodiments, the modification includes a 2′-methoxyethoxy (2′-O—CH2CH2OCH3, also known as 2′-O-(2-methoxyethyl) or 2′-MOE) (Martin et al., Helv. Chim. Acta, 1995, 78:486-504) i.e., an alkoxy-alkoxy group. Other typical modification include 2′-dimethylaminooxyethoxy, i.e., a O(CH2)2ON(CH3)2 group, also known as 2′-DMAOE, as described in examples hereinbelow, and 2′-dimethylaminoethoxyethoxy (also known in the art as 2′-O-dimethylaminoethoxyethyl or 2′-DMAEOE), i.e., 2′-O—CH2—O—CH2—N(CH2)2, also described in examples hereinbelow.
Other modifications include 2′-methoxy (2′-OCH3), 2′-aminopropoxy (2′-OCH2CH2CH2NH2) and 2′-fluoro (2′-F). Similar modifications may also be made at other positions on the dsRNA, particularly the 3′ position of the sugar on the 3′ terminal nucleotide or in 2′-5′ linked dsRNAs and the 5′ position of 5′ terminal nucleotide. DsRNAs may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar. Representative U.S. patents that teach the preparation of such modified sugar structures include, but are not limited to, U.S. Pat. Nos. 4,981,957; 5,118,800; 5,319,080; 5,359,044; 5,393,878; 5,446,137; 5,466,786; 5,514,785; 5,519,134; 5,567,811; 5,576,427; 5,591,722; 5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,658,873; 5,670,633; and 5,700,920, certain of which are commonly owned with the instant application, and each of which is herein incorporated by reference in its entirety.
DsRNAs may also include nucleobase (often referred to in the art simply as “base”) modifications or substitutions. As used herein, “unmodified” or “natural” nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl anal other 8-substituted adenines and guanines, 5-halo, particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-daazaadenine and 3-deazaguanine and 3-deazaadenine. Further nucleobases include those disclosed in U.S. Pat. No. 3,687,808, those disclosed in The Concise Encyclopedia Of Polymer Science And Engineering, pages 858-859, Kroschwitz, J. L, ed. John Wiley & Sons, 1990, these disclosed by Englisch et al., Angewandte Chemie, International Edition, 1991, 30, 613, and those disclosed by Sanghvi, Y S., Chapter 15, DsRNA Research and Applications, pages 289-302, Crooke, S. T. and Lebleu, B., Ed., CRC Press, 1993. Certain of these nucleobases are particularly useful for increasing the binding affinity of the oligomeric compounds featured in the invention. These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2° C. (Sanghvi, Y. S., Crooke, S. T. and Lebleu, B., Eds., DsRNA Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are typical base substitutions, particularly when combined with 2′-O-methoxyethyl sugar modifications.
Representative U.S. patents that teach the preparation of certain of the above noted modified nucleobases as well as other modified nucleobases include, but are not limited to, the above noted U.S. Pat. No. 3,687,808, as well as U.S. Pat. Nos. 4,845,205; 5,130,30; 5,134,066; 5,175,273; 5,367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908; 5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,594,121, 5,596,091; 5,614,617; and 5,681,941, each of which is herein incorporated by reference, and U.S. Pat. No. 5,750,692, also herein incorporated by reference.
Another modification of the dsRNAs featured in the invention involves chemically linking to the dsRNA one or more moieties or conjugates which enhance the activity, cellular distribution or cellular uptake of the dsRNA. Such moieties include but are not limited to lipid moieties such as a cholesterol moiety (Letsinger et al., Proc. Natl. Acid. Sci. USA, 199, 86, 6553-6556), cholic acid (Manoharan et al., Biorg. Med. Chem. Let., 1994 4 1053-1060), a thioether, e.g., beryl-5-tritylthiol (Manoharan et al., Ann. N.Y. Acad. Sci., 1992, 660, 306-309; Manoharan et al., Biorg. Med. Chem. Let., 1993, 3, 2765-2770), a thiocholesterol (Oberhauser et al., Nucl. Acids Res., 1992, 20, 533-538), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al., EMBO J, 1991, 10, 1111-1118; Kabanov et al., FEBS Lett., 1990, 259, 327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethyl-ammonium 1,2-di-O-hexadecyl-rac-glycero-3-Hphosphonate (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654; Shea et al., Nucl. Acids Res., 1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain (Manoharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264, 229-237), or an octadecylamine or hexylamino-carbonyloxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277, 923-937).
Representative U.S. patents that teach the preparation of such dsRNA conjugates include, but are not limited to, U.S. Pat. Nos. 4,828,979; 4,948,882; 5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552,538; 5,578,717, 5,580,731; 5,591,584; 5,109,124; 5,118,802; 5,138,045; 5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044; 4,605,735; 4,667,025; 4,762,779; 4,789,737; 4,824,941; 4,835,263; 4,876,335; 4,904,582; 4,958,013; 5,082,830; 5,112,963; 5,214,136; 5,082,830; 5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506; 5,262,536; 5,272,250; 5,292,873; 5,317,098; 5,371,241, 5,391,723; 5,416,203, 5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552; 5,567,810; 5,574,142; 5,585,481; 5,587,371; 5,595,726; 5,597,696; 5,599,923; 5,599,928 and 5,688,941, each of which is herein incorporated by reference.
It is not necessary for all positions in a given compound to be uniformly modified, and in fact more than one of the aforementioned modifications may be incorporated in a single compound or even at a single nucleoside within an dsRNA. The present invention also includes dsRNA compounds which are chimeric compounds. “Chimeric” dsRNA compounds or “chimeras,” in the context of this invention, are dsRNA compounds, particularly dsRNAs, which contain two or more chemically distinct regions, each made up of at least one monomer unit, i.e., a nucleotide in the case of an dsRNA compound. These dsRNAs typically contain at least one region wherein the dsRNA is modified so as to confer upon the dsRNA increased resistance to nuclease degradation, increased cellular uptake, and/or increased binding affinity for the target nucleic acid. An additional region of the dsRNA may serve as a substrate for enzymes capable of cleaving RNA:DNA or RNA:RNA hybrids. By way of example, RNase H is a cellular endonuclease which cleaves the RNA strand of an RNA:DNAduplex. Activation of RNase H, therefore, results in cleavage of the RNA target, thereby greatly enhancing the efficiency of dsRNA inhibition of gene expression. Consequently, comparable results can often be obtained with shorter dsRNAs when chimeric dsRNAs are used, compared to phosphorothioate deoxydsRNAs hybridizing to the same target region. Cleavage of the RNA target can be routinely detected by gel electrophoresis and, if necessary, associated nucleic acid hybridization techniques known in the art.
In certain instances, the dsRNA may be modified by a non-ligand group. A number of non-ligand molecules have been conjugated to dsRNAs in order to enhance the activity, cellular distribution or cellular uptake of the dsRNA, and procedures for performing such conjugations are available in the scientific literature. Such non-ligand moieties have included lipid moieties, such as cholesterol (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989, 86:6553), cholic acid (Manoharan et al., Bioorg. Med. Chem. Lett., 1994, 4:1053), a thioether, e.g., hexyl-5-tritylthiol (Manoharan et al., Ann. N.Y. Acad. Sci., 1992, 660:306; Manoharan et al., Bioorg. Med. Chem. Let., 1993, 3:2765), a thiocholesterol (Oberhauser et al., Nucl. Acids Res., 1992, 20:533), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al., EMBO J., 1991, 10:111; Kabanov et al., FEBS Lett., 1990, 259:327; Svinarchuk et al., Biochimie, 1993, 75:49), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate (Manoharan et al., Tetrahedron Lett., 1995, 36:3651; Shea et al., Nucl. Acids Res., 1990, 18:3777), a polyamine or a polyethylene glycol chain (Manoharan et al., Nucleosides & Nucleotides, 1995, 14:969), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36:3651), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264:229), or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277:923). Representative United States patents that teach the preparation of such dsRNA conjugates have been listed above. Typical conjugation protocols involve the synthesis of dsRNAs bearing an aminolinker at one or more positions of the sequence. The amino group is then reacted with the molecule being conjugated using appropriate coupling or activating reagents. The conjugation reaction may be performed either with the dsRNA still bound to the solid support or following cleavage of the dsRNA in solution phase. Purification of the dsRNA conjugate by HPLC typically affords the pure conjugate.
Vector Encoded dsRNAs
In another aspect, XBP-1 specific dsRNA molecules are expressed from transcription units inserted into DNA or RNA vectors (see, e.g., Couture, A, et al., TIG. (1996), 12:5-10; Skillern, A., et al., International PCT Publication No. WO 00/22113, Conrad, International PCT Publication No. WO 00/22114, and Conrad, U.S. Pat. No. 6,054,299). These transgenes can be introduced as a linear construct, a circular plasmid, or a viral vector, which can be incorporated and inherited as a transgene integrated into the host genome. The transgene can also be constructed to permit it to be inherited as an extrachromosomal plasmid (Gassmann, et al., Proc. Natl. Acad. Sci. USA (1995) 92:1292).
The individual strands of a dsRNA can be transcribed by promoters on two separate expression vectors and co-transfected into a target cell. Alternatively each individual strand of the dsRNA can be transcribed by promoters both of which are located on the same expression plasmid. In one embodiment, a dsRNA is expressed as an inverted repeat joined by a linker polynucleotide sequence such that the dsRNA has a stem and loop structure.
The recombinant dsRNA expression vectors are generally DNA plasmids or viral vectors. dsRNA expressing viral vectors can be constructed based on, but not limited to, adeno-associated virus (for a review, see Muzyczka, et al., Curr. Topics Micro. Immunol. (1992) 158:97-129)); adenovirus (see, for example, Berkner, et al., BioTechniques (1998) 6:616), Rosenfeld et al. (1991, Science 252:431-434), and Rosenfeld et al. (1992), Cell 68:143-155)); or alphavirus as well as others known in the art. Retroviruses have been used to introduce a variety of genes into many different cell types, including epithelial cells, in vitro and/or in vivo (see, e.g., Eglitis, et al., Science (1985) 230:1395-1398; Danos and Mulligan, Proc. Natl. Acad. Sci. USA (1998) 85:6460-6464; Wilson et al., 1988, Proc. NatI. Acad. Sci. USA 85:3014-3018; Armentano et al., 1990, Proc. NatI. Acad. Sci. USA 87:61416145; Huber et al., 1991, Proc. NatI. Acad. Sci. USA 88:8039-8043; Ferry et al., 1991, Proc. NatI. Acad. Sci. USA 88:8377-8381; Chowdhury et al., 1991, Science 254:1802-1805; van Beusechem. et al., 1992, Proc. Nad. Acad. Sci. USA 89:7640-19; Kay et al., 1992, Human Gene Therapy 3:641-647; Dai et al., 1992, Proc. Natl. Acad. Sci. USA 89:10892-10895; Hwu et al., 1993, J. Immunol. 150:4104-4115; U.S. Pat. No. 4,868,116; U.S. Pat. No. 4,980,286; PCT Application WO 89/07136; PCT Application WO 89/02468; PCT Application WO 89/05345; and PCT Application WO 92/07573). Recombinant retroviral vectors capable of transducing and expressing genes inserted into the genome of a cell can be produced by transfecting the recombinant retroviral genome into suitable packaging cell lines such as PA317 and Psi-CRIP (Comette et al., 1991, Human Gene Therapy 2:5-10; Cone et al., 1984, Proc. Natl. Acad. Sci. USA 81:6349). Recombinant adenoviral vectors can be used to infect a wide variety of cells and tissues in susceptible hosts (e.g., rat, hamster, dog, and chimpanzee) (Hsu et al., 1992, J. Infectious Disease, 166:769), and also have the advantage of not requiring mitotically active cells for infection.
Any viral vector capable of accepting the coding sequences for the dsRNA molecule(s) to be expressed can be used, for example vectors derived from adenovirus (AV); adeno-associated virus (AAV); retroviruses (e.g., lentiviruses (LV), Rhabdoviruses, murine leukemia virus); herpes virus, and the like. The tropism of viral vectors can be modified by pseudotyping the vectors with envelope proteins or other surface antigens from other viruses, or by substituting different viral capsid proteins, as appropriate.
For example, lentiviral vectors featured in the invention can be pseudotyped with surface proteins from vesicular stomatitis virus (VSV), rabies, Ebola, Mokola, and the like. AAV vectors featured in the invention can be made to target different cells by engineering the vectors to express different capsid protein serotypes. For example, an AAV vector expressing a serotype 2 capsid on a serotype 2 genome is called AAV 2/2. This serotype 2 capsid gene in the AAV 2/2 vector can be replaced by a serotype 5 capsid gene to produce an AAV 2/5 vector. Techniques for constructing AAV vectors which express different capsid protein serotypes are within the skill in the art; see, e.g., Rabinowitz J E et al. (2002), J Virol 76:791-801, the entire disclosure of which is herein incorporated by reference.
Selection of recombinant viral vectors suitable for use in the invention, methods for inserting nucleic acid sequences for expressing the dsRNA into the vector, and methods of delivering the viral vector to the cells of interest are within the skill in the art. See, for example, Dornburg R (1995), Gene Therap. 2: 301-310; Eglitis M A (1988), Biotechniques 6: 608-614; Miller A D (1990), Hum Gene Therap. 1: 5-14; Anderson W F (1998), Nature 392: 25-30; and Rubinson D A et al., Nat. Genet. 33: 401-406, the entire disclosures of which are herein incorporated by reference.
Viral vectors can be derived from AV and AAV. In one embodiment, the dsRNA featured in the invention is expressed as two separate, complementary single-stranded RNA molecules from a recombinant AAV vector having, for example, either the U6 or H1 RNA promoters, or the cytomegalovirus (CMV) promoter.
A suitable AV vector for expressing the dsRNA featured in the invention, a method for constructing the recombinant AV vector, and a method for delivering the vector into target cells, are described in Xia H et al. (2002), Nat. Biotech. 20: 1006-1010.
Suitable AAV vectors for expressing the dsRNA featured in the invention, methods for constructing the recombinant AV vector, and methods for delivering the vectors into target cells are described in Samulski R et al. (1987), J. Virol. 61: 3096-3101; Fisher K J et al. (1996), J. Virol, 70: 520-532; Samulski R et al. (1989), J. Virol. 63: 3822-3826; U.S. Pat. No. 5,252,479; U.S. Pat. No. 5,139,941; International Patent Application No. WO 94/13788; and International Patent Application No. WO 93/24641, the entire disclosures of which are herein incorporated by reference.
The promoter driving dsRNA expression in either a DNA plasmid or viral vector featured in the invention may be a eukaryotic RNA polymerase I (e.g., ribosomal RNA promoter), RNA polymerase II (e.g., CMV early promoter or actin promoter or U1 snRNA promoter) or generally RNA polymerase III promoter (e.g., U6 snRNA or 7SK RNA promoter) or a prokaryotic promoter, for example the T7 promoter, provided the expression plasmid also encodes T7 RNA polymerase required for transcription from a T7 promoter. The promoter can also direct transgene expression to the pancreas (see, e.g., the insulin regulatory sequence for pancreas (Bucchini et al., 1986, Proc. Natl. Acad. Sci. USA 83:2511-2515)).
In addition, expression of the transgene can be precisely regulated, for example, by using an inducible regulatory sequence and expression systems such as a regulatory sequence that is sensitive to certain physiological regulators, e.g., circulating glucose levels, or hormones (Docherty et al., 1994, FASEB J. 8:20-24). Such inducible expression systems, suitable for the control of transgene expression in cells or in mammals include regulation by ecdysone, by estrogen, progesterone, tetracycline, chemical inducers of dimerization, and isopropyl-beta-D1-thiogalactopyranoside (EPTG). A person skilled in the art would be able to choose the appropriate regulatory/promoter sequence based on the intended use of the dsRNA transgene.
Generally, recombinant vectors capable of expressing dsRNA molecules are delivered as described below, and persist in target cells. Alternatively, viral vectors can be used that provide for transient expression of dsRNA molecules. Such vectors can be repeatedly administered as necessary. Once expressed, the dsRNAs bind to target RNA and modulate its function or expression. Delivery of dsRNA expressing vectors can be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex-planted from the patient followed by reintroduction into the patient, or by any other means that allows for introduction into a desired target cell.
dsRNA expression DNA plasmids are typically transfected into target cells as a complex with cationic lipid carriers (e.g., Oligofectamine) or non-cationic lipid-based carriers (e.g., Transit-TKOTM). Multiple lipid transfections for dsRNA-mediated knockdowns targeting different regions of a single XBP-1 gene or multiple XBP-1 genes over a period of a week or more are also contemplated by the invention. Successful introduction of vectors into host cells can be monitored using various known methods. For example, transient transfection can be signaled with a reporter, such as a fluorescent marker, such as Green Fluorescent Protein (GFP). Stable transfection of cells ex vivo can be ensured using markers that provide the transfected cell with resistance to specific environmental factors (e.g., antibiotics and drugs), such as hygromycin B resistance.
The XBP-1 specific dsRNA molecules can also be inserted into vectors and used as gene therapy vectors for human patients. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see U.S. Pat. No. 5,328,470) or by stereotactic injection (see e.g., Chen et al. (1994) Proc. Natl. Acad. Sci. USA 91:3054-3057). The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can include a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g., retroviral vectors, the pharmaceutical preparation can include one or more cells which produce the gene delivery system.
III. Pharmaceutical Compositions Comprising dsRNA
In one embodiment, the invention provides pharmaceutical compositions comprising a dsRNA, as described herein, and a pharmaceutically acceptable carrier. The pharmaceutical composition comprising the dsRNA is useful for treating a disease or disorder associated with the expression or activity of the XBP-1 gene, such as pathological processes mediated by XBP-1 expression. Such pharmaceutical compositions are formulated based on the mode of delivery. One example is compositions that are formulated for systemic administration via parenteral delivery.
The pharmaceutical compositions featured herein are administered in dosages sufficient to inhibit expression of the XBP-1 genes. In general, a suitable dose of total dsRNA will be in the range of 0.01 to 200.0 milligrams per kilogram body weight of the recipient per day, generally in the range of 0.02 to 50 mg per kilogram body weight per day. For example, the dsRNA can be administered at 0.01 mg/kg, 0.1 mg/kg, 0.05 mg/kg, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 3 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg, or 50 mg/kg per single dose. The pharmaceutical composition may be administered once daily or the dsRNA may be administered as two, three, or more sub-doses at appropriate intervals throughout the day or even using continuous infusion or delivery through a controlled release formulation. In that case, the dsRNA contained in each sub-dose must be correspondingly smaller in order to achieve the total daily dosage. The dosage unit can also be compounded for delivery over several days, e.g., using a conventional sustained release formulation which provides sustained release of the dsRNA over a several day period. Sustained release formulations are well known in the art and are particularly useful for delivery of agents at a particular site, such as could be used with the agents of the present invention. In this embodiment, the dosage unit contains a corresponding multiple of the daily dose.
The skilled artisan will appreciate that certain factors may influence the dosage and timing required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general health and/or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of a composition can include a single treatment or a series of treatments. Estimates of effective dosages and in vivo half-lives for the individual dsRNAs encompassed by the invention can be made using conventional methodologies or on the basis of in vivo testing using an appropriate animal model, as described elsewhere herein.
Advances in mouse genetics have generated a number of mouse models for the study of various human diseases, such as pathological processes mediated by XBP-1 expression. Such models are used for in vivo testing of dsRNA, as well as for determining a therapeutically effective dose.
The present invention also includes pharmaceutical compositions and formulations which include the dsRNA compounds featured in the invention. The pharmaceutical compositions of the present invention may be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration may be topical (e.g., by a transdermal patch), pulmonary (e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, epidermal and transdermal), oral or parenteral. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; subdermal, e.g., via an implanted device; or intracranial, e.g., by intrathecal or intraventricular, administration.
Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable. Coated condoms, gloves and the like may also be useful. Suitable topical formulations include those in which the dsRNAs featured in the invention are in admixture with a topical delivery agent such as lipids, liposomes, fatty acids, fatty acid esters, steroids, chelating agents and surfactants. Suitable lipids and liposomes include neutral (e.g., dioleoylphosphatidyl DOPE ethanolamine, dimyristoylphosphatidyl choline DMPC, distearolyphosphatidyl choline) negative (e.g., dimyristoylphosphatidyl glycerol DMPG) and cationic (e.g., dioleoyltetramethylaminopropyl DOTAP and dioleoylphosphatidyl ethanolamine DOTMA). DsRNAs featured in the invention may be encapsulated within liposomes or may form complexes thereto, in particular to cationic liposomes. Alternatively, dsRNAs may be complexed to lipids, in particular to cationic lipids. Suitable fatty acids and esters include but are not limited arachidonic acid, oleic acid, eicosanoic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or a C1-10 alkyl ester (e.g., isopropylmyristate IPM), monoglyceride, diglyceride or pharmaceutically acceptable salt thereof. Topical formulations are described in detail in U.S. patent application Ser. No. 09/315,298 filed on May 20, 1999 which is incorporated herein by reference in its entirety.
In one embodiment, a dsRNA featured in the invention is fully encapsulated in the lipid formulation (e.g., to form a SPLP, pSPLP, SNALP, or other nucleic acid-lipid particle). As used herein, the term “SNALP” refers to a stable nucleic acid-lipid particle, including SPLP. As used herein, the term “SPLP” refers to a nucleic acid-lipid particle comprising plasmid DNA encapsulated within a lipid vesicle. SNALPs and SPLPs typically contain a cationic lipid, a non-cationic lipid, and a lipid that prevents aggregation of the particle (e.g., a PEG-lipid conjugate). SNALPs and SPLPs are extremely useful for systemic applications, as they exhibit extended circulation lifetimes following intravenous (i.v.) injection and accumulate at distal sites (e.g., sites physically separated from the administration site). SPLPs include “pSPLP,” which include an encapsulated condensing agent-nucleic acid complex as set forth in PCT Publication No. WO 00/03683. The particles of the present invention typically have a mean diameter of about 50 nm to about 150 nm, more typically about 60 nm to about 130 nm, more typically about 70 nm to about 110 nm, most typically about 70 to about 90 nm, and are substantially nontoxic. In addition, the nucleic acids when present in the nucleic acid-lipid particles of the present invention are resistant in aqueous solution to degradation with a nuclease. Nucleic acid-lipid particles and their method of preparation are disclosed in, e.g., U.S. Pat. Nos. 5,976,567; 5,981,501; 6,534,484; 6,586,410; 6,815,432; and PCT Publication No. WO 96/40964.
In one embodiment, the lipid to drug ratio (mass/mass ratio) (e.g., lipid to dsRNA ratio) will be in the range of from about 1:1 to about 50:1, from about 1:1 to about 25:1, from about 3:1 to about 15:1, from about 4:1 to about 10:1, from about 5:1 to about 9:1, or about 6:1 to about 9:1.
The cationic lipid may be, for example, N,N-dioleyl-N,N-dimethylammonium chloride (DODAC), N,N-distearyl-N,N-dimethylammonium bromide (DDAB), N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP), N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA), N,N-dimethyl-2,3-dioleyloxy)propylamine (DODMA), 1,2-DiLinoleyloxy-N,N-dimethylaminopropane (DLinDMA), 1,2-Dilinolenyloxy-N,N-dimethylaminopropane (DLenDMA), 1,2-Dilinoleylcarbamoyloxy-3-dimethylaminopropane (DLin-C-DAP), 1,2-Dilinoleyoxy-3-(dimethylamino)acetoxypropane (DLin-DAC), 1,2-Dilinoleyoxy-3-morpholinopropane (DLin-MA), 1,2-Dilinoleoyl-3-dimethylaminopropane (DLinDAP), 1,2-Dilinoleylthio-3-dimethylaminopropane (DLin-S-DMA), 1-Linoleoyl-2-linoleyloxy-3-dimethylaminopropane (DLin-2-DMAP), 1,2-Dilinoleyloxy-3-trimethylaminopropane chloride salt (DLin-TMA.Cl), 1,2-Dilinoleoyl-3-trimethylaminopropane chloride salt (DLin-TAP.Cl), 1,2-Dilinoleyloxy-3-(N-methylpiperazino)propane (DLin-MPZ), or 3-(N,N-Dilinoleylamino)-1,2-propanediol (DLinAP), 3-(N,N-Dioleylamino)-1,2-propanedio (DOAP), 1,2-Dilinoleyloxo-3-(2-N,N-dimethylamino)ethoxypropane (DLin-EG-DMA), 2,2-Dilinoleyl-4-dimethylaminomethyl-[1,3]-dioxolane (DLin-K-DMA), or a mixture thereof. The cationic lipid may comprise from about 20 mol % to about 50 mol % or about 40 mol % of the total lipid present in the particle.
The non-cationic lipid may be an anionic lipid or a neutral lipid including, but not limited to, distearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dioleoyl-phosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoyl-phosphatidylethanolamine (POPE), dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoyl phosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoyl-phosphatidyl-ethanolamine (DSPE), 16-O-monomethyl PE, 16-O-dimethyl PE, 18-1-trans PE, 1-stearoyl-2-oleoyl-phosphatidyethanolamine (SOPE), cholesterol, or a mixture thereof. The non-cationic lipid may be from about 5 mol % to about 90 mol %, about 10 mol %, or about 58 mol % if cholesterol is included, of the total lipid present in the particle.
The conjugated lipid that inhibits aggregation of particles may be, for example, a polyethyleneglycol (PEG)-lipid including, without limitation, a PEG-diacylglycerol (DAG), a PEG-dialkyloxypropyl (DAA), a PEG-phospholipid, a PEG-ceramide (Cer), or a mixture thereof. The PEG-DAA conjugate may be, for example, a PEG-dilauryloxypropyl (Ci2), a PEG-dimyristyloxypropyl (Ci4), a PEG-dipalmityloxypropyl (Ci6), or a PEG-distearyloxypropyl (C]8). The conjugated lipid that prevents aggregation of particles may be from 0 mol % to about 20 mol % or about 2 mol % of the total lipid present in the particle.
In some embodiments, the nucleic acid-lipid particle further includes cholesterol at, e.g., about 10 mol % to about 60 mol % or about 48 mol % of the total lipid present in the particle.
In one embodiment, the lipidoid ND98.4HCl (MW 1487) (Formula 1), Cholesterol (Sigma-Aldrich), and PEG-Ceramide C16 (Avanti Polar Lipids) can be used to prepare lipid-siRNA nanoparticles (i.e., LNP01 particles). Stock solutions of each in ethanol can be prepared as follows: ND98, 133 mg/mL; Cholesterol, 25 mg/mL, PEG-Ceramide C16, 100 mg/mL. The ND98, Cholesterol, and PEG-Ceramide C16 stock solutions can then be combined in a, e.g., 42:48:10 molar ratio. The combined lipid solution can be mixed with aqueous siRNA (e.g., in sodium acetate pH 5) such that the final ethanol concentration is about 35-45% and the final sodium acetate concentration is about 100-300 mM. Lipid-siRNA nanoparticles typically form spontaneously upon mixing. Depending on the desired particle size distribution, the resultant nanoparticle mixture can be extruded through a polycarbonate membrane (e.g., 100 nm cut-off) using, for example, a thermobarrel extruder, such as Lipex Extruder (Northern Lipids, Inc). In some cases, the extrusion step can be omitted. Ethanol removal and simultaneous buffer exchange can be accomplished by, for example, dialysis or tangential flow filtration. Buffer can be exchanged with, for example, phosphate buffered saline (PBS) at about pH 7, e.g., about pH 6.9, about pH 7.0, about pH 7.1, about pH 7.2, about pH 7.3, or about pH 7.4.




LNP01 formulations are described, e.g., in International Application Publication No. WO 2008/042973, which is hereby incorporated by reference.
Formulations prepared by either the standard or extrusion-free method can be characterized in similar manners. For example, formulations are typically characterized by visual inspection. They should be whitish translucent solutions free from aggregates or sediment. Particle size and particle size distribution of lipid-nanoparticles can be measured by light scattering using, for example, a Malvern Zetasizer Nano ZS (Malvern, USA). Particles should be about 20-300 nm, such as 40-100 nm in size. The particle size distribution should be unimodal. The total siRNA concentration in the formulation, as well as the entrapped fraction, is estimated using a dye exclusion assay. A sample of the formulated siRNA can be incubated with an RNA-binding dye, such as Ribogreen (Molecular Probes) in the presence or absence of a formulation disrupting surfactant, e.g., 0.5% Triton-X100. The total siRNA in the formulation can be determined by the signal from the sample containing the surfactant, relative to a standard curve. The entrapped fraction is determined by subtracting the “free” siRNA content (as measured by the signal in the absence of surfactant) from the total siRNA content. Percent entrapped siRNA is typically >85%. For SNALP formulation, the particle size is at least 30 nm, at least 40 nm, at least 50 nm, at least 60 nm, at least 70 nm, at least 80 nm, at least 90 nm, at least 100 nm, at least 110 nm, and at least 120 nm. The suitable range is typically about at least 50 nm to about at least 110 nm, about at least 60 nm to about at least 100 nm, or about at least 80 nm to about at least 90 nm.
Compositions and formulations for oral administration include powders or granules, microparticulates, nanoparticulates, suspensions or solutions in water or non-aqueous media, capsules, gel capsules, sachets, tablets or minitablets. Thickeners, flavoring agents, diluents, emulsifiers, dispersing aids or binders may be desirable. In some embodiments, oral formulations are those in which dsRNAs featured in the invention are administered in conjunction with one or more penetration enhancers surfactants and chelators. Suitable surfactants include fatty acids and/or esters or salts thereof, bile acids and/or salts thereof. Suitable bile acids/salts include chenodeoxycholic acid (CDCA) and ursodeoxychenodeoxycholic acid (UDCA), cholic acid, dehydrocholic acid, deoxycholic acid, glucholic acid, glycholic acid, glycodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, sodium tauro-24,25-dihydro-fusidate and sodium glycodihydrofusidate. Suitable fatty acids include arachidonic acid, undecanoic acid, oleic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or a monoglyceride, a diglyceride or a pharmaceutically acceptable salt thereof (e.g., sodium). In some embodiments, combinations of penetration enhancers are used, for example, fatty acids/salts in combination with bile acids/salts. One exemplary combination is the sodium salt of lauric acid, capric acid and UDCA. Further penetration enhancers include polyoxyethylene-9-lauryl ether, polyoxyethylene-20-cetyl ether. DsRNAs featured in the invention may be delivered orally, in granular form including sprayed dried particles, or complexed to form micro or nanoparticles. DsRNA complexing agents include poly-amino acids; polyimines; polyacrylates; polyalkylacrylates, polyoxethanes, polyalkylcyanoacrylates; cationized gelatins, albumins, starches, acrylates, polyethyleneglycols (PEG) and starches; polyalkylcyanoacrylates; DEAE-derivatized polyimines, pollulans, celluloses and starches. Suitable complexing agents include chitosan, N-trimethylchitosan, poly-L-lysine, polyhistidine, polyornithine, polyspermines, protamine, polyvinylpyridine, polythiodiethylaminomethylethylene P(TDAE), polyaminostyrene (e.g., p-amino), poly(methylcyanoacrylate), poly(ethylcyanoacrylate), poly(butylcyanoacrylate), poly(isobutylcyanoacrylate), poly(isohexylcynaoacrylate), DEAE-methacrylate, DEAE-hexylacrylate, DEAE-acrylamide, DEAE-albumin and DEAE-dextran, polymethylacrylate, polyhexylacrylate, poly(D,L-lactic acid), poly(DL-lactic-co-glycolic acid (PLGA), alginate, and polyethyleneglycol (PEG). Oral formulations for dsRNAs and their preparation are described in detail in U.S. application. Ser. No. 08/886,829 (filed Jul. 1, 1997), Ser. No. 09/108,673 (filed Jul. 1, 1998), Ser. No. 09/256,515 (filed Feb. 23, 1999), Ser. No. 09/082,624 (filed May 21, 1998) and Ser. No. 09/315,298 (filed May 20, 1999), each of which is incorporated herein by reference in their entirety.
Compositions and formulations for parenteral, intrathecal, intraventricular or intrahepatic administration may include sterile aqueous solutions which may also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carrier compounds and other pharmaceutically acceptable carriers or excipients.
Pharmaceutical compositions of the present invention include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions may be generated from a variety of components that include, but are not limited to, preformed liquids, self-emulsifying solids and self-emulsifying semisolids. Particularly preferred are formulations that target the liver when treating hepatic disorders such as hepatic carcinoma.
The pharmaceutical formulations of the present invention, which may conveniently be presented in unit dosage form, may be prepared according to conventional techniques well known in the pharmaceutical industry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product.
The compositions of the present invention may be formulated into any of many possible dosage forms such as, but not limited to, tablets, capsules, gel capsules, liquid syrups, soft gels, suppositories, and enemas. The compositions of the present invention may also be formulated as suspensions in aqueous, non-aqueous or mixed media. Aqueous suspensions may further contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers.
Emulsions
The compositions of the present invention may be prepared and formulated as emulsions. Emulsions are typically heterogenous systems of one liquid dispersed in another in the form of droplets usually exceeding 0.1.mu·m in diameter (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199; Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., Volume 1, p. 245; Block in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 2, p. 335; Higuchi et al., in Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 1985, p. 301). Emulsions are often biphasic systems comprising two immiscible liquid phases intimately mixed and dispersed with each other. In general, emulsions may be of either the water-in-oil (w/o) or the oil-in-water (o/w) variety. When an aqueous phase is finely divided into and dispersed as minute droplets into a bulk oily phase, the resulting composition is called a water-in-oil (w/o) emulsion. Alternatively, when an oily phase is finely divided into and dispersed as minute droplets into a bulk aqueous phase, the resulting composition is called an oil-in-water (o/w) emulsion. Emulsions may contain additional components in addition to the dispersed phases, and the active drug which may be present as a solution in either the aqueous phase, oily phase or itself as a separate phase. Pharmaceutical excipients such as emulsifiers, stabilizers, dyes, and anti-oxidants may also be present in emulsions as needed. Pharmaceutical emulsions may also be multiple emulsions that are comprised of more than two phases such as, for example, in the case of oil-in-water-in-oil (o/w/o) and water-in-oil-in-water (w/o/w) emulsions. Such complex formulations often provide certain advantages that simple binary emulsions do not. Multiple emulsions in which individual oil droplets of an o/w emulsion enclose small water droplets constitute a w/o/w emulsion. Likewise a system of oil droplets enclosed in globules of water stabilized in an oily continuous phase provides an o/w/o emulsion.
Emulsions are characterized by little or no thermodynamic stability. Often, the dispersed or discontinuous phase of the emulsion is well dispersed into the external or continuous phase and maintained in this form through the means of emulsifiers or the viscosity of the formulation. Either of the phases of the emulsion may be a semisolid or a solid, as is the case of emulsion-style ointment bases and creams. Other means of stabilizing emulsions entail the use of emulsifiers that may be incorporated into either phase of the emulsion. Emulsifiers may broadly be classified into four categories: synthetic surfactants, naturally occurring emulsifiers, absorption bases, and finely dispersed solids (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199).
Synthetic surfactants, also known as surface active agents, have found wide applicability in the formulation of emulsions and have been reviewed in the literature (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), Marcel Dekker, Inc., New York, N.Y., 1988, volume 1, p. 199). Surfactants are typically amphiphilic and comprise a hydrophilic and a hydrophobic portion. The ratio of the hydrophilic to the hydrophobic nature of the surfactant has been termed the hydrophile/lipophile balance (HLB) and is a valuable tool in categorizing and selecting surfactants in the preparation of formulations. Surfactants may be classified into different classes based on the nature of the hydrophilic group: nonionic, anionic, cationic and amphoteric (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285).
Naturally occurring emulsifiers used in emulsion formulations include lanolin, beeswax, phosphatides, lecithin and acacia. Absorption bases possess hydrophilic properties such that they can soak up water to form w/o emulsions yet retain their semisolid consistencies, such as anhydrous lanolin and hydrophilic petrolatum. Finely divided solids have also been used as good emulsifiers especially in combination with surfactants and in viscous preparations. These include polar inorganic solids, such as heavy metal hydroxides, nonswelling clays such as bentonite, attapulgite, hectorite, kaolin, montmorillonite, colloidal aluminum silicate and colloidal magnesium aluminum silicate, pigments and nonpolar solids such as carbon or glyceryl tristearate.
A large variety of non-emulsifying materials are also included in emulsion formulations and contribute to the properties of emulsions. These include fats, oils, waxes, fatty acids, fatty alcohols, fatty esters, humectants, hydrophilic colloids, preservatives and antioxidants (Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199).
Hydrophilic colloids or hydrocolloids include naturally occurring gums and synthetic polymers such as polysaccharides (for example, acacia, agar, alginic acid, carrageenan, guar gum, karaya gum, and tragacanth), cellulose derivatives (for example, carboxymethylcellulose and carboxypropylcellulose), and synthetic polymers (for example, carbomers, cellulose ethers, and carboxyvinyl polymers). These disperse or swell in water to form colloidal solutions that stabilize emulsions by forming strong interfacial films around the dispersed-phase droplets and by increasing the viscosity of the external phase.
Since emulsions often contain a number of ingredients such as carbohydrates, proteins, sterols and phosphatides that may readily support the growth of microbes, these formulations often incorporate preservatives. Commonly used preservatives included in emulsion formulations include methyl paraben, propyl paraben, quaternary ammonium salts, benzalkonium chloride, esters of p-hydroxybenzoic acid, and boric acid. Antioxidants are also commonly added to emulsion formulations to prevent deterioration of the formulation. Antioxidants used may be free radical scavengers such as tocopherols, alkyl gallates, butylated hydroxyanisole, butylated hydroxytoluene, or reducing agents such as ascorbic acid and sodium metabisulfite, and antioxidant synergists such as citric acid, tartaric acid, and lecithin.
The application of emulsion formulations via dermatological, oral and parenteral routes and methods for their manufacture have been reviewed in the literature (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Emulsion formulations for oral delivery have been very widely used because of ease of formulation, as well as efficacy from an absorption and bioavailability standpoint (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Mineral-oil base laxatives, oil-soluble vitamins and high fat nutritive preparations are among the materials that have commonly been administered orally as o/w emulsions.
In one embodiment of the present invention, the compositions of dsRNAs and nucleic acids are formulated as microemulsions. A microemulsion may be defined as a system of water, oil and amphiphile which is a single optically isotropic and thermodynamically stable liquid solution (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Typically microemulsions are systems that are prepared by first dispersing an oil in an aqueous surfactant solution and then adding a sufficient amount of a fourth component, generally an intermediate chain-length alcohol to form a transparent system. Therefore, microemulsions have also been described as thermodynamically stable, isotropically clear dispersions of two immiscible liquids that are stabilized by interfacial films of surface-active molecules (Leung and Shah, in: Controlled Release of Drugs: Polymers and Aggregate Systems, Rosoff, M., Ed., 1989, VCH Publishers, New York, pages 185-215). Microemulsions commonly are prepared via a combination of three to five components that include oil, water, surfactant, cosurfactant and electrolyte. Whether the microemulsion is of the water-in-oil (w/o) or an oil-in-water (o/w) type is dependent on the properties of the oil and surfactant used and on the structure and geometric packing of the polar heads and hydrocarbon tails of the surfactant molecules (Schott, in Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 1985, p. 271).
The phenomenological approach utilizing phase diagrams has been extensively studied and has yielded a comprehensive knowledge, to one skilled in the art, of how to formulate microemulsions (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335). Compared to conventional emulsions, microemulsions offer the advantage of solubilizing water-insoluble drugs in a formulation of thermodynamically stable droplets that are formed spontaneously.
Surfactants used in the preparation of microemulsions include, but are not limited to, ionic surfactants, non-ionic surfactants, Brij 96, polyoxyethylene oleyl ethers, polyglycerol fatty acid esters, tetraglycerol monolaurate (ML310), tetraglycerol monooleate (MO310), hexaglycerol monooleate (PO310), hexaglycerol pentaoleate (PO500), decaglycerol monocaprate (MCA750), decaglycerol monooleate (MO750), decaglycerol sequioleate (SO750), decaglycerol decaoleate (DAO750), alone or in combination with cosurfactants. The cosurfactant, usually a short-chain alcohol such as ethanol, 1-propanol, and 1-butanol, serves to increase the interfacial fluidity by penetrating into the surfactant film and consequently creating a disordered film because of the void space generated among surfactant molecules. Microemulsions may, however, be prepared without the use of cosurfactants and alcohol-free self-emulsifying microemulsion systems are known in the art. The aqueous phase may typically be, but is not limited to, water, an aqueous solution of the drug, glycerol, PEG300, PEG400, polyglycerols, propylene glycols, and derivatives of ethylene glycol. The oil phase may include, but is not limited to, materials such as Captex 300, Captex 355, Capmul MCM, fatty acid esters, medium chain (C8-C12) mono, di, and tri-glycerides, polyoxyethylated glyceryl fatty acid esters, fatty alcohols, polyglycolized glycerides, saturated polyglycolized C8-C10 glycerides, vegetable oils and silicone oil.
Microemulsions are particularly of interest from the standpoint of drug solubilization and the enhanced absorption of drugs. Lipid based microemulsions (both o/w and w/o) have been proposed to enhance the oral bioavailability of drugs, including peptides (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385-1390; Ritschel, Meth. Find. Exp. Clin. Pharmacol., 1993, 13, 205). Microemulsions afford advantages of improved drug solubilization, protection of drug from enzymatic hydrolysis, possible enhancement of drug absorption due to surfactant-induced alterations in membrane fluidity and permeability, ease of preparation, ease of oral administration over solid dosage forms, improved clinical potency, and decreased toxicity (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385; Ho et al., J. Pharm. Sci., 1996, 85, 138-143). Often microemulsions may form spontaneously when their components are brought together at ambient temperature. This may be particularly advantageous when formulating thermolabile drugs, peptides or dsRNAs. Microemulsions have also been effective in the transdermal delivery of active components in both cosmetic and pharmaceutical applications. It is expected that the microemulsion compositions and formulations of the present invention will facilitate the increased systemic absorption of dsRNAs and nucleic acids from the gastrointestinal tract, as well as improve the local cellular uptake of dsRNAs and nucleic acids.
Microemulsions of the present invention may also contain additional components and additives such as sorbitan monostearate (Grill 3), Labrasol, and penetration enhancers to improve the properties of the formulation and to enhance the absorption of the dsRNAs and nucleic acids of the present invention. Penetration enhancers used in the microemulsions of the present invention may be classified as belonging to one of five broad categories—surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92). Each of these classes has been discussed above.
Liposomes
There are many organized surfactant structures besides microemulsions that have been studied and used for the formulation of drugs. These include monolayers, micelles, bilayers and vesicles. Vesicles, such as liposomes, have attracted great interest because of their specificity and the duration of action they offer from the standpoint of drug delivery. As used in the present invention, the term “liposome” means a vesicle composed of amphiphilic lipids arranged in a spherical bilayer or bilayers.
Liposomes are unilamellar or multilamellar vesicles which have a membrane formed from a lipophilic material and an aqueous interior. The aqueous portion contains the composition to be delivered. Cationic liposomes possess the advantage of being able to fuse to the cell wall. Non-cationic liposomes, although not able to fuse as efficiently with the cell wall, are taken up by macrophages in vivo.
In order to cross intact mammalian skin, lipid vesicles must pass through a series of fine pores, each with a diameter less than 50 nm, under the influence of a suitable transdermal gradient. Therefore, it is desirable to use a liposome which is highly deformable and able to pass through such fine pores.
Further advantages of liposomes include; liposomes obtained from natural phospholipids are biocompatible and biodegradable; liposomes can incorporate a wide range of water and lipid soluble drugs; liposomes can protect encapsulated drugs in their internal compartments from metabolism and degradation (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Important considerations in the preparation of liposome formulations are the lipid surface charge, vesicle size and the aqueous volume of the liposomes.
Liposomes are useful for the transfer and delivery of active ingredients to the site of action. Because the liposomal membrane is structurally similar to biological membranes, when liposomes are applied to a tissue, the liposomes start to merge with the cellular membranes and as the merging of the liposome and cell progresses, the liposomal contents are emptied into the cell where the active agent may act.
Liposomal formulations have been the focus of extensive investigation as the mode of delivery for many drugs. There is growing evidence that for topical administration, liposomes present several advantages over other formulations. Such advantages include reduced side-effects related to high systemic absorption of the administered drug, increased accumulation of the administered drug at the desired target, and the ability to administer a wide variety of drugs, both hydrophilic and hydrophobic, into the skin.
Several reports have detailed the ability of liposomes to deliver agents including high-molecular weight DNA into the skin. Compounds including analgesics, antibodies, hormones and high-molecular weight DNAs have been administered to the skin. The majority of applications resulted in the targeting of the upper epidermis
Liposomes fall into two broad classes. Cationic liposomes are positively charged liposomes which interact with the negatively charged DNA molecules to form a stable complex. The positively charged DNA/liposome complex binds to the negatively charged cell surface and is internalized in an endosome. Due to the acidic pH within the endosome, the liposomes are ruptured, releasing their contents into the cell cytoplasm (Wang et al., Biochem. Biophys. Res. Commun., 1987, 147, 980-985).
Liposomes which are pH-sensitive or negatively-charged, entrap DNA rather than complex with it. Since both the DNA and the lipid are similarly charged, repulsion rather than complex formation occurs. Nevertheless, some DNA is entrapped within the aqueous interior of these liposomes. pH-sensitive liposomes have been used to deliver DNA encoding the thymidine kinase gene to cell monolayers in culture. Expression of the exogenous gene was detected in the target cells (Zhou et al., Journal of Controlled Release, 1992, 19, 269-274).
One major type of liposomal composition includes phospholipids other than naturally-derived phosphatidylcholine. Neutral liposome compositions, for example, can be formed from dimyristoyl phosphatidylcholine (DMPC) or dipalmitoyl phosphatidylcholine (DPPC). Anionic liposome compositions generally are formed from dimyristoyl phosphatidylglycerol, while anionic fusogenic liposomes are formed primarily from dioleoyl phosphatidylethanolamine (DOPE). Another type of liposomal composition is formed from phosphatidylcholine (PC) such as, for example, soybean PC, and egg PC. Another type is formed from mixtures of phospholipid and/or phosphatidylcholine and/or cholesterol.
Several studies have assessed the topical delivery of liposomal drug formulations to the skin. Application of liposomes containing interferon to guinea pig skin resulted in a reduction of skin herpes sores while delivery of interferon via other means (e.g., as a solution or as an emulsion) were ineffective (Weiner et al., Journal of Drug Targeting, 1992, 2, 405-410). Further, an additional study tested the efficacy of interferon administered as part of a liposomal formulation to the administration of interferon using an aqueous system, and concluded that the liposomal formulation was superior to aqueous administration (du Plessis et al., Antiviral Research, 1992, 18, 259-265).
Non-ionic liposomal systems have also been examined to determine their utility in the delivery of drugs to the skin, in particular systems comprising non-ionic surfactant and cholesterol. Non-ionic liposomal formulations comprising Novasome.TM. I (glyceryl dilaurate/cholesterol/po-lyoxyethylene-10-stearyl ether) and Novasome.TM. II (glyceryl distearate/cholesterol/polyoxyethylene-10-stearyl ether) were used to deliver cyclosporin-A into the dermis of mouse skin. Results indicated that such non-ionic liposomal systems were effective in facilitating the deposition of cyclosporin-A into different layers of the skin (Hu et al. S.T.P. Pharma. Sci., 1994, 4, 6, 466).
Liposomes also include “sterically stabilized” liposomes, a term which, as used herein, refers to liposomes comprising one or more specialized lipids that, when incorporated into liposomes, result in enhanced circulation lifetimes relative to liposomes lacking such specialized lipids. Examples of sterically stabilized liposomes are those in which part of the vesicle-forming lipid portion of the liposome (A) comprises one or more glycolipids, such as monosialoganglioside GM1, or (B) is derivatized with one or more hydrophilic polymers, such as a polyethylene glycol (PEG) moiety. While not wishing to be bound by any particular theory, it is thought in the art that, at least for sterically stabilized liposomes containing gangliosides, sphingomyelin, or PEG-derivatized lipids, the enhanced circulation half-life of these sterically stabilized liposomes derives from a reduced uptake into cells of the reticuloendothelial system (RES) (Allen et al., FEBS Letters, 1987, 223, 42; Wu et al., Cancer Research, 1993, 53, 3765).
Various liposomes comprising one or more glycolipids are known in the art. Papahadjopoulos et al. (Ann. N.Y. Acad. Sci., 1987, 507, 64) reported the ability of monosialoganglioside GM1, galactocerebroside sulfate and phosphatidylinositol to improve blood half-lives of liposomes. These findings were expounded upon by Gabizon et al. (Proc. Natl. Acad. Sci. U.S.A., 1988, 85, 6949). U.S. Pat. No. 4,837,028 and WO 88/04924, both to Allen et al., disclose liposomes comprising (1) sphingomyelin and (2) the ganglioside GM1 or a galactocerebroside sulfate ester. U.S. Pat. No. 5,543,152 (Webb et al.) discloses liposomes comprising sphingomyelin. Liposomes comprising 1,2-sn-dimyristoylphosphat-idylcholine are disclosed in WO 97/13499 (Lim et al).
Many liposomes comprising lipids derivatized with one or more hydrophilic polymers, and methods of preparation thereof, are known in the art. Sunamoto et al. (Bull. Chem. Soc. Jpn., 1980, 53, 2778) described liposomes comprising a nonionic detergent, 2C1215G, that contains a PEG moiety. Illum et al. (FEBS Lett., 1984, 167, 79) noted that hydrophilic coating of polystyrene particles with polymeric glycols results in significantly enhanced blood half-lives. Synthetic phospholipids modified by the attachment of carboxylic groups of polyalkylene glycols (e.g., PEG) are described by Sears (U.S. Pat. Nos. 4,426,330 and 4,534,899). Klibanov et al. (FEBS Lett., 1990, 268, 235) described experiments demonstrating that liposomes comprising phosphatidylethanolamine (PE) derivatized with PEG or PEG stearate have significant increases in blood circulation half-lives. Blume et al. (Biochimica et Biophysica Acta, 1990, 1029, 91) extended such observations to other PEG-derivatized phospholipids, e.g., DSPE-PEG, formed from the combination of distearoylphosphatidylethanolamine (DSPE) and PEG. Liposomes having covalently bound PEG moieties on their external surface are described in European Patent No. EP 0 445 131 B1 and WO 90/04384 to Fisher. Liposome compositions containing 1-20 mole percent of PE derivatized with PEG, and methods of use thereof, are described by Woodle et al. (U.S. Pat. Nos. 5,013,556 and 5,356,633) and Martin et al. (U.S. Pat. No. 5,213,804 and European Patent No. EP 0 496 813 B1). Liposomes comprising a number of other lipid-polymer conjugates are disclosed in WO 91/05545 and U.S. Pat. No. 5,225,212 (both to Martin et al.) and in WO 94/20073 (Zalipsky et al.) Liposomes comprising PEG-modified ceramide lipids are described in WO 96/10391 (Choi et al). U.S. Pat. No. 5,540,935 (Miyazaki et al.) and U.S. Pat. No. 5,556,948 (Tagawa et al.) describe PEG-containing liposomes that can be further derivatized with functional moieties on their surfaces.
A limited number of liposomes comprising nucleic acids are known in the art. WO 96/40062 to Thierry et al. discloses methods for encapsulating high molecular weight nucleic acids in liposomes. U.S. Pat. No. 5,264,221 to Tagawa et al. discloses protein-bonded liposomes and asserts that the contents of such liposomes may include an dsRNA RNA. U.S. Pat. No. 5,665,710 to Rahman et al. describes certain methods of encapsulating oligodeoxynucleotides in liposomes. WO 97/04787 to Love et al. discloses liposomes comprising dsRNA dsRNAs targeted to the raf gene.
Transfersomes are yet another type of liposomes, and are highly deformable lipid aggregates which are attractive candidates for drug delivery vehicles. Transfersomes may be described as lipid droplets which are so highly deformable that they are easily able to penetrate through pores which are smaller than the droplet. Transfersomes are adaptable to the environment in which they are used, e.g., they are self-optimizing (adaptive to the shape of pores in the skin), self-repairing, frequently reach their targets without fragmenting, and often self-loading. To make transfersomes it is possible to add surface edge-activators, usually surfactants, to a standard liposomal composition. Transfersomes have been used to deliver serum albumin to the skin. The transfersome-mediated delivery of serum albumin has been shown to be as effective as subcutaneous injection of a solution containing serum albumin.
Surfactants find wide application in formulations such as emulsions (including microemulsions) and liposomes. The most common way of classifying and ranking the properties of the many different types of surfactants, both natural and synthetic, is by the use of the hydrophile/lipophile balance (HLB). The nature of the hydrophilic group (also known as the “head”) provides the most useful means for categorizing the different surfactants used in formulations (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, N.Y., 1988, p. 285).
If the surfactant molecule is not ionized, it is classified as a nonionic surfactant. Nonionic surfactants find wide application in pharmaceutical and cosmetic products and are usable over a wide range of pH values. In general their HLB values range from 2 to about 18 depending on their structure. Nonionic surfactants include nonionic esters such as ethylene glycol esters, propylene glycol esters, glyceryl esters, polyglyceryl esters, sorbitan esters, sucrose esters, and ethoxylated esters. Nonionic alkanolamides and ethers such as fatty alcohol ethoxylates, propoxylated alcohols, and ethoxylated/propoxylated block polymers are also included in this class. The polyoxyethylene surfactants are the most popular members of the nonionic surfactant class.
If the surfactant molecule carries a negative charge when it is dissolved or dispersed in water, the surfactant is classified as anionic. Anionic surfactants include carboxylates such as soaps, acyl lactylates, acyl amides of amino acids, esters of sulfuric acid such as alkyl sulfates and ethoxylated alkyl sulfates, sulfonates such as alkyl benzene sulfonates, acyl isethionates, acyl taurates and sulfosuccinates, and phosphates. The most important members of the anionic surfactant class are the alkyl sulfates and the soaps.
If the surfactant molecule carries a positive charge when it is dissolved or dispersed in water, the surfactant is classified as cationic. Cationic surfactants include quaternary ammonium salts and ethoxylated amines. The quaternary ammonium salts are the most used members of this class.
If the surfactant molecule has the ability to carry either a positive or negative charge, the surfactant is classified as amphoteric. Amphoteric surfactants include acrylic acid derivatives, substituted alkylamides, N-alkylbetaines and phosphatides.
The use of surfactants in drug products, formulations and in emulsions has been reviewed (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, N.Y., 1988, p. 285).
Penetration Enhancers
In one embodiment, the present invention employs various penetration enhancers to effect the efficient delivery of nucleic acids, particularly dsRNAs, to the skin of animals. Most drugs are present in solution in both ionized and nonionized forms. However, usually only lipid soluble or lipophilic drugs readily cross cell membranes. It has been discovered that even non-lipophilic drugs may cross cell membranes if the membrane to be crossed is treated with a penetration enhancer. In addition to aiding the diffusion of non-lipophilic drugs across cell membranes, penetration enhancers also enhance the permeability of lipophilic drugs.
Penetration enhancers may be classified as belonging to one of five broad categories, i.e., surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92). Each of the above mentioned classes of penetration enhancers are described below in greater detail.
Surfactants: In connection with the present invention, surfactants (or “surface-active agents”) are chemical entities which, when dissolved in an aqueous solution, reduce the surface tension of the solution or the interfacial tension between the aqueous solution and another liquid, with the result that absorption of dsRNAs through the mucosa is enhanced. In addition to bile salts and fatty acids, these penetration enhancers include, for example, sodium lauryl sulfate, polyoxyethylene-9-lauryl ether and polyoxyethylene-20-cetyl ether) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92); and perfluorochemical emulsions, such as FC-43. Takahashi et al., J. Pharm. Pharmacol., 1988, 40, 252).
Fatty acids: Various fatty acids and their derivatives which act as penetration enhancers include, for example, oleic acid, lauric acid, capric acid (n-decanoic acid), myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein (1-monooleoyl-rac-glycerol), dilaurin, caprylic acid, arachidonic acid, glycerol 1-monocaprate, 1-dodecylazacycloheptan-2-one, acylcarnitines, acylcholines, C1-10 alkyl esters thereof (e.g., methyl, isopropyl and t-butyl), and mono- and di-glycerides thereof (i.e., oleate, laurate, caprate, myristate, palmitate, stearate, linoleate, etc.) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; El Hariri et al., J. Pharm. Pharmacol., 1992, 44, 651-654).
Bile salts: The physiological role of bile includes the facilitation of dispersion and absorption of lipids and fat-soluble vitamins (Brunton, Chapter 38 in: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9th Ed., Hardman et al. Eds., McGraw-Hill, New York, 1996, pp. 934-935). Various natural bile salts, and their synthetic derivatives, act as penetration enhancers. Thus the term “bile salts” includes any of the naturally occurring components of bile as well as any of their synthetic derivatives. Suitable bile salts include, for example, cholic acid (or its pharmaceutically acceptable sodium salt, sodium cholate), dehydrocholic acid (sodium dehydrocholate), deoxycholic acid (sodium deoxycholate), glucholic acid (sodium glucholate), glycholic acid (sodium glycocholate), glycodeoxycholic acid (sodium glycodeoxycholate), taurocholic acid (sodium taurocholate), taurodeoxycholic acid (sodium taurodeoxycholate), chenodeoxycholic acid (sodium chenodeoxycholate), ursodeoxycholic acid (UDCA), sodium tauro-24,25-dihydro-fusidate (STDHF), sodium glycodihydrofusidate and polyoxyethylene-9-lauryl ether (POE) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Swinyard, Chapter 39 In: Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., Mack Publishing Co., Easton, Pa., 1990, pages 782-783; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Yamamoto et al., J. Pharm. Exp. Ther., 1992, 263, 25; Yamashita et al., J. Pharm. Sci., 1990, 79, 579-583).
Chelating Agents: Chelating agents, as used in connection with the present invention, can be defined as compounds that remove metallic ions from solution by forming complexes therewith, with the result that absorption of dsRNAs through the mucosa is enhanced. With regards to their use as penetration enhancers in the present invention, chelating agents have the added advantage of also serving as DNase inhibitors, as most characterized DNA nucleases require a divalent metal ion for catalysis and are thus inhibited by chelating agents (Jarrett, J. Chromatogr., 1993, 618, 315-339). Suitable chelating agents include but are not limited to disodium ethylenediaminetetraacetate (EDTA), citric acid, salicylates (e.g., sodium salicylate, 5-methoxysalicylate and homovanilate), N-acyl derivatives of collagen, laureth-9 and N-amino acyl derivatives of beta-diketones (enamines) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Buur et al., J. Control Rel., 1990, 14, 43-51).
Non-chelating non-surfactants: As used herein, non-chelating non-surfactant penetration enhancing compounds can be defined as compounds that demonstrate insignificant activity as chelating agents or as surfactants but that nonetheless enhance absorption of dsRNAs through the alimentary mucosa (Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33). This class of penetration enhancers include, for example, unsaturated cyclic ureas, 1-alkyl- and 1-alkenylazacyclo-alkanone derivatives (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92); and non-steroidal anti-inflammatory agents such as diclofenac sodium, indomethacin and phenylbutazone (Yamashita et al., J. Pharm. Pharmacol., 1987, 39, 621-626).
Agents that enhance uptake of dsRNAs at the cellular level may also be added to the pharmaceutical and other compositions of the present invention. For example, cationic lipids, such as lipofectin (Junichi et al, U.S. Pat. No. 5,705,188), cationic glycerol derivatives, and polycationic molecules, such as polylysine (Lollo et al., PCT Application WO 97/30731), are also known to enhance the cellular uptake of dsRNAs.
Other agents may be utilized to enhance the penetration of the administered nucleic acids, including glycols such as ethylene glycol and propylene glycol, pyrrols such as 2-pyrrol, azones, and terpenes such as limonene and menthone.
Carriers
Certain compositions of the present invention also incorporate carrier compounds in the formulation. As used herein, “carrier compound” or “carrier” can refer to a nucleic acid, or analog thereof, which is inert (i.e., does not possess biological activity per se) but is recognized as a nucleic acid by in vivo processes that reduce the bioavailability of a nucleic acid having biological activity by, for example, degrading the biologically active nucleic acid or promoting its removal from circulation. The coadministration of a nucleic acid and a carrier compound, typically with an excess of the latter substance, can result in a substantial reduction of the amount of nucleic acid recovered in the liver, kidney or other extracirculatory reservoirs, presumably due to competition between the carrier compound and the nucleic acid for a common receptor. For example, the recovery of a partially phosphorothioate dsRNA in hepatic tissue can be reduced when it is coadministered with polyinosinic acid, dextran sulfate, polycytidic acid or 4-acetamido-4′isothiocyano-stilbene-2,2′-disulfonic acid (Miyao et al., DsRNA Res. Dev., 1995, 5, 115-121; Takakura et al., DsRNA & Nucl. Acid Drug Dev., 1996, 6, 177-183.
Excipients
In contrast to a carrier compound, a “pharmaceutical carrier” or “excipient” is a pharmaceutically acceptable solvent, suspending agent or any other pharmacologically inert vehicle for delivering one or more nucleic acids to an animal. The excipient may be liquid or solid and is selected, with the planned manner of administration in mind, so as to provide for the desired bulk, consistency, etc., when combined with a nucleic acid and the other components of a given pharmaceutical composition. Typical pharmaceutical carriers include, but are not limited to, binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose, etc.); fillers (e.g., lactose and other sugars, microcrystalline cellulose, pectin, gelatin, calcium sulfate, ethyl cellulose, polyacrylates or calcium hydrogen phosphate, etc.); lubricants (e.g., magnesium stearate, talc, silica, colloidal silicon dioxide, stearic acid, metallic stearates, hydrogenated vegetable oils, corn starch, polyethylene glycols, sodium benzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodium starch glycolate, etc.); and wetting agents (e.g., sodium lauryl sulphate, etc).
Pharmaceutically acceptable organic or inorganic excipient suitable for non-parenteral administration which do not deleteriously react with nucleic acids can also be used to formulate the compositions of the present invention. Suitable pharmaceutically acceptable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like.
Formulations for topical administration of nucleic acids may include sterile and non-sterile aqueous solutions, non-aqueous solutions in common solvents such as alcohols, or solutions of the nucleic acids in liquid or solid oil bases. The solutions may also contain buffers, diluents and other suitable additives. Pharmaceutically acceptable organic or inorganic excipients suitable for non-parenteral administration which do not deleteriously react with nucleic acids can be used.
Suitable pharmaceutically acceptable excipients include, but are not limited to, water, salt solutions, alcohol, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like.
Other Components
The compositions of the present invention may additionally contain other adjunct components conventionally found in pharmaceutical compositions, at their art-established usage levels. Thus, for example, the compositions may contain additional, compatible, pharmaceutically-active materials such as, for example, antipruritics, astringents, local anesthetics or anti-inflammatory agents, or may contain additional materials useful in physically formulating various dosage forms of the compositions of the present invention, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers. However, such materials, when added, should not unduly interfere with the biological activities of the components of the compositions of the present invention. The formulations can be sterilized and, if desired, mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, colorings, flavorings and/or aromatic substances and the like which do not deleteriously interact with the nucleic acid(s) of the formulation.
Aqueous suspensions may contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers.
In some embodiments, pharmaceutical compositions featured in the invention include (a) one or more dsRNA compounds and (b) one or more other chemotherapeutic agents which function by a non-RNAi mechanism. Examples of such chemotherapeutic agents include but are not limited to daunorubicin, daunomycin, dactinomycin, doxorubicin, epirubicin, idarubicin, esorubicin, bleomycin, mafosfamide, ifosfamide, cytosine arabinoside, bis-chloroethylnitrosurea, busulfan, mitomycin C, actinomycin D, mithramycin, prednisone, hydroxyprogesterone, testosterone, tamoxifen, dacarbazine, procarbazine, hexamethylmelamine, pentamethylmelamine, mitoxantrone, amsacrine, chlorambucil, methylcyclohexylnitrosurea, nitrogen mustards, melphalan, cyclophosphamide, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-azacytidine, hydroxyurea, deoxycoformycin, 4-hydroxyperoxycyclophosphor-amide, 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (5-FUdR), methotrexate (MTX), colchicine, taxol, vincristine, vinblastine, etoposide (VP-16), trimetrexate, irinotecan, topotecan, gemcitabine, teniposide, cisplatin and diethylstilbestrol (DES). See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed. 1987, pp. 1206-1228, Berkow et al., eds., Rahway, N.J. When used with the dsRNAs featured in the invention, such chemotherapeutic agents may be used individually (e.g., 5-FU and oligonucleotide), sequentially (e.g., 5-FU and oligonucleotide for a period of time followed by MTX and oligonucleotide), or in combination with one or more other such chemotherapeutic agents (e.g., 5-FU, MTX and oligonucleotide, or 5-FU, radiotherapy and oligonucleotide). Anti-inflammatory drugs, including but not limited to nonsteroidal anti-inflammatory drugs and corticosteroids, and antiviral drugs, including but not limited to ribivirin, vidarabine, acyclovir and ganciclovir, may also be combined in compositions featured in the invention. See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed., Berkow et al., eds., 1987, Rahway, N.J., pages 2499-2506 and 46-49, respectively). Other non-RNAi chemotherapeutic agents are also within the scope of this invention. Two or more combined compounds may be used together or sequentially.
Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD50/ED50. Compounds that exhibit high therapeutic indices are typical.
The data obtained from cell culture assays and animal studies can be used in formulation a range of dosage for use in humans. The dosage of compositions featured in the invention lies generally within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound used in the methods featured in the invention, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range of the compound or, when appropriate, of the polypeptide product of a target sequence (e.g., achieving a decreased concentration of the polypeptide) that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography.
In addition to their administration, as discussed above, the dsRNAs featured in the invention can be administered in combination with other known agents effective in treatment of pathological processes mediated by XBP-1 expression. In any event, the administering physician can adjust the amount and timing of dsRNA administration on the basis of results observed using standard measures of efficacy known in the art or described herein.
Methods for Treating Diseases Caused by Expression of the XBP-1 Gene
The invention relates in particular to the use of a dsRNA targeting XBP-1 and compositions containing at least one such dsRNA, for the treatment of an XBP-1-mediated disorder or disease. For example, a dsRNA targeting an XBP-1 gene can be useful for the treatment of a metabolic disease, such as Type II diabetes and metabolic syndrome, or a cardiovascular disease. “Metabolic syndrome” (also called metabolic syndrome X, X syndrome, insulin resistance syndrome, Reaven's syndrome, and CHAOS) is characterized by a group of metabolic risk factors including: abdominal obesity (excessive fat tissue in and around the abdomen), atherogenic dyslipidemia (blood fat disorders (including high triglycerides, low HDL cholesterol and high LDL cholesterol) that foster plaque build-up in artery walls), elevated blood pressure, insulin resistance or glucose intolerance (due to the body's inability to properly use insulin or blood sugar), a prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor-1 in the blood), and a proinflammatory state (e.g., elevated C-reactive protein in the blood). People with metabolic syndrome are at increased risk of coronary heart disease and other diseases related to plaque buildups in artery walls (e.g., stroke and peripheral vascular disease), and Type II diabetes. A “cardiovascular disease,” as used herein is a disorder that affects the heart or blood vessels, such as atherosclerosis, coronary artery disease, high blood pressure, congenital heart disease, aneurysm, a heart valve disease, a heart infection, or cardiomyopathy. Other metabolic diseases suitable for treatment with a dsRNA targeting XBP-1 include obesity and insulin resistance.
A dsRNA targeting XBP-1 is also useful for the treatment of a dyslipidemia, such as a hyperlidipemia (e.g., hypercholesterolemia), or a disorder associated with a dyslipidemia, such as atherosclerosis. A “hyperlipidemia” refers to elevated lipid levels in the blood (e.g., in plasma), such as elevated levels of one or more of cholesterol, LDL (low density lipoprotein), VLDL (very low density lipoprotein), triglycerides, or chylomicrons.
A dsRNA targeting XBP-1 is also useful for the treatment of liver disorders, such as a nonalcoholic fatty liver disease (NAFLD), which is a fatty inflammation of the liver not due to excessive use of alcohol, or cirrhosis. For example, a dsRNA targeting XBP-1 can be used to treat non-alcoholic steatohepatitis (NASH), which is one of the most extreme forms of NAFLD, and which is regarded as a major cause of cirrhosis of the liver of unknown cause.
A dsRNA targeting XBP-1 can also be useful for the treatment of cancer, such as a leukemia, e.g., ATLL. A dsRNA targeting XBP-1 can also be used to treat a myelopathy, e.g., tropical spastic paresis (TSP). TSP is a chronic and progressive disease of the nervous system that typically affects adults living in equatorial areas of the world and can cause progressive weakness, stiff muscles, muscle spasms, sensory disturbance, and sphincter dysfunction. A “myelopathy,” as used herein, is a neurological deficit related to the spinal cord.
A composition containing a dsRNA targeting XBP-1 may also be used to treat other tumors and cancers, such as breast cancer, lung cancer, head and neck cancer, brain cancer, abdominal cancer, colon cancer, colorectal cancer, esophagus cancer, gastrointestinal cancer, glioma, tongue cancer, neuroblastoma, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, Wilm's tumor, multiple myeloma and for the treatment of skin cancer, like melanoma, for the treatment of lymphomas and blood cancer.
Owing to the inhibitory effects on XBP-1 expression, a composition according to the invention or a pharmaceutical composition prepared therefrom can enhance the quality of life.
The invention further relates to the use of a dsRNA or a pharmaceutical composition thereof, e.g., for treating a metabolic disorder, cardiovascular disease, or an HTLV-1 mediated disorder, in combination with other pharmaceuticals and/or other therapeutic methods, e.g., with known pharmaceuticals and/or known therapeutic methods, such as, for example, those which are currently employed for treating these disorder. In one example, administration of a dsRNA targeting XBP-1 can be accompanied by a exercise regimen or by dietary restrictions. A dsRNA featured in the invention can also be administered with a drug or combination of drugs for managing Type II diabetes, e.g., a sulfonylurea, a biguanide, an alpha-glucosidase inhibitor, a thiazolidinedione (e.g., rosiglitazone or pioglitazone), a meglitinide, a D-phenylalanine derivative, an amylin synthetic derivatives, an incretin mimetic, metformin, or an insulin. Exemplary insulins include regular insulins (Humulin®, Novolin®), insulin lispro (Humalog®), insulin aspart (Novolog®), insulin glulisine (Apidra®), prompt insulin zinc (Semilente®, slightly slower acting), inhaled insulin (Exubera®), intermediate-acting insulins, isophane insulin, neutral protamine Hagedorn (NPH), insulin zinc (Lente®), extended insulin zinc insulin (Ultralente®), insulin glargine (Lantus®), and insulin detemir (Levemir®).
In another example, a composition containing a dsRNA targeting XBP-1 is administered in combination with a lipid-lowering drug, such as a statin, e.g., atorvastatin (Lipitor®) or simvastatin (Mevacor®); ezetimibe (Zetia®); a bile-acid sequestrant, such as Questran®; a fibrate, such as gemfibrozil (Lopid®) or fenofibrate (Tricor); or a compound that raises HDL levels, such as nicotinic acid (Niacin).
A dsRNA targeting XBP-1 can also be provided in combination with a vitamin, such as vitamin E or vitamin C, e.g., for treatment of a liver disorder, such as NAFLD or NASH.
In another example, a composition containing a dsRNA targeting XBP-1 is administered in combination with an antiviral drug, such as zidovudine, ribivirin, vidarabine, acyclovir and ganciclovir, or an anti-inflammatory drug, such as a nonsteroidal anti-inflammatory drugs or corticosteroid. See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed., Berkow et al., eds., 1987, Rahway, N.J., pages 2499-2506 and 46-49, respectively). Administration can also be in combination with an interferon, such as interferon alpha or interferon beta; lioresal, tizanidine, or oxybutynin.
In certain embodiments, administration is with a chemotherapy agent, such as deoxycoformycin, cisplatin, cyclophosphamide, 5-fluorouracil, adriamycin, daunorubicin, tamoxifen aunorubicin, daunomycin, dactinomycin, doxorubicin, epirubicin, idarubicin, esorubicin, bleomycin, mafosfamide, ifosfamide, cytosine arabinoside, bis-chloroethylnitrosurea, busulfan, mitomycin C, actinomycin D, mithramycin, prednisone, hydroxyprogesterone, testosterone, tamoxifen, dacarbazine, procarbazine, hexamethylmelamine, pentamethylmelamine, mitoxantrone, amsacrine, chlorambucil, methylcyclohexylnitrosurea, nitrogen mustards, melphalan, cyclophosphamide, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-azacytidine, hydroxyurea, deoxycoformycin, 4-hydroxyperoxycyclophosphoramide, 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (5-FUdR), methotrexate (MTX), colchicine, taxol, vincristine, vinblastine, etoposide (VP-16), trimetrexate, irinotecan, topotecan, gemcitabine, teniposide, cisplatin and diethylstilbestrol (DES). See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed. 1987, pp. 1206-1228, Berkow et al., eds., Rahway, N.J. When used with the dsRNAs featured in the invention, such chemotherapeutic agents may be used individually (e.g., deoxycoformycin and dsRNA), sequentially (e.g., antiviral and dsRNA for a period of time, followed by deoxycoformycin and dsRNA), or in combination with one or more other such agents (e.g., deoxycoformycin, antiviral and dsRNA, or deoxycoformycin, radiotherapy and dsRNA). Two or more combined compounds may be used together or sequentially.
Patients can be administered a therapeutic amount of dsRNA, such as 0.02, 0.1, 0.5 mg/kg, 1.0 mg/kg, 1.5 mg/kg, 2.0 mg/kg, or 2.5 mg/kg dsRNA. The dsRNA can be administered by intravenous infusion over a period of time, such as over a 5 minute, 10 minute, 15 minute, 20 minute, or 25 minute period. In some embodiments, the administration is repeated, for example, on a regular basis, such as biweekly (i.e., every two weeks) for one month, two months, three months, four months or longer. After an initial treatment regimen, the treatments can be administered on a less frequent basis. For example, after administration biweekly for three months, administration can be repeated once per month, for six months or a year or longer. Administration of the dsRNA can reduce LDL levels in the blood of the patient by at least 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80% or 90% or more.
Before administration of a full dose of a dsRNA targeting XBP-1, a patient can be administered a smaller dose, such as a 5% infusion reaction, and monitored for adverse effects, such as an allergic reaction. In another example, the patient can be monitored for unwanted immunostimulatory effects, such as increased cytokine (e.g., TNF-alpha or INF-alpha) levels.
Many XBP-1-associated diseases and disorders are hereditary. Therefore, a patient in need of a dsRNA targeting XBP-1 can be identified by taking a family history. A healthcare provider, such as a doctor, nurse, or family member, can take a family history before prescribing or administering a dsRNA. A DNA test may also be performed on the patient to identify a mutation in the target gene, before a dsRNA is administered to the patient.
Methods for Inhibiting Expression of the XBP-1 Gene
In yet another aspect, the invention provides a method for inhibiting the expression of an XBP-1 gene in a mammal. The method includes administering a composition featured in the invention to the mammal such that expression of the target XBP-1 gene is silenced.
When the organism to be treated is a mammal such as a human, the composition may be administered by any means known in the art including, but not limited to oral or parenteral routes, including intravenous, intramuscular, subcutaneous, transdermal, airway (aerosol), nasal, rectal, and topical (including buccal and sublingual) administration. In certain embodiments, the compositions are administered by intravenous infusion or injection.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the dsRNAs and methods featured in the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
EXAMPLES
Example 1
dsRNA Synthesis
Source of Reagents
Where the source of a reagent is not specifically given herein, such reagent may be obtained from any supplier of reagents for molecular biology at a quality/purity standard for application in molecular biology.
siRNA Synthesis
Single-stranded RNAs were produced by solid phase synthesis on a scale of 1 μmole using an Expedite 8909 synthesizer (Applied Biosystems, Applera Deutschland GmbH, Darmstadt, Germany) and controlled pore glass (CPG, 500 Å, Proligo Biochemie GmbH, Hamburg, Germany) as solid support. RNA and RNA containing 2′-O-methyl nucleotides were generated by solid phase synthesis employing the corresponding phosphoramidites and 2′-O-methyl phosphoramidites, respectively (Proligo Biochemie GmbH, Hamburg, Germany). These building blocks were incorporated at selected sites within the sequence of the oligoribonucleotide chain using standard nucleoside phosphoramidite chemistry such as described in Current protocols in nucleic acid chemistry, Beaucage, S. L. et al. (Edrs.), John Wiley & Sons, Inc., New York, N.Y., USA. Phosphorothioate linkages were introduced by replacement of the iodine oxidizer solution with a solution of the Beaucage reagent (Chruachem Ltd, Glasgow, UK) in acetonitrile (1%). Further ancillary reagents were obtained from Mallinckrodt Baker (Griesheim, Germany).
Deprotection and purification of the crude oligoribonucleotides by anion exchange HPLC were carried out according to established procedures. Yields and concentrations were determined by UV absorption of a solution of the respective RNA at a wavelength of 260 nm using a spectral photometer (DU 640B, Beckman Coulter GmbH, Unterschleiβheim, Germany). Double stranded RNA was generated by mixing an equimolar solution of complementary strands in annealing buffer (20 mM sodium phosphate, pH 6.8; 100 mM sodium chloride), heated in a water bath at 85-90° C. for 3 minutes and cooled to room temperature over a period of 3-4 hours. The annealed RNA solution was stored at −20° C. until use.
For the synthesis of 3′-cholesterol-conjugated siRNAs (herein referred to as -Chol-3′), an appropriately modified solid support is used for RNA synthesis. The modified solid support is prepared as follows:
Diethyl-2-azabutane-1,4-dicarboxylate AA




A 4.7 M aqueous solution of sodium hydroxide (50 mL) is added into a stirred, ice-cooled solution of ethyl glycinate hydrochloride (32.19 g, 0.23 mole) in water (50 mL). Then, ethyl acrylate (23.1 g, 0.23 mole) is added and the mixture stirred at room temperature until completion of the reaction is ascertained by TLC. After 19 h the solution is partitioned with dichloromethane (3×100 mL). The organic layer is dried with anhydrous sodium sulfate, filtered and evaporated. The residue is distilled to afford AA (28.8 g, 61%).
3-{Ethoxycarbonylmethyl-[6-(9H-fluoren-9-ylmethoxycarbonyl-amino)-hexanoyl]-amino}-propionic acid ethyl ester AB




Fmoc-6-amino-hexanoic acid (9.12 g, 25.83 mmol) is dissolved in dichloromethane (50 mL) and cooled with ice. Diisopropylcarbodiimde (3.25 g, 3.99 mL, 25.83 mmol) is added to the solution at 0° C. This is followed by the addition of Diethyl-azabutane-1,4-dicarboxylate (5 g, 24.6 mmol) and dimethylamino pyridine (0.305 g, 2.5 mmol). The solution is brought to room temperature and stirred further for 6 h. Completion of the reaction is ascertained by TLC. The reaction mixture is concentrated under vacuum and ethyl acetate is added to precipitate diisopropyl urea. The suspension is filtered. The filtrate is washed with 5% aqueous hydrochloric acid, 5% sodium bicarbonate and water. The combined organic layer is dried over sodium sulfate and concentrated to give the crude product which is purified by column chromatography (50% EtOAC/Hexanes) to yield 11.87 g (88%) of AB.
3-[(6-Amino-hexanoyl)-ethoxycarbonylmethyl-amino]-propionic acid ethyl ester AC




3-{Ethoxycarbonylmethyl-[6-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoyl]-amino}-propionic acid ethyl ester AB (11.5 g, 21.3 mmol) is dissolved in 20% piperidine in dimethylformamide at 0° C. The solution is continued stirring for 1 h. The reaction mixture is concentrated under vacuum, water is added to the residue, and the product is extracted with ethyl acetate. The crude product is purified by conversion into its hydrochloride salt.
3-({6-[17-(1,5-Dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yloxycarbonylamino]-hexanoyl}ethoxycarbonylmethyl-amino)-propionic acid ethyl ester AD




The hydrochloride salt of 3-[(6-Amino-hexanoyl)-ethoxycarbonylmethyl-amino]-propionic acid ethyl ester AC (4.7 g, 14.8 mmol) is taken up in dichloromethane. The suspension is cooled to 0° C. on ice. Diisopropylethylamine (3.87 g, 5.2 mL, 30 mmol) is added to the suspension. To the resulting solution, cholesteryl chloroformate (6.675 g, 14.8 mmol) is added. The reaction mixture is stirred overnight. The reaction mixture is diluted with dichloromethane and washed with 10% hydrochloric acid. The product is purified by flash chromatography (10.3 g, 92%).
1-{6-[17-(1,5-Dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a] phenanthren-3-yloxycarbonylamino]-hexanoyl}-4-oxo-pyrrolidine-3-carboxylic acid ethyl ester AE




Potassium t-butoxide (1.1 g, 9.8 mmol) is slurried in 30 mL of dry toluene. The mixture is cooled to 0° C. on ice, and 5 g (6.6 mmol) of diester AD is added slowly with stirring within 20 mins. The temperature is kept below 5° C. during the addition. The stirring is continued for 30 mins at 0° C., and 1 mL of glacial acetic acid is added, immediately followed by 4 g of NaH2PO4.H2O in 40 mL of water. The resultant mixture is extracted twice with 100 mL of dichloromethane each, and the combined organic extracts are washed twice with 10 mL of phosphate buffer each, dried, and evaporated to dryness. The residue is dissolved in 60 mL of toluene, cooled to 0° C. and extracted with three 50 mL portions of cold pH 9.5 carbonate buffer. The aqueous extracts are adjusted to pH 3 with phosphoric acid, and extracted with five 40 mL portions of chloroform which are combined, dried and evaporated to dryness. The residue is purified by column chromatography using 25% ethylacetate/hexane to afford 1.9 g of b-ketoester (39%).
[6-(3-Hydroxy-4-hydroxymethyl-pyrrolidin-1-yl)-6-oxo-hexyl]-carbamic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester AF




Methanol (2 mL) is added dropwise over a period of 1 h to a refluxing mixture of b-ketoester AE (1.5 g, 2.2 mmol) and sodium borohydride (0.226 g, 6 mmol) in tetrahydrofuran (10 mL). Stirring is continued at reflux temperature for 1 h. After cooling to room temperature, 1 N HCl (12.5 mL) is added, the mixture is extracted with ethylacetate (3×40 mL). The combined ethylacetate layer is dried over anhydrous sodium sulfate and concentrated under vacuum to yield the product which is purified by column chromatography (10% MeOH/CHCl3) (89%).
(6-{3-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-pyrrolidin-1-yl}-6-oxo-hexyl)-carbamic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester AG




Diol AF (1.25 gm 1.994 mmol) is dried by evaporating with pyridine (2×5 mL) in vacuo. Anhydrous pyridine (10 mL) and 4,4′-dimethoxytritylchloride (0.724 g, 2.13 mmol) are added with stirring. The reaction is carried out at room temperature overnight. The reaction is quenched by the addition of methanol. The reaction mixture is concentrated under vacuum and dichloromethane (50 mL) is added to the residue. The organic layer is washed with 1M aqueous sodium bicarbonate. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated. The residual pyridine is removed by evaporating with toluene. The crude product is purified by column chromatography (2% MeOH/Chloroform, Rf=0.5 in 5% MeOH/CHCl3) (1.75 g, 95%).
Succinic acid mono-(4-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-1-{6-[17-(1,5-dimethyl-hexyl)-10,13-dimethyl 2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H cyclopenta[a]phenanthren-3-yloxycarbonylamino]-hexanoyl}-pyrrolidin-3-yl) ester AH




Compound AG (1.0 g, 1.05 mmol) is mixed with succinic anhydride (0.150 g, 1.5 mmol) and DMAP (0.073 g, 0.6 mmol) and dried in a vacuum at 40° C. overnight. The mixture is dissolved in anhydrous dichloroethane (3 mL), triethylamine (0.318 g, 0.440 mL, 3.15 mmol) is added and the solution is stirred at room temperature under argon atmosphere for 16 h. It is then diluted with dichloromethane (40 mL) and washed with ice cold aqueous citric acid (5 wt %, 30 mL) and water (2×20 mL). The organic phase is dried over anhydrous sodium sulfate and concentrated to dryness. The residue is used as such for the next step.
Cholesterol derivatised CPG AI




Succinate AH (0.254 g, 0.242 mmol) is dissolved in a mixture of dichloromethane/acetonitrile (3:2, 3 mL). To that solution, DMAP (0.0296 g, 0.242 mmol) in acetonitrile (1.25 mL), 2,2′-Dithio-bis(5-nitropyridine) (0.075 g, 0.242 mmol) in acetonitrile/dichloroethane (3:1, 1.25 mL) are added successively. To the resulting solution triphenylphosphine (0.064 g, 0.242 mmol) in acetonitrile (0.6 ml) is added. The reaction mixture turns bright orange in color. The solution is agitated briefly using a wrist-action shaker (5 mins). Long chain alkyl amine-CPG (LCAA-CPG) (1.5 g, 61 mM) is added. The suspension is agitated for 2 h. The CPG is filtered through a sintered funnel and washed with acetonitrile, dichloromethane and ether successively. Unreacted amino groups are masked using acetic anhydride/pyridine. The achieved loading of the CPG was measured by taking UV measurement (37 mM/g).
The synthesis of siRNAs bearing a 5′-12-dodecanoic acid bisdecylamide group (herein referred to as “5′-C32-”) or a 5′-cholesteryl derivative group (herein referred to as “5′-Chol-”) is performed as described in WO 2004/065601, except that, for the cholesteryl derivative, the oxidation step is performed using the Beaucage reagent in order to introduce a phosphorothioate linkage at the 5′-end of the nucleic acid oligomer.
Nucleic acid sequences are represented below using standard nomenclature, and specifically the abbreviations of Table 1.







TABLE 1







Abbreviations of nucleotide monomers used in nucleic acid


sequence representation. It will be understood that these


monomers, when present in an oligonucleotide, are mutually linked


by 5′-3′-phosphodiester bonds.










Abbreviationa
Nucleotide(s)







A
Adenosine



C
Cytidine



G
Guanosine



T
thymidine



U
uridine



N
any nucleotide (G, A, C, U, or T)



a
2′-O-methyladenosine



c
2′-O-methylcytidine



g
2′-O-methylguanosine



u
2′-O-methyluridine



sT
phosphorothioate linkage










Example 2
Synthesis of XBP-1 dsRNAs
XBP-1 sequences were synthesized on MerMade 192 synthesizer at 1 μmol scale.
For all the sequences in Table 2, ‘endolight’ chemistry was applied as shown below and in Table 4.

    
    
        All pyrimidines (cytosine and uridine) in the sense strand were replaced with corresponding 2′-O-Methyl bases (2′ O-Methyl C and 2′-O-Methyl U)
        In the antisense strand, pyrimidines adjacent to (towards 5′ position) ribo A nucleoside were replaced with their corresponding 2-O-Methyl nucleosides
        A two base dTsdT extension at 3′ end of both sense and anti sense sequences was introduced
        The sequence file was converted to a text file to make it compatible for loading in the MerMade 192 synthesis software
    
    


Solid supported oligonucleotide synthesis using phosphoramidite chemistry was performed to synthesize the XBP-1 sequences.







TABLE 2







Exemplary XBP-1 dsRNAs













SEQ

SEQ





ID

ID


Oligo Name
NO:
sense (5′-3′)
NO:
antisense (5′-3′)















NM_001004210_1128-1146
2127
CCCAGCUGAUUAGUGUCUA
2128
UAGACACUAAUCAGCUGGG



 


NM_001004210_1129-1147
2129
CCAGCUGAUUAGUGUCUAA
2130
UUAGACACUAAUCAGCUGG


 


NM_001004210_677-695
2131
CUCCCAGAGGUCUACCCAG
2132
CUGGGUAGACCUCUGGGAG


 


NM_001004210_893-911
2133
GAUCACCCUGAAUUCAUUG
2134
CAAUGAAUUCAGGGUGAUC


 


NM_001004210_895-913
2135
UCACCCUGAAUUCAUUGUC
2136
GACAAUGAAUUCAGGGUGA


 


NM_001004210_1127-1145
2137
CCCCAGCUGAUUAGUGUCU
2138
AGACACUAAUCAGCUGGGG


 


NM_001004210_894-912
2139
AUCACCCUGAAUUCAUUGU
2140
ACAAUGAAUUCAGGGUGAU


 


NM_001004210_1760-1778
2141
CAUUUAUUUAAAACUACCC
2142
GGGUAGUUUUAAAUAAAUG


 


NM_001004210_215-233
2143
ACUGAAAAACAGAGUAGCA
2144
UGCUACUCUGUUUUUCAGU


 


NM_001004210_1759-1777
2145
CCAUUUAUUUAAAACUACC
2146
GGUAGUUUUAAAUAAAUGG


 


NM_001004210_367-385
2147
UUGAGAACCAGGAGUUAAG
2148
CUUAACUCCUGGUUCUCAA


 


NM_001004210_896-914
2149
CACCCUGAAUUCAUUGUCU
2150
AGACAAUGAAUUCAGGGUG


 


NM_001004210_214-232
2151
AACUGAAAAACAGAGUAGC
2152
GCUACUCUGUUUUUCAGUU


 


NM_001004210_216-234
2153
CUGAAAAACAGAGUAGCAG
2154
CUGCUACUCUGUUUUUCAG


 


XM_001103095_387-405
1
AGAAAAUCAGCUUUUACGA
2
UCGUAAAAGCUGAUUUUCU


 


XM_001103095_1151-1169
3
UCCCCAGCUGAUUAGUGUC
4
GACACUAAUCAGCUGGGGA


 


XM_001103095_1466-1484
5
UACUUAUUAUGUAAGGGUC
6
GACCCUUACAUAAUAAGUA


 


XM_001103095_1435-1453
7
UAUCUUAAAAGGGUGGUAG
8
CUACCACCCUUUUAAGAUA


 


XM_001103095_577-595
9
CCAUGGAUUCUGGCGGUAU
10
AUACCGCCAGAAUCCAUGG


 


XM_001103095_790-808
11
UUAAUGAACUAAUUCGUUU
12
AAACGAAUUAGUUCAUUAA


 


XM_001103095_1479-1497
13
AGGGUCAUUAGACAAAUGU
14
ACAUUUGUCUAAUGACCCU


 


XM_001103095_794-812
15
UGAACUAAUUCGUUUUGAC
16
GUCAAAACGAAUUAGUUCA


 


XM_001103095_1150-1168
23
UUCCCCAGCUGAUUAGUGU
24
ACACUAAUCAGCUGGGGAA


 


XM_001103095_1473-1491
25
UAUGUAAGGGUCAUUAGAC
26
GUCUAAUGACCCUUACAUA









The synthesis of the sequences in Tables 2 and 4 was performed at 1 μm scale in 96-well plates. The amidite solutions were prepared at 0.1M concentration and ethyl thio tetrazole (0.6M in acetonitrile) was used as an activator.
The synthesized sequences were cleaved and deprotected in 96-well plates, using methylamine in the first step and pyradine.3HF in the second step. The crude sequences thus obtained were precipitated using an acetone:ethanol mix, and the pellets were resuspended in 0.5M sodium acetate buffer. Samples from each sequence were analyzed by LC-MS and the resulting mass data confirmed the identity of the sequences. A selected set of samples was also analyzed by IEX chromatography.
The sequences were purified on an AKTA explorer purification system using a Source Q column. A single peak corresponding to the full length sequence was collected in the eluent and was subsequently analyzed for purity by ion exchange chromatography.
The purified sequences were desalted on a Sephadex G25 column using an AKTA purifier. The desalted XBP-1 sequences were analyzed for concentration and purity. The single strands were then submitted for annealing.







TABLE 3







XBP-1 oligos with Endolight Chemistry Modifications











Species specificity and





target sequence


Duplex
from 5′ to 3′ on
Oligo name
Oligo name


Name
mRNA transcript
Sense
Antisense





AD18027
NM_001004210_1128-1146
A-31668
A-31669


AD18028
NM_001004210_1129-1147
A-31670
A-31671


AD18029
NM_001004210_677-695
A-31672
A-31673


AD18030
NM_001004210_893-911
A-31674
A-31675


AD18031
NM_001004210_895-913
A-31676
A-31677


AD18032
NM_001004210_1127-1145
A-31678
A-31679


AD18033
NM_001004210_894-912
A-31680
A-31681


AD18034
NM_001004210_1760-1778
A-31682
A-31683


AD18035
NM_001004210_215-233
A-31684
A-31685


AD18036
NM_001004210_1759-1777
A-31686
A-31687


AD18037
NM_001004210_367-385
A-31688
A-31689


AD18038
NM_001004210_896-914
A-31690
A-31691


AD18039
NM_001004210_214-232
A-31692
A-31693


AD18040
NM_001004210_216-234
A-31694
A-31695


AD18041
XM_001103095_387-405
A-31696
A-31697


AD18042
XM_001103095_1151-1169
A-31698
A-31699


AD18043
XM_001103095_1466-1484
A-31700
A-31701


AD18044
XM_001103095_1435-1453
A-31702
A-31703


AD18045
XM_001103095_577-595
A-31704
A-31705


AD18046
XM_001103095_790-808
A-31706
A-31707


AD18047
XM_001103095_1479-1497
A-31708
A-31709


AD18048
XM_001103095_794-812
A-31710
A-31711


AD18049
XM_001103095_1150-1168
A-31712
A-31713


AD18050
XM_001103095_1473-1491
A-31714
A-31715
















TABLE 4







XBP-1 sequences with Endolight chemistry modifications












Oligo
SEQ

Oligo
SEQ



name
ID

name
ID


Sense
NO:
Sense (5′-3′)
Antisense
NO:
Antisense (5′-3′)
















A-31668
2155
cccAGcuGAuuAGuGucuAdTsdT
A-31669
2156
uAGAcACuAAUcAGCUGGGdTsdT



 


A-31670
2157
ccAGcuGAuuAGuGucuAAdTsdT
A-31671
2158
UuAGAcACuAAUcAGCUGGdTsdT


 


A-31672
2159
cucccAGAGGucuAcccAGdTsdT
A-31673
2160
CUGGGuAGACCUCUGGGAGdTsdT


 


A-31674
2161
GAucAcccuGAAuucAuuGdTsdT
A-31675
2162
cAAUGAAUUcAGGGUGAUCdTsdT


 


A-31676
2163
ucAcccuGAAuucAuuGucdTsdT
A-31677
2164
GAcAAUGAAUUcAGGGUGAdTsdT


 


A-31678
2165
ccccAGcuGAuuAGuGucudTsdT
A-31679
2166
AGAcAcuAAUcAGCUGGGGdTsdT


 


A-31680
2167
AucAcccuGAAuucAuuGudTsdT
A-31681
2168
ACAAUGAAUUcAGGGUGAUdTsdT


 


A-31682
2169
cAuuuAuuuAAAAcuAcccdTsdT
A-31683
2170
GGGuAGUUUuAAAuAAAUGdTsdT


 


A-31684
2171
AcuGAAAAAcAGAGuAGcAdTsdT
A-31685
2172
UGCuACUCUGUUUUUcAGUdTsdT


 


A-31686
2173
ccAuuuAuuuAAAAcuAccdTsdT
A-31687
2174
GGuAGUUUuAAAuAAAUGGdTsdT


 


A-31688
2175
uuGAGAAccAGGAGuuAAGdTsdT
A-31689
2176
CUuAACUCCUGGUUCUcAAdTsdT


 


A-31690
2177
cAcccuGAAuucAuuGucudTsdT
A-31691
2178
AGAcAAUGAAUUcAGGGUGdTsdT


 


A-31692
2179
AAcuGAAAAAcAGAGuAGcdTsdT
A-31693
2180
GCuACUCUGUUUUUcAGUUdTsdT


 


A-31694
2181
cuGAAAAAcAGAGuAGcAGdTsdT
A-31695
2182
CUGCuACUCUGUUUUUcAGdTsdT


 


A-31696
2183
AGAAAAucAGcuuuuAcGAdTsdT
A-31697
2184
UCGuAAAAGCUGAUUUUCUdTsdT


 


A-31698
2185
uccccAGcuGAuuAGuGucdTsdT
A-31699
2186
GACACuAAUcAGCUGGGGAdTsdT


 


A-31700
2187
uAcuuAuuAuGuAAGGGucdTsdT
A-31701
2188
GACCCUuAcAuAAuAAGuAdTsdT


 


A-31702
2189
uAucuuAAAAGGGuGGuAGdTsdT
A-31703
2190
CuACcACCCUUUuAAGAuAdTsdT


 


A-31704
2191
ccAuGGAuucuGGcGGuAudTsdT
A-31705
2192
AuACCGCcAGAAUCcAUGGdTsdT


 


A-31706
2193
uuAAuGAAcuAAuucGuuudTsdT
A-31707
2194
AAACGAAUuAGUUcAUuAAdTsdT


 


A-31708
2195
AGGGucAuuAGAcAAAuGudTsdT
A-31709
2196
AcAUUUGUCuAAUGACCCUdTsdT


 


A-31710
2197
uGAAcuAAuucGuuuuGAcdTsdT
A-31711
2198
GUcAAAACGAAUuAGUUcAdTsdT


 


A-31712
2199
uuccccAGcuGAuuAGuGudTsdT
A-31713
2200
AcACuAAUcAGCUGGGGAAdTsdT


 


A-31714
2201
uAuGuAAGGGucAuuAGAcdTsdT
A-31715
2202
GUCuAAUGACCCUuAcAuAdTsdT









Example 3
Single Concentration Silencing Experiment (% Knockdown Relative to Control 12 nM)
Transfection of PC-3 cells was performed in 6-well plates: 31.25 μl (for 12.5 nM) of 200 nM duplex was added to 500 μl Opti-MEM (Invitrogen, Carlsbad, Calif.) in a well of a 6-well plate. 5 μl LipofectamineTM RNAiMAX (Invitrogen, Carlsbad, Calif.) was added to the wells, mixed and incubated for 15 minutes. 2.0 ml complete growth media without Antibiotics containing 0.6×105 cells was added, and the mixture was mixed by rocking back and forth for 36 hours. Total RNA was isolated using Qiagen RNeasy kit (Qiagen, Valencia, Calif.) according to the manufacturer's instructions. RNA concentration was measured using a nanodrop and was diluted to 2 μg per 10 μl.
cDNA was synthesized using an ABI High-capacity cDNA reverse transcription kit (Applied Biosystems, Foster City, Calif.) and 2 μg total RNA. Quantitative PCR (qPCR) was performed using probes to amplify XBP-1 and 18S in the same reaction. All reactions were performed in triplicate.
qPCR data were analyzed using the ΔΔCt method using BlockiTTM fluorescent Oligo (Invitrogen, Carlsbad, Calif.), which does not target any human gene, as a negative control.
Generation of IC50s (for AD18028, AD18029, AD18037, AD18038, AD18040)
IC50s were generated for the 5 duplexes that showed the best silencing in the single concentration experiment.
Three sets of transfections were performed in two independent experiments using the dsRNAs shown in Table 4. In the first experiment, qPCR experiment 1 (qPCR1) and branched DNA (bDNA) results were obtained from different transfections that were done in parallel using the same cells and reagents. In the second experiment, qPCR2 results were generated from transfections that were done under the same conditions as the first experiment.
Transfection of PC-3 cells was performed in 96-well plates. The duplex concentrations tested were 50 nM, 10 nM, 5 nM, 1 nM, 0.5 nM, 0.1 nM, 0.05 nM, 0.01 nM, 0.005 nM, 0.001 nM, 0.0005 nM, and 0.0001 nM. Each dsRNA was diluted so that 5 μl would be added to 100 μl for each transfection to give the desired concentration. Transfections were performed using Opti-MEM and lipofectamine, and then cultured in EMEM.
RNA was extracted using an RNAqueous 96 kit (Applied Biosystems/Ambion, Austin, Tex.) according to manufactures instructions.
cDNA synthesis and qPCR were done as described above, and qPCR data were analyzed using the ΔΔCt method using AD-3966 as a control, which targets the Sid1 gene but has been shown to have no activity in cell based assays.
Branched DNA assays were performed using QuantiGene® 2.0 (Panomics, Fremont, Calif.). The bDNA data were analyzed by subtracting the average background from each triplicate sample, averaging the triplicate GAPDH (control probe) and TTR (experimental probe) then taking the ratio:
(experimental probe-background)/(control probe-background).
The results are shown in Tables 5 and 6.







TABLE 5







IC50 results for XBP-1 dsRNA





















IC50



Human
Mouse
Rat
Rhesus
IC50 (nM)
IC50 (nM)
(nM)


oligoName
antisScore
antisScore
antisScore
antisScore
qPCR 1
qPCR 2
bDNA

















AD18027
3
2
3
3





AD18028
3
2
3.2
3
0.019
0.011
0.034


AD18029
3
1.2
2.8
3
0.03
0.020
0.026


AD18030
3
2
1
2


AD18031
3
2
3
2.2


AD18032
3
2.2
3
2.8


AD18033
3
3
2.8
2


AD18034
2.2
2
2.8
2


AD18035
2.2
2
2
2.4


AD18036
2.2
2
2
2


AD18037
2.2
2
2
2.2
0.016
0.019
0.016


AD18038
2.2
2
3
2.2
0.004
0.003
0.006


AD18039
2.2
3
2
2.2


AD18040
2.2
2
2
2
0.057
0.052
0.065


AD18041
4
NH
NH
3.4


AD18042
4
NH
NH
3.2


AD18043
4
NH
NH
3


AD18044
3.2
NH
NH
3.2


AD18045
3.2
NH
NH
3.2


AD18046
3.2
NH
NH
3.2


AD18047
3.2
NH
NH
3


AD18048
3.2
NH
NH
3


AD18049
3
NH
NH
3.2


AD18050
3
NH
NH
3.2





NH = No homology;


bold = perfect match with hamster













TABLE 6







XBP-1 Silencing Data














%







knockdown




relative to




control
IC50
IC50
IC50




(12 nM)
(nM)
(nM)
(nM)



oligo Name
(36 hours)
qPCR 1
qPCR 2
bDNA

















AD18027
81.993






AD18028
90.581
0.019
0.011
0.034



AD18029
97.749
0.03
0.02
0.026



AD18030
82.845



AD18031
34.782



AD18032
84.893



AD18033
68.971



AD18034
42.962



AD18035
82.076



AD18036
77.26



AD18037
94.209
0.016
0.019
0.016



AD18038
93.239
0.004
0.003
0.006



AD18039
56.873



AD18040
93.75
0.057
0.052
0.065



AD18041
84.396



AD18042
ND



AD18043
27.804



AD18044
64.316



AD18045
14.933



AD18046
−2.101



AD18047
62.456



AD18048
74.534



AD18049
2.284



AD18050
59.621










Example 4
Screening siRNA Sequences for Immunostimulatory Ability
Human PBMC were isolated from freshly collected buffy coats obtained from healthy donors (Research Blood Components, Inc., Boston, Mass.) by a standard Ficoll-Hypaque density centrifugation. Freshly isolated cells (1×105/well) were seeded in 96-well plates and cultured in RPMI 1640 GlutaMax medium (Invitrogen) supplemented with 10% heat-inactivated fetal bovine serum and 1% antibiotic/antimycotic (Invitrogen).
siRNAs were transfected into PBMC using two separate transfection reagents: GenePorter 2 (GP2; Genlantis) and DOTAP (Roche Applied Science). The transfection reagent was first diluted in Opti-MEM (Invitrogen) for 5 minutes before mixing with an equal volume of Opti-MEM containing the siRNA. siRNA/transfection reagent complexes were incubated as specified by the reagent manufacturers' instructions and subsequently added to PBMC. siRNAs were used at a final concentration of 133 nM. The ratio of RNA to transfection reagent was 33 pmoles and 16.5 pmoles, respectively, per ul of GP2 and DOTAP.
Cytokines were detected and quantified in culture supernatants with a commercially available ELISA kit for IFN-α (BMS216INST) and TNF-α (BMS223INST); both from Bender MedSystems (Vienna, Austria).
The results are shown in Table 7.







TABLE 7







XBP-1 targeted siRNAs are not immunostimulatory


for human PBMC










Donor A
Donor B









pg/ml











Transfection
IFN-Ξ
TNF-Ξ
IFN-Ξ
TNF-Ξ





Medium only
−36 ± 5 
−20 ± 13
−35 ± 7 
125 ± 48


DOTAP only
−49 ± 5 
−39 ± 4 
−36 ± 11
110 ± 81


AD-1730
 −6 ± 11
1859 ± 276
141 ± 42
1082 ± 181


AD-1955
−35 ± 8 
32 ± 7
−40 ± 10
 59 ± 27


AD-2153
302 ± 32
 62 ± 46
531 ± 44
158 ± 26


AD-5048
473 ± 63
1244 ± 217
592 ± 41
 785 ± 121


AD-18028
−39 ± 9 
−39 ± 7 
−23 ± 16
162 ± 49


AD-18029
−35 ± 11
−31 ± 8 
−26 ± 16
 24 ± 40


AD-18037
−28 ± 20
−24 ± 14
30 ± 6
−44 ± 27


AD-18038
−24 ± 18
 −5 ± 17
−37 ± 11
 32 ± 56


AD-18040
−31 ± 17
−12 ± 17
−37 ± 8 
−43 ± 14









Cytokine Responses of Whole PBMC to Duplex siRNAs Targeting XBP-1
Freshly isolated PBMC from two normal donors (A and B) were transfected with test siRNAs using DOTAP and cultured for 24 hours. Subsequently, culture supernatants were collected and IFN-α and TNF-α levels measured by ELISA. AD-1730, AD-1955, and AD-2153 are sequences that bear no known homology to any human genes. AD-1730 and AD-2153 preferentially stimulate TNF-α and IFN-α, respectively. AD-5048 corresponds to a sequence that targets human Apolipoprotein B (Soutschek et al., 2004) and elicits both and IFN-α and TNF-α AD-1995 is a non-stimulatory sequence used as a negative control. The data shown are derived from a single experiment in which four replicate wells were transfected with each siRNA or were treated with either DOTAP or medium alone. Values represent the mean±standard deviation for four biological replicates.
Example 5
The Effect of XBP-1 siRNA on Hepatic Lipogenesis in Mice
Dietary carbohydrates regulate hepatic lipogenesis by controlling the expression of critical enzymes in glycolysis and lipogenic pathways. XBP-1, a regulator of the Unfolded Protein Response (UPR), is important for de novo fatty acid synthesis in the liver, a function unrelated to its role in the UPR. (Lee et al., Science (2009) 320:1492-1496) XBP-1 protein expression is induced in the liver by a high carbohydrate diet and controls the induction of genes involved in fatty acid synthesis. Selective deletion of XBP-1 in liver resulted in marked hypocholesterolemia and hypotriglyceridemia secondary to a decreased production of lipids from the liver. (Lee et al. (2009)) Notably, this phenotype was not accompanied by hepatic steatosis or significantly compromised protein secretory function.
XBP-1 accelerates de novo fatty acid synthesis in the liver while preserving normal hepatic lipid composition, a profile that is highly relevant to the treatment of diseases, such as atherosclerosis, that are associated with dyspipidemia. Inhibition of XBP-1 may also be useful therapeutics for the treatment of Nonalcoholic Fatty Liver Disease (NAFLD) and steatohepatitis (NASH), which lead to accelerated morbidity and mortality.
In order to determine whether XBP-1 downregulation by siRNAs would be an effective strategy to reduce lipid levels and treat dyslipidemias and metabolic syndromes, siRNAs were designed to target XBP-1.
Knock-Down of XBP-1 mRNA in the Liver and Decrease of Plasma Cholesterol Levels by Lipidoid Formulated siRNA
Animal dosing: Bolus dosing of LNP01 formulated siRNAs in C57/BL6 mice (5/group, 18-20 g body weight, Charles River Laboratories, MA) was performed by low volume tail vein injection using a 27 G needle. Mice were dosed with two siRNAs targeting XBP-1 (LNP01-18037 and LNP01-18038) and a control luciferase targeting siRNA (LNP01-1955) at 5 and 7.5 mg/kg. Animals were kept under an infrared lamp for approximately 3 min prior to dosing to ease injection. 48 hour post dose animals were sacrificed by CO2-asphyxiation. 0.2 ml blood was collected by retro-orbital bleeding. Liver was harvested and frozen in liquid nitrogen. Serum and livers were stored at −80° C. Total serum cholesterol in mouse serum was measured using the Wako Cholesterol E enzymatic colorimetric method (Wako Chemicals USA, Inc., Richmond, Va., USA) according to manufacturer's instructions. Measurements were taken on a VersaMaxTM Tunable microplate reader (Molecular Devices, Sunnyvale, Calif.) using SoftMax® Pro software. Message levels of the target gene XBP-1 were measured via bDNA analysis as below.
bDNA analysis: Frozen livers were grinded using 6850 Freezer/Mill Cryogenic Grinder (SPEX CentriPrep, Inc.) and powders stored at −80° C. until analysis.
XBP-1 mRNA levels were detected using the branched-DNA technology based QuantiGene® Reagent System (Panomics, Fremont, Calif., U.S.A.) according to the protocol. 10-20 mg of frozen liver powders was lysed in 600 ul of 0.3 ug/ml Proteinase K (Epicentre®, #MPRK092) in Tissue and Cell Lysis Solution (Epicentre®, #MTC096H) at 65° C. for 1 hour. Then 10 ul of the lysates were added to 90 μl of Lysis Working Reagent (1 volume of stock Lysis Mixture in two volumes of water) and incubated at 55° C. overnight on Panomics capture plates with probe sets specific to mouse XBP-1 and mouse GAPDH (Panomics, U.S.A.). Capture plates then were processed for signal amplification and detection according to the protocol and chemiluminescence was read as relative light units (RLUs) on a microplate luminometer Victor2-Light (Perkin Elmer). The ratio of XBP-1 mRNA to GAPDH mRNA in liver lysates was averaged over each treatment group and compared to a control group treated with PBS
As shown in FIG. 6, as compared to the PBS control, treatment of mice with compounds LNP01-18037, and LNP01-18038, but not with unrelated siRNA control LNP01-1955 resulted in significant and dose dependent (72-88%) lowering of XBP-1 transcript levels in mouse liver (as indicated by a smaller XBP-1 to GAPDH transcript ratio when normalized to a PBS control group), indicating that siRNA molecules were active in vivo. As shown in FIG. 6, the silencing activity translated in lowering of total cholesterol in those animals.
Example 6
Cleavage of XBP-1 siRNAs
5′RACE was used to examine the cleavage products of XBP-1 siRNAs isolated from livers of mice injected with the oligonucleotides.
Mice were injected with 5 mg/kg or 7.5 mg/kg lipid-formulated XBP-1 siRNAs (LNP01-18038, negative control siRNAs targeting luciferase (LNP01-1955), or PBS. Total RNA was isolated from powdered liver samples using Trizol (Invitrogen) and RNAeasy mini columns (Qiagen). Two micrograms of RNA were used for 5′RACE similar to the Generacer kit (Invitrogen) protocol. The oligonucleotide adaptor was ligated directly to total RNA using T4 RNA ligase (2U) for 1 hour at 37° C. The ligation mixture was reverse transcribed using the XBP-1-specific oligo 5′-GGAAGCAGAGAGTGGAGAAAGAAATGCTAAGG-3′ (SEQ ID NO:4335) using SuperscriptTM III (Invitrogen) for 1 hour at 50° C., then 15 min. at 70° C. cDNA was amplified using 3 ul of cDNA amplified with Platinum Taq (Invitrogen) for 35 cycles where Tm=62° C. with oligos 5′-CGACTGGAGCACGAGGACACTGACATGG-3′ (SEQ ID NO:4336) and 5′-CCAGTGTTATGTGGCTCTTTAGACACTAATCAG-3′ (SEQ ID NO:4337). PCR products were examined by gel electrophoresis, purified, and cloned into pCR4-TOPO vector for sequencing (Invitrogen).
PCR experiments on the 5′ RACE product were performed in a blind fashion. One round of PCR was performed using Tm=62° C., for 35 cycles. The expected XBP-1 product size was 320 bp. The PCR products were roughly the correct size in all experimental samples, but products appeared to exhibit a high level of degradation the same location as the siRNA-intended cleavage site. Three bands from each of the experimental groups were cut from agarose gels for cloning and sequencing.
The control groups yielded clones with several degradation products resulting from cleavage around but not located at the expected cleavage site. The expected and observed cleavage products in the negative control samples are shown in FIG. 1A. The AD18038 siRNA was expected to cleave after nucleotide 925 in the XBP-1 transcript (see FIGS. 1A, 1B, and 3). Thus, no cleavage products at nucleotide position 925 were expected, and in fact, none were observed, in the negative control products (FIG. 1A). Degradation products in the negative control samples were found at positions −49, −35, −32(2), −31, −30(2), −28, −24, −22, −16(2), −17, −15, −14, −12, −11, −9, +8, +13, +65, and +68, relative to the intended cleavage site of the XBP-1 siRNA AD18038.
The expected siRNA-mediated cleavage product was found in 76.5% of the clones derived from the AD18038-treated groups (FIG. 1B). Degradation products were found from cleavage at positions −30, −10, −8, −5, −3, +1, +3, and +14, relative to the intended cleavage site of the XBP-1 siRNA AD18038.







TABLE 8







XBP-1 human/Rhesus siRNAs












Oligo Name/

SEQ

SEQ



Positions on target

ID

ID


sequence (5′to 3′)
sense (5′-3′)
NO:
antisense (5′-3′)
NO:















NM_005080_390-408
AGAAAAUCAGCUUUUACGA
1
UCGUAAAAGCUGAUUUUCU
2



 


NM_005080_1184-1202
UCCCCAGCUGAUUAGUGUC
3
GACACUAAUCAGCUGGGGA
4


 


NM_005080_1494-1512
UACUUAUUAUGUAAGGGUC
5
GACCCUUACAUAAUAAGUA
6


 


NM_005080_1463-1481
UAUCUUAAAAGGGUGGUAG
7
CUACCACCCUUUUAAGAUA
8


 


NM_005080_610-628
CCAUGGAUUCUGGCGGUAU
9
AUACCGCCAGAAUCCAUGG
10


 


NM_005080_823-841
UUAAUGAACUAAUUCGUUU
11
AAACGAAUUAGUUCAUUAA
12


 


NM_005080_1507-1525
AGGGUCAUUAGACAAAUGU
13
ACAUUUGUCUAAUGACCCU
14


 


NM_005080_827-845
UGAACUAAUUCGUUUUGAC
15
GUCAAAACGAAUUAGUUCA
16


 


NM_005080_1503-1521
UGUAAGGGUCAUUAGACAA
17
UUGUCUAAUGACCCUUACA
18


 


NM_005080_829-847
AACUAAUUCGUUUUGACCA
19
UGGUCAAAACGAAUUAGUU
20


 


NM_005080_1783-1801
UAUUUAAAACUACCCAUGC
21
GCAUGGGUAGUUUUAAAUA
22


 


NM_005080_1183-1201
UUCCCCAGCUGAUUAGUGU
23
ACACUAAUCAGCUGGGGAA
24


 


NM_005080_1501-1519
UAUGUAAGGGUCAUUAGAC
25
GUCUAAUGACCCUUACAUA
26


 


NM_005080_1504-1522
GUAAGGGUCAUUAGACAAA
27
UUUGUCUAAUGACCCUUAC
28


 


NM_005080_734-752
GCUCCCAGAGGUCUACCCA
29
UGGGUAGACCUCUGGGAGC
30


 


NM_005080_893-911
GAGCCAAGCUAAUGUGGUA
31
UACCACAUUAGCUUGGCUC
32


 


NM_005080_1064-1082
CUGCCUACUGGAUGCUUAC
33
GUAAGCAUCCAGUAGGCAG
34


 


NM_005080_1066-1084
GCCUACUGGAUGCUUACAG
35
CUGUAAGCAUCCAGUAGGC
36


 


NM_005080_1136-1154
GCUUGGUGUAAACCAUUCU
37
AGAAUGGUUUACACCAAGC
38


 


NM_005080_1137-1155
CUUGGUGUAAACCAUUCUU
39
AAGAAUGGUUUACACCAAG
40


 


NM_005080_1182-1200
UUUCCCCAGCUGAUUAGUG
41
CACUAAUCAGCUGGGGAAA
42


 


NM_005080_1186-1204
CCCAGCUGAUUAGUGUCUA
43
UAGACACUAAUCAGCUGGG
44


 


NM_005080_1189-1207
AGCUGAUUAGUGUCUAAGG
45
CCUUAGACACUAAUCAGCU
46


 


NM_005080_1224-1242
UGCCCUUUUCCUUGACUAU
47
AUAGUCAAGGAAAAGGGCA
48


 


NM_005080_1229-1247
UUUUCCUUGACUAUUACAC
49
GUGUAAUAGUCAAGGAAAA
50


 


NM_005080_1235-1253
UUGACUAUUACACUGCCUG
51
CAGGCAGUGUAAUAGUCAA
52


 


NM_005080_1236-1254
UGACUAUUACACUGCCUGG
53
CCAGGCAGUGUAAUAGUCA
54


 


NM_005080_1438-1456
ACUACAGCUUUUAAGAUUG
55
CAAUCUUAAAAGCUGUAGU
56


 


NM_005080_1441-1459
ACAGCUUUUAAGAUUGUAC
57
GUACAAUCUUAAAAGCUGU
58


 


NM_005080_1442-1460
CAGCUUUUAAGAUUGUACU
59
AGUACAAUCUUAAAAGCUG
60


 


NM_005080_1493-1511
AUACUUAUUAUGUAAGGGU
61
ACCCUUACAUAAUAAGUAU
62


 


NM_005080_1502-1520
AUGUAAGGGUCAUUAGACA
63
UGUCUAAUGACCCUUACAU
64


 


NM_005080_1506-1524
AAGGGUCAUUAGACAAAUG
65
CAUUUGUCUAAUGACCCUU
66


 


NM_005080_1594-1612
UUGCCUCCAGUUUUAGGUC
67
GACCUAAAACUGGAGGCAA
68


 


NM_005080_1790-1808
AACUACCCAUGCAAUUAAA
69
UUUAAUUGCAUGGGUAGUU
70


 


NM_005080_304-322
ACUGCCAGAGAUCGAAAGA
71
UCUUUCGAUCUCUGGCAGU
72


 


NM_005080_305-323
CUGCCAGAGAUCGAAAGAA
73
UUCUUUCGAUCUCUGGCAG
74


 


NM_005080_395-413
AUCAGCUUUUACGAGAGAA
75
UUCUCUCGUAAAAGCUGAU
76


 


NM_005080_609-627
CCCAUGGAUUCUGGCGGUA
77
UACCGCCAGAAUCCAUGGG
78


 


NM_005080_611-629
CAUGGAUUCUGGCGGUAUU
79
AAUACCGCCAGAAUCCAUG
80


 


NM_005080_617-635
UUCUGGCGGUAUUGACUCU
81
AGAGUCAAUACCGCCAGAA
82


 


NM_005080_621-639
GGCGGUAUUGACUCUUCAG
83
CUGAAGAGUCAAUACCGCC
84


 


NM_005080_641-659
UUCAGAGUCUGAUAUCCUG
85
CAGGAUAUCAGACUCUGAA
86


 


NM_005080_648-666
UCUGAUAUCCUGUUGGGCA
87
UGCCCAACAGGAUAUCAGA
88


 


NM_005080_651-669
GAUAUCCUGUUGGGCAUUC
89
GAAUGCCCAACAGGAUAUC
90


 


NM_005080_735-753
CUCCCAGAGGUCUACCCAG
91
CUGGGUAGACCUCUGGGAG
92


 


NM_005080_753-771
GAAGGACCCAGUUCCUUAC
93
GUAAGGAACUGGGUCCUUC
94


 


NM_005080_794-812
GGGGACGUCAUCAGCCAAG
95
CUUGGCUGAUGACGUCCCC
96


 


NM_005080_826-844
AUGAACUAAUUCGUUUUGA
97
UCAAAACGAAUUAGUUCAU
98


 


NM_005080_836-854
UCGUUUUGACCACAUAUAU
99
AUAUAUGUGGUCAAAACGA
100


 


NM_005080_840-858
UUUGACCACAUAUAUACCA
101
UGGUAUAUAUGUGGUCAAA
102


 


NM_005080_841-859
UUGACCACAUAUAUACCAA
103
UUGGUAUAUAUGUGGUCAA
104


 


NM_005080_847-865
ACAUAUAUACCAAGCCCCU
105
AGGGGCUUGGUAUAUAUGU
106


 


NM_005080_894-912
AGCCAAGCUAAUGUGGUAG
107
CUACCACAUUAGCUUGGCU
108


 


NM_005080_895-913
GCCAAGCUAAUGUGGUAGU
109
ACUACCACAUUAGCUUGGC
110


 


NM_005080_896-914
CCAAGCUAAUGUGGUAGUG
111
CACUACCACAUUAGCUUGG
112


 


NM_005080_899-917
AGCUAAUGUGGUAGUGAAA
113
UUUCACUACCACAUUAGCU
114


 


NM_005080_908-926
GGUAGUGAAAAUCGAGGAA
115
UUCCUCGAUUUUCACUACC
116


 


NM_005080_917-935
AAUCGAGGAAGCACCUCUC
117
GAGAGGUGCUUCCUCGAUU
118


 


NM_005080_937-955
GCCCCUCAGAGAAUGAUCA
119
UGAUCAUUCUCUGAGGGGC
120


 


NM_005080_950-968
UGAUCACCCUGAAUUCAUU
121
AAUGAAUUCAGGGUGAUCA
122


 


NM_005080_1185-1203
CCCCAGCUGAUUAGUGUCU
123
AGACACUAAUCAGCUGGGG
124


 


NM_005080_1187-1205
CCAGCUGAUUAGUGUCUAA
125
UUAGACACUAAUCAGCUGG
126


 


NM_005080_1153-1171
CUUGGGAGGACACUUUUGC
127
GCAAAAGUGUCCUCCCAAG
128


 


NM_005080_1787-1805
UAAAACUACCCAUGCAAUU
129
AAUUGCAUGGGUAGUUUUA
130


 


NM_005080_606-624
CUCCCCAUGGAUUCUGGCG
131
CGCCAGAAUCCAUGGGGAG
132


 


NM_005080_1019-1037
UAUCUCAAAUCUGCUUUCA
133
UGAAAGCAGAUUUGAGAUA
134


 


NM_005080_1072-1090
UGGAUGCUUACAGUGACUG
135
CAGUCACUGUAAGCAUCCA
136


 


NM_005080_1228-1246
CUUUUCCUUGACUAUUACA
137
UGUAAUAGUCAAGGAAAAG
138


 


NM_005080_1461-1479
UUUAUCUUAAAAGGGUGGU
139
ACCACCCUUUUAAGAUAAA
140


 


NM_005080_1495-1513
ACUUAUUAUGUAAGGGUCA
141
UGACCCUUACAUAAUAAGU
142


 


NM_005080_1496-1514
CUUAUUAUGUAAGGGUCAU
143
AUGACCCUUACAUAAUAAG
144


 


NM_005080_1500-1518
UUAUGUAAGGGUCAUUAGA
145
UCUAAUGACCCUUACAUAA
146


 


NM_005080_1644-1662
CCUGCUGAGGGGGCUCUUU
147
AAAGAGCCCCCUCAGCAGG
148


 


NM_005080_1708-1726
AUAGAAAUUUACUAUGUAA
149
UUACAUAGUAAAUUUCUAU
150


 


NM_005080_302-320
AGACUGCCAGAGAUCGAAA
151
UUUCGAUCUCUGGCAGUCU
152


 


NM_005080_607-625
UCCCCAUGGAUUCUGGCGG
153
CCGCCAGAAUCCAUGGGGA
154


 


NM_005080_824-842
UAAUGAACUAAUUCGUUUU
155
AAAACGAAUUAGUUCAUUA
156


 


NM_005080_953-971
UCACCCUGAAUUCAUUGUC
157
GACAAUGAAUUCAGGGUGA
158


 


NM_005080_1011-1029
GAGCUGGGUAUCUCAAAUC
159
GAUUUGAGAUACCCAGCUC
160


 


NM_005080_1230-1248
UUUCCUUGACUAUUACACU
161
AGUGUAAUAGUCAAGGAAA
162


 


NM_005080_1231-1249
UUCCUUGACUAUUACACUG
163
CAGUGUAAUAGUCAAGGAA
164


 


NM_005080_1290-1308
AAAGCCAAAAUAGAGAGUA
165
UACUCUCUAUUUUGGCUUU
166


 


NM_005080_1331-1349
AUUUGUUCAGAUCUCAUAG
167
CUAUGAGAUCUGAACAAAU
168


 


NM_005080_1460-1478
UUUUAUCUUAAAAGGGUGG
169
CCACCCUUUUAAGAUAAAA
170


 


NM_005080_1670-1688
GUAUACUUCAAGUAAGAUC
171
GAUCUUACUUGAAGUAUAC
172


 


NM_005080_1671-1689
UAUACUUCAAGUAAGAUCA
173
UGAUCUUACUUGAAGUAUA
174


 


NM_005080_1735-1753
UGGAAUUUUUUCCUGCUAG
175
CUAGCAGGAAAAAAUUCCA
176


 


NM_005080_1744-1762
UUCCUGCUAGUGUAGCUUC
177
GAAGCUACACUAGCAGGAA
178


 


NM_005080_1796-1814
CCAUGCAAUUAAAAGGUAC
179
GUACCUUUUAAUUGCAUGG
180


 


NM_005080_343-361
GAACAGCAAGUGGUAGAUU
181
AAUCUACCACUUGCUGUUC
182


 


NM_005080_374-392
ACCAAAAACUUUUGCUAGA
183
UCUAGCAAAAGUUUUUGGU
184


 


NM_005080_375-393
CCAAAAACUUUUGCUAGAA
185
UUCUAGCAAAAGUUUUUGG
186


 


NM_005080_608-626
CCCCAUGGAUUCUGGCGGU
187
ACCGCCAGAAUCCAUGGGG
188


 


NM_005080_652-670
AUAUCCUGUUGGGCAUUCU
189
AGAAUGCCCAACAGGAUAU
190


 


NM_005080_686-704
AGUCAUGUUCUUCAAAUGC
191
GCAUUUGAAGAACAUGACU
192


 


NM_005080_909-927
GUAGUGAAAAUCGAGGAAG
193
CUUCCUCGAUUUUCACUAC
194


 


NM_005080_951-969
GAUCACCCUGAAUUCAUUG
195
CAAUGAAUUCAGGGUGAUC
196


 


NM_005080_952-970
AUCACCCUGAAUUCAUUGU
197
ACAAUGAAUUCAGGGUGAU
198


 


NM_005080_825-843
AAUGAACUAAUUCGUUUUG
199
CAAAACGAAUUAGUUCAUU
200


 


NM_005080_1194-1212
AUUAGUGUCUAAGGAAUGA
201
UCAUUCCUUAGACACUAAU
202


 


NM_005080_831-849
CUAAUUCGUUUUGACCACA
203
UGUGGUCAAAACGAAUUAG
204


 


NM_005080_835-853
UUCGUUUUGACCACAUAUA
205
UAUAUGUGGUCAAAACGAA
206


 


NM_005080_869-887
CUUAGAGAUACCCUCUGAG
207
CUCAGAGGGUAUCUCUAAG
208


 


NM_005080_1246-1264
ACUGCCUGGAGGAUAGCAG
209
CUGCUAUCCUCCAGGCAGU
210


 


NM_005080_1453-1471
AUUGUACUUUUAUCUUAAA
211
UUUAAGAUAAAAGUACAAU
212


 


NM_005080_1512-1530
CAUUAGACAAAUGUCUUGA
213
UCAAGACAUUUGUCUAAUG
214


 


NM_005080_1546-1564
UAUGAAUGGUUCUUUAUCA
215
UGAUAAAGAACCAUUCAUA
216


 


NM_005080_1789-1807
AAACUACCCAUGCAAUUAA
217
UUAAUUGCAUGGGUAGUUU
218


 


NM_005080_325-343
GCUCGAAUGAGUGAGCUGG
219
CCAGCUCACUCAUUCGAGC
220


 


NM_005080_393-411
AAAUCAGCUUUUACGAGAG
221
CUCUCGUAAAAGCUGAUUU
222


 


NM_005080_788-806
GUCAGUGGGGACGUCAUCA
223
UGAUGACGUCCCCACUGAC
224


 


NM_005080_821-839
CAUUAAUGAACUAAUUCGU
225
ACGAAUUAGUUCAUUAAUG
226


 


NM_005080_1514-1532
UUAGACAAAUGUCUUGAAG
227
CUUCAAGACAUUUGUCUAA
228


 


NM_005080_1797-1815
CAUGCAAUUAAAAGGUACA
229
UGUACCUUUUAAUUGCAUG
230


 


NM_005080_833-851
AAUUCGUUUUGACCACAUA
231
UAUGUGGUCAAAACGAAUU
232


 


NM_005080_1509-1527
GGUCAUUAGACAAAUGUCU
233
AGACAUUUGUCUAAUGACC
234


 


NM_005080_1802-1820
AAUUAAAAGGUACAAUGCA
235
UGCAUUGUACCUUUUAAUU
236


 


NM_005080_391-409
GAAAAUCAGCUUUUACGAG
237
CUCGUAAAAGCUGAUUUUC
238


 


NM_005080_843-861
GACCACAUAUAUACCAAGC
239
GCUUGGUAUAUAUGUGGUC
240


 


NM_005080_1508-1526
GGGUCAUUAGACAAAUGUC
241
GACAUUUGUCUAAUGACCC
242


 


NM_005080_1754-1772
UGUAGCUUCUGAAAGGUGC
243
GCACCUUUCAGAAGCUACA
244


 


NM_005080_430-448
GUUGAGAACCAGGAGUUAA
245
UUAACUCCUGGUUCUCAAC
246


 


NM_005080_437-455
ACCAGGAGUUAAGACAGCG
247
CGCUGUCUUAACUCCUGGU
248


 


NM_005080_1465-1483
UCUUAAAAGGGUGGUAGUU
249
AACUACCACCCUUUUAAGA
250


 


NM_005080_1742-1760
UUUUCCUGCUAGUGUAGCU
251
AGCUACACUAGCAGGAAAA
252


 


NM_005080_438-456
CCAGGAGUUAAGACAGCGC
253
GCGCUGUCUUAACUCCUGG
254


 


NM_005080_1060-1078
CUUCCUGCCUACUGGAUGC
255
GCAUCCAGUAGGCAGGAAG
256


 


NM_005080_1067-1085
CCUACUGGAUGCUUACAGU
257
ACUGUAAGCAUCCAGUAGG
258


 


NM_005080_1197-1215
AGUGUCUAAGGAAUGAUCC
259
GGAUCAUUCCUUAGACACU
260


 


NM_005080_1198-1216
GUGUCUAAGGAAUGAUCCA
261
UGGAUCAUUCCUUAGACAC
262


 


NM_005080_1424-1442
UACUAUAAUUGAGAACUAC
263
GUAGUUCUCAAUUAUAGUA
264


 


NM_005080_1464-1482
AUCUUAAAAGGGUGGUAGU
265
ACUACCACCCUUUUAAGAU
266


 


NM_005080_616-634
AUUCUGGCGGUAUUGACUC
267
GAGUCAAUACCGCCAGAAU
268


 


NM_005080_757-775
GACCCAGUUCCUUACCAGC
269
GCUGGUAAGGAACUGGGUC
270


 


NM_005080_785-803
UCUGUCAGUGGGGACGUCA
271
UGACGUCCCCACUGACAGA
272


 


NM_005080_819-837
GCCAUUAAUGAACUAAUUC
273
GAAUUAGUUCAUUAAUGGC
274


 


NM_005080_842-860
UGACCACAUAUAUACCAAG
275
CUUGGUAUAUAUGUGGUCA
276


 


NM_005080_845-863
CCACAUAUAUACCAAGCCC
277
GGGCUUGGUAUAUAUGUGG
278


 


NM_005080_1013-1031
GCUGGGUAUCUCAAAUCUG
279
CAGAUUUGAGAUACCCAGC
280


 


NM_005080_1431-1449
AUUGAGAACUACAGCUUUU
281
AAAAGCUGUAGUUCUCAAU
282


 


NM_005080_1673-1691
UACUUCAAGUAAGAUCAAG
283
CUUGAUCUUACUUGAAGUA
284


 


NM_005080_283-301
AAAAACAGAGUAGCAGCUC
285
GAGCUGCUACUCUGUUUUU
286


 


NM_005080_838-856
GUUUUGACCACAUAUAUAC
287
GUAUAUAUGUGGUCAAAAC
288


 


NM_005080_279-297
ACUGAAAAACAGAGUAGCA
289
UGCUACUCUGUUUUUCAGU
290


 


NM_005080_633-651
UCUUCAGAUUCAGAGUCUG
291
CAGACUCUGAAUCUGAAGA
292


 


NM_005080_1024-1042
CAAAUCUGCUUUCAUCCAG
293
CUGGAUGAAAGCAGAUUUG
294


 


NM_005080_1147-1165
ACCAUUCUUGGGAGGACAC
295
GUGUCCUCCCAAGAAUGGU
296


 


NM_005080_1154-1172
UUGGGAGGACACUUUUGCC
297
GGCAAAAGUGUCCUCCCAA
298


 


NM_005080_1188-1206
CAGCUGAUUAGUGUCUAAG
299
CUUAGACACUAAUCAGCUG
300


 


NM_005080_1192-1210
UGAUUAGUGUCUAAGGAAU
301
AUUCCUUAGACACUAAUCA
302


 


NM_005080_1195-1213
UUAGUGUCUAAGGAAUGAU
303
AUCAUUCCUUAGACACUAA
304


 


NM_005080_1238-1256
ACUAUUACACUGCCUGGAG
305
CUCCAGGCAGUGUAAUAGU
306


 


NM_005080_1548-1566
UGAAUGGUUCUUUAUCAUU
307
AAUGAUAAAGAACCAUUCA
308


 


NM_005080_1549-1567
GAAUGGUUCUUUAUCAUUU
309
AAAUGAUAAAGAACCAUUC
310


 


NM_005080_1677-1695
UCAAGUAAGAUCAAGAAUC
311
GAUUCUUGAUCUUACUUGA
312


 


NM_005080_1707-1725
UAUAGAAAUUUACUAUGUA
313
UACAUAGUAAAUUUCUAUA
314


 


NM_005080_1713-1731
AAUUUACUAUGUAAAUGCU
315
AGCAUUUACAUAGUAAAUU
316


 


NM_005080_1786-1804
UUAAAACUACCCAUGCAAU
317
AUUGCAUGGGUAGUUUUAA
318


 


NM_005080_210-228
GCUGCCCCAGGCGCGCAAG
319
CUUGCGCGCCUGGGGCAGC
320


 


NM_005080_278-296
AACUGAAAAACAGAGUAGC
321
GCUACUCUGUUUUUCAGUU
322


 


NM_005080_284-302
AAAACAGAGUAGCAGCUCA
323
UGAGCUGCUACUCUGUUUU
324


 


NM_005080_290-308
GAGUAGCAGCUCAGACUGC
325
GCAGUCUGAGCUGCUACUC
326


 


NM_005080_342-360
GGAACAGCAAGUGGUAGAU
327
AUCUACCACUUGCUGUUCC
328


 


NM_005080_431-449
UUGAGAACCAGGAGUUAAG
329
CUUAACUCCUGGUUCUCAA
330


 


NM_005080_576-594
GCAGGCCCAGUUGUCACCC
331
GGGUGACAACUGGGCCUGC
332


 


NM_005080_602-620
ACAUCUCCCCAUGGAUUCU
333
AGAAUCCAUGGGGAGAUGU
334


 


NM_005080_618-636
UCUGGCGGUAUUGACUCUU
335
AAGAGUCAAUACCGCCAGA
336


 


NM_005080_678-696
UUGGACCCAGUCAUGUUCU
337
AGAACAUGACUGGGUCCAA
338


 


NM_005080_796-814
GGACGUCAUCAGCCAAGCU
339
AGCUUGGCUGAUGACGUCC
340


 


NM_005080_940-958
CCUCAGAGAAUGAUCACCC
341
GGGUGAUCAUUCUCUGAGG
342


 


NM_005080_954-972
CACCCUGAAUUCAUUGUCU
343
AGACAAUGAAUUCAGGGUG
344


 


NM_005080_977-995
GAAGGAAGAACCUGUAGAA
345
UUCUACAGGUUCUUCCUUC
346


 


NM_005080_1018-1036
GUAUCUCAAAUCUGCUUUC
347
GAAAGCAGAUUUGAGAUAC
348


 


NM_005080_1026-1044
AAUCUGCUUUCAUCCAGCC
349
GGCUGGAUGAAAGCAGAUU
350


 


NM_005080_1138-1156
UUGGUGUAAACCAUUCUUG
351
CAAGAAUGGUUUACACCAA
352


 


NM_005080_1141-1159
GUGUAAACCAUUCUUGGGA
353
UCCCAAGAAUGGUUUACAC
354


 


NM_005080_1142-1160
UGUAAACCAUUCUUGGGAG
355
CUCCCAAGAAUGGUUUACA
356


 


NM_005080_1155-1173
UGGGAGGACACUUUUGCCA
357
UGGCAAAAGUGUCCUCCCA
358


 


NM_005080_1158-1176
GAGGACACUUUUGCCAAUG
359
CAUUGGCAAAAGUGUCCUC
360


 


NM_005080_1193-1211
GAUUAGUGUCUAAGGAAUG
361
CAUUCCUUAGACACUAAUC
362


 


NM_005080_1196-1214
UAGUGUCUAAGGAAUGAUC
363
GAUCAUUCCUUAGACACUA
364


 


NM_005080_1219-1237
ACUGUUGCCCUUUUCCUUG
365
CAAGGAAAAGGGCAACAGU
366


 


NM_005080_107-125
UGUCGGGGCAGCCCGCCUC
367
GAGGCGGGCUGCCCCGACA
368


 


NM_005080_108-126
GUCGGGGCAGCCCGCCUCC
369
GGAGGCGGGCUGCCCCGAC
370


 


NM_005080_1505-1523
UAAGGGUCAUUAGACAAAU
371
AUUUGUCUAAUGACCCUUA
372


 


NM_005080_1567-1585
UCUCUUCCCCCUUUUUGGC
373
GCCAAAAAGGGGGAAGAGA
374


 


NM_005080_1672-1690
AUACUUCAAGUAAGAUCAA
375
UUGAUCUUACUUGAAGUAU
376


 


NM_005080_1678-1696
CAAGUAAGAUCAAGAAUCU
377
AGAUUCUUGAUCUUACUUG
378


 


NM_005080_1778-1796
CCAUUUAUUUAAAACUACC
379
GGUAGUUUUAAAUAAAUGG
380


 


NM_005080_1779-1797
CAUUUAUUUAAAACUACCC
381
GGGUAGUUUUAAAUAAAUG
382


 


NM_005080_280-298
CUGAAAAACAGAGUAGCAG
383
CUGCUACUCUGUUUUUCAG
384


 


NM_005080_282-300
GAAAAACAGAGUAGCAGCU
385
AGCUGCUACUCUGUUUUUC
386


 


NM_005080_288-306
CAGAGUAGCAGCUCAGACU
387
AGUCUGAGCUGCUACUCUG
388


 


NM_005080_291-309
AGUAGCAGCUCAGACUGCC
389
GGCAGUCUGAGCUGCUACU
390


 


NM_005080_347-365
AGCAAGUGGUAGAUUUAGA
391
UCUAAAUCUACCACUUGCU
392


 


NM_005080_397-415
CAGCUUUUACGAGAGAAAA
393
UUUUCUCUCGUAAAAGCUG
394


 


NM_005080_398-416
AGCUUUUACGAGAGAAAAC
395
GUUUUCUCUCGUAAAAGCU
396


 


NM_005080_399-417
GCUUUUACGAGAGAAAACU
397
AGUUUUCUCUCGUAAAAGC
398


 


NM_005080_512-530
UGAGGCCAGUGGCCGGGUC
399
GACCCGGCCACUGGCCUCA
400


 


NM_005080_517-535
CCAGUGGCCGGGUCUGCUG
401
CAGCAGACCCGGCCACUGG
402


 


NM_005080_596-614
UCCAGAACAUCUCCCCAUG
403
CAUGGGGAGAUGUUCUGGA
404


 


NM_005080_598-616
CAGAACAUCUCCCCAUGGA
405
UCCAUGGGGAGAUGUUCUG
406


 


NM_005080_601-619
AACAUCUCCCCAUGGAUUC
407
GAAUCCAUGGGGAGAUGUU
408


 


NM_005080_605-623
UCUCCCCAUGGAUUCUGGC
409
GCCAGAAUCCAUGGGGAGA
410


 


NM_005080_661-679
UGGGCAUUCUGGACAACUU
411
AAGUUGUCCAGAAUGCCCA
412


 


NM_005080_688-706
UCAUGUUCUUCAAAUGCCC
413
GGGCAUUUGAAGAACAUGA
414


 


NM_005080_691-709
UGUUCUUCAAAUGCCCUUC
415
GAAGGGCAUUUGAAGAACA
416


 


NM_005080_828-846
GAACUAAUUCGUUUUGACC
417
GGUCAAAACGAAUUAGUUC
418


 


NM_005080_830-848
ACUAAUUCGUUUUGACCAC
419
GUGGUCAAAACGAAUUAGU
420


 


NM_005080_834-852
AUUCGUUUUGACCACAUAU
421
AUAUGUGGUCAAAACGAAU
422


 


NM_005080_846-864
CACAUAUAUACCAAGCCCC
423
GGGGCUUGGUAUAUAUGUG
424


 


NM_005080_870-888
UUAGAGAUACCCUCUGAGA
425
UCUCAGAGGGUAUCUCUAA
426


 


NM_005080_891-909
GAGAGCCAAGCUAAUGUGG
427
CCACAUUAGCUUGGCUCUC
428


 


NM_005080_900-918
GCUAAUGUGGUAGUGAAAA
429
UUUUCACUACCACAUUAGC
430


 


NM_005080_911-929
AGUGAAAAUCGAGGAAGCA
431
UGCUUCCUCGAUUUUCACU
432


 


NM_005080_912-930
GUGAAAAUCGAGGAAGCAC
433
GUGCUUCCUCGAUUUUCAC
434


 


NM_005080_979-997
AGGAAGAACCUGUAGAAGA
435
UCUUCUACAGGUUCUUCCU
436


 


NM_005080_1366-1384
GUCUUUUGACAUCCAGCAG
437
CUGCUGGAUGUCAAAAGAC
438


 


NM_005080_150-168
GGCCCUGCCGCUCAUGGUG
439
CACCAUGAGCGGCAGGGCC
440


 


NM_005080_1437-1455
AACUACAGCUUUUAAGAUU
441
AAUCUUAAAAGCUGUAGUU
442


 


NM_005080_482-500
AAGAGGAGGCGGAAGCCAA
443
TTGGCTTCCGCCTCCTCTT
444


 


NM_005080_580-598
GCCCAGUUGUCACCCCUCC
445
GGAGGGGUGACAACUGGGC
446


 


NM_005080_613-631
UGGAUUCUGGCGGUAUUGA
447
UCAAUACCGCCAGAAUCCA
448


 


NM_005080_1065-1083
UGCCUACUGGAUGCUUACA
449
UGUAAGCAUCCAGUAGGCA
450


 


NM_005080_614-632
GGAUUCUGGCGGUAUUGAC
451
GUCAAUACCGCCAGAAUCC
452


 


NM_005080_640-658
AUUCAGAGUCUGAUAUCCU
453
AGGAUAUCAGACUCUGAAU
454


 


NM_005080_1014-1032
CUGGGUAUCUCAAAUCUGC
455
GCAGAUUUGAGAUACCCAG
456


 


NM_005080_1015-1033
UGGGUAUCUCAAAUCUGCU
457
AGCAGAUUUGAGAUACCCA
458


 


NM_005080_1146-1164
AACCAUUCUUGGGAGGACA
459
UGUCCUCCCAAGAAUGGUU
460


 


NM_005080_1232-1250
UCCUUGACUAUUACACUGC
461
GCAGUGUAAUAGUCAAGGA
462


 


NM_005080_1234-1252
CUUGACUAUUACACUGCCU
463
AGGCAGUGUAAUAGUCAAG
464


 


NM_005080_1237-1255
GACUAUUACACUGCCUGGA
465
UCCAGGCAGUGUAAUAGUC
466


 


NM_005080_1443-1461
AGCUUUUAAGAUUGUACUU
467
AAGUACAAUCUUAAAAGCU
468


 


NM_005080_1462-1480
UUAUCUUAAAAGGGUGGUA
469
UACCACCCUUUUAAGAUAA
470


 


NM_005080_1510-1528
GUCAUUAGACAAAUGUCUU
471
AAGACAUUUGUCUAAUGAC
472


 


NM_005080_1591-1609
GGCUUGCCUCCAGUUUUAG
473
CUAAAACUGGAGGCAAGCC
474


 


NM_005080_1615-1633
UUAGUUUGCUUCUGUAAGC
475
GCUUACAGAAGCAAACUAA
476


 


NM_005080_1716-1734
UUACUAUGUAAAUGCUUGA
477
UCAAGCAUUUACAUAGUAA
478


 


NM_005080_1718-1736
ACUAUGUAAAUGCUUGAUG
479
CAUCAAGCAUUUACAUAGU
480


 


NM_005080_1725-1743
AAAUGCUUGAUGGAAUUUU
481
AAAAUUCCAUCAAGCAUUU
482


 


NM_005080_1748-1766
UGCUAGUGUAGCUUCUGAA
483
UUCAGAAGCUACACUAGCA
484


 


NM_005080_1780-1798
AUUUAUUUAAAACUACCCA
485
UGGGUAGUUUUAAAUAAAU
486


 


NM_005080_1794-1812
ACCCAUGCAAUUAAAAGGU
487
ACCUUUUAAUUGCAUGGGU
488


 


NM_005080_156-174
GCCGCUCAUGGUGCCAGCC
489
GGCUGGCACCAUGAGCGGC
490


 


NM_005080_299-317
CUCAGACUGCCAGAGAUCG
491
CGAUCUCUGGCAGUCUGAG
492


 


NM_005080_344-362
AACAGCAAGUGGUAGAUUU
493
AAAUCUACCACUUGCUGUU
494


 


NM_005080_371-389
AGAACCAAAAACUUUUGCU
495
AGCAAAAGUUUUUGGUUCU
496


 


NM_005080_373-391
AACCAAAAACUUUUGCUAG
497
CUAGCAAAAGUUUUUGGUU
498


 


NM_005080_524-542
CCGGGUCUGCUGAGUCCGC
499
GCGGACUCAGCAGACCCGG
500


 


NM_005080_525-543
CGGGUCUGCUGAGUCCGCA
501
UGCGGACUCAGCAGACCCG
502


 


NM_005080_612-630
AUGGAUUCUGGCGGUAUUG
503
CAAUACCGCCAGAAUCCAU
504


 


NM_005080_615-633
GAUUCUGGCGGUAUUGACU
505
AGUCAAUACCGCCAGAAUC
506


 


NM_005080_645-663
GAGUCUGAUAUCCUGUUGG
507
CCAACAGGAUAUCAGACUC
508


 


NM_005080_792-810
GUGGGGACGUCAUCAGCCA
509
UGGCUGAUGACGUCCCCAC
510


 


NM_005080_905-923
UGUGGUAGUGAAAAUCGAG
511
CUCGAUUUUCACUACCACA
512


 


NM_005080_976-994
UGAAGGAAGAACCUGUAGA
513
UCUACAGGUUCUUCCUUCA
514


 


NM_005080_1244-1262
ACACUGCCUGGAGGAUAGC
515
GCUAUCCUCCAGGCAGUGU
516


 


NM_005080_1791-1809
ACUACCCAUGCAAUUAAAA
517
UUUUAAUUGCAUGGGUAGU
518


 


NM_005080_755-773
AGGACCCAGUUCCUUACCA
519
UGGUAAGGAACUGGGUCCU
520


 


NM_005080_799-817
CGUCAUCAGCCAAGCUGGA
521
UCCAGCUUGGCUGAUGACG
522


 


NM_005080_832-850
UAAUUCGUUUUGACCACAU
523
AUGUGGUCAAAACGAAUUA
524


 


NM_005080_839-857
UUUUGACCACAUAUAUACC
525
GGUAUAUAUGUGGUCAAAA
526


 


NM_005080_100-118
CUGCUUCUGUCGGGGCAGC
527
GCUGCCCCGACAGAAGCAG
528


 


NM_005080_281-299
UGAAAAACAGAGUAGCAGC
529
GCUGCUACUCUGUUUUUCA
530


 


NM_005080_822-840
AUUAAUGAACUAAUUCGUU
531
AACGAAUUAGUUCAUUAAU
532


 


NM_005080_1152-1170
UCUUGGGAGGACACUUUUG
533
CAAAAGUGUCCUCCCAAGA
534


 


NM_005080_1191-1209
CUGAUUAGUGUCUAAGGAA
535
UUCCUUAGACACUAAUCAG
536


 


NM_005080_1225-1243
GCCCUUUUCCUUGACUAUU
537
AAUAGUCAAGGAAAAGGGC
538


 


NM_005080_1227-1245
CCUUUUCCUUGACUAUUAC
539
GUAAUAGUCAAGGAAAAGG
540


 


NM_005080_1239-1257
CUAUUACACUGCCUGGAGG
541
CCUCCAGGCAGUGUAAUAG
542


 


NM_005080_1430-1448
AAUUGAGAACUACAGCUUU
543
AAAGCUGUAGUUCUCAAUU
544


 


NM_005080_1499-1517
AUUAUGUAAGGGUCAUUAG
545
CUAAUGACCCUUACAUAAU
546


 


NM_005080_1553-1571
GGUUCUUUAUCAUUUCUCU
547
AGAGAAAUGAUAAAGAACC
548


 


NM_005080_1585-1603
CAUCCUGGCUUGCCUCCAG
549
CUGGAGGCAAGCCAGGAUG
550


 


NM_005080_1592-1610
GCUUGCCUCCAGUUUUAGG
551
CCUAAAACUGGAGGCAAGC
552


 


NM_005080_1743-1761
UUUCCUGCUAGUGUAGCUU
553
AAGCUACACUAGCAGGAAA
554


 


NM_005080_154-172
CUGCCGCUCAUGGUGCCAG
555
CUGGCACCAUGAGCGGCAG
556


 


NM_005080_193-211
GAGGCAGCGAGCGGGGGGC
557
GCCCCCCGCTCGCTGCCTC
558


 


NM_005080_199-217
GCGAGCGGGGGGCUGCCCC
559
GGGGCAGCCCCCCGCUCGC
560


 


NM_005080_292-310
GUAGCAGCUCAGACUGCCA
561
UGGCAGUCUGAGCUGCUAC
562


 


NM_005080_341-359
UGGAACAGCAAGUGGUAGA
563
UCUACCACUUGCUGUUCCA
564


 


NM_005080_377-395
AAAAACUUUUGCUAGAAAA
565
UUUUCUAGCAAAAGUUUUU
566


 


NM_005080_519-537
AGUGGCCGGGUCUGCUGAG
567
CUCAGCAGACCCGGCCACU
568


 


NM_005080_522-540
GGCCGGGUCUGCUGAGUCC
569
GGACUCAGCAGACCCGGCC
570


 


NM_005080_577-595
CAGGCCCAGUUGUCACCCC
571
GGGGUGACAACUGGGCCUG
572


 


NM_005080_599-617
AGAACAUCUCCCCAUGGAU
573
AUCCAUGGGGAGAUGUUCU
574


 


NM_005080_754-772
AAGGACCCAGUUCCUUACC
575
GGUAAGGAACUGGGUCCUU
576


 


NM_005080_888-906
ACAGAGAGCCAAGCUAAUG
577
CAUUAGCUUGGCUCUCUGU
578


 


NM_005080_939-957
CCCUCAGAGAAUGAUCACC
579
GGUGAUCAUUCUCUGAGGG
580


 


NM_005080_964-982
UCAUUGUCUCAGUGAAGGA
581
UCCUUCACUGAGACAAUGA
582


 


NM_005080_1012-1030
AGCUGGGUAUCUCAAAUCU
583
AGAUUUGAGAUACCCAGCU
584


 


NM_005080_1016-1034
GGGUAUCUCAAAUCUGCUU
585
AAGCAGAUUUGAGAUACCC
586


 


NM_005080_1020-1038
AUCUCAAAUCUGCUUUCAU
587
AUGAAAGCAGAUUUGAGAU
588


 


NM_005080_1025-1043
AAAUCUGCUUUCAUCCAGC
589
GCUGGAUGAAAGCAGAUUU
590


 


NM_005080_1027-1045
AUCUGCUUUCAUCCAGCCA
591
UGGCUGGAUGAAAGCAGAU
592


 


NM_005080_1028-1046
UCUGCUUUCAUCCAGCCAC
593
GUGGCUGGAUGAAAGCAGA
594


 


NM_005080_1030-1048
UGCUUUCAUCCAGCCACUG
595
CAGUGGCUGGAUGAAAGCA
596


 


NM_005080_1031-1049
GCUUUCAUCCAGCCACUGC
597
GCAGUGGCUGGAUGAAAGC
598


 


NM_005080_1032-1050
CUUUCAUCCAGCCACUGCC
599
GGCAGUGGCUGGAUGAAAG
600


 


NM_005080_1033-1051
UUUCAUCCAGCCACUGCCC
601
GGGCAGUGGCUGGAUGAAA
602


 


NM_005080_1056-1074
CCAUCUUCCUGCCUACUGG
603
CCAGUAGGCAGGAAGAUGG
604


 


NM_005080_1057-1075
CAUCUUCCUGCCUACUGGA
605
UCCAGUAGGCAGGAAGAUG
606


 


NM_005080_1058-1076
AUCUUCCUGCCUACUGGAU
607
AUCCAGUAGGCAGGAAGAU
608


 


NM_005080_1059-1077
UCUUCCUGCCUACUGGAUG
609
CAUCCAGUAGGCAGGAAGA
610


 


NM_005080_1061-1079
UUCCUGCCUACUGGAUGCU
611
AGCAUCCAGUAGGCAGGAA
612


 


NM_005080_1063-1081
CCUGCCUACUGGAUGCUUA
613
UAAGCAUCCAGUAGGCAGG
614


 


NM_005080_1069-1087
UACUGGAUGCUUACAGUGA
615
UCACUGUAAGCAUCCAGUA
616


 


NM_005080_1071-1089
CUGGAUGCUUACAGUGACU
617
AGUCACUGUAAGCAUCCAG
618


 


NM_005080_1073-1091
GGAUGCUUACAGUGACUGU
619
ACAGUCACUGUAAGCAUCC
620


 


NM_005080_1075-1093
AUGCUUACAGUGACUGUGG
621
CCACAGUCACUGUAAGCAU
622


 


NM_005080_1076-1094
UGCUUACAGUGACUGUGGA
623
UCCACAGUCACUGUAAGCA
624


 


NM_005080_1078-1096
CUUACAGUGACUGUGGAUA
625
UAUCCACAGUCACUGUAAG
626


 


NM_005080_1139-1157
UGGUGUAAACCAUUCUUGG
627
CCAAGAAUGGUUUACACCA
628


 


NM_005080_1140-1158
GGUGUAAACCAUUCUUGGG
629
CCCAAGAAUGGUUUACACC
630


 


NM_005080_1143-1161
GUAAACCAUUCUUGGGAGG
631
CCUCCCAAGAAUGGUUUAC
632


 


NM_005080_1144-1162
UAAACCAUUCUUGGGAGGA
633
UCCUCCCAAGAAUGGUUUA
634


 


NM_005080_1145-1163
AAACCAUUCUUGGGAGGAC
635
GUCCUCCCAAGAAUGGUUU
636


 


NM_005080_1148-1166
CCAUUCUUGGGAGGACACU
637
AGUGUCCUCCCAAGAAUGG
638


 


NM_005080_1156-1174
GGGAGGACACUUUUGCCAA
639
UUGGCAAAAGUGUCCUCCC
640


 


NM_005080_1157-1175
GGAGGACACUUUUGCCAAU
641
AUUGGCAAAAGUGUCCUCC
642


 


NM_005080_1159-1177
AGGACACUUUUGCCAAUGA
643
UCAUUGGCAAAAGUGUCCU
644


 


NM_005080_1160-1178
GGACACUUUUGCCAAUGAA
645
UUCAUUGGCAAAAGUGUCC
646


 


NM_005080_1190-1208
GCUGAUUAGUGUCUAAGGA
647
UCCUUAGACACUAAUCAGC
648


 


NM_005080_1218-1236
UACUGUUGCCCUUUUCCUU
649
AAGGAAAAGGGCAACAGUA
650


 


NM_005080_1220-1238
CUGUUGCCCUUUUCCUUGA
651
UCAAGGAAAAGGGCAACAG
652


 


NM_005080_1221-1239
UGUUGCCCUUUUCCUUGAC
653
GUCAAGGAAAAGGGCAACA
654


 


NM_005080_1233-1251
CCUUGACUAUUACACUGCC
655
GGCAGUGUAAUAGUCAAGG
656


 


NM_005080_1240-1258
UAUUACACUGCCUGGAGGA
657
UCCUCCAGGCAGUGUAAUA
658


 


NM_005080_1241-1259
AUUACACUGCCUGGAGGAU
659
AUCCUCCAGGCAGUGUAAU
660


 


NM_005080_1242-1260
UUACACUGCCUGGAGGAUA
661
UAUCCUCCAGGCAGUGUAA
662


 


NM_005080_1243-1261
UACACUGCCUGGAGGAUAG
663
CUAUCCUCCAGGCAGUGUA
664


 


NM_005080_1282-1300
UCAUUCAAAAAGCCAAAAU
665
AUUUUGGCUUUUUGAAUGA
666


 


NM_005080_1287-1305
CAAAAAGCCAAAAUAGAGA
667
UCUCUAUUUUGGCUUUUUG
668


 


NM_005080_1289-1307
AAAAGCCAAAAUAGAGAGU
669
ACUCUCUAUUUUGGCUUUU
670


 


NM_005080_1310-1328
ACAGUCCUAGAGAAUUCCU
671
AGGAAUUCUCUAGGACUGU
672


 


NM_005080_1330-1348
UAUUUGUUCAGAUCUCAUA
673
UAUGAGAUCUGAACAAAUA
674


 


NM_005080_1332-1350
UUUGUUCAGAUCUCAUAGA
675
UCUAUGAGAUCUGAACAAA
676


 


NM_005080_1333-1351
UUGUUCAGAUCUCAUAGAU
677
AUCUAUGAGAUCUGAACAA
678


 


NM_005080_1369-1387
UUUUGACAUCCAGCAGUCC
679
GGACUGCUGGAUGUCAAAA
680


 


NM_005080_1370-1388
UUUGACAUCCAGCAGUCCA
681
UGGACUGCUGGAUGUCAAA
682


 


NM_005080_1371-1389
UUGACAUCCAGCAGUCCAA
683
UUGGACUGCUGGAUGUCAA
684


 


NM_005080_101-119
UGCUUCUGUCGGGGCAGCC
685
GGCUGCCCCGACAGAAGCA
686


 


NM_005080_1418-1436
AAAUAUUACUAUAAUUGAG
687
CUCAAUUAUAGUAAUAUUU
688


 


NM_005080_1419-1437
AAUAUUACUAUAAUUGAGA
689
UCUCAAUUAUAGUAAUAUU
690


 


NM_005080_1422-1440
AUUACUAUAAUUGAGAACU
691
AGUUCUCAAUUAUAGUAAU
692


 


NM_005080_102-120
GCUUCUGUCGGGGCAGCCC
693
GGGCUGCCCCGACAGAAGC
694


 


NM_005080_1423-1441
UUACUAUAAUUGAGAACUA
695
UAGUUCUCAAUUAUAGUAA
696


 


NM_005080_1425-1443
ACUAUAAUUGAGAACUACA
697
UGUAGUUCUCAAUUAUAGU
698


 


NM_005080_1427-1445
UAUAAUUGAGAACUACAGC
699
GCUGUAGUUCUCAAUUAUA
700


 


NM_005080_1428-1446
AUAAUUGAGAACUACAGCU
701
AGCUGUAGUUCUCAAUUAU
702


 


NM_005080_1429-1447
UAAUUGAGAACUACAGCUU
703
AAGCUGUAGUUCUCAAUUA
704


 


NM_005080_1432-1450
UUGAGAACUACAGCUUUUA
705
UAAAAGCUGUAGUUCUCAA
706


 


NM_005080_1433-1451
UGAGAACUACAGCUUUUAA
707
UUAAAAGCUGUAGUUCUCA
708


 


NM_005080_1435-1453
AGAACUACAGCUUUUAAGA
709
UCUUAAAAGCUGUAGUUCU
710


 


NM_005080_1439-1457
CUACAGCUUUUAAGAUUGU
711
ACAAUCUUAAAAGCUGUAG
712


 


NM_005080_104-122
UUCUGUCGGGGCAGCCCGC
713
GCGGGCUGCCCCGACAGAA
714


 


NM_005080_1444-1462
GCUUUUAAGAUUGUACUUU
715
AAAGUACAAUCUUAAAAGC
716


 


NM_005080_1445-1463
CUUUUAAGAUUGUACUUUU
717
AAAAGUACAAUCUUAAAAG
718


 


NM_005080_1446-1464
UUUUAAGAUUGUACUUUUA
719
UAAAAGUACAAUCUUAAAA
720


 


NM_005080_1447-1465
UUUAAGAUUGUACUUUUAU
721
AUAAAAGUACAAUCUUAAA
722


 


NM_005080_1448-1466
UUAAGAUUGUACUUUUAUC
723
GAUAAAAGUACAAUCUUAA
724


 


NM_005080_1451-1469
AGAUUGUACUUUUAUCUUA
725
UAAGAUAAAAGUACAAUCU
726


 


NM_005080_1454-1472
UUGUACUUUUAUCUUAAAA
727
UUUUAAGAUAAAAGUACAA
728


 


NM_005080_1458-1476
ACUUUUAUCUUAAAAGGGU
729
ACCCUUUUAAGAUAAAAGU
730


 


NM_005080_1459-1477
CUUUUAUCUUAAAAGGGUG
731
CACCCUUUUAAGAUAAAAG
732


 


NM_005080_106-124
CUGUCGGGGCAGCCCGCCU
733
AGGCGGGCUGCCCCGACAG
734


 


NM_005080_1466-1484
CUUAAAAGGGUGGUAGUUU
735
AAACUACCACCCUUUUAAG
736


 


NM_005080_1486-1504
CCCUAAAAUACUUAUUAUG
737
CAUAAUAAGUAUUUUAGGG
738


 


NM_005080_1487-1505
CCUAAAAUACUUAUUAUGU
739
ACAUAAUAAGUAUUUUAGG
740


 


NM_005080_1489-1507
UAAAAUACUUAUUAUGUAA
741
UUACAUAAUAAGUAUUUUA
742


 


NM_005080_1490-1508
AAAAUACUUAUUAUGUAAG
743
CUUACAUAAUAAGUAUUUU
744


 


NM_005080_1491-1509
AAAUACUUAUUAUGUAAGG
745
CCUUACAUAAUAAGUAUUU
746


 


NM_005080_109-127
UCGGGGCAGCCCGCCUCCG
747
CGGAGGCGGGCUGCCCCGA
748


 


NM_005080_1497-1515
UUAUUAUGUAAGGGUCAUU
749
AAUGACCCUUACAUAAUAA
750


 


NM_005080_1498-1516
UAUUAUGUAAGGGUCAUUA
751
UAAUGACCCUUACAUAAUA
752


 


NM_005080_110-128
CGGGGCAGCCCGCCUCCGC
753
GCGGAGGCGGGCUGCCCCG
754


 


NM_005080_1511-1529
UCAUUAGACAAAUGUCUUG
755
CAAGACAUUUGUCUAAUGA
756


 


NM_005080_1513-1531
AUUAGACAAAUGUCUUGAA
757
UUCAAGACAUUUGUCUAAU
758


 


NM_005080_1516-1534
AGACAAAUGUCUUGAAGUA
759
UACUUCAAGACAUUUGUCU
760


 


NM_005080_1517-1535
GACAAAUGUCUUGAAGUAG
761
CUACUUCAAGACAUUUGUC
762


 


NM_005080_1518-1536
ACAAAUGUCUUGAAGUAGA
763
UCUACUUCAAGACAUUUGU
764


 


NM_005080_1547-1565
AUGAAUGGUUCUUUAUCAU
765
AUGAUAAAGAACCAUUCAU
766


 


NM_005080_1550-1568
AAUGGUUCUUUAUCAUUUC
767
GAAAUGAUAAAGAACCAUU
768


 


NM_005080_1551-1569
AUGGUUCUUUAUCAUUUCU
769
AGAAAUGAUAAAGAACCAU
770


 


NM_005080_1552-1570
UGGUUCUUUAUCAUUUCUC
771
GAGAAAUGAUAAAGAACCA
772


 


NM_005080_1554-1572
GUUCUUUAUCAUUUCUCUU
773
AAGAGAAAUGAUAAAGAAC
774


 


NM_005080_1559-1577
UUAUCAUUUCUCUUCCCCC
775
GGGGGAAGAGAAAUGAUAA
776


 


NM_005080_1560-1578
UAUCAUUUCUCUUCCCCCU
777
AGGGGGAAGAGAAAUGAUA
778


 


NM_005080_1563-1581
CAUUUCUCUUCCCCCUUUU
779
AAAAGGGGGAAGAGAAAUG
780


 


NM_005080_1565-1583
UUUCUCUUCCCCCUUUUUG
781
CAAAAAGGGGGAAGAGAAA
782


 


NM_005080_1566-1584
UUCUCUUCCCCCUUUUUGG
783
CCAAAAAGGGGGAAGAGAA
784


 


NM_005080_1570-1588
CUUCCCCCUUUUUGGCAUC
785
GAUGCCAAAAAGGGGGAAG
786


 


NM_005080_1573-1591
CCCCCUUUUUGGCAUCCUG
787
CAGGAUGCCAAAAAGGGGG
788


 


NM_005080_1578-1596
UUUUUGGCAUCCUGGCUUG
789
CAAGCCAGGAUGCCAAAAA
790


 


NM_005080_1579-1597
UUUUGGCAUCCUGGCUUGC
791
GCAAGCCAGGAUGCCAAAA
792


 


NM_005080_1580-1598
UUUGGCAUCCUGGCUUGCC
793
GGCAAGCCAGGAUGCCAAA
794


 


NM_005080_1581-1599
UUGGCAUCCUGGCUUGCCU
795
AGGCAAGCCAGGAUGCCAA
796


 


NM_005080_1583-1601
GGCAUCCUGGCUUGCCUCC
797
GGAGGCAAGCCAGGAUGCC
798


 


NM_005080_1584-1602
GCAUCCUGGCUUGCCUCCA
799
UGGAGGCAAGCCAGGAUGC
800


 


NM_005080_1586-1604
AUCCUGGCUUGCCUCCAGU
801
ACUGGAGGCAAGCCAGGAU
802


 


NM_005080_1589-1607
CUGGCUUGCCUCCAGUUUU
803
AAAACUGGAGGCAAGCCAG
804


 


NM_005080_1590-1608
UGGCUUGCCUCCAGUUUUA
805
UAAAACUGGAGGCAAGCCA
806


 


NM_005080_1595-1613
UGCCUCCAGUUUUAGGUCC
807
GGACCUAAAACUGGAGGCA
808


 


NM_005080_1616-1634
UAGUUUGCUUCUGUAAGCA
809
UGCUUACAGAAGCAAACUA
810


 


NM_005080_1617-1635
AGUUUGCUUCUGUAAGCAA
811
UUGCUUACAGAAGCAAACU
812


 


NM_005080_1643-1661
ACCUGCUGAGGGGGCUCUU
813
AAGAGCCCCCUCAGCAGGU
814


 


NM_005080_1645-1663
CUGCUGAGGGGGCUCUUUC
815
GAAAGAGCCCCCUCAGCAG
816


 


NM_005080_1646-1664
UGCUGAGGGGGCUCUUUCC
817
GGAAAGAGCCCCCUCAGCA
818


 


NM_005080_1647-1665
GCUGAGGGGGCUCUUUCCC
819
GGGAAAGAGCCCCCUCAGC
820


 


NM_005080_1648-1666
CUGAGGGGGCUCUUUCCCU
821
AGGGAAAGAGCCCCCUCAG
822


 


NM_005080_1649-1667
UGAGGGGGCUCUUUCCCUC
823
GAGGGAAAGAGCCCCCUCA
824


 


NM_005080_1679-1697
AAGUAAGAUCAAGAAUCUU
825
AAGAUUCUUGAUCUUACUU
826


 


NM_005080_1680-1698
AGUAAGAUCAAGAAUCUUU
827
AAAGAUUCUUGAUCUUACU
828


 


NM_005080_1681-1699
GUAAGAUCAAGAAUCUUUU
829
AAAAGAUUCUUGAUCUUAC
830


 


NM_005080_1682-1700
UAAGAUCAAGAAUCUUUUG
831
CAAAAGAUUCUUGAUCUUA
832


 


NM_005080_1683-1701
AAGAUCAAGAAUCUUUUGU
833
ACAAAAGAUUCUUGAUCUU
834


 


NM_005080_1684-1702
AGAUCAAGAAUCUUUUGUG
835
CACAAAAGAUUCUUGAUCU
836


 


NM_005080_1687-1705
UCAAGAAUCUUUUGUGAAA
837
UUUCACAAAAGAUUCUUGA
838


 


NM_005080_1709-1727
UAGAAAUUUACUAUGUAAA
839
UUUACAUAGUAAAUUUCUA
840


 


NM_005080_1710-1728
AGAAAUUUACUAUGUAAAU
841
AUUUACAUAGUAAAUUUCU
842


 


NM_005080_1711-1729
GAAAUUUACUAUGUAAAUG
843
CAUUUACAUAGUAAAUUUC
844


 


NM_005080_1712-1730
AAAUUUACUAUGUAAAUGC
845
GCAUUUACAUAGUAAAUUU
846


 


NM_005080_1714-1732
AUUUACUAUGUAAAUGCUU
847
AAGCAUUUACAUAGUAAAU
848


 


NM_005080_1715-1733
UUUACUAUGUAAAUGCUUG
849
CAAGCAUUUACAUAGUAAA
850


 


NM_005080_1717-1735
UACUAUGUAAAUGCUUGAU
851
AUCAAGCAUUUACAUAGUA
852


 


NM_005080_1719-1737
CUAUGUAAAUGCUUGAUGG
853
CCAUCAAGCAUUUACAUAG
854


 


NM_005080_1721-1739
AUGUAAAUGCUUGAUGGAA
855
UUCCAUCAAGCAUUUACAU
856


 


NM_005080_1722-1740
UGUAAAUGCUUGAUGGAAU
857
AUUCCAUCAAGCAUUUACA
858


 


NM_005080_1723-1741
GUAAAUGCUUGAUGGAAUU
859
AAUUCCAUCAAGCAUUUAC
860


 


NM_005080_1726-1744
AAUGCUUGAUGGAAUUUUU
861
AAAAAUUCCAUCAAGCAUU
862


 


NM_005080_1727-1745
AUGCUUGAUGGAAUUUUUU
863
AAAAAAUUCCAUCAAGCAU
864


 


NM_005080_1728-1746
UGCUUGAUGGAAUUUUUUC
865
GAAAAAAUUCCAUCAAGCA
866


 


NM_005080_1729-1747
GCUUGAUGGAAUUUUUUCC
867
GGAAAAAAUUCCAUCAAGC
868


 


NM_005080_1736-1754
GGAAUUUUUUCCUGCUAGU
869
ACUAGCAGGAAAAAAUUCC
870


 


NM_005080_1739-1757
AUUUUUUCCUGCUAGUGUA
871
UACACUAGCAGGAAAAAAU
872


 


NM_005080_1746-1764
CCUGCUAGUGUAGCUUCUG
873
CAGAAGCUACACUAGCAGG
874


 


NM_005080_1747-1765
CUGCUAGUGUAGCUUCUGA
875
UCAGAAGCUACACUAGCAG
876


 


NM_005080_1749-1767
GCUAGUGUAGCUUCUGAAA
877
UUUCAGAAGCUACACUAGC
878


 


NM_005080_1750-1768
CUAGUGUAGCUUCUGAAAG
879
CUUUCAGAAGCUACACUAG
880


 


NM_005080_1751-1769
UAGUGUAGCUUCUGAAAGG
881
CCUUUCAGAAGCUACACUA
882


 


NM_005080_1752-1770
AGUGUAGCUUCUGAAAGGU
883
ACCUUUCAGAAGCUACACU
884


 


NM_005080_1753-1771
GUGUAGCUUCUGAAAGGUG
885
CACCUUUCAGAAGCUACAC
886


 


NM_005080_1755-1773
GUAGCUUCUGAAAGGUGCU
887
AGCACCUUUCAGAAGCUAC
888


 


NM_005080_1758-1776
GCUUCUGAAAGGUGCUUUC
889
GAAAGCACCUUUCAGAAGC
890


 


NM_005080_1781-1799
UUUAUUUAAAACUACCCAU
891
AUGGGUAGUUUUAAAUAAA
892


 


NM_005080_1782-1800
UUAUUUAAAACUACCCAUG
893
CAUGGGUAGUUUUAAAUAA
894


 


NM_005080_1784-1802
AUUUAAAACUACCCAUGCA
895
UGCAUGGGUAGUUUUAAAU
896


 


NM_005080_1785-1803
UUUAAAACUACCCAUGCAA
897
UUGCAUGGGUAGUUUUAAA
898


 


NM_005080_1788-1806
AAAACUACCCAUGCAAUUA
899
UAAUUGCAUGGGUAGUUUU
900


 


NM_005080_1792-1810
CUACCCAUGCAAUUAAAAG
901
CUUUUAAUUGCAUGGGUAG
902


 


NM_005080_1793-1811
UACCCAUGCAAUUAAAAGG
903
CCUUUUAAUUGCAUGGGUA
904


 


NM_005080_1795-1813
CCCAUGCAAUUAAAAGGUA
905
UACCUUUUAAUUGCAUGGG
906


 


NM_005080_1798-1816
AUGCAAUUAAAAGGUACAA
907
UUGUACCUUUUAAUUGCAU
908


 


NM_005080_1799-1817
UGCAAUUAAAAGGUACAAU
909
AUUGUACCUUUUAAUUGCA
910


 


NM_005080_1800-1818
GCAAUUAAAAGGUACAAUG
911
CAUUGUACCUUUUAAUUGC
912


 


NM_005080_1801-1819
CAAUUAAAAGGUACAAUGC
913
GCAUUGUACCUUUUAAUUG
914


 


NM_005080_146-164
GCCAGGCCCUGCCGCUCAU
915
AUGAGCGGCAGGGCCUGGC
916


 


NM_005080_147-165
CCAGGCCCUGCCGCUCAUG
917
CAUGAGCGGCAGGGCCUGG
918


 


NM_005080_148-166
CAGGCCCUGCCGCUCAUGG
919
CCAUGAGCGGCAGGGCCUG
920


 


NM_005080_149-167
AGGCCCUGCCGCUCAUGGU
921
ACCAUGAGCGGCAGGGCCU
922


 


NM_005080_155-173
UGCCGCUCAUGGUGCCAGC
923
GCUGGCACCAUGAGCGGCA
924


 


NM_005080_157-175
CCGCUCAUGGUGCCAGCCC
925
GGGCUGGCACCAUGAGCGG
926


 


NM_005080_158-176
CGCUCAUGGUGCCAGCCCA
927
UGGGCUGGCACCAUGAGCG
928


 


NM_005080_159-177
GCUCAUGGUGCCAGCCCAG
929
CUGGGCUGGCACCAUGAGC
930


 


NM_005080_188-206
GCCCGGAGGCAGCGAGCGG
931
CCGCTCGCTGCCTCCGGGC
932


 


NM_005080_189-207
CCCGGAGGCAGCGAGCGGG
933
CCCGCTCGCTGCCTCCGGG
934


 


NM_005080_195-213
GGCAGCGAGCGGGGGGCUG
935
CAGCCCCCCGCUCGCUGCC
936


 


NM_005080_196-214
GCAGCGAGCGGGGGGCUGC
937
GCAGCCCCCCGCUCGCUGC
938


 


NM_005080_197-215
CAGCGAGCGGGGGGCUGCC
939
GGCAGCCCCCCGCUCGCUG
940


 


NM_005080_198-216
AGCGAGCGGGGGGCUGCCC
941
GGGCAGCCCCCCGCUCGCU
942


 


NM_005080_205-223
GGGGGGCUGCCCCAGGCGC
943
GCGCCUGGGGCAGCCCCCC
944


 


NM_005080_206-224
GGGGGCUGCCCCAGGCGCG
945
CGCGCCUGGGGCAGCCCCC
946


 


NM_005080_207-225
GGGGCUGCCCCAGGCGCGC
947
GCGCGCCUGGGGCAGCCCC
948


 


NM_005080_211-229
CUGCCCCAGGCGCGCAAGC
949
GCUUGCGCGCCUGGGGCAG
950


 


NM_005080_250-268
AGCCCCGAGGAGAAGGCGC
951
GCGCCTTCTCCTCGGGGCT
952


 


NM_005080_256-274
GAGGAGAAGGCGCUGAGGA
953
UCCUCAGCGCCUUCUCCUC
954


 


NM_005080_263-281
AGGCGCUGAGGAGGAAACU
955
AGUUUCCUCCUCAGCGCCU
956


 


NM_005080_264-282
GGCGCUGAGGAGGAAACUG
957
CAGUUUCCUCCUCAGCGCC
958


 


NM_005080_285-303
AAACAGAGUAGCAGCUCAG
959
CUGAGCUGCUACUCUGUUU
960


 


NM_005080_286-304
AACAGAGUAGCAGCUCAGA
961
UCUGAGCUGCUACUCUGUU
962


 


NM_005080_287-305
ACAGAGUAGCAGCUCAGAC
963
GUCUGAGCUGCUACUCUGU
964


 


NM_005080_294-312
AGCAGCUCAGACUGCCAGA
965
UCUGGCAGUCUGAGCUGCU
966


 


NM_005080_295-313
GCAGCUCAGACUGCCAGAG
967
CUCUGGCAGUCUGAGCUGC
968


 


NM_005080_296-314
CAGCUCAGACUGCCAGAGA
969
UCUCUGGCAGUCUGAGCUG
970


 


NM_005080_298-316
GCUCAGACUGCCAGAGAUC
971
GAUCUCUGGCAGUCUGAGC
972


 


NM_005080_303-321
GACUGCCAGAGAUCGAAAG
973
CUUUCGAUCUCUGGCAGUC
974


 


NM_005080_332-350
UGAGUGAGCUGGAACAGCA
975
UGCUGUUCCAGCUCACUCA
976


 


NM_005080_339-357
GCUGGAACAGCAAGUGGUA
977
UACCACUUGCUGUUCCAGC
978


 


NM_005080_340-358
CUGGAACAGCAAGUGGUAG
979
CUACCACUUGCUGUUCCAG
980


 


NM_005080_345-363
ACAGCAAGUGGUAGAUUUA
981
UAAAUCUACCACUUGCUGU
982


 


NM_005080_346-364
CAGCAAGUGGUAGAUUUAG
983
CUAAAUCUACCACUUGCUG
984


 


NM_005080_348-366
GCAAGUGGUAGAUUUAGAA
985
UUCUAAAUCUACCACUUGC
986


 


NM_005080_349-367
CAAGUGGUAGAUUUAGAAG
987
CUUCUAAAUCUACCACUUG
988


 


NM_005080_352-370
GUGGUAGAUUUAGAAGAAG
989
CUUCUUCUAAAUCUACCAC
990


 


NM_005080_353-371
UGGUAGAUUUAGAAGAAGA
991
UCUUCUUCUAAAUCUACCA
992


 


NM_005080_354-372
GGUAGAUUUAGAAGAAGAG
993
CUCUUCUUCUAAAUCUACC
994


 


NM_005080_355-373
GUAGAUUUAGAAGAAGAGA
995
UCUCUUCUUCUAAAUCUAC
996


 


NM_005080_361-379
UUAGAAGAAGAGAACCAAA
997
UUUGGUUCUCUUCUUCUAA
998


 


NM_005080_366-384
AGAAGAGAACCAAAAACUU
999
AAGUUUUUGGUUCUCUUCU
1000


 


NM_005080_369-387
AGAGAACCAAAAACUUUUG
1001
CAAAAGUUUUUGGUUCUCU
1002


 


NM_005080_370-388
GAGAACCAAAAACUUUUGC
1003
GCAAAAGUUUUUGGUUCUC
1004


 


NM_005080_372-390
GAACCAAAAACUUUUGCUA
1005
UAGCAAAAGUUUUUGGUUC
1006


 


NM_005080_376-394
CAAAAACUUUUGCUAGAAA
1007
UUUCUAGCAAAAGUUUUUG
1008


 


NM_005080_381-399
ACUUUUGCUAGAAAAUCAG
1009
CUGAUUUUCUAGCAAAAGU
1010


 


NM_005080_384-402
UUUGCUAGAAAAUCAGCUU
1011
AAGCUGAUUUUCUAGCAAA
1012


 


NM_005080_388-406
CUAGAAAAUCAGCUUUUAC
1013
GUAAAAGCUGAUUUUCUAG
1014


 


NM_005080_392-410
AAAAUCAGCUUUUACGAGA
1015
UCUCGUAAAAGCUGAUUUU
1016


 


NM_005080_394-412
AAUCAGCUUUUACGAGAGA
1017
UCUCUCGUAAAAGCUGAUU
1018


 


NM_005080_396-414
UCAGCUUUUACGAGAGAAA
1019
UUUCUCUCGUAAAAGCUGA
1020


 


NM_005080_400-418
CUUUUACGAGAGAAAACUC
1021
GAGUUUUCUCUCGUAAAAG
1022


 


NM_005080_421-439
GGCCUUGUAGUUGAGAACC
1023
GGUUCUCAACUACAAGGCC
1024


 


NM_005080_422-440
GCCUUGUAGUUGAGAACCA
1025
UGGUUCUCAACUACAAGGC
1026


 


NM_005080_423-441
CCUUGUAGUUGAGAACCAG
1027
CUGGUUCUCAACUACAAGG
1028


 


NM_005080_425-443
UUGUAGUUGAGAACCAGGA
1029
UCCUGGUUCUCAACUACAA
1030


 


NM_005080_428-446
UAGUUGAGAACCAGGAGUU
1031
AACUCCUGGUUCUCAACUA
1032


 


NM_005080_429-447
AGUUGAGAACCAGGAGUUA
1033
UAACUCCUGGUUCUCAACU
1034


 


NM_005080_432-450
UGAGAACCAGGAGUUAAGA
1035
UCUUAACUCCUGGUUCUCA
1036


 


NM_005080_433-451
GAGAACCAGGAGUUAAGAC
1037
GUCUUAACUCCUGGUUCUC
1038


 


NM_005080_434-452
AGAACCAGGAGUUAAGACA
1039
UGUCUUAACUCCUGGUUCU
1040


 


NM_005080_435-453
GAACCAGGAGUUAAGACAG
1041
CUGUCUUAACUCCUGGUUC
1042


 


NM_005080_436-454
AACCAGGAGUUAAGACAGC
1043
GCUGUCUUAACUCCUGGUU
1044


 


NM_005080_459-477
GGGGAUGGAUGCCCUGGUU
1045
AACCAGGGCAUCCAUCCCC
1046


 


NM_005080_460-478
GGGAUGGAUGCCCUGGUUG
1047
CAACCAGGGCAUCCAUCCC
1048


 


NM_005080_462-480
GAUGGAUGCCCUGGUUGCU
1049
AGCAACCAGGGCAUCCAUC
1050


 


NM_005080_486-504
GGAGGCGGAAGCCAAGGGG
1051
CCCCTTGGCTTCCGCCTCC
1052


 


NM_005080_510-528
AGUGAGGCCAGUGGCCGGG
1053
CCCGGCCACUGGCCUCACU
1054


 


NM_005080_513-531
GAGGCCAGUGGCCGGGUCU
1055
AGACCCGGCCACUGGCCUC
1056


 


NM_005080_514-532
AGGCCAGUGGCCGGGUCUG
1057
CAGACCCGGCCACUGGCCU
1058


 


NM_005080_515-533
GGCCAGUGGCCGGGUCUGC
1059
GCAGACCCGGCCACUGGCC
1060


 


NM_005080_516-534
GCCAGUGGCCGGGUCUGCU
1061
AGCAGACCCGGCCACUGGC
1062


 


NM_005080_520-538
GUGGCCGGGUCUGCUGAGU
1063
ACUCAGCAGACCCGGCCAC
1064


 


NM_005080_521-539
UGGCCGGGUCUGCUGAGUC
1065
GACUCAGCAGACCCGGCCA
1066


 


NM_005080_523-541
GCCGGGUCUGCUGAGUCCG
1067
CGGACUCAGCAGACCCGGC
1068


 


NM_005080_578-596
AGGCCCAGUUGUCACCCCU
1069
AGGGGUGACAACUGGGCCU
1070


 


NM_005080_581-599
CCCAGUUGUCACCCCUCCA
1071
UGGAGGGGUGACAACUGGG
1072


 


NM_005080_582-600
CCAGUUGUCACCCCUCCAG
1073
CUGGAGGGGUGACAACUGG
1074


 


NM_005080_583-601
CAGUUGUCACCCCUCCAGA
1075
UCUGGAGGGGUGACAACUG
1076


 


NM_005080_584-602
AGUUGUCACCCCUCCAGAA
1077
UUCUGGAGGGGUGACAACU
1078


 


NM_005080_585-603
GUUGUCACCCCUCCAGAAC
1079
GUUCUGGAGGGGUGACAAC
1080


 


NM_005080_586-604
UUGUCACCCCUCCAGAACA
1081
UGUUCUGGAGGGGUGACAA
1082


 


NM_005080_587-605
UGUCACCCCUCCAGAACAU
1083
AUGUUCUGGAGGGGUGACA
1084


 


NM_005080_588-606
GUCACCCCUCCAGAACAUC
1085
GAUGUUCUGGAGGGGUGAC
1086


 


NM_005080_589-607
UCACCCCUCCAGAACAUCU
1087
AGAUGUUCUGGAGGGGUGA
1088


 


NM_005080_590-608
CACCCCUCCAGAACAUCUC
1089
GAGAUGUUCUGGAGGGGUG
1090


 


NM_005080_591-609
ACCCCUCCAGAACAUCUCC
1091
GGAGAUGUUCUGGAGGGGU
1092


 


NM_005080_597-615
CCAGAACAUCUCCCCAUGG
1093
CCAUGGGGAGAUGUUCUGG
1094


 


NM_005080_600-618
GAACAUCUCCCCAUGGAUU
1095
AAUCCAUGGGGAGAUGUUC
1096


 


NM_005080_603-621
CAUCUCCCCAUGGAUUCUG
1097
CAGAAUCCAUGGGGAGAUG
1098


 


NM_005080_619-637
CUGGCGGUAUUGACUCUUC
1099
GAAGAGUCAAUACCGCCAG
1100


 


NM_005080_620-638
UGGCGGUAUUGACUCUUCA
1101
UGAAGAGUCAAUACCGCCA
1102


 


NM_005080_622-640
GCGGUAUUGACUCUUCAGA
1103
UCUGAAGAGUCAAUACCGC
1104


 


NM_005080_623-641
CGGUAUUGACUCUUCAGAU
1105
AUCUGAAGAGUCAAUACCG
1106


 


NM_005080_624-642
GGUAUUGACUCUUCAGAUU
1107
AAUCUGAAGAGUCAAUACC
1108


 


NM_005080_625-643
GUAUUGACUCUUCAGAUUC
1109
GAAUCUGAAGAGUCAAUAC
1110


 


NM_005080_626-644
UAUUGACUCUUCAGAUUCA
1111
UGAAUCUGAAGAGUCAAUA
1112


 


NM_005080_629-647
UGACUCUUCAGAUUCAGAG
1113
CUCUGAAUCUGAAGAGUCA
1114


 


NM_005080_632-650
CUCUUCAGAUUCAGAGUCU
1115
AGACUCUGAAUCUGAAGAG
1116


 


NM_005080_634-652
CUUCAGAUUCAGAGUCUGA
1117
UCAGACUCUGAAUCUGAAG
1118


 


NM_005080_637-655
CAGAUUCAGAGUCUGAUAU
1119
AUAUCAGACUCUGAAUCUG
1120


 


NM_005080_638-656
AGAUUCAGAGUCUGAUAUC
1121
GAUAUCAGACUCUGAAUCU
1122


 


NM_005080_639-657
GAUUCAGAGUCUGAUAUCC
1123
GGAUAUCAGACUCUGAAUC
1124


 


NM_005080_642-660
UCAGAGUCUGAUAUCCUGU
1125
ACAGGAUAUCAGACUCUGA
1126


 


NM_005080_643-661
CAGAGUCUGAUAUCCUGUU
1127
AACAGGAUAUCAGACUCUG
1128


 


NM_005080_644-662
AGAGUCUGAUAUCCUGUUG
1129
CAACAGGAUAUCAGACUCU
1130


 


NM_005080_646-664
AGUCUGAUAUCCUGUUGGG
1131
CCCAACAGGAUAUCAGACU
1132


 


NM_005080_649-667
CUGAUAUCCUGUUGGGCAU
1133
AUGCCCAACAGGAUAUCAG
1134


 


NM_005080_650-668
UGAUAUCCUGUUGGGCAUU
1135
AAUGCCCAACAGGAUAUCA
1136


 


NM_005080_653-671
UAUCCUGUUGGGCAUUCUG
1137
CAGAAUGCCCAACAGGAUA
1138


 


NM_005080_658-676
UGUUGGGCAUUCUGGACAA
1139
UUGUCCAGAAUGCCCAACA
1140


 


NM_005080_659-677
GUUGGGCAUUCUGGACAAC
1141
GUUGUCCAGAAUGCCCAAC
1142


 


NM_005080_660-678
UUGGGCAUUCUGGACAACU
1143
AGUUGUCCAGAAUGCCCAA
1144


 


NM_005080_663-681
GGCAUUCUGGACAACUUGG
1145
CCAAGUUGUCCAGAAUGCC
1146


 


NM_005080_664-682
GCAUUCUGGACAACUUGGA
1147
UCCAAGUUGUCCAGAAUGC
1148


 


NM_005080_668-686
UCUGGACAACUUGGACCCA
1149
UGGGUCCAAGUUGUCCAGA
1150


 


NM_005080_671-689
GGACAACUUGGACCCAGUC
1151
GACUGGGUCCAAGUUGUCC
1152


 


NM_005080_676-694
ACUUGGACCCAGUCAUGUU
1153
AACAUGACUGGGUCCAAGU
1154


 


NM_005080_677-695
CUUGGACCCAGUCAUGUUC
1155
GAACAUGACUGGGUCCAAG
1156


 


NM_005080_679-697
UGGACCCAGUCAUGUUCUU
1157
AAGAACAUGACUGGGUCCA
1158


 


NM_005080_680-698
GGACCCAGUCAUGUUCUUC
1159
GAAGAACAUGACUGGGUCC
1160


 


NM_005080_682-700
ACCCAGUCAUGUUCUUCAA
1161
UUGAAGAACAUGACUGGGU
1162


 


NM_005080_687-705
GUCAUGUUCUUCAAAUGCC
1163
GGCAUUUGAAGAACAUGAC
1164


 


NM_005080_689-707
CAUGUUCUUCAAAUGCCCU
1165
AGGGCAUUUGAAGAACAUG
1166


 


NM_005080_695-713
CUUCAAAUGCCCUUCCCCA
1167
UGGGGAAGGGCAUUUGAAG
1168


 


NM_005080_696-714
UUCAAAUGCCCUUCCCCAG
1169
CUGGGGAAGGGCAUUUGAA
1170


 


NM_005080_698-716
CAAAUGCCCUUCCCCAGAG
1171
CUCUGGGGAAGGGCAUUUG
1172


 


NM_005080_731-749
GGAGCUCCCAGAGGUCUAC
1173
GUAGACCUCUGGGAGCUCC
1174


 


NM_005080_732-750
GAGCUCCCAGAGGUCUACC
1175
GGUAGACCUCUGGGAGCUC
1176


 


NM_005080_733-751
AGCUCCCAGAGGUCUACCC
1177
GGGUAGACCUCUGGGAGCU
1178


 


NM_005080_736-754
UCCCAGAGGUCUACCCAGA
1179
UCUGGGUAGACCUCUGGGA
1180


 


NM_005080_737-755
CCCAGAGGUCUACCCAGAA
1181
UUCUGGGUAGACCUCUGGG
1182


 


NM_005080_738-756
CCAGAGGUCUACCCAGAAG
1183
CUUCUGGGUAGACCUCUGG
1184


 


NM_005080_740-758
AGAGGUCUACCCAGAAGGA
1185
UCCUUCUGGGUAGACCUCU
1186


 


NM_005080_741-759
GAGGUCUACCCAGAAGGAC
1187
GUCCUUCUGGGUAGACCUC
1188


 


NM_005080_742-760
AGGUCUACCCAGAAGGACC
1189
GGUCCUUCUGGGUAGACCU
1190


 


NM_005080_743-761
GGUCUACCCAGAAGGACCC
1191
GGGUCCUUCUGGGUAGACC
1192


 


NM_005080_748-766
ACCCAGAAGGACCCAGUUC
1193
GAACUGGGUCCUUCUGGGU
1194


 


NM_005080_749-767
CCCAGAAGGACCCAGUUCC
1195
GGAACUGGGUCCUUCUGGG
1196


 


NM_005080_750-768
CCAGAAGGACCCAGUUCCU
1197
AGGAACUGGGUCCUUCUGG
1198


 


NM_005080_751-769
CAGAAGGACCCAGUUCCUU
1199
AAGGAACUGGGUCCUUCUG
1200


 


NM_005080_752-770
AGAAGGACCCAGUUCCUUA
1201
UAAGGAACUGGGUCCUUCU
1202


 


NM_005080_756-774
GGACCCAGUUCCUUACCAG
1203
CUGGUAAGGAACUGGGUCC
1204


 


NM_005080_758-776
ACCCAGUUCCUUACCAGCC
1205
GGCUGGUAAGGAACUGGGU
1206


 


NM_005080_759-777
CCCAGUUCCUUACCAGCCU
1207
AGGCUGGUAAGGAACUGGG
1208


 


NM_005080_760-778
CCAGUUCCUUACCAGCCUC
1209
GAGGCUGGUAAGGAACUGG
1210


 


NM_005080_761-779
CAGUUCCUUACCAGCCUCC
1211
GGAGGCUGGUAAGGAACUG
1212


 


NM_005080_762-780
AGUUCCUUACCAGCCUCCC
1213
GGGAGGCUGGUAAGGAACU
1214


 


NM_005080_767-785
CUUACCAGCCUCCCUUUCU
1215
AGAAAGGGAGGCUGGUAAG
1216


 


NM_005080_769-787
UACCAGCCUCCCUUUCUCU
1217
AGAGAAAGGGAGGCUGGUA
1218


 


NM_005080_773-791
AGCCUCCCUUUCUCUGUCA
1219
UGACAGAGAAAGGGAGGCU
1220


 


NM_005080_779-797
CCUUUCUCUGUCAGUGGGG
1221
CCCCACUGACAGAGAAAGG
1222


 


NM_005080_786-804
CUGUCAGUGGGGACGUCAU
1223
AUGACGUCCCCACUGACAG
1224


 


NM_005080_787-805
UGUCAGUGGGGACGUCAUC
1225
GAUGACGUCCCCACUGACA
1226


 


NM_005080_789-807
UCAGUGGGGACGUCAUCAG
1227
CUGAUGACGUCCCCACUGA
1228


 


NM_005080_793-811
UGGGGACGUCAUCAGCCAA
1229
UUGGCUGAUGACGUCCCCA
1230


 


NM_005080_795-813
GGGACGUCAUCAGCCAAGC
1231
GCUUGGCUGAUGACGUCCC
1232


 


NM_005080_797-815
GACGUCAUCAGCCAAGCUG
1233
CAGCUUGGCUGAUGACGUC
1234


 


NM_005080_798-816
ACGUCAUCAGCCAAGCUGG
1235
CCAGCUUGGCUGAUGACGU
1236


 


NM_005080_800-818
GUCAUCAGCCAAGCUGGAA
1237
UUCCAGCUUGGCUGAUGAC
1238


 


NM_005080_804-822
UCAGCCAAGCUGGAAGCCA
1239
UGGCUUCCAGCUUGGCUGA
1240


 


NM_005080_806-824
AGCCAAGCUGGAAGCCAUU
1241
AAUGGCUUCCAGCUUGGCU
1242


 


NM_005080_807-825
GCCAAGCUGGAAGCCAUUA
1243
UAAUGGCUUCCAGCUUGGC
1244


 


NM_005080_808-826
CCAAGCUGGAAGCCAUUAA
1245
UUAAUGGCUUCCAGCUUGG
1246


 


NM_005080_809-827
CAAGCUGGAAGCCAUUAAU
1247
AUUAAUGGCUUCCAGCUUG
1248


 


NM_005080_810-828
AAGCUGGAAGCCAUUAAUG
1249
CAUUAAUGGCUUCCAGCUU
1250


 


NM_005080_811-829
AGCUGGAAGCCAUUAAUGA
1251
UCAUUAAUGGCUUCCAGCU
1252


 


NM_005080_813-831
CUGGAAGCCAUUAAUGAAC
1253
GUUCAUUAAUGGCUUCCAG
1254


 


NM_005080_814-832
UGGAAGCCAUUAAUGAACU
1255
AGUUCAUUAAUGGCUUCCA
1256


 


NM_005080_818-836
AGCCAUUAAUGAACUAAUU
1257
AAUUAGUUCAUUAAUGGCU
1258


 


NM_005080_820-838
CCAUUAAUGAACUAAUUCG
1259
CGAAUUAGUUCAUUAAUGG
1260


 


NM_005080_837-855
CGUUUUGACCACAUAUAUA
1261
UAUAUAUGUGGUCAAAACG
1262


 


NM_005080_844-862
ACCACAUAUAUACCAAGCC
1263
GGCUUGGUAUAUAUGUGGU
1264


 


NM_005080_872-890
AGAGAUACCCUCUGAGACA
1265
UGUCUCAGAGGGUAUCUCU
1266


 


NM_005080_873-891
GAGAUACCCUCUGAGACAG
1267
CUGUCUCAGAGGGUAUCUC
1268


 


NM_005080_874-892
AGAUACCCUCUGAGACAGA
1269
UCUGUCUCAGAGGGUAUCU
1270


 


NM_005080_876-894
AUACCCUCUGAGACAGAGA
1271
UCUCUGUCUCAGAGGGUAU
1272


 


NM_005080_889-907
CAGAGAGCCAAGCUAAUGU
1273
ACAUUAGCUUGGCUCUCUG
1274


 


NM_005080_890-908
AGAGAGCCAAGCUAAUGUG
1275
CACAUUAGCUUGGCUCUCU
1276


 


NM_005080_897-915
CAAGCUAAUGUGGUAGUGA
1277
UCACUACCACAUUAGCUUG
1278


 


NM_005080_898-916
AAGCUAAUGUGGUAGUGAA
1279
UUCACUACCACAUUAGCUU
1280


 


NM_005080_901-919
CUAAUGUGGUAGUGAAAAU
1281
AUUUUCACUACCACAUUAG
1282


 


NM_005080_903-921
AAUGUGGUAGUGAAAAUCG
1283
CGAUUUUCACUACCACAUU
1284


 


NM_005080_904-922
AUGUGGUAGUGAAAAUCGA
1285
UCGAUUUUCACUACCACAU
1286


 


NM_005080_906-924
GUGGUAGUGAAAAUCGAGG
1287
CCUCGAUUUUCACUACCAC
1288


 


NM_005080_907-925
UGGUAGUGAAAAUCGAGGA
1289
UCCUCGAUUUUCACUACCA
1290


 


NM_005080_910-928
UAGUGAAAAUCGAGGAAGC
1291
GCUUCCUCGAUUUUCACUA
1292


 


NM_005080_913-931
UGAAAAUCGAGGAAGCACC
1293
GGUGCUUCCUCGAUUUUCA
1294


 


NM_005080_916-934
AAAUCGAGGAAGCACCUCU
1295
AGAGGUGCUUCCUCGAUUU
1296


 


NM_005080_918-936
AUCGAGGAAGCACCUCUCA
1297
UGAGAGGUGCUUCCUCGAU
1298


 


NM_005080_919-937
UCGAGGAAGCACCUCUCAG
1299
CUGAGAGGUGCUUCCUCGA
1300


 


NM_005080_920-938
CGAGGAAGCACCUCUCAGC
1301
GCUGAGAGGUGCUUCCUCG
1302


 


NM_005080_922-940
AGGAAGCACCUCUCAGCCC
1303
GGGCUGAGAGGUGCUUCCU
1304


 


NM_005080_923-941
GGAAGCACCUCUCAGCCCC
1305
GGGGCUGAGAGGUGCUUCC
1306


 


NM_005080_929-947
ACCUCUCAGCCCCUCAGAG
1307
CUCUGAGGGGCUGAGAGGU
1308


 


NM_005080_930-948
CCUCUCAGCCCCUCAGAGA
1309
UCUCUGAGGGGCUGAGAGG
1310


 


NM_005080_931-949
CUCUCAGCCCCUCAGAGAA
1311
UUCUCUGAGGGGCUGAGAG
1312


 


NM_005080_932-950
UCUCAGCCCCUCAGAGAAU
1313
AUUCUCUGAGGGGCUGAGA
1314


 


NM_005080_933-951
CUCAGCCCCUCAGAGAAUG
1315
CAUUCUCUGAGGGGCUGAG
1316


 


NM_005080_934-952
UCAGCCCCUCAGAGAAUGA
1317
UCAUUCUCUGAGGGGCUGA
1318


 


NM_005080_935-953
CAGCCCCUCAGAGAAUGAU
1319
AUCAUUCUCUGAGGGGCUG
1320


 


NM_005080_936-954
AGCCCCUCAGAGAAUGAUC
1321
GAUCAUUCUCUGAGGGGCU
1322


 


NM_005080_938-956
CCCCUCAGAGAAUGAUCAC
1323
GUGAUCAUUCUCUGAGGGG
1324


 


NM_005080_941-959
CUCAGAGAAUGAUCACCCU
1325
AGGGUGAUCAUUCUCUGAG
1326


 


NM_005080_942-960
UCAGAGAAUGAUCACCCUG
1327
CAGGGUGAUCAUUCUCUGA
1328


 


NM_005080_943-961
CAGAGAAUGAUCACCCUGA
1329
UCAGGGUGAUCAUUCUCUG
1330


 


NM_005080_944-962
AGAGAAUGAUCACCCUGAA
1331
UUCAGGGUGAUCAUUCUCU
1332


 


NM_005080_946-964
AGAAUGAUCACCCUGAAUU
1333
AAUUCAGGGUGAUCAUUCU
1334


 


NM_005080_947-965
GAAUGAUCACCCUGAAUUC
1335
GAAUUCAGGGUGAUCAUUC
1336


 


NM_005080_948-966
AAUGAUCACCCUGAAUUCA
1337
UGAAUUCAGGGUGAUCAUU
1338


 


NM_005080_949-967
AUGAUCACCCUGAAUUCAU
1339
AUGAAUUCAGGGUGAUCAU
1340


 


NM_005080_955-973
ACCCUGAAUUCAUUGUCUC
1341
GAGACAAUGAAUUCAGGGU
1342


 


NM_005080_956-974
CCCUGAAUUCAUUGUCUCA
1343
UGAGACAAUGAAUUCAGGG
1344


 


NM_005080_957-975
CCUGAAUUCAUUGUCUCAG
1345
CUGAGACAAUGAAUUCAGG
1346


 


NM_005080_960-978
GAAUUCAUUGUCUCAGUGA
1347
UCACUGAGACAAUGAAUUC
1348


 


NM_005080_961-979
AAUUCAUUGUCUCAGUGAA
1349
UUCACUGAGACAAUGAAUU
1350


 


NM_005080_965-983
CAUUGUCUCAGUGAAGGAA
1351
UUCCUUCACUGAGACAAUG
1352


 


NM_005080_967-985
UUGUCUCAGUGAAGGAAGA
1353
UCUUCCUUCACUGAGACAA
1354


 


NM_005080_968-986
UGUCUCAGUGAAGGAAGAA
1355
UUCUUCCUUCACUGAGACA
1356


 


NM_005080_971-989
CUCAGUGAAGGAAGAACCU
1357
AGGUUCUUCCUUCACUGAG
1358


 


NM_005080_972-990
UCAGUGAAGGAAGAACCUG
1359
CAGGUUCUUCCUUCACUGA
1360


 


NM_005080_973-991
CAGUGAAGGAAGAACCUGU
1361
ACAGGUUCUUCCUUCACUG
1362


 


NM_005080_980-998
GGAAGAACCUGUAGAAGAU
1363
AUCUUCUACAGGUUCUUCC
1364


 


NM_005080_984-1002
GAACCUGUAGAAGAUGACC
1365
GGUCAUCUUCUACAGGUUC
1366


 


NM_005080_986-1004
ACCUGUAGAAGAUGACCUC
1367
GAGGUCAUCUUCUACAGGU
1368


 


NM_005080_1023-1041
UCAAAUCUGCUUUCAUCCA
1369
UGGAUGAAAGCAGAUUUGA
1370


 


NM_005080_1151-1169
UUCUUGGGAGGACACUUUU
1371
AAAAGUGUCCUCCCAAGAA
1372


 


NM_005080_1367-1385
UCUUUUGACAUCCAGCAGU
1373
ACUGCUGGAUGUCAAAAGA
1374


 


NM_005080_1414-1432
UAAGAAAUAUUACUAUAAU
1375
AUUAUAGUAAUAUUUCUUA
1376


 


NM_005080_1415-1433
AAGAAAUAUUACUAUAAUU
1377
AAUUAUAGUAAUAUUUCUU
1378


 


NM_005080_1674-1692
ACUUCAAGUAAGAUCAAGA
1379
UCUUGAUCUUACUUGAAGU
1380


 


NM_005080_1675-1693
CUUCAAGUAAGAUCAAGAA
1381
UUCUUGAUCUUACUUGAAG
1382


 


NM_005080_330-348
AAUGAGUGAGCUGGAACAG
1383
CUGUUCCAGCUCACUCAUU
1384


 


NM_005080_333-351
GAGUGAGCUGGAACAGCAA
1385
UUGCUGUUCCAGCUCACUC
1386


 


NM_005080_592-610
CCCCUCCAGAACAUCUCCC
1387
GGGAGAUGUUCUGGAGGGG
1388


 


NM_005080_665-683
CAUUCUGGACAACUUGGAC
1389
GUCCAAGUUGUCCAGAAUG
1390


 


NM_005080_815-833
GGAAGCCAUUAAUGAACUA
1391
UAGUUCAUUAAUGGCUUCC
1392


 


NM_005080_1029-1047
CUGCUUUCAUCCAGCCACU
1393
AGUGGCUGGAUGAAAGCAG
1394


 


NM_005080_1077-1095
GCUUACAGUGACUGUGGAU
1395
AUCCACAGUCACUGUAAGC
1396


 


NM_005080_1222-1240
GUUGCCCUUUUCCUUGACU
1397
AGUCAAGGAAAAGGGCAAC
1398


 


NM_005080_1285-1303
UUCAAAAAGCCAAAAUAGA
1399
UCUAUUUUGGCUUUUUGAA
1400


 


NM_005080_1334-1352
UGUUCAGAUCUCAUAGAUG
1401
CAUCUAUGAGAUCUGAACA
1402


 


NM_005080_1335-1353
GUUCAGAUCUCAUAGAUGA
1403
UCAUCUAUGAGAUCUGAAC
1404


 


NM_005080_1436-1454
GAACUACAGCUUUUAAGAU
1405
AUCUUAAAAGCUGUAGUUC
1406


 


NM_005080_1449-1467
UAAGAUUGUACUUUUAUCU
1407
AGAUAAAAGUACAAUCUUA
1408


 


NM_005080_1450-1468
AAGAUUGUACUUUUAUCUU
1409
AAGAUAAAAGUACAAUCUU
1410


 


NM_005080_114-132
GCAGCCCGCCUCCGCCGCC
1411
GGCGGCGGAGGCGGGCUGC
1412


 


NM_005080_1555-1573
UUCUUUAUCAUUUCUCUUC
1413
GAAGAGAAAUGAUAAAGAA
1414


 


NM_005080_1556-1574
UCUUUAUCAUUUCUCUUCC
1415
GGAAGAGAAAUGAUAAAGA
1416


 


NM_005080_1561-1579
AUCAUUUCUCUUCCCCCUU
1417
AAGGGGGAAGAGAAAUGAU
1418


 


NM_005080_1562-1580
UCAUUUCUCUUCCCCCUUU
1419
AAAGGGGGAAGAGAAAUGA
1420


 


NM_005080_1569-1587
UCUUCCCCCUUUUUGGCAU
1421
AUGCCAAAAAGGGGGAAGA
1422


 


NM_005080_1588-1606
CCUGGCUUGCCUCCAGUUU
1423
AAACUGGAGGCAAGCCAGG
1424


 


NM_005080_1640-1658
AACACCUGCUGAGGGGGCU
1425
AGCCCCCUCAGCAGGUGUU
1426


 


NM_005080_1641-1659
ACACCUGCUGAGGGGGCUC
1427
GAGCCCCCUCAGCAGGUGU
1428


 


NM_005080_1642-1660
CACCUGCUGAGGGGGCUCU
1429
AGAGCCCCCUCAGCAGGUG
1430


 


NM_005080_1650-1668
GAGGGGGCUCUUUCCCUCA
1431
UGAGGGAAAGAGCCCCCUC
1432


 


NM_005080_1686-1704
AUCAAGAAUCUUUUGUGAA
1433
UUCACAAAAGAUUCUUGAU
1434


 


NM_005080_1745-1763
UCCUGCUAGUGUAGCUUCU
1435
AGAAGCUACACUAGCAGGA
1436


 


NM_005080_138-156
CCCGGCCGGCCAGGCCCUG
1437
CAGGGCCUGGCCGGCCGGG
1438


 


NM_005080_145-163
GGCCAGGCCCUGCCGCUCA
1439
UGAGCGGCAGGGCCUGGCC
1440


 


NM_005080_190-208
CCGGAGGCAGCGAGCGGGG
1441
CCCCGCTCGCTGCCTCCGG
1442


 


NM_005080_191-209
CGGAGGCAGCGAGCGGGGG
1443
CCCCCGCTCGCTGCCTCCG
1444


 


NM_005080_192-210
GGAGGCAGCGAGCGGGGGG
1445
CCCCCCGCTCGCTGCCTCC
1446


 


NM_005080_259-277
GAGAAGGCGCUGAGGAGGA
1447
UCCUCCUCAGCGCCUUCUC
1448


 


NM_005080_261-279
GAAGGCGCUGAGGAGGAAA
1449
UUUCCUCCUCAGCGCCUUC
1450


 


NM_005080_289-307
AGAGUAGCAGCUCAGACUG
1451
CAGUCUGAGCUGCUACUCU
1452


 


NM_005080_363-381
AGAAGAAGAGAACCAAAAA
1453
TTTTTGGTTCTCTTCTTCT
1454


 


NM_005080_365-383
AAGAAGAGAACCAAAAACU
1455
AGUUUUUGGUUCUCUUCUU
1456


 


NM_005080_385-403
UUGCUAGAAAAUCAGCUUU
1457
AAAGCUGAUUUUCUAGCAA
1458


 


NM_005080_461-479
GGAUGGAUGCCCUGGUUGC
1459
GCAACCAGGGCAUCCAUCC
1460


 


NM_005080_490-508
GCGGAAGCCAAGGGGAAUG
1461
CAUUCCCCUUGGCUUCCGC
1462


 


NM_005080_518-536
CAGUGGCCGGGUCUGCUGA
1463
UCAGCAGACCCGGCCACUG
1464


 


NM_005080_673-691
ACAACUUGGACCCAGUCAU
1465
AUGACUGGGUCCAAGUUGU
1466


 


NM_005080_685-703
CAGUCAUGUUCUUCAAAUG
1467
CAUUUGAAGAACAUGACUG
1468


 


NM_005080_730-748
AGGAGCUCCCAGAGGUCUA
1469
UAGACCUCUGGGAGCUCCU
1470


 


NM_005080_772-790
CAGCCUCCCUUUCUCUGUC
1471
GACAGAGAAAGGGAGGCUG
1472


 


NM_005080_801-819
UCAUCAGCCAAGCUGGAAG
1473
CUUCCAGCUUGGCUGAUGA
1474


 


NM_005080_817-835
AAGCCAUUAAUGAACUAAU
1475
AUUAGUUCAUUAAUGGCUU
1476


 


NM_005080_887-905
GACAGAGAGCCAAGCUAAU
1477
AUUAGCUUGGCUCUCUGUC
1478


 


NM_005080_924-942
GAAGCACCUCUCAGCCCCU
1479
AGGGGCUGAGAGGUGCUUC
1480


 


NM_005080_927-945
GCACCUCUCAGCCCCUCAG
1481
CUGAGGGGCUGAGAGGUGC
1482


 


NM_005080_928-946
CACCUCUCAGCCCCUCAGA
1483
UCUGAGGGGCUGAGAGGUG
1484


 


NM_005080_974-992
AGUGAAGGAAGAACCUGUA
1485
UACAGGUUCUUCCUUCACU
1486


 


NM_005080_985-1003
AACCUGUAGAAGAUGACCU
1487
AGGUCAUCUUCUACAGGUU
1488


 


NM_005080_187-205
AGCCCGGAGGCAGCGAGCG
1489
CGCTCGCTGCCTCCGGGCT
1490


 


NM_005080_672-690
GACAACUUGGACCCAGUCA
1491
UGACUGGGUCCAAGUUGUC
1492


 


NM_005080_771-789
CCAGCCUCCCUUUCUCUGU
1493
ACAGAGAAAGGGAGGCUGG
1494


 


NM_005080_1740-1758
UUUUUUCCUGCUAGUGUAG
1495
CUACACUAGCAGGAAAAAA
1496


 


NM_005080_1741-1759
UUUUUCCUGCUAGUGUAGC
1497
GCUACACUAGCAGGAAAAA
1498


 


NM_005080_662-680
GGGCAUUCUGGACAACUUG
1499
CAAGUUGUCCAGAAUGCCC
1500


 


NM_005080_1070-1088
ACUGGAUGCUUACAGUGAC
1501
GUCACUGUAAGCAUCCAGU
1502


 


NM_005080_631-649
ACUCUUCAGAUUCAGAGUC
1503
GACUCUGAAUCUGAAGAGU
1504


 


NM_005080_647-665
GUCUGAUAUCCUGUUGGGC
1505
GCCCAACAGGAUAUCAGAC
1506


 


NM_005080_791-809
AGUGGGGACGUCAUCAGCC
1507
GGCUGAUGACGUCCCCACU
1508


 


NM_005080_981-999
GAAGAACCUGUAGAAGAUG
1509
CAUCUUCUACAGGUUCUUC
1510


 


NM_005080_1068-1086
CUACUGGAUGCUUACAGUG
1511
CACUGUAAGCAUCCAGUAG
1512


 


NM_005080_1391-1409
GUAUUGAGACAUAUUACUG
1513
CAGUAAUAUGUCUCAAUAC
1514


 


NM_005080_1426-1444
CUAUAAUUGAGAACUACAG
1515
CUGUAGUUCUCAAUUAUAG
1516


 


NM_005080_103-121
CUUCUGUCGGGGCAGCCCG
1517
CGGGCUGCCCCGACAGAAG
1518


 


NM_005080_1457-1475
UACUUUUAUCUUAAAAGGG
1519
CCCUUUUAAGAUAAAAGUA
1520


 


NM_005080_1568-1586
CUCUUCCCCCUUUUUGGCA
1521
UGCCAAAAAGGGGGAAGAG
1522


 


NM_005080_1574-1592
CCCCUUUUUGGCAUCCUGG
1523
CCAGGAUGCCAAAAAGGGG
1524


 


NM_005080_1577-1595
CUUUUUGGCAUCCUGGCUU
1525
AAGCCAGGAUGCCAAAAAG
1526


 


NM_005080_1730-1748
CUUGAUGGAAUUUUUUCCU
1527
AGGAAAAAAUUCCAUCAAG
1528


 


NM_005080_1731-1749
UUGAUGGAAUUUUUUCCUG
1529
CAGGAAAAAAUUCCAUCAA
1530


 


NM_005080_1732-1750
UGAUGGAAUUUUUUCCUGC
1531
GCAGGAAAAAAUUCCAUCA
1532


 


NM_005080_293-311
UAGCAGCUCAGACUGCCAG
1533
CUGGCAGUCUGAGCUGCUA
1534


 


NM_005080_350-368
AAGUGGUAGAUUUAGAAGA
1535
UCUUCUAAAUCUACCACUU
1536


 


NM_005080_351-369
AGUGGUAGAUUUAGAAGAA
1537
UUCUUCUAAAUCUACCACU
1538


 


NM_005080_630-648
GACUCUUCAGAUUCAGAGU
1539
ACUCUGAAUCUGAAGAGUC
1540


 


NM_005080_657-675
CUGUUGGGCAUUCUGGACA
1541
UGUCCAGAAUGCCCAACAG
1542


 


NM_005080_670-688
UGGACAACUUGGACCCAGU
1543
ACUGGGUCCAAGUUGUCCA
1544


 


NM_005080_692-710
GUUCUUCAAAUGCCCUUCC
1545
GGAAGGGCAUUUGAAGAAC
1546


 


NM_005080_778-796
CCCUUUCUCUGUCAGUGGG
1547
CCCACUGACAGAGAAAGGG
1548


 


NM_005080_790-808
CAGUGGGGACGUCAUCAGC
1549
GCUGAUGACGUCCCCACUG
1550


 


NM_005080_970-988
UCUCAGUGAAGGAAGAACC
1551
GGUUCUUCCUUCACUGAGA
1552


 


NM_005080_1162-1180
ACACUUUUGCCAAUGAACU
1553
AGUUCAUUGGCAAAAGUGU
1554


 


NM_005080_1368-1386
CUUUUGACAUCCAGCAGUC
1555
GACUGCUGGAUGUCAAAAG
1556


 


NM_005080_1515-1533
UAGACAAAUGUCUUGAAGU
1557
ACUUCAAGACAUUUGUCUA
1558


 


NM_005080_1541-1559
GAAUUUAUGAAUGGUUCUU
1559
AAGAACCAUUCAUAAAUUC
1560


 


NM_005080_1542-1560
AAUUUAUGAAUGGUUCUUU
1561
AAAGAACCAUUCAUAAAUU
1562


 


NM_005080_1571-1589
UUCCCCCUUUUUGGCAUCC
1563
GGAUGCCAAAAAGGGGGAA
1564


 


NM_005080_151-169
GCCCUGCCGCUCAUGGUGC
1565
GCACCAUGAGCGGCAGGGC
1566


 


NM_005080_160-178
CUCAUGGUGCCAGCCCAGA
1567
UCUGGGCUGGCACCAUGAG
1568


 


NM_005080_326-344
CUCGAAUGAGUGAGCUGGA
1569
UCCAGCUCACUCAUUCGAG
1570


 


NM_005080_327-345
UCGAAUGAGUGAGCUGGAA
1571
UUCCAGCUCACUCAUUCGA
1572


 


NM_005080_331-349
AUGAGUGAGCUGGAACAGC
1573
GCUGUUCCAGCUCACUCAU
1574


 


NM_005080_424-442
CUUGUAGUUGAGAACCAGG
1575
CCUGGUUCUCAACUACAAG
1576


 


NM_005080_483-501
AGAGGAGGCGGAAGCCAAG
1577
CTTGGCTTCCGCCTCCTCT
1578


 


NM_005080_579-597
GGCCCAGUUGUCACCCCUC
1579
GAGGGGUGACAACUGGGCC
1580


 


NM_005080_745-763
UCUACCCAGAAGGACCCAG
1581
CUGGGUCCUUCUGGGUAGA
1582


 


NM_005080_746-764
CUACCCAGAAGGACCCAGU
1583
ACUGGGUCCUUCUGGGUAG
1584


 


NM_005080_812-830
GCUGGAAGCCAUUAAUGAA
1585
UUCAUUAAUGGCUUCCAGC
1586


 


NM_005080_871-889
UAGAGAUACCCUCUGAGAC
1587
GUCUCAGAGGGUAUCUCUA
1588


 


NM_005080_892-910
AGAGCCAAGCUAAUGUGGU
1589
ACCACAUUAGCUUGGCUCU
1590


 


NM_005080_978-996
AAGGAAGAACCUGUAGAAG
1591
CUUCUACAGGUUCUUCCUU
1592


 


NM_005080_982-1000
AAGAACCUGUAGAAGAUGA
1593
UCAUCUUCUACAGGUUCUU
1594


 


NM_005080_257-275
AGGAGAAGGCGCUGAGGAG
1595
CUCCUCAGCGCCUUCUCCU
1596


 


NM_005080_364-382
GAAGAAGAGAACCAAAAAC
1597
GTTTTTGGTTCTCTTCTTC
1598


 


NM_005080_816-834
GAAGCCAUUAAUGAACUAA
1599
UUAGUUCAUUAAUGGCUUC
1600


 


NM_005080_884-902
UGAGACAGAGAGCCAAGCU
1601
AGCUUGGCUCUCUGUCUCA
1602


 


NM_005080_925-943
AAGCACCUCUCAGCCCCUC
1603
GAGGGGCUGAGAGGUGCUU
1604


 


NM_005080_1440-1458
UACAGCUUUUAAGAUUGUA
1605
UACAAUCUUAAAAGCUGUA
1606


 


NM_005080_784-802
CUCUGUCAGUGGGGACGUC
1607
GACGUCCCCACUGACAGAG
1608


 


NM_005080_1593-1611
CUUGCCUCCAGUUUUAGGU
1609
ACCUAAAACUGGAGGCAAG
1610


 


NM_005080_301-319
CAGACUGCCAGAGAUCGAA
1611
UUCGAUCUCUGGCAGUCUG
1612


 


NM_005080_674-692
CAACUUGGACCCAGUCAUG
1613
CAUGACUGGGUCCAAGUUG
1614


 


NM_005080_783-801
UCUCUGUCAGUGGGGACGU
1615
ACGUCCCCACUGACAGAGA
1616


 


NM_005080_921-939
GAGGAAGCACCUCUCAGCC
1617
GGCUGAGAGGUGCUUCCUC
1618


 


NM_005080_1226-1244
CCCUUUUCCUUGACUAUUA
1619
UAAUAGUCAAGGAAAAGGG
1620


 


NM_005080_1283-1301
CAUUCAAAAAGCCAAAAUA
1621
UAUUUUGGCUUUUUGAAUG
1622


 


NM_005080_1416-1434
AGAAAUAUUACUAUAAUUG
1623
CAAUUAUAGUAAUAUUUCU
1624


 


NM_005080_1420-1438
AUAUUACUAUAAUUGAGAA
1625
UUCUCAAUUAUAGUAAUAU
1626


 


NM_005080_1488-1506
CUAAAAUACUUAUUAUGUA
1627
UACAUAAUAAGUAUUUUAG
1628


 


NM_005080_1492-1510
AAUACUUAUUAUGUAAGGG
1629
CCCUUACAUAAUAAGUAUU
1630


 


NM_005080_111-129
GGGGCAGCCCGCCUCCGCC
1631
GGCGGAGGCGGGCUGCCCC
1632


 


NM_005080_1639-1657
GAACACCUGCUGAGGGGGC
1633
GCCCCCUCAGCAGGUGUUC
1634


 


NM_005080_1685-1703
GAUCAAGAAUCUUUUGUGA
1635
UCACAAAAGAUUCUUGAUC
1636


 


NM_005080_1733-1751
GAUGGAAUUUUUUCCUGCU
1637
AGCAGGAAAAAAUUCCAUC
1638


 


NM_005080_1734-1752
AUGGAAUUUUUUCCUGCUA
1639
UAGCAGGAAAAAAUUCCAU
1640


 


NM_005080_1737-1755
GAAUUUUUUCCUGCUAGUG
1641
CACUAGCAGGAAAAAAUUC
1642


 


NM_005080_1756-1774
UAGCUUCUGAAAGGUGCUU
1643
AAGCACCUUUCAGAAGCUA
1644


 


NM_005080_1757-1775
AGCUUCUGAAAGGUGCUUU
1645
AAAGCACCUUUCAGAAGCU
1646


 


NM_005080_152-170
CCCUGCCGCUCAUGGUGCC
1647
GGCACCAUGAGCGGCAGGG
1648


 


NM_005080_153-171
CCUGCCGCUCAUGGUGCCA
1649
UGGCACCAUGAGCGGCAGG
1650


 


NM_005080_163-181
AUGGUGCCAGCCCAGAGAG
1651
CUCUCUGGGCUGGCACCAU
1652


 


NM_005080_167-185
UGCCAGCCCAGAGAGGGGC
1653
GCCCCUCUCUGGGCUGGCA
1654


 


NM_005080_200-218
CGAGCGGGGGGCUGCCCCA
1655
UGGGGCAGCCCCCCGCUCG
1656


 


NM_005080_252-270
CCCCGAGGAGAAGGCGCUG
1657
CAGCGCCUUCUCCUCGGGG
1658


 


NM_005080_255-273
CGAGGAGAAGGCGCUGAGG
1659
CCUCAGCGCCUUCUCCUCG
1660


 


NM_005080_260-278
AGAAGGCGCUGAGGAGGAA
1661
UUCCUCCUCAGCGCCUUCU
1662


 


NM_005080_271-289
AGGAGGAAACUGAAAAACA
1663
UGUUUUUCAGUUUCCUCCU
1664


 


NM_005080_297-315
AGCUCAGACUGCCAGAGAU
1665
AUCUCUGGCAGUCUGAGCU
1666


 


NM_005080_300-318
UCAGACUGCCAGAGAUCGA
1667
UCGAUCUCUGGCAGUCUGA
1668


 


NM_005080_335-353
GUGAGCUGGAACAGCAAGU
1669
ACUUGCUGUUCCAGCUCAC
1670


 


NM_005080_368-386
AAGAGAACCAAAAACUUUU
1671
AAAAGUUUUUGGUUCUCUU
1672


 


NM_005080_378-396
AAAACUUUUGCUAGAAAAU
1673
AUUUUCUAGCAAAAGUUUU
1674


 


NM_005080_379-397
AAACUUUUGCUAGAAAAUC
1675
GAUUUUCUAGCAAAAGUUU
1676


 


NM_005080_380-398
AACUUUUGCUAGAAAAUCA
1677
UGAUUUUCUAGCAAAAGUU
1678


 


NM_005080_389-407
UAGAAAAUCAGCUUUUACG
1679
CGUAAAAGCUGAUUUUCUA
1680


 


NM_005080_426-444
UGUAGUUGAGAACCAGGAG
1681
CUCCUGGUUCUCAACUACA
1682


 


NM_005080_427-445
GUAGUUGAGAACCAGGAGU
1683
ACUCCUGGUUCUCAACUAC
1684


 


NM_005080_485-503
AGGAGGCGGAAGCCAAGGG
1685
CCCTTGGCTTCCGCCTCCT
1686


 


NM_005080_487-505
GAGGCGGAAGCCAAGGGGA
1687
TCCCCTTGGCTTCCGCCTC
1688


 


NM_005080_488-506
AGGCGGAAGCCAAGGGGAA
1689
TTCCCCTTGGCTTCCGCCT
1690


 


NM_005080_511-529
GUGAGGCCAGUGGCCGGGU
1691
ACCCGGCCACUGGCCUCAC
1692


 


NM_005080_526-544
GGGUCUGCUGAGUCCGCAG
1693
CUGCGGACUCAGCAGACCC
1694


 


NM_005080_575-593
UGCAGGCCCAGUUGUCACC
1695
GGUGACAACUGGGCCUGCA
1696


 


NM_005080_593-611
CCCUCCAGAACAUCUCCCC
1697
GGGGAGAUGUUCUGGAGGG
1698


 


NM_005080_595-613
CUCCAGAACAUCUCCCCAU
1699
AUGGGGAGAUGUUCUGGAG
1700


 


NM_005080_654-672
AUCCUGUUGGGCAUUCUGG
1701
CCAGAAUGCCCAACAGGAU
1702


 


NM_005080_675-693
AACUUGGACCCAGUCAUGU
1703
ACAUGACUGGGUCCAAGUU
1704


 


NM_005080_683-701
CCCAGUCAUGUUCUUCAAA
1705
UUUGAAGAACAUGACUGGG
1706


 


NM_005080_684-702
CCAGUCAUGUUCUUCAAAU
1707
AUUUGAAGAACAUGACUGG
1708


 


NM_005080_693-711
UUCUUCAAAUGCCCUUCCC
1709
GGGAAGGGCAUUUGAAGAA
1710


 


NM_005080_694-712
UCUUCAAAUGCCCUUCCCC
1711
GGGGAAGGGCAUUUGAAGA
1712


 


NM_005080_726-744
CUGGAGGAGCUCCCAGAGG
1713
CCUCUGGGAGCUCCUCCAG
1714


 


NM_005080_744-762
GUCUACCCAGAAGGACCCA
1715
UGGGUCCUUCUGGGUAGAC
1716


 


NM_005080_765-783
UCCUUACCAGCCUCCCUUU
1717
AAAGGGAGGCUGGUAAGGA
1718


 


NM_005080_768-786
UUACCAGCCUCCCUUUCUC
1719
GAGAAAGGGAGGCUGGUAA
1720


 


NM_005080_777-795
UCCCUUUCUCUGUCAGUGG
1721
CCACUGACAGAGAAAGGGA
1722


 


NM_005080_802-820
CAUCAGCCAAGCUGGAAGC
1723
GCUUCCAGCUUGGCUGAUG
1724


 


NM_005080_877-895
UACCCUCUGAGACAGAGAG
1725
CUCUCUGUCUCAGAGGGUA
1726


 


NM_005080_878-896
ACCCUCUGAGACAGAGAGC
1727
GCUCUCUGUCUCAGAGGGU
1728


 


NM_005080_885-903
GAGACAGAGAGCCAAGCUA
1729
UAGCUUGGCUCUCUGUCUC
1730


 


NM_005080_886-904
AGACAGAGAGCCAAGCUAA
1731
UUAGCUUGGCUCUCUGUCU
1732


 


NM_005080_966-984
AUUGUCUCAGUGAAGGAAG
1733
CUUCCUUCACUGAGACAAU
1734


 


NM_005080_969-987
GUCUCAGUGAAGGAAGAAC
1735
GUUCUUCCUUCACUGAGAC
1736


 


NM_005080_1245-1263
CACUGCCUGGAGGAUAGCA
1737
UGCUAUCCUCCAGGCAGUG
1738


 


NM_005080_1738-1756
AAUUUUUUCCUGCUAGUGU
1739
ACACUAGCAGGAAAAAAUU
1740


 


NM_005080_194-212
AGGCAGCGAGCGGGGGGCU
1741
AGCCCCCCGCUCGCUGCCU
1742


 


NM_005080_209-227
GGCUGCCCCAGGCGCGCAA
1743
UUGCGCGCCUGGGGCAGCC
1744


 


NM_005080_269-287
UGAGGAGGAAACUGAAAAA
1745
UUUUUCAGUUUCCUCCUCA
1746


 


NM_005080_902-920
UAAUGUGGUAGUGAAAAUC
1747
GAUUUUCACUACCACAUUA
1748


 


NM_005080_50-68
UGGUGGUGGUGGCAGCCGC
1749
GCGGCUGCCACCACCACCA
1750


 


NM_005080_1017-1035
GGUAUCUCAAAUCUGCUUU
1751
AAAGCAGAUUUGAGAUACC
1752


 


NM_005080_1021-1039
UCUCAAAUCUGCUUUCAUC
1753
GAUGAAAGCAGAUUUGAGA
1754


 


NM_005080_1022-1040
CUCAAAUCUGCUUUCAUCC
1755
GGAUGAAAGCAGAUUUGAG
1756


 


NM_005080_1062-1080
UCCUGCCUACUGGAUGCUU
1757
AAGCAUCCAGUAGGCAGGA
1758


 


NM_005080_1074-1092
GAUGCUUACAGUGACUGUG
1759
CACAGUCACUGUAAGCAUC
1760


 


NM_005080_1116-1134
UUCAGUGACAUGUCCUCUC
1761
GAGAGGACAUGUCACUGAA
1762


 


NM_005080_1149-1167
CAUUCUUGGGAGGACACUU
1763
AAGUGUCCUCCCAAGAAUG
1764


 


NM_005080_1150-1168
AUUCUUGGGAGGACACUUU
1765
AAAGUGUCCUCCCAAGAAU
1766


 


NM_005080_1161-1179
GACACUUUUGCCAAUGAAC
1767
GUUCAUUGGCAAAAGUGUC
1768


 


NM_005080_1223-1241
UUGCCCUUUUCCUUGACUA
1769
UAGUCAAGGAAAAGGGCAA
1770


 


NM_005080_1280-1298
CUUCAUUCAAAAAGCCAAA
1771
UUUGGCUUUUUGAAUGAAG
1772


 


NM_005080_1281-1299
UUCAUUCAAAAAGCCAAAA
1773
UUUUGGCUUUUUGAAUGAA
1774


 


NM_005080_1284-1302
AUUCAAAAAGCCAAAAUAG
1775
CUAUUUUGGCUUUUUGAAU
1776


 


NM_005080_1286-1304
UCAAAAAGCCAAAAUAGAG
1777
CUCUAUUUUGGCUUUUUGA
1778


 


NM_005080_1288-1306
AAAAAGCCAAAAUAGAGAG
1779
CUCUCUAUUUUGGCUUUUU
1780


 


NM_005080_1365-1383
UGUCUUUUGACAUCCAGCA
1781
UGCUGGAUGUCAAAAGACA
1782


 


NM_005080_1417-1435
GAAAUAUUACUAUAAUUGA
1783
UCAAUUAUAGUAAUAUUUC
1784


 


NM_005080_1421-1439
UAUUACUAUAAUUGAGAAC
1785
GUUCUCAAUUAUAGUAAUA
1786


 


NM_005080_1434-1452
GAGAACUACAGCUUUUAAG
1787
CUUAAAAGCUGUAGUUCUC
1788


 


NM_005080_1452-1470
GAUUGUACUUUUAUCUUAA
1789
UUAAGAUAAAAGUACAAUC
1790


 


NM_005080_105-123
UCUGUCGGGGCAGCCCGCC
1791
GGCGGGCUGCCCCGACAGA
1792


 


NM_005080_1455-1473
UGUACUUUUAUCUUAAAAG
1793
CUUUUAAGAUAAAAGUACA
1794


 


NM_005080_112-130
GGGCAGCCCGCCUCCGCCG
1795
CGGCGGAGGCGGGCUGCCC
1796


 


NM_005080_113-131
GGCAGCCCGCCUCCGCCGC
1797
GCGGCGGAGGCGGGCUGCC
1798


 


NM_005080_1543-1561
AUUUAUGAAUGGUUCUUUA
1799
UAAAGAACCAUUCAUAAAU
1800


 


NM_005080_1544-1562
UUUAUGAAUGGUUCUUUAU
1801
AUAAAGAACCAUUCAUAAA
1802


 


NM_005080_1557-1575
CUUUAUCAUUUCUCUUCCC
1803
GGGAAGAGAAAUGAUAAAG
1804


 


NM_005080_115-133
CAGCCCGCCUCCGCCGCCG
1805
CGGCGGCGGAGGCGGGCUG
1806


 


NM_005080_1564-1582
AUUUCUCUUCCCCCUUUUU
1807
AAAAAGGGGGAAGAGAAAU
1808


 


NM_005080_1572-1590
UCCCCCUUUUUGGCAUCCU
1809
AGGAUGCCAAAAAGGGGGA
1810


 


NM_005080_1575-1593
CCCUUUUUGGCAUCCUGGC
1811
GCCAGGAUGCCAAAAAGGG
1812


 


NM_005080_1576-1594
CCUUUUUGGCAUCCUGGCU
1813
AGCCAGGAUGCCAAAAAGG
1814


 


NM_005080_117-135
GCCCGCCUCCGCCGCCGGA
1815
UCCGGCGGCGGAGGCGGGC
1816


 


NM_005080_1582-1600
UGGCAUCCUGGCUUGCCUC
1817
GAGGCAAGCCAGGAUGCCA
1818


 


NM_005080_1587-1605
UCCUGGCUUGCCUCCAGUU
1819
AACUGGAGGCAAGCCAGGA
1820


 


NM_005080_118-136
CCCGCCUCCGCCGCCGGAG
1821
CUCCGGCGGCGGAGGCGGG
1822


 


NM_005080_119-137
CCGCCUCCGCCGCCGGAGC
1823
GCUCCGGCGGCGGAGGCGG
1824


 


NM_005080_120-138
CGCCUCCGCCGCCGGAGCC
1825
GGCUCCGGCGGCGGAGGCG
1826


 


NM_005080_124-142
UCCGCCGCCGGAGCCCCGG
1827
CCGGGGCUCCGGCGGCGGA
1828


 


NM_005080_126-144
CGCCGCCGGAGCCCCGGCC
1829
GGCCGGGGCTCCGGCGGCG
1830


 


NM_005080_1676-1694
UUCAAGUAAGAUCAAGAAU
1831
AUUCUUGAUCUUACUUGAA
1832


 


NM_005080_127-145
GCCGCCGGAGCCCCGGCCG
1833
CGGCCGGGGCTCCGGCGGC
1834


 


NM_005080_129-147
CGCCGGAGCCCCGGCCGGC
1835
GCCGGCCGGGGCTCCGGCG
1836


 


NM_005080_130-148
GCCGGAGCCCCGGCCGGCC
1837
GGCCGGCCGGGGCTCCGGC
1838


 


NM_005080_131-149
CCGGAGCCCCGGCCGGCCA
1839
TGGCCGGCCGGGGCTCCGG
1840


 


NM_005080_1720-1738
UAUGUAAAUGCUUGAUGGA
1841
UCCAUCAAGCAUUUACAUA
1842


 


NM_005080_1724-1742
UAAAUGCUUGAUGGAAUUU
1843
AAAUUCCAUCAAGCAUUUA
1844


 


NM_005080_132-150
CGGAGCCCCGGCCGGCCAG
1845
CTGGCCGGCCGGGGCTCCG
1846


 


NM_005080_133-151
GGAGCCCCGGCCGGCCAGG
1847
CCTGGCCGGCCGGGGCTCC
1848


 


NM_005080_134-152
GAGCCCCGGCCGGCCAGGC
1849
GCCTGGCCGGCCGGGGCTC
1850


 


NM_005080_136-154
GCCCCGGCCGGCCAGGCCC
1851
GGGCCTGGCCGGCCGGGGC
1852


 


NM_005080_1777-1795
UCCAUUUAUUUAAAACUAC
1853
GUAGUUUUAAAUAAAUGGA
1854


 


NM_005080_137-155
CCCCGGCCGGCCAGGCCCU
1855
AGGGCCUGGCCGGCCGGGG
1856


 


NM_005080_139-157
CCGGCCGGCCAGGCCCUGC
1857
GCAGGGCCUGGCCGGCCGG
1858


 


NM_005080_140-158
CGGCCGGCCAGGCCCUGCC
1859
GGCAGGGCCUGGCCGGCCG
1860


 


NM_005080_141-159
GGCCGGCCAGGCCCUGCCG
1861
CGGCAGGGCCUGGCCGGCC
1862


 


NM_005080_142-160
GCCGGCCAGGCCCUGCCGC
1863
GCGGCAGGGCCUGGCCGGC
1864


 


NM_005080_143-161
CCGGCCAGGCCCUGCCGCU
1865
AGCGGCAGGGCCUGGCCGG
1866


 


NM_005080_144-162
CGGCCAGGCCCUGCCGCUC
1867
GAGCGGCAGGGCCUGGCCG
1868


 


NM_005080_161-179
UCAUGGUGCCAGCCCAGAG
1869
CUCUGGGCUGGCACCAUGA
1870


 


NM_005080_162-180
CAUGGUGCCAGCCCAGAGA
1871
UCUCUGGGCUGGCACCAUG
1872


 


NM_005080_164-182
UGGUGCCAGCCCAGAGAGG
1873
CCUCUCUGGGCUGGCACCA
1874


 


NM_005080_165-183
GGUGCCAGCCCAGAGAGGG
1875
CCCUCUCUGGGCUGGCACC
1876


 


NM_005080_166-184
GUGCCAGCCCAGAGAGGGG
1877
CCCCUCUCUGGGCUGGCAC
1878


 


NM_005080_201-219
GAGCGGGGGGCUGCCCCAG
1879
CUGGGGCAGCCCCCCGCUC
1880


 


NM_005080_202-220
AGCGGGGGGCUGCCCCAGG
1881
CCUGGGGCAGCCCCCCGCU
1882


 


NM_005080_203-221
GCGGGGGGCUGCCCCAGGC
1883
GCCUGGGGCAGCCCCCCGC
1884


 


NM_005080_204-222
CGGGGGGCUGCCCCAGGCG
1885
CGCCUGGGGCAGCCCCCCG
1886


 


NM_005080_208-226
GGGCUGCCCCAGGCGCGCA
1887
UGCGCGCCUGGGGCAGCCC
1888


 


NM_005080_212-230
UGCCCCAGGCGCGCAAGCG
1889
CGCUUGCGCGCCUGGGGCA
1890


 


NM_005080_248-266
UGAGCCCCGAGGAGAAGGC
1891
GCCUUCUCCUCGGGGCUCA
1892


 


NM_005080_251-269
GCCCCGAGGAGAAGGCGCU
1893
AGCGCCUUCUCCUCGGGGC
1894


 


NM_005080_258-276
GGAGAAGGCGCUGAGGAGG
1895
CCUCCUCAGCGCCUUCUCC
1896


 


NM_005080_262-280
AAGGCGCUGAGGAGGAAAC
1897
GUUUCCUCCUCAGCGCCUU
1898


 


NM_005080_265-283
GCGCUGAGGAGGAAACUGA
1899
UCAGUUUCCUCCUCAGCGC
1900


 


NM_005080_266-284
CGCUGAGGAGGAAACUGAA
1901
UUCAGUUUCCUCCUCAGCG
1902


 


NM_005080_267-285
GCUGAGGAGGAAACUGAAA
1903
UUUCAGUUUCCUCCUCAGC
1904


 


NM_005080_268-286
CUGAGGAGGAAACUGAAAA
1905
UUUUCAGUUUCCUCCUCAG
1906


 


NM_005080_270-288
GAGGAGGAAACUGAAAAAC
1907
GUUUUUCAGUUUCCUCCUC
1908


 


NM_005080_272-290
GGAGGAAACUGAAAAACAG
1909
CUGUUUUUCAGUUUCCUCC
1910


 


NM_005080_273-291
GAGGAAACUGAAAAACAGA
1911
UCUGUUUUUCAGUUUCCUC
1912


 


NM_005080_277-295
AAACUGAAAAACAGAGUAG
1913
CUACUCUGUUUUUCAGUUU
1914


 


NM_005080_328-346
CGAAUGAGUGAGCUGGAAC
1915
GUUCCAGCUCACUCAUUCG
1916


 


NM_005080_329-347
GAAUGAGUGAGCUGGAACA
1917
UGUUCCAGCUCACUCAUUC
1918


 


NM_005080_334-352
AGUGAGCUGGAACAGCAAG
1919
CUUGCUGUUCCAGCUCACU
1920


 


NM_005080_336-354
UGAGCUGGAACAGCAAGUG
1921
CACUUGCUGUUCCAGCUCA
1922


 


NM_005080_337-355
GAGCUGGAACAGCAAGUGG
1923
CCACUUGCUGUUCCAGCUC
1924


 


NM_005080_338-356
AGCUGGAACAGCAAGUGGU
1925
ACCACUUGCUGUUCCAGCU
1926


 


NM_005080_356-374
UAGAUUUAGAAGAAGAGAA
1927
UUCUCUUCUUCUAAAUCUA
1928


 


NM_005080_357-375
AGAUUUAGAAGAAGAGAAC
1929
GUUCUCUUCUUCUAAAUCU
1930


 


NM_005080_359-377
AUUUAGAAGAAGAGAACCA
1931
UGGUUCUCUUCUUCUAAAU
1932


 


NM_005080_360-378
UUUAGAAGAAGAGAACCAA
1933
UUGGUUCUCUUCUUCUAAA
1934


 


NM_005080_362-380
UAGAAGAAGAGAACCAAAA
1935
UUUUGGUUCUCUUCUUCUA
1936


 


NM_005080_367-385
GAAGAGAACCAAAAACUUU
1937
AAAGUUUUUGGUUCUCUUC
1938


 


NM_005080_382-400
CUUUUGCUAGAAAAUCAGC
1939
GCUGAUUUUCUAGCAAAAG
1940


 


NM_005080_386-404
UGCUAGAAAAUCAGCUUUU
1941
AAAAGCUGAUUUUCUAGCA
1942


 


NM_005080_401-419
UUUUACGAGAGAAAACUCA
1943
UGAGUUUUCUCUCGUAAAA
1944


 


NM_005080_458-476
UGGGGAUGGAUGCCCUGGU
1945
ACCAGGGCAUCCAUCCCCA
1946


 


NM_005080_484-502
GAGGAGGCGGAAGCCAAGG
1947
CCTTGGCTTCCGCCTCCTC
1948


 


NM_005080_489-507
GGCGGAAGCCAAGGGGAAU
1949
AUUCCCCUUGGCUUCCGCC
1950


 


NM_005080_574-592
GUGCAGGCCCAGUUGUCAC
1951
GUGACAACUGGGCCUGCAC
1952


 


NM_005080_594-612
CCUCCAGAACAUCUCCCCA
1953
UGGGGAGAUGUUCUGGAGG
1954


 


NM_005080_604-622
AUCUCCCCAUGGAUUCUGG
1955
CCAGAAUCCAUGGGGAGAU
1956


 


NM_005080_627-645
AUUGACUCUUCAGAUUCAG
1957
CUGAAUCUGAAGAGUCAAU
1958


 


NM_005080_635-653
UUCAGAUUCAGAGUCUGAU
1959
AUCAGACUCUGAAUCUGAA
1960


 


NM_005080_636-654
UCAGAUUCAGAGUCUGAUA
1961
UAUCAGACUCUGAAUCUGA
1962


 


NM_005080_666-684
AUUCUGGACAACUUGGACC
1963
GGUCCAAGUUGUCCAGAAU
1964


 


NM_005080_667-685
UUCUGGACAACUUGGACCC
1965
GGGUCCAAGUUGUCCAGAA
1966


 


NM_005080_669-687
CUGGACAACUUGGACCCAG
1967
CUGGGUCCAAGUUGUCCAG
1968


 


NM_005080_681-699
GACCCAGUCAUGUUCUUCA
1969
UGAAGAACAUGACUGGGUC
1970


 


NM_005080_690-708
AUGUUCUUCAAAUGCCCUU
1971
AAGGGCAUUUGAAGAACAU
1972


 


NM_005080_718-736
CUGCCAGCCUGGAGGAGCU
1973
AGCUCCUCCAGGCUGGCAG
1974


 


NM_005080_722-740
CAGCCUGGAGGAGCUCCCA
1975
UGGGAGCUCCUCCAGGCUG
1976


 


NM_005080_723-741
AGCCUGGAGGAGCUCCCAG
1977
CUGGGAGCUCCUCCAGGCU
1978


 


NM_005080_724-742
GCCUGGAGGAGCUCCCAGA
1979
UCUGGGAGCUCCUCCAGGC
1980


 


NM_005080_725-743
CCUGGAGGAGCUCCCAGAG
1981
CUCUGGGAGCUCCUCCAGG
1982


 


NM_005080_727-745
UGGAGGAGCUCCCAGAGGU
1983
ACCUCUGGGAGCUCCUCCA
1984


 


NM_005080_728-746
GGAGGAGCUCCCAGAGGUC
1985
GACCUCUGGGAGCUCCUCC
1986


 


NM_005080_739-757
CAGAGGUCUACCCAGAAGG
1987
CCUUCUGGGUAGACCUCUG
1988


 


NM_005080_747-765
UACCCAGAAGGACCCAGUU
1989
AACUGGGUCCUUCUGGGUA
1990


 


NM_005080_763-781
GUUCCUUACCAGCCUCCCU
1991
AGGGAGGCUGGUAAGGAAC
1992


 


NM_005080_764-782
UUCCUUACCAGCCUCCCUU
1993
AAGGGAGGCUGGUAAGGAA
1994


 


NM_005080_766-784
CCUUACCAGCCUCCCUUUC
1995
GAAAGGGAGGCUGGUAAGG
1996


 


NM_005080_770-788
ACCAGCCUCCCUUUCUCUG
1997
CAGAGAAAGGGAGGCUGGU
1998


 


NM_005080_774-792
GCCUCCCUUUCUCUGUCAG
1999
CUGACAGAGAAAGGGAGGC
2000


 


NM_005080_780-798
CUUUCUCUGUCAGUGGGGA
2001
UCCCCACUGACAGAGAAAG
2002


 


NM_005080_781-799
UUUCUCUGUCAGUGGGGAC
2003
GUCCCCACUGACAGAGAAA
2004


 


NM_005080_805-823
CAGCCAAGCUGGAAGCCAU
2005
AUGGCUUCCAGCUUGGCUG
2006


 


NM_005080_44-62
GAGCUAUGGUGGUGGUGGC
2007
GCCACCACCACCAUAGCUC
2008


 


NM_005080_45-63
AGCUAUGGUGGUGGUGGCA
2009
UGCCACCACCACCAUAGCU
2010


 


NM_005080_868-886
UCUUAGAGAUACCCUCUGA
2011
UCAGAGGGUAUCUCUAAGA
2012


 


NM_005080_875-893
GAUACCCUCUGAGACAGAG
2013
CUCUGUCUCAGAGGGUAUC
2014


 


NM_005080_47-65
CUAUGGUGGUGGUGGCAGC
2015
GCUGCCACCACCACCAUAG
2016


 


NM_005080_879-897
CCCUCUGAGACAGAGAGCC
2017
GGCUCUCUGUCUCAGAGGG
2018


 


NM_005080_880-898
CCUCUGAGACAGAGAGCCA
2019
UGGCUCUCUGUCUCAGAGG
2020


 


NM_005080_881-899
CUCUGAGACAGAGAGCCAA
2021
UUGGCUCUCUGUCUCAGAG
2022


 


NM_005080_882-900
UCUGAGACAGAGAGCCAAG
2023
CUUGGCUCUCUGUCUCAGA
2024


 


NM_005080_883-901
CUGAGACAGAGAGCCAAGC
2025
GCUUGGCUCUCUGUCUCAG
2026


 


NM_005080_49-67
AUGGUGGUGGUGGCAGCCG
2027
CGGCUGCCACCACCACCAU
2028


 


NM_005080_914-932
GAAAAUCGAGGAAGCACCU
2029
AGGUGCUUCCUCGAUUUUC
2030


 


NM_005080_915-933
AAAAUCGAGGAAGCACCUC
2031
GAGGUGCUUCCUCGAUUUU
2032


 


NM_005080_926-944
AGCACCUCUCAGCCCCUCA
2033
UGAGGGGCUGAGAGGUGCU
2034


 


NM_005080_945-963
GAGAAUGAUCACCCUGAAU
2035
AUUCAGGGUGAUCAUUCUC
2036


 


NM_005080_958-976
CUGAAUUCAUUGUCUCAGU
2037
ACUGAGACAAUGAAUUCAG
2038


 


NM_005080_959-977
UGAAUUCAUUGUCUCAGUG
2039
CACUGAGACAAUGAAUUCA
2040


 


NM_005080_962-980
AUUCAUUGUCUCAGUGAAG
2041
CUUCACUGAGACAAUGAAU
2042


 


NM_005080_975-993
GUGAAGGAAGAACCUGUAG
2043
CUACAGGUUCUUCCUUCAC
2044


 


NM_005080_983-1001
AGAACCUGUAGAAGAUGAC
2045
GUCAUCUUCUACAGGUUCU
2046


 


NM_005080_128-146
CCGCCGGAGCCCCGGCCGG
2047
CCGGCCGGGGCTCCGGCGG
2048


 


NM_005080_249-267
GAGCCCCGAGGAGAAGGCG
2049
CGCCTTCTCCTCGGGGCTC
2050


 


NM_005080_697-715
UCAAAUGCCCUUCCCCAGA
2051
UCUGGGGAAGGGCAUUUGA
2052


 


NM_005080_729-747
GAGGAGCUCCCAGAGGUCU
2053
AGACCUCUGGGAGCUCCUC
2054


 


NM_005080_776-794
CUCCCUUUCUCUGUCAGUG
2055
CACUGACAGAGAAAGGGAG
2056


 


NM_005080_803-821
AUCAGCCAAGCUGGAAGCC
2057
GGCUUCCAGCUUGGCUGAU
2058


 


NM_005080_254-272
CCGAGGAGAAGGCGCUGAG
2059
CUCAGCGCCUUCUCCUCGG
2060


 


NM_005080_383-401
UUUUGCUAGAAAAUCAGCU
2061
AGCUGAUUUUCUAGCAAAA
2062


 


NM_005080_116-134
AGCCCGCCUCCGCCGCCGG
2063
CCGGCGGCGGAGGCGGGCU
2064


 


NM_005080_123-141
CUCCGCCGCCGGAGCCCCG
2065
CGGGGCUCCGGCGGCGGAG
2066


 


NM_005080_125-143
CCGCCGCCGGAGCCCCGGC
2067
GCCGGGGCTCCGGCGGCGG
2068


 


NM_005080_135-153
AGCCCCGGCCGGCCAGGCC
2069
GGCCTGGCCGGCCGGGGCT
2070


 


NM_005080_253-271
CCCGAGGAGAAGGCGCUGA
2071
UCAGCGCCUUCUCCUCGGG
2072


 


NM_005080_274-292
AGGAAACUGAAAAACAGAG
2073
CUCUGUUUUUCAGUUUCCU
2074


 


NM_005080_655-673
UCCUGUUGGGCAUUCUGGA
2075
UCCAGAAUGCCCAACAGGA
2076


 


NM_005080_775-793
CCUCCCUUUCUCUGUCAGU
2077
ACUGACAGAGAAAGGGAGG
2078


 


NM_005080_46-64
GCUAUGGUGGUGGUGGCAG
2079
CUGCCACCACCACCAUAGC
2080


 


NM_005080_1456-1474
GUACUUUUAUCUUAAAAGG
2081
CCUUUUAAGAUAAAAGUAC
2082


 


NM_005080_1545-1563
UUAUGAAUGGUUCUUUAUC
2083
GAUAAAGAACCAUUCAUAA
2084


 


NM_005080_1558-1576
UUUAUCAUUUCUCUUCCCC
2085
GGGGAAGAGAAAUGAUAAA
2086


 


NM_005080_121-139
GCCUCCGCCGCCGGAGCCC
2087
GGGCUCCGGCGGCGGAGGC
2088


 


NM_005080_122-140
CCUCCGCCGCCGGAGCCCC
2089
GGGGCUCCGGCGGCGGAGG
2090


 


NM_005080_247-265
CUGAGCCCCGAGGAGAAGG
2091
CCUUCUCCUCGGGGCUCAG
2092


 


NM_005080_275-293
GGAAACUGAAAAACAGAGU
2093
ACUCUGUUUUUCAGUUUCC
2094


 


NM_005080_276-294
GAAACUGAAAAACAGAGUA
2095
UACUCUGUUUUUCAGUUUC
2096


 


NM_005080_358-376
GAUUUAGAAGAAGAGAACC
2097
GGUUCUCUUCUUCUAAAUC
2098


 


NM_005080_387-405
GCUAGAAAAUCAGCUUUUA
2099
UAAAAGCUGAUUUUCUAGC
2100


 


NM_005080_628-646
UUGACUCUUCAGAUUCAGA
2101
UCUGAAUCUGAAGAGUCAA
2102


 


NM_005080_656-674
CCUGUUGGGCAUUCUGGAC
2103
GUCCAGAAUGCCCAACAGG
2104


 


NM_005080_719-737
UGCCAGCCUGGAGGAGCUC
2105
GAGCUCCUCCAGGCUGGCA
2106


 


NM_005080_720-738
GCCAGCCUGGAGGAGCUCC
2107
GGAGCUCCUCCAGGCUGGC
2108


 


NM_005080_721-739
CCAGCCUGGAGGAGCUCCC
2109
GGGAGCUCCUCCAGGCUGG
2110


 


NM_005080_782-800
UUCUCUGUCAGUGGGGACG
2111
CGUCCCCACUGACAGAGAA
2112


 


NM_005080_867-885
GUCUUAGAGAUACCCUCUG
2113
CAGAGGGUAUCUCUAAGAC
2114


 


NM_005080_48-66
UAUGGUGGUGGUGGCAGCC
2115
GGCUGCCACCACCACCAUA
2116


 


NM_005080_963-981
UUCAUUGUCUCAGUGAAGG
2117
CCUUCACUGAGACAAUGAA
2118





Gene XBP1


reference transcript NM_005080 (human XBP1 mRNA, FIG. 2)


Notes


19mers found in both human and rhesus













TABLE 9







XBP-1 human/Rhesus siRNAs with 3′ dinucleotide overhangs.











Oligo Name/
sense (5′-3′)
SEQ
antisense (5′-3′)
SEQ


location of
with 3′ dinucleotide
ID
with 3′ dinucleotide
ID


target sequence
overhang
NO:
overhang
NO:





NM_005080_390-408
AGAAAAUCAGCUUUUACGANN
2203
UCGUAAAAGCUGAUUUUCUNN
2204


 


NM_005080_1184-1202
UCCCCAGCUGAUUAGUGUCNN
2205
GACACUAAUCAGCUGGGGANN
2206


 


NM_005080_1494-1512
UACUUAUUAUGUAAGGGUCNN
2207
GACCCUUACAUAAUAAGUANN
2208


 


NM_005080_1463-1481
UAUCUUAAAAGGGUGGUAGNN
2209
CUACCACCCUUUUAAGAUANN
2210


 


NM_005080_610-628
CCAUGGAUUCUGGCGGUAUNN
2211
AUACCGCCAGAAUCCAUGGNN
2212


 


NM_005080_823-841
UUAAUGAACUAAUUCGUUUNN
2213
AAACGAAUUAGUUCAUUAANN
2214


 


NM_005080_1507-1525
AGGGUCAUUAGACAAAUGUNN
2215
ACAUUUGUCUAAUGACCCUNN
2216


 


NM_005080_827-845
UGAACUAAUUCGUUUUGACNN
2217
GUCAAAACGAAUUAGUUCANN
2218


 


NM_005080_1503-1521
UGUAAGGGUCAUUAGACAANN
2219
UUGUCUAAUGACCCUUACANN
2220


 


NM_005080_829-847
AACUAAUUCGUUUUGACCANN
2221
UGGUCAAAACGAAUUAGUUNN
2222


 


NM_005080_1783-1801
UAUUUAAAACUACCCAUGCNN
2223
GCAUGGGUAGUUUUAAAUANN
2224


 


NM_005080_1183-1201
UUCCCCAGCUGAUUAGUGUNN
2225
ACACUAAUCAGCUGGGGAANN
2226


 


NM_005080_1501-1519
UAUGUAAGGGUCAUUAGACNN
2227
GUCUAAUGACCCUUACAUANN
2228


 


NM_005080_1504-1522
GUAAGGGUCAUUAGACAAANN
2229
UUUGUCUAAUGACCCUUACNN
2230


 


NM_005080_734-752
GCUCCCAGAGGUCUACCCANN
2231
UGGGUAGACCUCUGGGAGCNN
2232


 


NM_005080_893-911
GAGCCAAGCUAAUGUGGUANN
2233
UACCACAUUAGCUUGGCUCNN
2234


 


NM_005080_1064-1082
CUGCCUACUGGAUGCUUACNN
2235
GUAAGCAUCCAGUAGGCAGNN
2236


 


NM_005080_1066-1084
GCCUACUGGAUGCUUACAGNN
2237
CUGUAAGCAUCCAGUAGGCNN
2238


 


NM_005080_1136-1154
GCUUGGUGUAAACCAUUCUNN
2239
AGAAUGGUUUACACCAAGCNN
2240


 


NM_005080_1137-1155
CUUGGUGUAAACCAUUCUUNN
2241
AAGAAUGGUUUACACCAAGNN
2242


 


NM_005080_1182-1200
UUUCCCCAGCUGAUUAGUGNN
2243
CACUAAUCAGCUGGGGAAANN
2244


 


NM_005080_1186-1204
CCCAGCUGAUUAGUGUCUANN
2245
UAGACACUAAUCAGCUGGGNN
2246


 


NM_005080_1189-1207
AGCUGAUUAGUGUCUAAGGNN
2247
CCUUAGACACUAAUCAGCUNN
2248


 


NM_005080_1224-1242
UGCCCUUUUCCUUGACUAUNN
2249
AUAGUCAAGGAAAAGGGCANN
2250


 


NM_005080_1229-1247
UUUUCCUUGACUAUUACACNN
2251
GUGUAAUAGUCAAGGAAAANN
2252


 


NM_005080_1235-1253
UUGACUAUUACACUGCCUGNN
2253
CAGGCAGUGUAAUAGUCAANN
2254


 


NM_005080_1236-1254
UGACUAUUACACUGCCUGGNN
2255
CCAGGCAGUGUAAUAGUCANN
2256


 


NM_005080_1438-1456
ACUACAGCUUUUAAGAUUGNN
2257
CAAUCUUAAAAGCUGUAGUNN
2258


 


NM_005080_1441-1459
ACAGCUUUUAAGAUUGUACNN
2259
GUACAAUCUUAAAAGCUGUNN
2260


 


NM_005080_1442-1460
CAGCUUUUAAGAUUGUACUNN
2261
AGUACAAUCUUAAAAGCUGNN
2262


 


NM_005080_1493-1511
AUACUUAUUAUGUAAGGGUNN
2263
ACCCUUACAUAAUAAGUAUNN
2264


 


NM_005080_1502-1520
AUGUAAGGGUCAUUAGACANN
2265
UGUCUAAUGACCCUUACAUNN
2266


 


NM_005080_1506-1524
AAGGGUCAUUAGACAAAUGNN
2267
CAUUUGUCUAAUGACCCUUNN
2268


 


NM_005080_1594-1612
UUGCCUCCAGUUUUAGGUCNN
2269
GACCUAAAACUGGAGGCAANN
2270


 


NM_005080_1790-1808
AACUACCCAUGCAAUUAAANN
2271
UUUAAUUGCAUGGGUAGUUNN
2272


 


NM_005080_304-322
ACUGCCAGAGAUCGAAAGANN
2273
UCUUUCGAUCUCUGGCAGUNN
2274


 


NM_005080_305-323
CUGCCAGAGAUCGAAAGAANN
2275
UUCUUUCGAUCUCUGGCAGNN
2276


 


NM_005080_395-413
AUCAGCUUUUACGAGAGAANN
2277
UUCUCUCGUAAAAGCUGAUNN
2278


 


NM_005080_609-627
CCCAUGGAUUCUGGCGGUANN
2279
UACCGCCAGAAUCCAUGGGNN
2280


 


NM_005080_611-629
CAUGGAUUCUGGCGGUAUUNN
2281
AAUACCGCCAGAAUCCAUGNN
2282


 


NM_005080_617-635
UUCUGGCGGUAUUGACUCUNN
2283
AGAGUCAAUACCGCCAGAANN
2284


 


NM_005080_621-639
GGCGGUAUUGACUCUUCAGNN
2285
CUGAAGAGUCAAUACCGCCNN
2286


 


NM_005080_641-659
UUCAGAGUCUGAUAUCCUGNN
2287
CAGGAUAUCAGACUCUGAANN
2288


 


NM_005080_648-666
UCUGAUAUCCUGUUGGGCANN
2289
UGCCCAACAGGAUAUCAGANN
2290


 


NM_005080_651-669
GAUAUCCUGUUGGGCAUUCNN
2291
GAAUGCCCAACAGGAUAUCNN
2292


 


NM_005080_735-753
CUCCCAGAGGUCUACCCAGNN
2293
CUGGGUAGACCUCUGGGAGNN
2294


 


NM_005080_753-771
GAAGGACCCAGUUCCUUACNN
2295
GUAAGGAACUGGGUCCUUCNN
2296


 


NM_005080_794-812
GGGGACGUCAUCAGCCAAGNN
2297
CUUGGCUGAUGACGUCCCCNN
2298


 


NM_005080_826-844
AUGAACUAAUUCGUUUUGANN
2299
UCAAAACGAAUUAGUUCAUNN
2300


 


NM_005080_836-854
UCGUUUUGACCACAUAUAUNN
2301
AUAUAUGUGGUCAAAACGANN
2302


 


NM_005080_840-858
UUUGACCACAUAUAUACCANN
2303
UGGUAUAUAUGUGGUCAAANN
2304


 


NM_005080_841-859
UUGACCACAUAUAUACCAANN
2305
UUGGUAUAUAUGUGGUCAANN
2306


 


NM_005080_847-865
ACAUAUAUACCAAGCCCCUNN
2307
AGGGGCUUGGUAUAUAUGUNN
2308


 


NM_005080_894-912
AGCCAAGCUAAUGUGGUAGNN
2309
CUACCACAUUAGCUUGGCUNN
2310


 


NM_005080_895-913
GCCAAGCUAAUGUGGUAGUNN
2311
ACUACCACAUUAGCUUGGCNN
2312


 


NM_005080_896-914
CCAAGCUAAUGUGGUAGUGNN
2313
CACUACCACAUUAGCUUGGNN
2314


 


NM_005080_899-917
AGCUAAUGUGGUAGUGAAANN
2315
UUUCACUACCACAUUAGCUNN
2316


 


NM_005080_908-926
GGUAGUGAAAAUCGAGGAANN
2317
UUCCUCGAUUUUCACUACCNN
2318


 


NM_005080_917-935
AAUCGAGGAAGCACCUCUCNN
2319
GAGAGGUGCUUCCUCGAUUNN
2320


 


NM_005080_937-955
GCCCCUCAGAGAAUGAUCANN
2321
UGAUCAUUCUCUGAGGGGCNN
2322


 


NM_005080_950-968
UGAUCACCCUGAAUUCAUUNN
2323
AAUGAAUUCAGGGUGAUCANN
2324


 


NM_005080_1185-1203
CCCCAGCUGAUUAGUGUCUNN
2325
AGACACUAAUCAGCUGGGGNN
2326


 


NM_005080_1187-1205
CCAGCUGAUUAGUGUCUAANN
2327
UUAGACACUAAUCAGCUGGNN
2328


 


NM_005080_1153-1171
CUUGGGAGGACACUUUUGCNN
2329
GCAAAAGUGUCCUCCCAAGNN
2330


 


NM_005080_1787-1805
UAAAACUACCCAUGCAAUUNN
2331
AAUUGCAUGGGUAGUUUUANN
2332


 


NM_005080_606-624
CUCCCCAUGGAUUCUGGCGNN
2333
CGCCAGAAUCCAUGGGGAGNN
2334


 


NM_005080_1019-1037
UAUCUCAAAUCUGCUUUCANN
2335
UGAAAGCAGAUUUGAGAUANN
2336


 


NM_005080_1072-1090
UGGAUGCUUACAGUGACUGNN
2337
CAGUCACUGUAAGCAUCCANN
2338


 


NM_005080_1228-1246
CUUUUCCUUGACUAUUACANN
2339
UGUAAUAGUCAAGGAAAAGNN
2340


 


NM_005080_1461-1479
UUUAUCUUAAAAGGGUGGUNN
2341
ACCACCCUUUUAAGAUAAANN
2342


 


NM_005080_1495-1513
ACUUAUUAUGUAAGGGUCANN
2343
UGACCCUUACAUAAUAAGUNN
2344


 


NM_005080_1496-1514
CUUAUUAUGUAAGGGUCAUNN
2345
AUGACCCUUACAUAAUAAGNN
2346


 


NM_005080_1500-1518
UUAUGUAAGGGUCAUUAGANN
2347
UCUAAUGACCCUUACAUAANN
2348


 


NM_005080_1644-1662
CCUGCUGAGGGGGCUCUUUNN
2349
AAAGAGCCCCCUCAGCAGGNN
2350


 


NM_005080_1708-1726
AUAGAAAUUUACUAUGUAANN
2351
UUACAUAGUAAAUUUCUAUNN
2352


 


NM_005080_302-320
AGACUGCCAGAGAUCGAAANN
2353
UUUCGAUCUCUGGCAGUCUNN
2354


 


NM_005080_607-625
UCCCCAUGGAUUCUGGCGGNN
2355
CCGCCAGAAUCCAUGGGGANN
2356


 


NM_005080_824-842
UAAUGAACUAAUUCGUUUUNN
2357
AAAACGAAUUAGUUCAUUANN
2358


 


NM_005080_953-971
UCACCCUGAAUUCAUUGUCNN
2359
GACAAUGAAUUCAGGGUGANN
2360


 


NM_005080_1011-1029
GAGCUGGGUAUCUCAAAUCNN
2361
GAUUUGAGAUACCCAGCUCNN
2362


 


NM_005080_1230-1248
UUUCCUUGACUAUUACACUNN
2363
AGUGUAAUAGUCAAGGAAANN
2364


 


NM_005080_1231-1249
UUCCUUGACUAUUACACUGNN
2365
CAGUGUAAUAGUCAAGGAANN
2366


 


NM_005080_1290-1308
AAAGCCAAAAUAGAGAGUANN
2367
UACUCUCUAUUUUGGCUUUNN
2368


 


NM_005080_1331-1349
AUUUGUUCAGAUCUCAUAGNN
2369
CUAUGAGAUCUGAACAAAUNN
2370


 


NM_005080_1460-1478
UUUUAUCUUAAAAGGGUGGNN
2371
CCACCCUUUUAAGAUAAAANN
2372


 


NM_005080_1670-1688
GUAUACUUCAAGUAAGAUCNN
2373
GAUCUUACUUGAAGUAUACNN
2374


 


NM_005080_1671-1689
UAUACUUCAAGUAAGAUCANN
2375
UGAUCUUACUUGAAGUAUANN
2376


 


NM_005080_1735-1753
UGGAAUUUUUUCCUGCUAGNN
2377
CUAGCAGGAAAAAAUUCCANN
2378


 


NM_005080_1744-1762
UUCCUGCUAGUGUAGCUUCNN
2379
GAAGCUACACUAGCAGGAANN
2380


 


NM_005080_1796-1814
CCAUGCAAUUAAAAGGUACNN
2381
GUACCUUUUAAUUGCAUGGNN
2382


 


NM_005080_343-361
GAACAGCAAGUGGUAGAUUNN
2383
AAUCUACCACUUGCUGUUCNN
2384


 


NM_005080_374-392
ACCAAAAACUUUUGCUAGANN
2385
UCUAGCAAAAGUUUUUGGUNN
2386


 


NM_005080_375-393
CCAAAAACUUUUGCUAGAANN
2387
UUCUAGCAAAAGUUUUUGGNN
2388


 


NM_005080_608-626
CCCCAUGGAUUCUGGCGGUNN
2389
ACCGCCAGAAUCCAUGGGGNN
2390


 


NM_005080_652-670
AUAUCCUGUUGGGCAUUCUNN
2391
AGAAUGCCCAACAGGAUAUNN
2392


 


NM_005080_686-704
AGUCAUGUUCUUCAAAUGCNN
2393
GCAUUUGAAGAACAUGACUNN
2394


 


NM_005080_909-927
GUAGUGAAAAUCGAGGAAGNN
2395
CUUCCUCGAUUUUCACUACNN
2396


 


NM_005080_951-969
GAUCACCCUGAAUUCAUUGNN
2397
CAAUGAAUUCAGGGUGAUCNN
2398


 


NM_005080_952-970
AUCACCCUGAAUUCAUUGUNN
2399
ACAAUGAAUUCAGGGUGAUNN
2400


 


NM_005080_825-843
AAUGAACUAAUUCGUUUUGNN
2401
CAAAACGAAUUAGUUCAUUNN
2402


 


NM_005080_1194-1212
AUUAGUGUCUAAGGAAUGANN
2403
UCAUUCCUUAGACACUAAUNN
2404


 


NM_005080_831-849
CUAAUUCGUUUUGACCACANN
2405
UGUGGUCAAAACGAAUUAGNN
2406


 


NM_005080_835-853
UUCGUUUUGACCACAUAUANN
2407
UAUAUGUGGUCAAAACGAANN
2408


 


NM_005080_869-887
CUUAGAGAUACCCUCUGAGNN
2409
CUCAGAGGGUAUCUCUAAGNN
2410


 


NM_005080_1246-1264
ACUGCCUGGAGGAUAGCAGNN
2411
CUGCUAUCCUCCAGGCAGUNN
2412


 


NM_005080_1453-1471
AUUGUACUUUUAUCUUAAANN
2413
UUUAAGAUAAAAGUACAAUNN
2414


 


NM_005080_1512-1530
CAUUAGACAAAUGUCUUGANN
2415
UCAAGACAUUUGUCUAAUGNN
2416


 


NM_005080_1546-1564
UAUGAAUGGUUCUUUAUCANN
2417
UGAUAAAGAACCAUUCAUANN
2418


 


NM_005080_1789-1807
AAACUACCCAUGCAAUUAANN
2419
UUAAUUGCAUGGGUAGUUUNN
2420


 


NM_005080_325-343
GCUCGAAUGAGUGAGCUGGNN
2421
CCAGCUCACUCAUUCGAGCNN
2422


 


NM_005080_393-411
AAAUCAGCUUUUACGAGAGNN
2423
CUCUCGUAAAAGCUGAUUUNN
2424


 


NM_005080_788-806
GUCAGUGGGGACGUCAUCANN
2425
UGAUGACGUCCCCACUGACNN
2426


 


NM_005080_821-839
CAUUAAUGAACUAAUUCGUNN
2427
ACGAAUUAGUUCAUUAAUGNN
2428


 


NM_005080_1514-1532
UUAGACAAAUGUCUUGAAGNN
2429
CUUCAAGACAUUUGUCUAANN
2430


 


NM_005080_1797-1815
CAUGCAAUUAAAAGGUACANN
2431
UGUACCUUUUAAUUGCAUGNN
2432


 


NM_005080_833-851
AAUUCGUUUUGACCACAUANN
2433
UAUGUGGUCAAAACGAAUUNN
2434


 


NM_005080_1509-1527
GGUCAUUAGACAAAUGUCUNN
2435
AGACAUUUGUCUAAUGACCNN
2436


 


NM_005080_1802-1820
AAUUAAAAGGUACAAUGCANN
2437
UGCAUUGUACCUUUUAAUUNN
2438


 


NM_005080_391-409
GAAAAUCAGCUUUUACGAGNN
2439
CUCGUAAAAGCUGAUUUUCNN
2440


 


NM_005080_843-861
GACCACAUAUAUACCAAGCNN
2441
GCUUGGUAUAUAUGUGGUCNN
2442


 


NM_005080_1508-1526
GGGUCAUUAGACAAAUGUCNN
2443
GACAUUUGUCUAAUGACCCNN
2444


 


NM_005080_1754-1772
UGUAGCUUCUGAAAGGUGCNN
2445
GCACCUUUCAGAAGCUACANN
2446


 


NM_005080_430-448
GUUGAGAACCAGGAGUUAANN
2447
UUAACUCCUGGUUCUCAACNN
2448


 


NM_005080_437-455
ACCAGGAGUUAAGACAGCGNN
2449
CGCUGUCUUAACUCCUGGUNN
2450


 


NM_005080_1465-1483
UCUUAAAAGGGUGGUAGUUNN
2451
AACUACCACCCUUUUAAGANN
2452


 


NM_005080_1742-1760
UUUUCCUGCUAGUGUAGCUNN
2453
AGCUACACUAGCAGGAAAANN
2454


 


NM_005080_438-456
CCAGGAGUUAAGACAGCGCNN
2455
GCGCUGUCUUAACUCCUGGNN
2456


 


NM_005080_1060-1078
CUUCCUGCCUACUGGAUGCNN
2457
GCAUCCAGUAGGCAGGAAGNN
2458


 


NM_005080_1067-1085
CCUACUGGAUGCUUACAGUNN
2459
ACUGUAAGCAUCCAGUAGGNN
2460


 


NM_005080_1197-1215
AGUGUCUAAGGAAUGAUCCNN
2461
GGAUCAUUCCUUAGACACUNN
2462


 


NM_005080_1198-1216
GUGUCUAAGGAAUGAUCCANN
2463
UGGAUCAUUCCUUAGACACNN
2464


 


NM_005080_1424-1442
UACUAUAAUUGAGAACUACNN
2465
GUAGUUCUCAAUUAUAGUANN
2466


 


NM_005080_1464-1482
AUCUUAAAAGGGUGGUAGUNN
2467
ACUACCACCCUUUUAAGAUNN
2468


 


NM_005080_616-634
AUUCUGGCGGUAUUGACUCNN
2469
GAGUCAAUACCGCCAGAAUNN
2470


 


NM_005080_757-775
GACCCAGUUCCUUACCAGCNN
2471
GCUGGUAAGGAACUGGGUCNN
2472


 


NM_005080_785-803
UCUGUCAGUGGGGACGUCANN
2473
UGACGUCCCCACUGACAGANN
2474


 


NM_005080_819-837
GCCAUUAAUGAACUAAUUCNN
2475
GAAUUAGUUCAUUAAUGGCNN
2476


 


NM_005080_842-860
UGACCACAUAUAUACCAAGNN
2477
CUUGGUAUAUAUGUGGUCANN
2478


 


NM_005080_845-863
CCACAUAUAUACCAAGCCCNN
2479
GGGCUUGGUAUAUAUGUGGNN
2480


 


NM_005080_1013-1031
GCUGGGUAUCUCAAAUCUGNN
2481
CAGAUUUGAGAUACCCAGCNN
2482


 


NM_005080_1431-1449
AUUGAGAACUACAGCUUUUNN
2483
AAAAGCUGUAGUUCUCAAUNN
2484


 


NM_005080_1673-1691
UACUUCAAGUAAGAUCAAGNN
2485
CUUGAUCUUACUUGAAGUANN
2486


 


NM_005080_283-301
AAAAACAGAGUAGCAGCUCNN
2487
GAGCUGCUACUCUGUUUUUNN
2488


 


NM_005080_838-856
GUUUUGACCACAUAUAUACNN
2489
GUAUAUAUGUGGUCAAAACNN
2490


 


NM_005080_279-297
ACUGAAAAACAGAGUAGCANN
2491
UGCUACUCUGUUUUUCAGUNN
2492


 


NM_005080_633-651
UCUUCAGAUUCAGAGUCUGNN
2493
CAGACUCUGAAUCUGAAGANN
2494


 


NM_005080_1024-1042
CAAAUCUGCUUUCAUCCAGNN
2495
CUGGAUGAAAGCAGAUUUGNN
2496


 


NM_005080_1147-1165
ACCAUUCUUGGGAGGACACNN
2497
GUGUCCUCCCAAGAAUGGUNN
2498


 


NM_005080_1154-1172
UUGGGAGGACACUUUUGCCNN
2499
GGCAAAAGUGUCCUCCCAANN
2500


 


NM_005080_1188-1206
CAGCUGAUUAGUGUCUAAGNN
2501
CUUAGACACUAAUCAGCUGNN
2502


 


NM_005080_1192-1210
UGAUUAGUGUCUAAGGAAUNN
2503
AUUCCUUAGACACUAAUCANN
2504


 


NM_005080_1195-1213
UUAGUGUCUAAGGAAUGAUNN
2505
AUCAUUCCUUAGACACUAANN
2506


 


NM_005080_1238-1256
ACUAUUACACUGCCUGGAGNN
2507
CUCCAGGCAGUGUAAUAGUNN
2508


 


NM_005080_1548-1566
UGAAUGGUUCUUUAUCAUUNN
2509
AAUGAUAAAGAACCAUUCANN
2510


 


NM_005080_1549-1567
GAAUGGUUCUUUAUCAUUUNN
2511
AAAUGAUAAAGAACCAUUCNN
2512


 


NM_005080_1677-1695
UCAAGUAAGAUCAAGAAUCNN
2513
GAUUCUUGAUCUUACUUGANN
2514


 


NM_005080_1707-1725
UAUAGAAAUUUACUAUGUANN
2515
UACAUAGUAAAUUUCUAUANN
2516


 


NM_005080_1713-1731
AAUUUACUAUGUAAAUGCUNN
2517
AGCAUUUACAUAGUAAAUUNN
2518


 


NM_005080_1786-1804
UUAAAACUACCCAUGCAAUNN
2519
AUUGCAUGGGUAGUUUUAANN
2520


 


NM_005080_210-228
GCUGCCCCAGGCGCGCAAGNN
2521
CUUGCGCGCCUGGGGCAGCNN
2522


 


NM_005080_278-296
AACUGAAAAACAGAGUAGCNN
2523
GCUACUCUGUUUUUCAGUUNN
2524


 


NM_005080_284-302
AAAACAGAGUAGCAGCUCANN
2525
UGAGCUGCUACUCUGUUUUNN
2526


 


NM_005080_290-308
GAGUAGCAGCUCAGACUGCNN
2527
GCAGUCUGAGCUGCUACUCNN
2528


 


NM_005080_342-360
GGAACAGCAAGUGGUAGAUNN
2529
AUCUACCACUUGCUGUUCCNN
2530


 


NM_005080_431-449
UUGAGAACCAGGAGUUAAGNN
2531
CUUAACUCCUGGUUCUCAANN
2532


 


NM_005080_576-594
GCAGGCCCAGUUGUCACCCNN
2533
GGGUGACAACUGGGCCUGCNN
2534


 


NM_005080_602-620
ACAUCUCCCCAUGGAUUCUNN
2535
AGAAUCCAUGGGGAGAUGUNN
2536


 


NM_005080_618-636
UCUGGCGGUAUUGACUCUUNN
2537
AAGAGUCAAUACCGCCAGANN
2538


 


NM_005080_678-696
UUGGACCCAGUCAUGUUCUNN
2539
AGAACAUGACUGGGUCCAANN
2540


 


NM_005080_796-814
GGACGUCAUCAGCCAAGCUNN
2541
AGCUUGGCUGAUGACGUCCNN
2542


 


NM_005080_940-958
CCUCAGAGAAUGAUCACCCNN
2543
GGGUGAUCAUUCUCUGAGGNN
2544


 


NM_005080_954-972
CACCCUGAAUUCAUUGUCUNN
2545
AGACAAUGAAUUCAGGGUGNN
2546


 


NM_005080_977-995
GAAGGAAGAACCUGUAGAANN
2547
UUCUACAGGUUCUUCCUUCNN
2548


 


NM_005080_1018-1036
GUAUCUCAAAUCUGCUUUCNN
2549
GAAAGCAGAUUUGAGAUACNN
2550


 


NM_005080_1026-1044
AAUCUGCUUUCAUCCAGCCNN
2551
GGCUGGAUGAAAGCAGAUUNN
2552


 


NM_005080_1138-1156
UUGGUGUAAACCAUUCUUGNN
2553
CAAGAAUGGUUUACACCAANN
2554


 


NM_005080_1141-1159
GUGUAAACCAUUCUUGGGANN
2555
UCCCAAGAAUGGUUUACACNN
2556


 


NM_005080_1142-1160
UGUAAACCAUUCUUGGGAGNN
2557
CUCCCAAGAAUGGUUUACANN
2558


 


NM_005080_1155-1173
UGGGAGGACACUUUUGCCANN
2559
UGGCAAAAGUGUCCUCCCANN
2560


 


NM_005080_1158-1176
GAGGACACUUUUGCCAAUGNN
2561
CAUUGGCAAAAGUGUCCUCNN
2562


 


NM_005080_1193-1211
GAUUAGUGUCUAAGGAAUGNN
2563
CAUUCCUUAGACACUAAUCNN
2564


 


NM_005080_1196-1214
UAGUGUCUAAGGAAUGAUCNN
2565
GAUCAUUCCUUAGACACUANN
2566


 


NM_005080_1219-1237
ACUGUUGCCCUUUUCCUUGNN
2567
CAAGGAAAAGGGCAACAGUNN
2568


 


NM_005080_107-125
UGUCGGGGCAGCCCGCCUCNN
2569
GAGGCGGGCUGCCCCGACANN
2570


 


NM_005080_108-126
GUCGGGGCAGCCCGCCUCCNN
2571
GGAGGCGGGCUGCCCCGACNN
2572


 


NM_005080_1505-1523
UAAGGGUCAUUAGACAAAUNN
2573
AUUUGUCUAAUGACCCUUANN
2574


 


NM_005080_1567-1585
UCUCUUCCCCCUUUUUGGCNN
2575
GCCAAAAAGGGGGAAGAGANN
2576


 


NM_005080_1672-1690
AUACUUCAAGUAAGAUCAANN
2577
UUGAUCUUACUUGAAGUAUNN
2578


 


NM_005080_1678-1696
CAAGUAAGAUCAAGAAUCUNN
2579
AGAUUCUUGAUCUUACUUGNN
2580


 


NM_005080_1778-1796
CCAUUUAUUUAAAACUACCNN
2581
GGUAGUUUUAAAUAAAUGGNN
2582


 


NM_005080_1779-1797
CAUUUAUUUAAAACUACCCNN
2583
GGGUAGUUUUAAAUAAAUGNN
2584


 


NM_005080_280-298
CUGAAAAACAGAGUAGCAGNN
2585
CUGCUACUCUGUUUUUCAGNN
2586


 


NM_005080_282-300
GAAAAACAGAGUAGCAGCUNN
2587
AGCUGCUACUCUGUUUUUCNN
2588


 


NM_005080_288-306
CAGAGUAGCAGCUCAGACUNN
2589
AGUCUGAGCUGCUACUCUGNN
2590


 


NM_005080_291-309
AGUAGCAGCUCAGACUGCCNN
2591
GGCAGUCUGAGCUGCUACUNN
2592


 


NM_005080_347-365
AGCAAGUGGUAGAUUUAGANN
2593
UCUAAAUCUACCACUUGCUNN
2594


 


NM_005080_397-415
CAGCUUUUACGAGAGAAAANN
2595
UUUUCUCUCGUAAAAGCUGNN
2596


 


NM_005080_398-416
AGCUUUUACGAGAGAAAACNN
2597
GUUUUCUCUCGUAAAAGCUNN
2598


 


NM_005080_399-417
GCUUUUACGAGAGAAAACUNN
2599
AGUUUUCUCUCGUAAAAGCNN
2600


 


NM_005080_512-530
UGAGGCCAGUGGCCGGGUCNN
2601
GACCCGGCCACUGGCCUCANN
2602


 


NM_005080_517-535
CCAGUGGCCGGGUCUGCUGNN
2603
CAGCAGACCCGGCCACUGGNN
2604


 


NM_005080_596-614
UCCAGAACAUCUCCCCAUGNN
2605
CAUGGGGAGAUGUUCUGGANN
2606


 


NM_005080_598-616
CAGAACAUCUCCCCAUGGANN
2607
UCCAUGGGGAGAUGUUCUGNN
2608


 


NM_005080_601-619
AACAUCUCCCCAUGGAUUCNN
2609
GAAUCCAUGGGGAGAUGUUNN
2610


 


NM_005080_605-623
UCUCCCCAUGGAUUCUGGCNN
2611
GCCAGAAUCCAUGGGGAGANN
2612


 


NM_005080_661-679
UGGGCAUUCUGGACAACUUNN
2613
AAGUUGUCCAGAAUGCCCANN
2614


 


NM_005080_688-706
UCAUGUUCUUCAAAUGCCCNN
2615
GGGCAUUUGAAGAACAUGANN
2616


 


NM_005080_691-709
UGUUCUUCAAAUGCCCUUCNN
2617
GAAGGGCAUUUGAAGAACANN
2618


 


NM_005080_828-846
GAACUAAUUCGUUUUGACCNN
2619
GGUCAAAACGAAUUAGUUCNN
2620


 


NM_005080_830-848
ACUAAUUCGUUUUGACCACNN
2621
GUGGUCAAAACGAAUUAGUNN
2622


 


NM_005080_834-852
AUUCGUUUUGACCACAUAUNN
2623
AUAUGUGGUCAAAACGAAUNN
2624


 


NM_005080_846-864
CACAUAUAUACCAAGCCCCNN
2625
GGGGCUUGGUAUAUAUGUGNN
2626


 


NM_005080_870-888
UUAGAGAUACCCUCUGAGANN
2627
UCUCAGAGGGUAUCUCUAANN
2628


 


NM_005080_891-909
GAGAGCCAAGCUAAUGUGGNN
2629
CCACAUUAGCUUGGCUCUCNN
2630


 


NM_005080_900-918
GCUAAUGUGGUAGUGAAAANN
2631
UUUUCACUACCACAUUAGCNN
2632


 


NM_005080_911-929
AGUGAAAAUCGAGGAAGCANN
2633
UGCUUCCUCGAUUUUCACUNN
2634


 


NM_005080_912-930
GUGAAAAUCGAGGAAGCACNN
2635
GUGCUUCCUCGAUUUUCACNN
2636


 


NM_005080_979-997
AGGAAGAACCUGUAGAAGANN
2637
UCUUCUACAGGUUCUUCCUNN
2638


 


NM_005080_1366-1384
GUCUUUUGACAUCCAGCAGNN
2639
CUGCUGGAUGUCAAAAGACNN
2640


 


NM_005080_150-168
GGCCCUGCCGCUCAUGGUGNN
2641
CACCAUGAGCGGCAGGGCCNN
2642


 


NM_005080_1437-1455
AACUACAGCUUUUAAGAUUNN
2643
AAUCUUAAAAGCUGUAGUUNN
2644


 


NM_005080_482-500
AAGAGGAGGCGGAAGCCAANN
2645
TTGGCTTCCGCCTCCTCTTNN
2646


 


NM_005080_580-598
GCCCAGUUGUCACCCCUCCNN
2647
GGAGGGGUGACAACUGGGCNN
2648


 


NM_005080_613-631
UGGAUUCUGGCGGUAUUGANN
2649
UCAAUACCGCCAGAAUCCANN
2650


 


NM_005080_1065-1083
UGCCUACUGGAUGCUUACANN
2651
UGUAAGCAUCCAGUAGGCANN
2652


 


NM_005080_614-632
GGAUUCUGGCGGUAUUGACNN
2653
GUCAAUACCGCCAGAAUCCNN
2654


 


NM_005080_640-658
AUUCAGAGUCUGAUAUCCUNN
2655
AGGAUAUCAGACUCUGAAUNN
2656


 


NM_005080_1014-1032
CUGGGUAUCUCAAAUCUGCNN
2657
GCAGAUUUGAGAUACCCAGNN
2658


 


NM_005080_1015-1033
UGGGUAUCUCAAAUCUGCUNN
2659
AGCAGAUUUGAGAUACCCANN
2660


 


NM_005080_1146-1164
AACCAUUCUUGGGAGGACANN
2661
UGUCCUCCCAAGAAUGGUUNN
2662


 


NM_005080_1232-1250
UCCUUGACUAUUACACUGCNN
2663
GCAGUGUAAUAGUCAAGGANN
2664


 


NM_005080_1234-1252
CUUGACUAUUACACUGCCUNN
2665
AGGCAGUGUAAUAGUCAAGNN
2666


 


NM_005080_1237-1255
GACUAUUACACUGCCUGGANN
2667
UCCAGGCAGUGUAAUAGUCNN
2668


 


NM_005080_1443-1461
AGCUUUUAAGAUUGUACUUNN
2669
AAGUACAAUCUUAAAAGCUNN
2670


 


NM_005080_1462-1480
UUAUCUUAAAAGGGUGGUANN
2671
UACCACCCUUUUAAGAUAANN
2672


 


NM_005080_1510-1528
GUCAUUAGACAAAUGUCUUNN
2673
AAGACAUUUGUCUAAUGACNN
2674


 


NM_005080_1591-1609
GGCUUGCCUCCAGUUUUAGNN
2675
CUAAAACUGGAGGCAAGCCNN
2676


 


NM_005080_1615-1633
UUAGUUUGCUUCUGUAAGCNN
2677
GCUUACAGAAGCAAACUAANN
2678


 


NM_005080_1716-1734
UUACUAUGUAAAUGCUUGANN
2679
UCAAGCAUUUACAUAGUAANN
2680


 


NM_005080_1718-1736
ACUAUGUAAAUGCUUGAUGNN
2681
CAUCAAGCAUUUACAUAGUNN
2682


 


NM_005080_1725-1743
AAAUGCUUGAUGGAAUUUUNN
2683
AAAAUUCCAUCAAGCAUUUNN
2684


 


NM_005080_1748-1766
UGCUAGUGUAGCUUCUGAANN
2685
UUCAGAAGCUACACUAGCANN
2686


 


NM_005080_1780-1798
AUUUAUUUAAAACUACCCANN
2687
UGGGUAGUUUUAAAUAAAUNN
2688


 


NM_005080_1794-1812
ACCCAUGCAAUUAAAAGGUNN
2689
ACCUUUUAAUUGCAUGGGUNN
2690


 


NM_005080_156-174
GCCGCUCAUGGUGCCAGCCNN
2691
GGCUGGCACCAUGAGCGGCNN
2692


 


NM_005080_299-317
CUCAGACUGCCAGAGAUCGNN
2693
CGAUCUCUGGCAGUCUGAGNN
2694


 


NM_005080_344-362
AACAGCAAGUGGUAGAUUUNN
2695
AAAUCUACCACUUGCUGUUNN
2696


 


NM_005080_371-389
AGAACCAAAAACUUUUGCUNN
2697
AGCAAAAGUUUUUGGUUCUNN
2698


 


NM_005080_373-391
AACCAAAAACUUUUGCUAGNN
2699
CUAGCAAAAGUUUUUGGUUNN
2700


 


NM_005080_524-542
CCGGGUCUGCUGAGUCCGCNN
2701
GCGGACUCAGCAGACCCGGNN
2702


 


NM_005080_525-543
CGGGUCUGCUGAGUCCGCANN
2703
UGCGGACUCAGCAGACCCGNN
2704


 


NM_005080_612-630
AUGGAUUCUGGCGGUAUUGNN
2705
CAAUACCGCCAGAAUCCAUNN
2706


 


NM_005080_615-633
GAUUCUGGCGGUAUUGACUNN
2707
AGUCAAUACCGCCAGAAUCNN
2708


 


NM_005080_645-663
GAGUCUGAUAUCCUGUUGGNN
2709
CCAACAGGAUAUCAGACUCNN
2710


 


NM_005080_792-810
GUGGGGACGUCAUCAGCCANN
2711
UGGCUGAUGACGUCCCCACNN
2712


 


NM_005080_905-923
UGUGGUAGUGAAAAUCGAGNN
2713
CUCGAUUUUCACUACCACANN
2714


 


NM_005080_976-994
UGAAGGAAGAACCUGUAGANN
2715
UCUACAGGUUCUUCCUUCANN
2716


 


NM_005080_1244-1262
ACACUGCCUGGAGGAUAGCNN
2717
GCUAUCCUCCAGGCAGUGUNN
2718


 


NM_005080_1791-1809
ACUACCCAUGCAAUUAAAANN
2719
UUUUAAUUGCAUGGGUAGUNN
2720


 


NM_005080_755-773
AGGACCCAGUUCCUUACCANN
2721
UGGUAAGGAACUGGGUCCUNN
2722


 


NM_005080_799-817
CGUCAUCAGCCAAGCUGGANN
2723
UCCAGCUUGGCUGAUGACGNN
2724


 


NM_005080_832-850
UAAUUCGUUUUGACCACAUNN
2725
AUGUGGUCAAAACGAAUUANN
2726


 


NM_005080_839-857
UUUUGACCACAUAUAUACCNN
2727
GGUAUAUAUGUGGUCAAAANN
2728


 


NM_005080_100-118
CUGCUUCUGUCGGGGCAGCNN
2729
GCUGCCCCGACAGAAGCAGNN
2730


 


NM_005080_281-299
UGAAAAACAGAGUAGCAGCNN
2731
GCUGCUACUCUGUUUUUCANN
2732


 


NM_005080_822-840
AUUAAUGAACUAAUUCGUUNN
2733
AACGAAUUAGUUCAUUAAUNN
2734


 


NM_005080_1152-1170
UCUUGGGAGGACACUUUUGNN
2735
CAAAAGUGUCCUCCCAAGANN
2736


 


NM_005080_1191-1209
CUGAUUAGUGUCUAAGGAANN
2737
UUCCUUAGACACUAAUCAGNN
2738


 


NM_005080_1225-1243
GCCCUUUUCCUUGACUAUUNN
2739
AAUAGUCAAGGAAAAGGGCNN
2740


 


NM_005080_1227-1245
CCUUUUCCUUGACUAUUACNN
2741
GUAAUAGUCAAGGAAAAGGNN
2742


 


NM_005080_1239-1257
CUAUUACACUGCCUGGAGGNN
2743
CCUCCAGGCAGUGUAAUAGNN
2744


 


NM_005080_1430-1448
AAUUGAGAACUACAGCUUUNN
2745
AAAGCUGUAGUUCUCAAUUNN
2746


 


NM_005080_1499-1517
AUUAUGUAAGGGUCAUUAGNN
2747
CUAAUGACCCUUACAUAAUNN
2748


 


NM_005080_1553-1571
GGUUCUUUAUCAUUUCUCUNN
2749
AGAGAAAUGAUAAAGAACCNN
2750


 


NM_005080_1585-1603
CAUCCUGGCUUGCCUCCAGNN
2751
CUGGAGGCAAGCCAGGAUGNN
2752


 


NM_005080_1592-1610
GCUUGCCUCCAGUUUUAGGNN
2753
CCUAAAACUGGAGGCAAGCNN
2754


 


NM_005080_1743-1761
UUUCCUGCUAGUGUAGCUUNN
2755
AAGCUACACUAGCAGGAAANN
2756


 


NM_005080_154-172
CUGCCGCUCAUGGUGCCAGNN
2757
CUGGCACCAUGAGCGGCAGNN
2758


 


NM_005080_193-211
GAGGCAGCGAGCGGGGGGCNN
2759
GCCCCCCGCTCGCTGCCTCNN
2760


 


NM_005080_199-217
GCGAGCGGGGGGCUGCCCCNN
2761
GGGGCAGCCCCCCGCUCGCNN
2762


 


NM_005080_292-310
GUAGCAGCUCAGACUGCCANN
2763
UGGCAGUCUGAGCUGCUACNN
2764


 


NM_005080_341-359
UGGAACAGCAAGUGGUAGANN
2765
UCUACCACUUGCUGUUCCANN
2766


 


NM_005080_377-395
AAAAACUUUUGCUAGAAAANN
2767
UUUUCUAGCAAAAGUUUUUNN
2768


 


NM_005080_519-537
AGUGGCCGGGUCUGCUGAGNN
2769
CUCAGCAGACCCGGCCACUNN
2770


 


NM_005080_522-540
GGCCGGGUCUGCUGAGUCCNN
2771
GGACUCAGCAGACCCGGCCNN
2772


 


NM_005080_577-595
CAGGCCCAGUUGUCACCCCNN
2773
GGGGUGACAACUGGGCCUGNN
2774


 


NM_005080_599-617
AGAACAUCUCCCCAUGGAUNN
2775
AUCCAUGGGGAGAUGUUCUNN
2776


 


NM_005080_754-772
AAGGACCCAGUUCCUUACCNN
2777
GGUAAGGAACUGGGUCCUUNN
2778


 


NM_005080_888-906
ACAGAGAGCCAAGCUAAUGNN
2779
CAUUAGCUUGGCUCUCUGUNN
2780


 


NM_005080_939-957
CCCUCAGAGAAUGAUCACCNN
2781
GGUGAUCAUUCUCUGAGGGNN
2782


 


NM_005080_964-982
UCAUUGUCUCAGUGAAGGANN
2783
UCCUUCACUGAGACAAUGANN
2784


 


NM_005080_1012-1030
AGCUGGGUAUCUCAAAUCUNN
2785
AGAUUUGAGAUACCCAGCUNN
2786


 


NM_005080_1016-1034
GGGUAUCUCAAAUCUGCUUNN
2787
AAGCAGAUUUGAGAUACCCNN
2788


 


NM_005080_1020-1038
AUCUCAAAUCUGCUUUCAUNN
2789
AUGAAAGCAGAUUUGAGAUNN
2790


 


NM_005080_1025-1043
AAAUCUGCUUUCAUCCAGCNN
2791
GCUGGAUGAAAGCAGAUUUNN
2792


 


NM_005080_1027-1045
AUCUGCUUUCAUCCAGCCANN
2793
UGGCUGGAUGAAAGCAGAUNN
2794


 


NM_005080_1028-1046
UCUGCUUUCAUCCAGCCACNN
2795
GUGGCUGGAUGAAAGCAGANN
2796


 


NM_005080_1030-1048
UGCUUUCAUCCAGCCACUGNN
2797
CAGUGGCUGGAUGAAAGCANN
2798


 


NM_005080_1031-1049
GCUUUCAUCCAGCCACUGCNN
2799
GCAGUGGCUGGAUGAAAGCNN
2800


 


NM_005080_1032-1050
CUUUCAUCCAGCCACUGCCNN
2801
GGCAGUGGCUGGAUGAAAGNN
2802


 


NM_005080_1033-1051
UUUCAUCCAGCCACUGCCCNN
2803
GGGCAGUGGCUGGAUGAAANN
2804


 


NM_005080_1056-1074
CCAUCUUCCUGCCUACUGGNN
2805
CCAGUAGGCAGGAAGAUGGNN
2806


 


NM_005080_1057-1075
CAUCUUCCUGCCUACUGGANN
2807
UCCAGUAGGCAGGAAGAUGNN
2808


 


NM_005080_1058-1076
AUCUUCCUGCCUACUGGAUNN
2809
AUCCAGUAGGCAGGAAGAUNN
2810


 


NM_005080_1059-1077
UCUUCCUGCCUACUGGAUGNN
2811
CAUCCAGUAGGCAGGAAGANN
2812


 


NM_005080_1061-1079
UUCCUGCCUACUGGAUGCUNN
2813
AGCAUCCAGUAGGCAGGAANN
2814


 


NM_005080_1063-1081
CCUGCCUACUGGAUGCUUANN
2815
UAAGCAUCCAGUAGGCAGGNN
2816


 


NM_005080_1069-1087
UACUGGAUGCUUACAGUGANN
2817
UCACUGUAAGCAUCCAGUANN
2818


 


NM_005080_1071-1089
CUGGAUGCUUACAGUGACUNN
2819
AGUCACUGUAAGCAUCCAGNN
2820


 


NM_005080_1073-1091
GGAUGCUUACAGUGACUGUNN
2821
ACAGUCACUGUAAGCAUCCNN
2822


 


NM_005080_1075-1093
AUGCUUACAGUGACUGUGGNN
2823
CCACAGUCACUGUAAGCAUNN
2824


 


NM_005080_1076-1094
UGCUUACAGUGACUGUGGANN
2825
UCCACAGUCACUGUAAGCANN
2826


 


NM_005080_1078-1096
CUUACAGUGACUGUGGAUANN
2827
UAUCCACAGUCACUGUAAGNN
2828


 


NM_005080_1139-1157
UGGUGUAAACCAUUCUUGGNN
2829
CCAAGAAUGGUUUACACCANN
2830


 


NM_005080_1140-1158
GGUGUAAACCAUUCUUGGGNN
2831
CCCAAGAAUGGUUUACACCNN
2832


 


NM_005080_1143-1161
GUAAACCAUUCUUGGGAGGNN
2833
CCUCCCAAGAAUGGUUUACNN
2834


 


NM_005080_1144-1162
UAAACCAUUCUUGGGAGGANN
2835
UCCUCCCAAGAAUGGUUUANN
2836


 


NM_005080_1145-1163
AAACCAUUCUUGGGAGGACNN
2837
GUCCUCCCAAGAAUGGUUUNN
2838


 


NM_005080_1148-1166
CCAUUCUUGGGAGGACACUNN
2839
AGUGUCCUCCCAAGAAUGGNN
2840


 


NM_005080_1156-1174
GGGAGGACACUUUUGCCAANN
2841
UUGGCAAAAGUGUCCUCCCNN
2842


 


NM_005080_1157-1175
GGAGGACACUUUUGCCAAUNN
2843
AUUGGCAAAAGUGUCCUCCNN
2844


 


NM_005080_1159-1177
AGGACACUUUUGCCAAUGANN
2845
UCAUUGGCAAAAGUGUCCUNN
2846


 


NM_005080_1160-1178
GGACACUUUUGCCAAUGAANN
2847
UUCAUUGGCAAAAGUGUCCNN
2848


 


NM_005080_1190-1208
GCUGAUUAGUGUCUAAGGANN
2849
UCCUUAGACACUAAUCAGCNN
2850


 


NM_005080_1218-1236
UACUGUUGCCCUUUUCCUUNN
2851
AAGGAAAAGGGCAACAGUANN
2852


 


NM_005080_1220-1238
CUGUUGCCCUUUUCCUUGANN
2853
UCAAGGAAAAGGGCAACAGNN
2854


 


NM_005080_1221-1239
UGUUGCCCUUUUCCUUGACNN
2855
GUCAAGGAAAAGGGCAACANN
2856


 


NM_005080_1233-1251
CCUUGACUAUUACACUGCCNN
2857
GGCAGUGUAAUAGUCAAGGNN
2858


 


NM_005080_1240-1258
UAUUACACUGCCUGGAGGANN
2859
UCCUCCAGGCAGUGUAAUANN
2860


 


NM_005080_1241-1259
AUUACACUGCCUGGAGGAUNN
2861
AUCCUCCAGGCAGUGUAAUNN
2862


 


NM_005080_1242-1260
UUACACUGCCUGGAGGAUANN
2863
UAUCCUCCAGGCAGUGUAANN
2864


 


NM_005080_1243-1261
UACACUGCCUGGAGGAUAGNN
2865
CUAUCCUCCAGGCAGUGUANN
2866


 


NM_005080_1282-1300
UCAUUCAAAAAGCCAAAAUNN
2867
AUUUUGGCUUUUUGAAUGANN
2868


 


NM_005080_1287-1305
CAAAAAGCCAAAAUAGAGANN
2869
UCUCUAUUUUGGCUUUUUGNN
2870


 


NM_005080_1289-1307
AAAAGCCAAAAUAGAGAGUNN
2871
ACUCUCUAUUUUGGCUUUUNN
2872


 


NM_005080_1310-1328
ACAGUCCUAGAGAAUUCCUNN
2873
AGGAAUUCUCUAGGACUGUNN
2874


 


NM_005080_1330-1348
UAUUUGUUCAGAUCUCAUANN
2875
UAUGAGAUCUGAACAAAUANN
2876


 


NM_005080_1332-1350
UUUGUUCAGAUCUCAUAGANN
2877
UCUAUGAGAUCUGAACAAANN
2878


 


NM_005080_1333-1351
UUGUUCAGAUCUCAUAGAUNN
2879
AUCUAUGAGAUCUGAACAANN
2880


 


NM_005080_1369-1387
UUUUGACAUCCAGCAGUCCNN
2881
GGACUGCUGGAUGUCAAAANN
2882


 


NM_005080_1370-1388
UUUGACAUCCAGCAGUCCANN
2883
UGGACUGCUGGAUGUCAAANN
2884


 


NM_005080_1371-1389
UUGACAUCCAGCAGUCCAANN
2885
UUGGACUGCUGGAUGUCAANN
2886


 


NM_005080_101-119
UGCUUCUGUCGGGGCAGCCNN
2887
GGCUGCCCCGACAGAAGCANN
2888


 


NM_005080_1418-1436
AAAUAUUACUAUAAUUGAGNN
2889
CUCAAUUAUAGUAAUAUUUNN
2890


 


NM_005080_1419-1437
AAUAUUACUAUAAUUGAGANN
2891
UCUCAAUUAUAGUAAUAUUNN
2892


 


NM_005080_1422-1440
AUUACUAUAAUUGAGAACUNN
2893
AGUUCUCAAUUAUAGUAAUNN
2894


 


NM_005080_102-120
GCUUCUGUCGGGGCAGCCCNN
2895
GGGCUGCCCCGACAGAAGCNN
2896


 


NM_005080_1423-1441
UUACUAUAAUUGAGAACUANN
2897
UAGUUCUCAAUUAUAGUAANN
2898


 


NM_005080_1425-1443
ACUAUAAUUGAGAACUACANN
2899
UGUAGUUCUCAAUUAUAGUNN
2900


 


NM_005080_1427-1445
UAUAAUUGAGAACUACAGCNN
2901
GCUGUAGUUCUCAAUUAUANN
2902


 


NM_005080_1428-1446
AUAAUUGAGAACUACAGCUNN
2903
AGCUGUAGUUCUCAAUUAUNN
2904


 


NM_005080_1429-1447
UAAUUGAGAACUACAGCUUNN
2905
AAGCUGUAGUUCUCAAUUANN
2906


 


NM_005080_1432-1450
UUGAGAACUACAGCUUUUANN
2907
UAAAAGCUGUAGUUCUCAANN
2908


 


NM_005080_1433-1451
UGAGAACUACAGCUUUUAANN
2909
UUAAAAGCUGUAGUUCUCANN
2910


 


NM_005080_1435-1453
AGAACUACAGCUUUUAAGANN
2911
UCUUAAAAGCUGUAGUUCUNN
2912


 


NM_005080_1439-1457
CUACAGCUUUUAAGAUUGUNN
2913
ACAAUCUUAAAAGCUGUAGNN
2914


 


NM_005080_104-122
UUCUGUCGGGGCAGCCCGCNN
2915
GCGGGCUGCCCCGACAGAANN
2916


 


NM_005080_1444-1462
GCUUUUAAGAUUGUACUUUNN
2917
AAAGUACAAUCUUAAAAGCNN
2918


 


NM_005080_1445-1463
CUUUUAAGAUUGUACUUUUNN
2919
AAAAGUACAAUCUUAAAAGNN
2920


 


NM_005080_1446-1464
UUUUAAGAUUGUACUUUUANN
2921
UAAAAGUACAAUCUUAAAANN
2922


 


NM_005080_1447-1465
UUUAAGAUUGUACUUUUAUNN
2923
AUAAAAGUACAAUCUUAAANN
2924


 


NM_005080_1448-1466
UUAAGAUUGUACUUUUAUCNN
2925
GAUAAAAGUACAAUCUUAANN
2926


 


NM_005080_1451-1469
AGAUUGUACUUUUAUCUUANN
2927
UAAGAUAAAAGUACAAUCUNN
2928


 


NM_005080_1454-1472
UUGUACUUUUAUCUUAAAANN
2929
UUUUAAGAUAAAAGUACAANN
2930


 


NM_005080_1458-1476
ACUUUUAUCUUAAAAGGGUNN
2931
ACCCUUUUAAGAUAAAAGUNN
2932


 


NM_005080_1459-1477
CUUUUAUCUUAAAAGGGUGNN
2933
CACCCUUUUAAGAUAAAAGNN
2934


 


NM_005080_106-124
CUGUCGGGGCAGCCCGCCUNN
2935
AGGCGGGCUGCCCCGACAGNN
2936


 


NM_005080_1466-1484
CUUAAAAGGGUGGUAGUUUNN
2937
AAACUACCACCCUUUUAAGNN
2938


 


NM_005080_1486-1504
CCCUAAAAUACUUAUUAUGNN
2939
CAUAAUAAGUAUUUUAGGGNN
2940


 


NM_005080_1487-1505
CCUAAAAUACUUAUUAUGUNN
2941
ACAUAAUAAGUAUUUUAGGNN
2942


 


NM_005080_1489-1507
UAAAAUACUUAUUAUGUAANN
2943
UUACAUAAUAAGUAUUUUANN
2944


 


NM_005080_1490-1508
AAAAUACUUAUUAUGUAAGNN
2945
CUUACAUAAUAAGUAUUUUNN
2946


 


NM_005080_1491-1509
AAAUACUUAUUAUGUAAGGNN
2947
CCUUACAUAAUAAGUAUUUNN
2948


 


NM_005080_109-127
UCGGGGCAGCCCGCCUCCGNN
2949
CGGAGGCGGGCUGCCCCGANN
2950


 


NM_005080_1497-1515
UUAUUAUGUAAGGGUCAUUNN
2951
AAUGACCCUUACAUAAUAANN
2952


 


NM_005080_1498-1516
UAUUAUGUAAGGGUCAUUANN
2953
UAAUGACCCUUACAUAAUANN
2954


 


NM_005080_110-128
CGGGGCAGCCCGCCUCCGCNN
2955
GCGGAGGCGGGCUGCCCCGNN
2956


 


NM_005080_1511-1529
UCAUUAGACAAAUGUCUUGNN
2957
CAAGACAUUUGUCUAAUGANN
2958


 


NM_005080_1513-1531
AUUAGACAAAUGUCUUGAANN
2959
UUCAAGACAUUUGUCUAAUNN
2960


 


NM_005080_1516-1534
AGACAAAUGUCUUGAAGUANN
2961
UACUUCAAGACAUUUGUCUNN
2962


 


NM_005080_1517-1535
GACAAAUGUCUUGAAGUAGNN
2963
CUACUUCAAGACAUUUGUCNN
2964


 


NM_005080_1518-1536
ACAAAUGUCUUGAAGUAGANN
2965
UCUACUUCAAGACAUUUGUNN
2966


 


NM_005080_1547-1565
AUGAAUGGUUCUUUAUCAUNN
2967
AUGAUAAAGAACCAUUCAUNN
2968


 


NM_005080_1550-1568
AAUGGUUCUUUAUCAUUUCNN
2969
GAAAUGAUAAAGAACCAUUNN
2970


 


NM_005080_1551-1569
AUGGUUCUUUAUCAUUUCUNN
2971
AGAAAUGAUAAAGAACCAUNN
2972


 


NM_005080_1552-1570
UGGUUCUUUAUCAUUUCUCNN
2973
GAGAAAUGAUAAAGAACCANN
2974


 


NM_005080_1554-1572
GUUCUUUAUCAUUUCUCUUNN
2975
AAGAGAAAUGAUAAAGAACNN
2976


 


NM_005080_1559-1577
UUAUCAUUUCUCUUCCCCCNN
2977
GGGGGAAGAGAAAUGAUAANN
2978


 


NM_005080_1560-1578
UAUCAUUUCUCUUCCCCCUNN
2979
AGGGGGAAGAGAAAUGAUANN
2980


 


NM_005080_1563-1581
CAUUUCUCUUCCCCCUUUUNN
2981
AAAAGGGGGAAGAGAAAUGNN
2982


 


NM_005080_1565-1583
UUUCUCUUCCCCCUUUUUGNN
2983
CAAAAAGGGGGAAGAGAAANN
2984


 


NM_005080_1566-1584
UUCUCUUCCCCCUUUUUGGNN
2985
CCAAAAAGGGGGAAGAGAANN
2986


 


NM_005080_1570-1588
CUUCCCCCUUUUUGGCAUCNN
2987
GAUGCCAAAAAGGGGGAAGNN
2988


 


NM_005080_1573-1591
CCCCCUUUUUGGCAUCCUGNN
2989
CAGGAUGCCAAAAAGGGGGNN
2990


 


NM_005080_1578-1596
UUUUUGGCAUCCUGGCUUGNN
2991
CAAGCCAGGAUGCCAAAAANN
2992


 


NM_005080_1579-1597
UUUUGGCAUCCUGGCUUGCNN
2993
GCAAGCCAGGAUGCCAAAANN
2994


 


NM_005080_1580-1598
UUUGGCAUCCUGGCUUGCCNN
2995
GGCAAGCCAGGAUGCCAAANN
2996


 


NM_005080_1581-1599
UUGGCAUCCUGGCUUGCCUNN
2997
AGGCAAGCCAGGAUGCCAANN
2998


 


NM_005080_1583-1601
GGCAUCCUGGCUUGCCUCCNN
2999
GGAGGCAAGCCAGGAUGCCNN
3000


 


NM_005080_1584-1602
GCAUCCUGGCUUGCCUCCANN
3001
UGGAGGCAAGCCAGGAUGCNN
3002


 


NM_005080_1586-1604
AUCCUGGCUUGCCUCCAGUNN
3003
ACUGGAGGCAAGCCAGGAUNN
3004


 


NM_005080_1589-1607
CUGGCUUGCCUCCAGUUUUNN
3005
AAAACUGGAGGCAAGCCAGNN
3006


 


NM_005080_1590-1608
UGGCUUGCCUCCAGUUUUANN
3007
UAAAACUGGAGGCAAGCCANN
3008


 


NM_005080_1595-1613
UGCCUCCAGUUUUAGGUCCNN
3009
GGACCUAAAACUGGAGGCANN
3010


 


NM_005080_1616-1634
UAGUUUGCUUCUGUAAGCANN
3011
UGCUUACAGAAGCAAACUANN
3012


 


NM_005080_1617-1635
AGUUUGCUUCUGUAAGCAANN
3013
UUGCUUACAGAAGCAAACUNN
3014


 


NM_005080_1643-1661
ACCUGCUGAGGGGGCUCUUNN
3015
AAGAGCCCCCUCAGCAGGUNN
3016


 


NM_005080_1645-1663
CUGCUGAGGGGGCUCUUUCNN
3017
GAAAGAGCCCCCUCAGCAGNN
3018


 


NM_005080_1646-1664
UGCUGAGGGGGCUCUUUCCNN
3019
GGAAAGAGCCCCCUCAGCANN
3020


 


NM_005080_1647-1665
GCUGAGGGGGCUCUUUCCCNN
3021
GGGAAAGAGCCCCCUCAGCNN
3022


 


NM_005080_1648-1666
CUGAGGGGGCUCUUUCCCUNN
3023
AGGGAAAGAGCCCCCUCAGNN
3024


 


NM_005080_1649-1667
UGAGGGGGCUCUUUCCCUCNN
3025
GAGGGAAAGAGCCCCCUCANN
3026


 


NM_005080_1679-1697
AAGUAAGAUCAAGAAUCUUNN
3027
AAGAUUCUUGAUCUUACUUNN
3028


 


NM_005080_1680-1698
AGUAAGAUCAAGAAUCUUUNN
3029
AAAGAUUCUUGAUCUUACUNN
3030


 


NM_005080_1681-1699
GUAAGAUCAAGAAUCUUUUNN
3031
AAAAGAUUCUUGAUCUUACNN
3032


 


NM_005080_1682-1700
UAAGAUCAAGAAUCUUUUGNN
3033
CAAAAGAUUCUUGAUCUUANN
3034


 


NM_005080_1683-1701
AAGAUCAAGAAUCUUUUGUNN
3035
ACAAAAGAUUCUUGAUCUUNN
3036


 


NM_005080_1684-1702
AGAUCAAGAAUCUUUUGUGNN
3037
CACAAAAGAUUCUUGAUCUNN
3038


 


NM_005080_1687-1705
UCAAGAAUCUUUUGUGAAANN
3039
UUUCACAAAAGAUUCUUGANN
3040


 


NM_005080_1709-1727
UAGAAAUUUACUAUGUAAANN
3041
UUUACAUAGUAAAUUUCUANN
3042


 


NM_005080_1710-1728
AGAAAUUUACUAUGUAAAUNN
3043
AUUUACAUAGUAAAUUUCUNN
3044


 


NM_005080_1711-1729
GAAAUUUACUAUGUAAAUGNN
3045
CAUUUACAUAGUAAAUUUCNN
3046


 


NM_005080_1712-1730
AAAUUUACUAUGUAAAUGCNN
3047
GCAUUUACAUAGUAAAUUUNN
3048


 


NM_005080_1714-1732
AUUUACUAUGUAAAUGCUUNN
3049
AAGCAUUUACAUAGUAAAUNN
3050


 


NM_005080_1715-1733
UUUACUAUGUAAAUGCUUGNN
3051
CAAGCAUUUACAUAGUAAANN
3052


 


NM_005080_1717-1735
UACUAUGUAAAUGCUUGAUNN
3053
AUCAAGCAUUUACAUAGUANN
3054


 


NM_005080_1719-1737
CUAUGUAAAUGCUUGAUGGNN
3055
CCAUCAAGCAUUUACAUAGNN
3056


 


NM_005080_1721-1739
AUGUAAAUGCUUGAUGGAANN
3057
UUCCAUCAAGCAUUUACAUNN
3058


 


NM_005080_1722-1740
UGUAAAUGCUUGAUGGAAUNN
3059
AUUCCAUCAAGCAUUUACANN
3060


 


NM_005080_1723-1741
GUAAAUGCUUGAUGGAAUUNN
3061
AAUUCCAUCAAGCAUUUACNN
3062


 


NM_005080_1726-1744
AAUGCUUGAUGGAAUUUUUNN
3063
AAAAAUUCCAUCAAGCAUUNN
3064


 


NM_005080_1727-1745
AUGCUUGAUGGAAUUUUUUNN
3065
AAAAAAUUCCAUCAAGCAUNN
3066


 


NM_005080_1728-1746
UGCUUGAUGGAAUUUUUUCNN
3067
GAAAAAAUUCCAUCAAGCANN
3068


 


NM_005080_1729-1747
GCUUGAUGGAAUUUUUUCCNN
3069
GGAAAAAAUUCCAUCAAGCNN
3070


 


NM_005080_1736-1754
GGAAUUUUUUCCUGCUAGUNN
3071
ACUAGCAGGAAAAAAUUCCNN
3072


 


NM_005080_1739-1757
AUUUUUUCCUGCUAGUGUANN
3073
UACACUAGCAGGAAAAAAUNN
3074


 


NM_005080_1746-1764
CCUGCUAGUGUAGCUUCUGNN
3075
CAGAAGCUACACUAGCAGGNN
3076


 


NM_005080_1747-1765
CUGCUAGUGUAGCUUCUGANN
3077
UCAGAAGCUACACUAGCAGNN
3078


 


NM_005080_1749-1767
GCUAGUGUAGCUUCUGAAANN
3079
UUUCAGAAGCUACACUAGCNN
3080


 


NM_005080_1750-1768
CUAGUGUAGCUUCUGAAAGNN
3081
CUUUCAGAAGCUACACUAGNN
3082


 


NM_005080_1751-1769
UAGUGUAGCUUCUGAAAGGNN
3083
CCUUUCAGAAGCUACACUANN
3084


 


NM_005080_1752-1770
AGUGUAGCUUCUGAAAGGUNN
3085
ACCUUUCAGAAGCUACACUNN
3086


 


NM_005080_1753-1771
GUGUAGCUUCUGAAAGGUGNN
3087
CACCUUUCAGAAGCUACACNN
3088


 


NM_005080_1755-1773
GUAGCUUCUGAAAGGUGCUNN
3089
AGCACCUUUCAGAAGCUACNN
3090


 


NM_005080_1758-1776
GCUUCUGAAAGGUGCUUUCNN
3091
GAAAGCACCUUUCAGAAGCNN
3092


 


NM_005080_1781-1799
UUUAUUUAAAACUACCCAUNN
3093
AUGGGUAGUUUUAAAUAAANN
3094


 


NM_005080_1782-1800
UUAUUUAAAACUACCCAUGNN
3095
CAUGGGUAGUUUUAAAUAANN
3096


 


NM_005080_1784-1802
AUUUAAAACUACCCAUGCANN
3097
UGCAUGGGUAGUUUUAAAUNN
3098


 


NM_005080_1785-1803
UUUAAAACUACCCAUGCAANN
3099
UUGCAUGGGUAGUUUUAAANN
3100


 


NM_005080_1788-1806
AAAACUACCCAUGCAAUUANN
3101
UAAUUGCAUGGGUAGUUUUNN
3102


 


NM_005080_1792-1810
CUACCCAUGCAAUUAAAAGNN
3103
CUUUUAAUUGCAUGGGUAGNN
3104


 


NM_005080_1793-1811
UACCCAUGCAAUUAAAAGGNN
3105
CCUUUUAAUUGCAUGGGUANN
3106


 


NM_005080_1795-1813
CCCAUGCAAUUAAAAGGUANN
3107
UACCUUUUAAUUGCAUGGGNN
3108


 


NM_005080_1798-1816
AUGCAAUUAAAAGGUACAANN
3109
UUGUACCUUUUAAUUGCAUNN
3110


 


NM_005080_1799-1817
UGCAAUUAAAAGGUACAAUNN
3111
AUUGUACCUUUUAAUUGCANN
3112


 


NM_005080_1800-1818
GCAAUUAAAAGGUACAAUGNN
3113
CAUUGUACCUUUUAAUUGCNN
3114


 


NM_005080_1801-1819
CAAUUAAAAGGUACAAUGCNN
3115
GCAUUGUACCUUUUAAUUGNN
3116


 


NM_005080_146-164
GCCAGGCCCUGCCGCUCAUNN
3117
AUGAGCGGCAGGGCCUGGCNN
3118


 


NM_005080_147-165
CCAGGCCCUGCCGCUCAUGNN
3119
CAUGAGCGGCAGGGCCUGGNN
3120


 


NM_005080_148-166
CAGGCCCUGCCGCUCAUGGNN
3121
CCAUGAGCGGCAGGGCCUGNN
3122


 


NM_005080_149-167
AGGCCCUGCCGCUCAUGGUNN
3123
ACCAUGAGCGGCAGGGCCUNN
3124


 


NM_005080_155-173
UGCCGCUCAUGGUGCCAGCNN
3125
GCUGGCACCAUGAGCGGCANN
3126


 


NM_005080_157-175
CCGCUCAUGGUGCCAGCCCNN
3127
GGGCUGGCACCAUGAGCGGNN
3128


 


NM_005080_158-176
CGCUCAUGGUGCCAGCCCANN
3129
UGGGCUGGCACCAUGAGCGNN
3130


 


NM_005080_159-177
GCUCAUGGUGCCAGCCCAGNN
3131
CUGGGCUGGCACCAUGAGCNN
3132


 


NM_005080_188-206
GCCCGGAGGCAGCGAGCGGNN
3133
CCGCTCGCTGCCTCCGGGCNN
3134


 


NM_005080_189-207
CCCGGAGGCAGCGAGCGGGNN
3135
CCCGCTCGCTGCCTCCGGGNN
3136


 


NM_005080_195-213
GGCAGCGAGCGGGGGGCUGNN
3137
CAGCCCCCCGCUCGCUGCCNN
3138


 


NM_005080_196-214
GCAGCGAGCGGGGGGCUGCNN
3139
GCAGCCCCCCGCUCGCUGCNN
3140


 


NM_005080_197-215
CAGCGAGCGGGGGGCUGCCNN
3141
GGCAGCCCCCCGCUCGCUGNN
3142


 


NM_005080_198-216
AGCGAGCGGGGGGCUGCCCNN
3143
GGGCAGCCCCCCGCUCGCUNN
3144


 


NM_005080_205-223
GGGGGGCUGCCCCAGGCGCNN
3145
GCGCCUGGGGCAGCCCCCCNN
3146


 


NM_005080_206-224
GGGGGCUGCCCCAGGCGCGNN
3147
CGCGCCUGGGGCAGCCCCCNN
3148


 


NM_005080_207-225
GGGGCUGCCCCAGGCGCGCNN
3149
GCGCGCCUGGGGCAGCCCCNN
3150


 


NM_005080_211-229
CUGCCCCAGGCGCGCAAGCNN
3151
GCUUGCGCGCCUGGGGCAGNN
3152


 


NM_005080_250-268
AGCCCCGAGGAGAAGGCGCNN
3153
GCGCCTTCTCCTCGGGGCTNN
3154


 


NM_005080_256-274
GAGGAGAAGGCGCUGAGGANN
3155
UCCUCAGCGCCUUCUCCUCNN
3156


 


NM_005080_263-281
AGGCGCUGAGGAGGAAACUNN
3157
AGUUUCCUCCUCAGCGCCUNN
3158


 


NM_005080_264-282
GGCGCUGAGGAGGAAACUGNN
3159
CAGUUUCCUCCUCAGCGCCNN
3160


 


NM_005080_285-303
AAACAGAGUAGCAGCUCAGNN
3161
CUGAGCUGCUACUCUGUUUNN
3162


 


NM_005080_286-304
AACAGAGUAGCAGCUCAGANN
3163
UCUGAGCUGCUACUCUGUUNN
3164


 


NM_005080_287-305
ACAGAGUAGCAGCUCAGACNN
3165
GUCUGAGCUGCUACUCUGUNN
3166


 


NM_005080_294-312
AGCAGCUCAGACUGCCAGANN
3167
UCUGGCAGUCUGAGCUGCUNN
3168


 


NM_005080_295-313
GCAGCUCAGACUGCCAGAGNN
3169
CUCUGGCAGUCUGAGCUGCNN
3170


 


NM_005080_296-314
CAGCUCAGACUGCCAGAGANN
3171
UCUCUGGCAGUCUGAGCUGNN
3172


 


NM_005080_298-316
GCUCAGACUGCCAGAGAUCNN
3173
GAUCUCUGGCAGUCUGAGCNN
3174


 


NM_005080_303-321
GACUGCCAGAGAUCGAAAGNN
3175
CUUUCGAUCUCUGGCAGUCNN
3176


 


NM_005080_332-350
UGAGUGAGCUGGAACAGCANN
3177
UGCUGUUCCAGCUCACUCANN
3178


 


NM_005080_339-357
GCUGGAACAGCAAGUGGUANN
3179
UACCACUUGCUGUUCCAGCNN
3180


 


NM_005080_340-358
CUGGAACAGCAAGUGGUAGNN
3181
CUACCACUUGCUGUUCCAGNN
3182


 


NM_005080_345-363
ACAGCAAGUGGUAGAUUUANN
3183
UAAAUCUACCACUUGCUGUNN
3184


 


NM_005080_346-364
CAGCAAGUGGUAGAUUUAGNN
3185
CUAAAUCUACCACUUGCUGNN
3186


 


NM_005080_348-366
GCAAGUGGUAGAUUUAGAANN
3187
UUCUAAAUCUACCACUUGCNN
3188


 


NM_005080_349-367
CAAGUGGUAGAUUUAGAAGNN
3189
CUUCUAAAUCUACCACUUGNN
3190


 


NM_005080_352-370
GUGGUAGAUUUAGAAGAAGNN
3191
CUUCUUCUAAAUCUACCACNN
3192


 


NM_005080_353-371
UGGUAGAUUUAGAAGAAGANN
3193
UCUUCUUCUAAAUCUACCANN
3194


 


NM_005080_354-372
GGUAGAUUUAGAAGAAGAGNN
3195
CUCUUCUUCUAAAUCUACCNN
3196


 


NM_005080_355-373
GUAGAUUUAGAAGAAGAGANN
3197
UCUCUUCUUCUAAAUCUACNN
3198


 


NM_005080_361-379
UUAGAAGAAGAGAACCAAANN
3199
UUUGGUUCUCUUCUUCUAANN
3200


 


NM_005080_366-384
AGAAGAGAACCAAAAACUUNN
3201
AAGUUUUUGGUUCUCUUCUNN
3202


 


NM_005080_369-387
AGAGAACCAAAAACUUUUGNN
3203
CAAAAGUUUUUGGUUCUCUNN
3204


 


NM_005080_370-388
GAGAACCAAAAACUUUUGCNN
3205
GCAAAAGUUUUUGGUUCUCNN
3206


 


NM_005080_372-390
GAACCAAAAACUUUUGCUANN
3207
UAGCAAAAGUUUUUGGUUCNN
3208


 


NM_005080_376-394
CAAAAACUUUUGCUAGAAANN
3209
UUUCUAGCAAAAGUUUUUGNN
3210


 


NM_005080_381-399
ACUUUUGCUAGAAAAUCAGNN
3211
CUGAUUUUCUAGCAAAAGUNN
3212


 


NM_005080_384-402
UUUGCUAGAAAAUCAGCUUNN
3213
AAGCUGAUUUUCUAGCAAANN
3214


 


NM_005080_388-406
CUAGAAAAUCAGCUUUUACNN
3215
GUAAAAGCUGAUUUUCUAGNN
3216


 


NM_005080_392-410
AAAAUCAGCUUUUACGAGANN
3217
UCUCGUAAAAGCUGAUUUUNN
3218


 


NM_005080_394-412
AAUCAGCUUUUACGAGAGANN
3219
UCUCUCGUAAAAGCUGAUUNN
3220


 


NM_005080_396-414
UCAGCUUUUACGAGAGAAANN
3221
UUUCUCUCGUAAAAGCUGANN
3222


 


NM_005080_400-418
CUUUUACGAGAGAAAACUCNN
3223
GAGUUUUCUCUCGUAAAAGNN
3224


 


NM_005080_421-439
GGCCUUGUAGUUGAGAACCNN
3225
GGUUCUCAACUACAAGGCCNN
3226


 


NM_005080_422-440
GCCUUGUAGUUGAGAACCANN
3227
UGGUUCUCAACUACAAGGCNN
3228


 


NM_005080_423-441
CCUUGUAGUUGAGAACCAGNN
3229
CUGGUUCUCAACUACAAGGNN
3230


 


NM_005080_425-443
UUGUAGUUGAGAACCAGGANN
3231
UCCUGGUUCUCAACUACAANN
3232


 


NM_005080_428-446
UAGUUGAGAACCAGGAGUUNN
3233
AACUCCUGGUUCUCAACUANN
3234


 


NM_005080_429-447
AGUUGAGAACCAGGAGUUANN
3235
UAACUCCUGGUUCUCAACUNN
3236


 


NM_005080_432-450
UGAGAACCAGGAGUUAAGANN
3237
UCUUAACUCCUGGUUCUCANN
3238


 


NM_005080_433-451
GAGAACCAGGAGUUAAGACNN
3239
GUCUUAACUCCUGGUUCUCNN
3240


 


NM_005080_434-452
AGAACCAGGAGUUAAGACANN
3241
UGUCUUAACUCCUGGUUCUNN
3242


 


NM_005080_435-453
GAACCAGGAGUUAAGACAGNN
3243
CUGUCUUAACUCCUGGUUCNN
3244


 


NM_005080_436-454
AACCAGGAGUUAAGACAGCNN
3245
GCUGUCUUAACUCCUGGUUNN
3246


 


NM_005080_459-477
GGGGAUGGAUGCCCUGGUUNN
3247
AACCAGGGCAUCCAUCCCCNN
3248


 


NM_005080_460-478
GGGAUGGAUGCCCUGGUUGNN
3249
CAACCAGGGCAUCCAUCCCNN
3250


 


NM_005080_462-480
GAUGGAUGCCCUGGUUGCUNN
3251
AGCAACCAGGGCAUCCAUCNN
3252


 


NM_005080_486-504
GGAGGCGGAAGCCAAGGGGNN
3253
CCCCTTGGCTTCCGCCTCCNN
3254


 


NM_005080_510-528
AGUGAGGCCAGUGGCCGGGNN
3255
CCCGGCCACUGGCCUCACUNN
3256


 


NM_005080_513-531
GAGGCCAGUGGCCGGGUCUNN
3257
AGACCCGGCCACUGGCCUCNN
3258


 


NM_005080_514-532
AGGCCAGUGGCCGGGUCUGNN
3259
CAGACCCGGCCACUGGCCUNN
3260


 


NM_005080_515-533
GGCCAGUGGCCGGGUCUGCNN
3261
GCAGACCCGGCCACUGGCCNN
3262


 


NM_005080_516-534
GCCAGUGGCCGGGUCUGCUNN
3263
AGCAGACCCGGCCACUGGCNN
3264


 


NM_005080_520-538
GUGGCCGGGUCUGCUGAGUNN
3265
ACUCAGCAGACCCGGCCACNN
3266


 


NM_005080_521-539
UGGCCGGGUCUGCUGAGUCNN
3267
GACUCAGCAGACCCGGCCANN
3268


 


NM_005080_523-541
GCCGGGUCUGCUGAGUCCGNN
3269
CGGACUCAGCAGACCCGGCNN
3270


 


NM_005080_578-596
AGGCCCAGUUGUCACCCCUNN
3271
AGGGGUGACAACUGGGCCUNN
3272


 


NM_005080_581-599
CCCAGUUGUCACCCCUCCANN
3273
UGGAGGGGUGACAACUGGGNN
3274


 


NM_005080_582-600
CCAGUUGUCACCCCUCCAGNN
3275
CUGGAGGGGUGACAACUGGNN
3276


 


NM_005080_583-601
CAGUUGUCACCCCUCCAGANN
3277
UCUGGAGGGGUGACAACUGNN
3278


 


NM_005080_584-602
AGUUGUCACCCCUCCAGAANN
3279
UUCUGGAGGGGUGACAACUNN
3280


 


NM_005080_585-603
GUUGUCACCCCUCCAGAACNN
3281
GUUCUGGAGGGGUGACAACNN
3282


 


NM_005080_586-604
UUGUCACCCCUCCAGAACANN
3283
UGUUCUGGAGGGGUGACAANN
3284


 


NM_005080_587-605
UGUCACCCCUCCAGAACAUNN
3285
AUGUUCUGGAGGGGUGACANN
3286


 


NM_005080_588-606
GUCACCCCUCCAGAACAUCNN
3287
GAUGUUCUGGAGGGGUGACNN
3288


 


NM_005080_589-607
UCACCCCUCCAGAACAUCUNN
3289
AGAUGUUCUGGAGGGGUGANN
3290


 


NM_005080_590-608
CACCCCUCCAGAACAUCUCNN
3291
GAGAUGUUCUGGAGGGGUGNN
3292


 


NM_005080_591-609
ACCCCUCCAGAACAUCUCCNN
3293
GGAGAUGUUCUGGAGGGGUNN
3294


 


NM_005080_597-615
CCAGAACAUCUCCCCAUGGNN
3295
CCAUGGGGAGAUGUUCUGGNN
3296


 


NM_005080_600-618
GAACAUCUCCCCAUGGAUUNN
3297
AAUCCAUGGGGAGAUGUUCNN
3298


 


NM_005080_603-621
CAUCUCCCCAUGGAUUCUGNN
3299
CAGAAUCCAUGGGGAGAUGNN
3300


 


NM_005080_619-637
CUGGCGGUAUUGACUCUUCNN
3301
GAAGAGUCAAUACCGCCAGNN
3302


 


NM_005080_620-638
UGGCGGUAUUGACUCUUCANN
3303
UGAAGAGUCAAUACCGCCANN
3304


 


NM_005080_622-640
GCGGUAUUGACUCUUCAGANN
3305
UCUGAAGAGUCAAUACCGCNN
3306


 


NM_005080_623-641
CGGUAUUGACUCUUCAGAUNN
3307
AUCUGAAGAGUCAAUACCGNN
3308


 


NM_005080_624-642
GGUAUUGACUCUUCAGAUUNN
3309
AAUCUGAAGAGUCAAUACCNN
3310


 


NM_005080_625-643
GUAUUGACUCUUCAGAUUCNN
3311
GAAUCUGAAGAGUCAAUACNN
3312


 


NM_005080_626-644
UAUUGACUCUUCAGAUUCANN
3313
UGAAUCUGAAGAGUCAAUANN
3314


 


NM_005080_629-647
UGACUCUUCAGAUUCAGAGNN
3315
CUCUGAAUCUGAAGAGUCANN
3316


 


NM_005080_632-650
CUCUUCAGAUUCAGAGUCUNN
3317
AGACUCUGAAUCUGAAGAGNN
3318


 


NM_005080_634-652
CUUCAGAUUCAGAGUCUGANN
3319
UCAGACUCUGAAUCUGAAGNN
3320


 


NM_005080_637-655
CAGAUUCAGAGUCUGAUAUNN
3321
AUAUCAGACUCUGAAUCUGNN
3322


 


NM_005080_638-656
AGAUUCAGAGUCUGAUAUCNN
3323
GAUAUCAGACUCUGAAUCUNN
3324


 


NM_005080_639-657
GAUUCAGAGUCUGAUAUCCNN
3325
GGAUAUCAGACUCUGAAUCNN
3326


 


NM_005080_642-660
UCAGAGUCUGAUAUCCUGUNN
3327
ACAGGAUAUCAGACUCUGANN
3328


 


NM_005080_643-661
CAGAGUCUGAUAUCCUGUUNN
3329
AACAGGAUAUCAGACUCUGNN
3330


 


NM_005080_644-662
AGAGUCUGAUAUCCUGUUGNN
3331
CAACAGGAUAUCAGACUCUNN
3332


 


NM_005080_646-664
AGUCUGAUAUCCUGUUGGGNN
3333
CCCAACAGGAUAUCAGACUNN
3334


 


NM_005080_649-667
CUGAUAUCCUGUUGGGCAUNN
3335
AUGCCCAACAGGAUAUCAGNN
3336


 


NM_005080_650-668
UGAUAUCCUGUUGGGCAUUNN
3337
AAUGCCCAACAGGAUAUCANN
3338


 


NM_005080_653-671
UAUCCUGUUGGGCAUUCUGNN
3339
CAGAAUGCCCAACAGGAUANN
3340


 


NM_005080_658-676
UGUUGGGCAUUCUGGACAANN
3341
UUGUCCAGAAUGCCCAACANN
3342


 


NM_005080_659-677
GUUGGGCAUUCUGGACAACNN
3343
GUUGUCCAGAAUGCCCAACNN
3344


 


NM_005080_660-678
UUGGGCAUUCUGGACAACUNN
3345
AGUUGUCCAGAAUGCCCAANN
3346


 


NM_005080_663-681
GGCAUUCUGGACAACUUGGNN
3347
CCAAGUUGUCCAGAAUGCCNN
3348


 


NM_005080_664-682
GCAUUCUGGACAACUUGGANN
3349
UCCAAGUUGUCCAGAAUGCNN
3350


 


NM_005080_668-686
UCUGGACAACUUGGACCCANN
3351
UGGGUCCAAGUUGUCCAGANN
3352


 


NM_005080_671-689
GGACAACUUGGACCCAGUCNN
3353
GACUGGGUCCAAGUUGUCCNN
3354


 


NM_005080_676-694
ACUUGGACCCAGUCAUGUUNN
3355
AACAUGACUGGGUCCAAGUNN
3356


 


NM_005080_677-695
CUUGGACCCAGUCAUGUUCNN
3357
GAACAUGACUGGGUCCAAGNN
3358


 


NM_005080_679-697
UGGACCCAGUCAUGUUCUUNN
3359
AAGAACAUGACUGGGUCCANN
3360


 


NM_005080_680-698
GGACCCAGUCAUGUUCUUCNN
3361
GAAGAACAUGACUGGGUCCNN
3362


 


NM_005080_682-700
ACCCAGUCAUGUUCUUCAANN
3363
UUGAAGAACAUGACUGGGUNN
3364


 


NM_005080_687-705
GUCAUGUUCUUCAAAUGCCNN
3365
GGCAUUUGAAGAACAUGACNN
3366


 


NM_005080_689-707
CAUGUUCUUCAAAUGCCCUNN
3367
AGGGCAUUUGAAGAACAUGNN
3368


 


NM_005080_695-713
CUUCAAAUGCCCUUCCCCANN
3369
UGGGGAAGGGCAUUUGAAGNN
3370


 


NM_005080_696-714
UUCAAAUGCCCUUCCCCAGNN
3371
CUGGGGAAGGGCAUUUGAANN
3372


 


NM_005080_698-716
CAAAUGCCCUUCCCCAGAGNN
3373
CUCUGGGGAAGGGCAUUUGNN
3374


 


NM_005080_731-749
GGAGCUCCCAGAGGUCUACNN
3375
GUAGACCUCUGGGAGCUCCNN
3376


 


NM_005080_732-750
GAGCUCCCAGAGGUCUACCNN
3377
GGUAGACCUCUGGGAGCUCNN
3378


 


NM_005080_733-751
AGCUCCCAGAGGUCUACCCNN
3379
GGGUAGACCUCUGGGAGCUNN
3380


 


NM_005080_736-754
UCCCAGAGGUCUACCCAGANN
3381
UCUGGGUAGACCUCUGGGANN
3382


 


NM_005080_737-755
CCCAGAGGUCUACCCAGAANN
3383
UUCUGGGUAGACCUCUGGGNN
3384


 


NM_005080_738-756
CCAGAGGUCUACCCAGAAGNN
3385
CUUCUGGGUAGACCUCUGGNN
3386


 


NM_005080_740-758
AGAGGUCUACCCAGAAGGANN
3387
UCCUUCUGGGUAGACCUCUNN
3388


 


NM_005080_741-759
GAGGUCUACCCAGAAGGACNN
3389
GUCCUUCUGGGUAGACCUCNN
3390


 


NM_005080_742-760
AGGUCUACCCAGAAGGACCNN
3391
GGUCCUUCUGGGUAGACCUNN
3392


 


NM_005080_743-761
GGUCUACCCAGAAGGACCCNN
3393
GGGUCCUUCUGGGUAGACCNN
3394


 


NM_005080_748-766
ACCCAGAAGGACCCAGUUCNN
3395
GAACUGGGUCCUUCUGGGUNN
3396


 


NM_005080_749-767
CCCAGAAGGACCCAGUUCCNN
3397
GGAACUGGGUCCUUCUGGGNN
3398


 


NM_005080_750-768
CCAGAAGGACCCAGUUCCUNN
3399
AGGAACUGGGUCCUUCUGGNN
3400


 


NM_005080_751-769
CAGAAGGACCCAGUUCCUUNN
3401
AAGGAACUGGGUCCUUCUGNN
3402


 


NM_005080_752-770
AGAAGGACCCAGUUCCUUANN
3403
UAAGGAACUGGGUCCUUCUNN
3404


 


NM_005080_756-774
GGACCCAGUUCCUUACCAGNN
3405
CUGGUAAGGAACUGGGUCCNN
3406


 


NM_005080_758-776
ACCCAGUUCCUUACCAGCCNN
3407
GGCUGGUAAGGAACUGGGUNN
3408


 


NM_005080_759-777
CCCAGUUCCUUACCAGCCUNN
3409
AGGCUGGUAAGGAACUGGGNN
3410


 


NM_005080_760-778
CCAGUUCCUUACCAGCCUCNN
3411
GAGGCUGGUAAGGAACUGGNN
3412


 


NM_005080_761-779
CAGUUCCUUACCAGCCUCCNN
3413
GGAGGCUGGUAAGGAACUGNN
3414


 


NM_005080_762-780
AGUUCCUUACCAGCCUCCCNN
3415
GGGAGGCUGGUAAGGAACUNN
3416


 


NM_005080_767-785
CUUACCAGCCUCCCUUUCUNN
3417
AGAAAGGGAGGCUGGUAAGNN
3418


 


NM_005080_769-787
UACCAGCCUCCCUUUCUCUNN
3419
AGAGAAAGGGAGGCUGGUANN
3420


 


NM_005080_773-791
AGCCUCCCUUUCUCUGUCANN
3421
UGACAGAGAAAGGGAGGCUNN
3422


 


NM_005080_779-797
CCUUUCUCUGUCAGUGGGGNN
3423
CCCCACUGACAGAGAAAGGNN
3424


 


NM_005080_786-804
CUGUCAGUGGGGACGUCAUNN
3425
AUGACGUCCCCACUGACAGNN
3426


 


NM_005080_787-805
UGUCAGUGGGGACGUCAUCNN
3427
GAUGACGUCCCCACUGACANN
3428


 


NM_005080_789-807
UCAGUGGGGACGUCAUCAGNN
3429
CUGAUGACGUCCCCACUGANN
3430


 


NM_005080_793-811
UGGGGACGUCAUCAGCCAANN
3431
UUGGCUGAUGACGUCCCCANN
3432


 


NM_005080_795-813
GGGACGUCAUCAGCCAAGCNN
3433
GCUUGGCUGAUGACGUCCCNN
3434


 


NM_005080_797-815
GACGUCAUCAGCCAAGCUGNN
3435
CAGCUUGGCUGAUGACGUCNN
3436


 


NM_005080_798-816
ACGUCAUCAGCCAAGCUGGNN
3437
CCAGCUUGGCUGAUGACGUNN
3438


 


NM_005080_800-818
GUCAUCAGCCAAGCUGGAANN
3439
UUCCAGCUUGGCUGAUGACNN
3440


 


NM_005080_804-822
UCAGCCAAGCUGGAAGCCANN
3441
UGGCUUCCAGCUUGGCUGANN
3442


 


NM_005080_806-824
AGCCAAGCUGGAAGCCAUUNN
3443
AAUGGCUUCCAGCUUGGCUNN
3444


 


NM_005080_807-825
GCCAAGCUGGAAGCCAUUANN
3445
UAAUGGCUUCCAGCUUGGCNN
3446


 


NM_005080_808-826
CCAAGCUGGAAGCCAUUAANN
3447
UUAAUGGCUUCCAGCUUGGNN
3448


 


NM_005080_809-827
CAAGCUGGAAGCCAUUAAUNN
3449
AUUAAUGGCUUCCAGCUUGNN
3450


 


NM_005080_810-828
AAGCUGGAAGCCAUUAAUGNN
3451
CAUUAAUGGCUUCCAGCUUNN
3452


 


NM_005080_811-829
AGCUGGAAGCCAUUAAUGANN
3453
UCAUUAAUGGCUUCCAGCUNN
3454


 


NM_005080_813-831
CUGGAAGCCAUUAAUGAACNN
3455
GUUCAUUAAUGGCUUCCAGNN
3456


 


NM_005080_814-832
UGGAAGCCAUUAAUGAACUNN
3457
AGUUCAUUAAUGGCUUCCANN
3458


 


NM_005080_818-836
AGCCAUUAAUGAACUAAUUNN
3459
AAUUAGUUCAUUAAUGGCUNN
3460


 


NM_005080_820-838
CCAUUAAUGAACUAAUUCGNN
3461
CGAAUUAGUUCAUUAAUGGNN
3462


 


NM_005080_837-855
CGUUUUGACCACAUAUAUANN
3463
UAUAUAUGUGGUCAAAACGNN
3464


 


NM_005080_844-862
ACCACAUAUAUACCAAGCCNN
3465
GGCUUGGUAUAUAUGUGGUNN
3466


 


NM_005080_872-890
AGAGAUACCCUCUGAGACANN
3467
UGUCUCAGAGGGUAUCUCUNN
3468


 


NM_005080_873-891
GAGAUACCCUCUGAGACAGNN
3469
CUGUCUCAGAGGGUAUCUCNN
3470


 


NM_005080_874-892
AGAUACCCUCUGAGACAGANN
3471
UCUGUCUCAGAGGGUAUCUNN
3472


 


NM_005080_876-894
AUACCCUCUGAGACAGAGANN
3473
UCUCUGUCUCAGAGGGUAUNN
3474


 


NM_005080_889-907
CAGAGAGCCAAGCUAAUGUNN
3475
ACAUUAGCUUGGCUCUCUGNN
3476


 


NM_005080_890-908
AGAGAGCCAAGCUAAUGUGNN
3477
CACAUUAGCUUGGCUCUCUNN
3478


 


NM_005080_897-915
CAAGCUAAUGUGGUAGUGANN
3479
UCACUACCACAUUAGCUUGNN
3480


 


NM_005080_898-916
AAGCUAAUGUGGUAGUGAANN
3481
UUCACUACCACAUUAGCUUNN
3482


 


NM_005080_901-919
CUAAUGUGGUAGUGAAAAUNN
3483
AUUUUCACUACCACAUUAGNN
3484


 


NM_005080_903-921
AAUGUGGUAGUGAAAAUCGNN
3485
CGAUUUUCACUACCACAUUNN
3486


 


NM_005080_904-922
AUGUGGUAGUGAAAAUCGANN
3487
UCGAUUUUCACUACCACAUNN
3488


 


NM_005080_906-924
GUGGUAGUGAAAAUCGAGGNN
3489
CCUCGAUUUUCACUACCACNN
3490


 


NM_005080_907-925
UGGUAGUGAAAAUCGAGGANN
3491
UCCUCGAUUUUCACUACCANN
3492


 


NM_005080_910-928
UAGUGAAAAUCGAGGAAGCNN
3493
GCUUCCUCGAUUUUCACUANN
3494


 


NM_005080_913-931
UGAAAAUCGAGGAAGCACCNN
3495
GGUGCUUCCUCGAUUUUCANN
3496


 


NM_005080_916-934
AAAUCGAGGAAGCACCUCUNN
3497
AGAGGUGCUUCCUCGAUUUNN
3498


 


NM_005080_918-936
AUCGAGGAAGCACCUCUCANN
3499
UGAGAGGUGCUUCCUCGAUNN
3500


 


NM_005080_919-937
UCGAGGAAGCACCUCUCAGNN
3501
CUGAGAGGUGCUUCCUCGANN
3502


 


NM_005080_920-938
CGAGGAAGCACCUCUCAGCNN
3503
GCUGAGAGGUGCUUCCUCGNN
3504


 


NM_005080_922-940
AGGAAGCACCUCUCAGCCCNN
3505
GGGCUGAGAGGUGCUUCCUNN
3506


 


NM_005080_923-941
GGAAGCACCUCUCAGCCCCNN
3507
GGGGCUGAGAGGUGCUUCCNN
3508


 


NM_005080_929-947
ACCUCUCAGCCCCUCAGAGNN
3509
CUCUGAGGGGCUGAGAGGUNN
3510


 


NM_005080_930-948
CCUCUCAGCCCCUCAGAGANN
3511
UCUCUGAGGGGCUGAGAGGNN
3512


 


NM_005080_931-949
CUCUCAGCCCCUCAGAGAANN
3513
UUCUCUGAGGGGCUGAGAGNN
3514


 


NM_005080_932-950
UCUCAGCCCCUCAGAGAAUNN
3515
AUUCUCUGAGGGGCUGAGANN
3516


 


NM_005080_933-951
CUCAGCCCCUCAGAGAAUGNN
3517
CAUUCUCUGAGGGGCUGAGNN
3518


 


NM_005080_934-952
UCAGCCCCUCAGAGAAUGANN
3519
UCAUUCUCUGAGGGGCUGANN
3520


 


NM_005080_935-953
CAGCCCCUCAGAGAAUGAUNN
3521
AUCAUUCUCUGAGGGGCUGNN
3522


 


NM_005080_936-954
AGCCCCUCAGAGAAUGAUCNN
3523
GAUCAUUCUCUGAGGGGCUNN
3524


 


NM_005080_938-956
CCCCUCAGAGAAUGAUCACNN
3525
GUGAUCAUUCUCUGAGGGGNN
3526


 


NM_005080_941-959
CUCAGAGAAUGAUCACCCUNN
3527
AGGGUGAUCAUUCUCUGAGNN
3528


 


NM_005080_942-960
UCAGAGAAUGAUCACCCUGNN
3529
CAGGGUGAUCAUUCUCUGANN
3530


 


NM_005080_943-961
CAGAGAAUGAUCACCCUGANN
3531
UCAGGGUGAUCAUUCUCUGNN
3532


 


NM_005080_944-962
AGAGAAUGAUCACCCUGAANN
3533
UUCAGGGUGAUCAUUCUCUNN
3534


 


NM_005080_946-964
AGAAUGAUCACCCUGAAUUNN
3535
AAUUCAGGGUGAUCAUUCUNN
3536


 


NM_005080_947-965
GAAUGAUCACCCUGAAUUCNN
3537
GAAUUCAGGGUGAUCAUUCNN
3538


 


NM_005080_948-966
AAUGAUCACCCUGAAUUCANN
3539
UGAAUUCAGGGUGAUCAUUNN
3540


 


NM_005080_949-967
AUGAUCACCCUGAAUUCAUNN
3541
AUGAAUUCAGGGUGAUCAUNN
3542


 


NM_005080_955-973
ACCCUGAAUUCAUUGUCUCNN
3543
GAGACAAUGAAUUCAGGGUNN
3544


 


NM_005080_956-974
CCCUGAAUUCAUUGUCUCANN
3545
UGAGACAAUGAAUUCAGGGNN
3546


 


NM_005080_957-975
CCUGAAUUCAUUGUCUCAGNN
3547
CUGAGACAAUGAAUUCAGGNN
3548


 


NM_005080_960-978
GAAUUCAUUGUCUCAGUGANN
3549
UCACUGAGACAAUGAAUUCNN
3550


 


NM_005080_961-979
AAUUCAUUGUCUCAGUGAANN
3551
UUCACUGAGACAAUGAAUUNN
3552


 


NM_005080_965-983
CAUUGUCUCAGUGAAGGAANN
3553
UUCCUUCACUGAGACAAUGNN
3554


 


NM_005080_967-985
UUGUCUCAGUGAAGGAAGANN
3555
UCUUCCUUCACUGAGACAANN
3556


 


NM_005080_968-986
UGUCUCAGUGAAGGAAGAANN
3557
UUCUUCCUUCACUGAGACANN
3558


 


NM_005080_971-989
CUCAGUGAAGGAAGAACCUNN
3559
AGGUUCUUCCUUCACUGAGNN
3560


 


NM_005080_972-990
UCAGUGAAGGAAGAACCUGNN
3561
CAGGUUCUUCCUUCACUGANN
3562


 


NM_005080_973-991
CAGUGAAGGAAGAACCUGUNN
3563
ACAGGUUCUUCCUUCACUGNN
3564


 


NM_005080_980-998
GGAAGAACCUGUAGAAGAUNN
3565
AUCUUCUACAGGUUCUUCCNN
3566


 


NM_005080_984-1002
GAACCUGUAGAAGAUGACCNN
3567
GGUCAUCUUCUACAGGUUCNN
3568


 


NM_005080_986-1004
ACCUGUAGAAGAUGACCUCNN
3569
GAGGUCAUCUUCUACAGGUNN
3570


 


NM_005080_1023-1041
UCAAAUCUGCUUUCAUCCANN
3571
UGGAUGAAAGCAGAUUUGANN
3572


 


NM_005080_1151-1169
UUCUUGGGAGGACACUUUUNN
3573
AAAAGUGUCCUCCCAAGAANN
3574


 


NM_005080_1367-1385
UCUUUUGACAUCCAGCAGUNN
3575
ACUGCUGGAUGUCAAAAGANN
3576


 


NM_005080_1414-1432
UAAGAAAUAUUACUAUAAUNN
3577
AUUAUAGUAAUAUUUCUUANN
3578


 


NM_005080_1415-1433
AAGAAAUAUUACUAUAAUUNN
3579
AAUUAUAGUAAUAUUUCUUNN
3580


 


NM_005080_1674-1692
ACUUCAAGUAAGAUCAAGANN
3581
UCUUGAUCUUACUUGAAGUNN
3582


 


NM_005080_1675-1693
CUUCAAGUAAGAUCAAGAANN
3583
UUCUUGAUCUUACUUGAAGNN
3584


 


NM_005080_330-348
AAUGAGUGAGCUGGAACAGNN
3585
CUGUUCCAGCUCACUCAUUNN
3586


 


NM_005080_333-351
GAGUGAGCUGGAACAGCAANN
3587
UUGCUGUUCCAGCUCACUCNN
3588


 


NM_005080_592-610
CCCCUCCAGAACAUCUCCCNN
3589
GGGAGAUGUUCUGGAGGGGNN
3590


 


NM_005080_665-683
CAUUCUGGACAACUUGGACNN
3591
GUCCAAGUUGUCCAGAAUGNN
3592


 


NM_005080_815-833
GGAAGCCAUUAAUGAACUANN
3593
UAGUUCAUUAAUGGCUUCCNN
3594


 


NM_005080_1029-1047
CUGCUUUCAUCCAGCCACUNN
3595
AGUGGCUGGAUGAAAGCAGNN
3596


 


NM_005080_1077-1095
GCUUACAGUGACUGUGGAUNN
3597
AUCCACAGUCACUGUAAGCNN
3598


 


NM_005080_1222-1240
GUUGCCCUUUUCCUUGACUNN
3599
AGUCAAGGAAAAGGGCAACNN
3600


 


NM_005080_1285-1303
UUCAAAAAGCCAAAAUAGANN
3601
UCUAUUUUGGCUUUUUGAANN
3602


 


NM_005080_1334-1352
UGUUCAGAUCUCAUAGAUGNN
3603
CAUCUAUGAGAUCUGAACANN
3604


 


NM_005080_1335-1353
GUUCAGAUCUCAUAGAUGANN
3605
UCAUCUAUGAGAUCUGAACNN
3606


 


NM_005080_1436-1454
GAACUACAGCUUUUAAGAUNN
3607
AUCUUAAAAGCUGUAGUUCNN
3608


 


NM_005080_1449-1467
UAAGAUUGUACUUUUAUCUNN
3609
AGAUAAAAGUACAAUCUUANN
3610


 


NM_005080_1450-1468
AAGAUUGUACUUUUAUCUUNN
3611
AAGAUAAAAGUACAAUCUUNN
3612


 


NM_005080_114-132
GCAGCCCGCCUCCGCCGCCNN
3613
GGCGGCGGAGGCGGGCUGCNN
3614


 


NM_005080_1555-1573
UUCUUUAUCAUUUCUCUUCNN
3615
GAAGAGAAAUGAUAAAGAANN
3616


 


NM_005080_1556-1574
UCUUUAUCAUUUCUCUUCCNN
3617
GGAAGAGAAAUGAUAAAGANN
3618


 


NM_005080_1561-1579
AUCAUUUCUCUUCCCCCUUNN
3619
AAGGGGGAAGAGAAAUGAUNN
3620


 


NM_005080_1562-1580
UCAUUUCUCUUCCCCCUUUNN
3621
AAAGGGGGAAGAGAAAUGANN
3622


 


NM_005080_1569-1587
UCUUCCCCCUUUUUGGCAUNN
3623
AUGCCAAAAAGGGGGAAGANN
3624


 


NM_005080_1588-1606
CCUGGCUUGCCUCCAGUUUNN
3625
AAACUGGAGGCAAGCCAGGNN
3626


 


NM_005080_1640-1658
AACACCUGCUGAGGGGGCUNN
3627
AGCCCCCUCAGCAGGUGUUNN
3628


 


NM_005080_1641-1659
ACACCUGCUGAGGGGGCUCNN
3629
GAGCCCCCUCAGCAGGUGUNN
3630


 


NM_005080_1642-1660
CACCUGCUGAGGGGGCUCUNN
3631
AGAGCCCCCUCAGCAGGUGNN
3632


 


NM_005080_1650-1668
GAGGGGGCUCUUUCCCUCANN
3633
UGAGGGAAAGAGCCCCCUCNN
3634


 


NM_005080_1686-1704
AUCAAGAAUCUUUUGUGAANN
3635
UUCACAAAAGAUUCUUGAUNN
3636


 


NM_005080_1745-1763
UCCUGCUAGUGUAGCUUCUNN
3637
AGAAGCUACACUAGCAGGANN
3638


 


NM_005080_138-156
CCCGGCCGGCCAGGCCCUGNN
3639
CAGGGCCUGGCCGGCCGGGNN
3640


 


NM_005080_145-163
GGCCAGGCCCUGCCGCUCANN
3641
UGAGCGGCAGGGCCUGGCCNN
3642


 


NM_005080_190-208
CCGGAGGCAGCGAGCGGGGNN
3643
CCCCGCTCGCTGCCTCCGGNN
3644


 


NM_005080_191-209
CGGAGGCAGCGAGCGGGGGNN
3645
CCCCCGCTCGCTGCCTCCGNN
3646


 


NM_005080_192-210
GGAGGCAGCGAGCGGGGGGNN
3647
CCCCCCGCTCGCTGCCTCCNN
3648


 


NM_005080_259-277
GAGAAGGCGCUGAGGAGGANN
3649
UCCUCCUCAGCGCCUUCUCNN
3650


 


NM_005080_261-279
GAAGGCGCUGAGGAGGAAANN
3651
UUUCCUCCUCAGCGCCUUCNN
3652


 


NM_005080_289-307
AGAGUAGCAGCUCAGACUGNN
3653
CAGUCUGAGCUGCUACUCUNN
3654


 


NM_005080_363-381
AGAAGAAGAGAACCAAAAANN
3655
TTTTTGGTTCTCTTCTTCTNN
3656


 


NM_005080_365-383
AAGAAGAGAACCAAAAACUNN
3657
AGUUUUUGGUUCUCUUCUUNN
3658


 


NM_005080_385-403
UUGCUAGAAAAUCAGCUUUNN
3659
AAAGCUGAUUUUCUAGCAANN
3660


 


NM_005080_461-479
GGAUGGAUGCCCUGGUUGCNN
3661
GCAACCAGGGCAUCCAUCCNN
3662


 


NM_005080_490-508
GCGGAAGCCAAGGGGAAUGNN
3663
CAUUCCCCUUGGCUUCCGCNN
3664


 


NM_005080_518-536
CAGUGGCCGGGUCUGCUGANN
3665
UCAGCAGACCCGGCCACUGNN
3666


 


NM_005080_673-691
ACAACUUGGACCCAGUCAUNN
3667
AUGACUGGGUCCAAGUUGUNN
3668


 


NM_005080_685-703
CAGUCAUGUUCUUCAAAUGNN
3669
CAUUUGAAGAACAUGACUGNN
3670


 


NM_005080_730-748
AGGAGCUCCCAGAGGUCUANN
3671
UAGACCUCUGGGAGCUCCUNN
3672


 


NM_005080_772-790
CAGCCUCCCUUUCUCUGUCNN
3673
GACAGAGAAAGGGAGGCUGNN
3674


 


NM_005080_801-819
UCAUCAGCCAAGCUGGAAGNN
3675
CUUCCAGCUUGGCUGAUGANN
3676


 


NM_005080_817-835
AAGCCAUUAAUGAACUAAUNN
3677
AUUAGUUCAUUAAUGGCUUNN
3678


 


NM_005080_887-905
GACAGAGAGCCAAGCUAAUNN
3679
AUUAGCUUGGCUCUCUGUCNN
3680


 


NM_005080_924-942
GAAGCACCUCUCAGCCCCUNN
3681
AGGGGCUGAGAGGUGCUUCNN
3682


 


NM_005080_927-945
GCACCUCUCAGCCCCUCAGNN
3683
CUGAGGGGCUGAGAGGUGCNN
3684


 


NM_005080_928-946
CACCUCUCAGCCCCUCAGANN
3685
UCUGAGGGGCUGAGAGGUGNN
3686


 


NM_005080_974-992
AGUGAAGGAAGAACCUGUANN
3687
UACAGGUUCUUCCUUCACUNN
3688


 


NM_005080_985-1003
AACCUGUAGAAGAUGACCUNN
3689
AGGUCAUCUUCUACAGGUUNN
3690


 


NM_005080_187-205
AGCCCGGAGGCAGCGAGCGNN
3691
CGCTCGCTGCCTCCGGGCTNN
3692


 


NM_005080_672-690
GACAACUUGGACCCAGUCANN
3693
UGACUGGGUCCAAGUUGUCNN
3694


 


NM_005080_771-789
CCAGCCUCCCUUUCUCUGUNN
3695
ACAGAGAAAGGGAGGCUGGNN
3696


 


NM_005080_1740-1758
UUUUUUCCUGCUAGUGUAGNN
3697
CUACACUAGCAGGAAAAAANN
3698


 


NM_005080_1741-1759
UUUUUCCUGCUAGUGUAGCNN
3699
GCUACACUAGCAGGAAAAANN
3700


 


NM_005080_662-680
GGGCAUUCUGGACAACUUGNN
3701
CAAGUUGUCCAGAAUGCCCNN
3702


 


NM_005080_1070-1088
ACUGGAUGCUUACAGUGACNN
3703
GUCACUGUAAGCAUCCAGUNN
3704


 


NM_005080_631-649
ACUCUUCAGAUUCAGAGUCNN
3705
GACUCUGAAUCUGAAGAGUNN
3706


 


NM_005080_647-665
GUCUGAUAUCCUGUUGGGCNN
3707
GCCCAACAGGAUAUCAGACNN
3708


 


NM_005080_791-809
AGUGGGGACGUCAUCAGCCNN
3709
GGCUGAUGACGUCCCCACUNN
3710


 


NM_005080_981-999
GAAGAACCUGUAGAAGAUGNN
3711
CAUCUUCUACAGGUUCUUCNN
3712


 


NM_005080_1068-1086
CUACUGGAUGCUUACAGUGNN
3713
CACUGUAAGCAUCCAGUAGNN
3714


 


NM_005080_1391-1409
GUAUUGAGACAUAUUACUGNN
3715
CAGUAAUAUGUCUCAAUACNN
3716


 


NM_005080_1426-1444
CUAUAAUUGAGAACUACAGNN
3717
CUGUAGUUCUCAAUUAUAGNN
3718


 


NM_005080_103-121
CUUCUGUCGGGGCAGCCCGNN
3719
CGGGCUGCCCCGACAGAAGNN
3720


 


NM_005080_1457-1475
UACUUUUAUCUUAAAAGGGNN
3721
CCCUUUUAAGAUAAAAGUANN
3722


 


NM_005080_1568-1586
CUCUUCCCCCUUUUUGGCANN
3723
UGCCAAAAAGGGGGAAGAGNN
3724


 


NM_005080_1574-1592
CCCCUUUUUGGCAUCCUGGNN
3725
CCAGGAUGCCAAAAAGGGGNN
3726


 


NM_005080_1577-1595
CUUUUUGGCAUCCUGGCUUNN
3727
AAGCCAGGAUGCCAAAAAGNN
3728


 


NM_005080_1730-1748
CUUGAUGGAAUUUUUUCCUNN
3729
AGGAAAAAAUUCCAUCAAGNN
3730


 


NM_005080_1731-1749
UUGAUGGAAUUUUUUCCUGNN
3731
CAGGAAAAAAUUCCAUCAANN
3732


 


NM_005080_1732-1750
UGAUGGAAUUUUUUCCUGCNN
3733
GCAGGAAAAAAUUCCAUCANN
3734


 


NM_005080_293-311
UAGCAGCUCAGACUGCCAGNN
3735
CUGGCAGUCUGAGCUGCUANN
3736


 


NM_005080_350-368
AAGUGGUAGAUUUAGAAGANN
3737
UCUUCUAAAUCUACCACUUNN
3738


 


NM_005080_351-369
AGUGGUAGAUUUAGAAGAANN
3739
UUCUUCUAAAUCUACCACUNN
3740


 


NM_005080_630-648
GACUCUUCAGAUUCAGAGUNN
3741
ACUCUGAAUCUGAAGAGUCNN
3742


 


NM_005080_657-675
CUGUUGGGCAUUCUGGACANN
3743
UGUCCAGAAUGCCCAACAGNN
3744


 


NM_005080_670-688
UGGACAACUUGGACCCAGUNN
3745
ACUGGGUCCAAGUUGUCCANN
3746


 


NM_005080_692-710
GUUCUUCAAAUGCCCUUCCNN
3747
GGAAGGGCAUUUGAAGAACNN
3748


 


NM_005080_778-796
CCCUUUCUCUGUCAGUGGGNN
3749
CCCACUGACAGAGAAAGGGNN
3750


 


NM_005080_790-808
CAGUGGGGACGUCAUCAGCNN
3751
GCUGAUGACGUCCCCACUGNN
3752


 


NM_005080_970-988
UCUCAGUGAAGGAAGAACCNN
3753
GGUUCUUCCUUCACUGAGANN
3754


 


NM_005080_1162-1180
ACACUUUUGCCAAUGAACUNN
3755
AGUUCAUUGGCAAAAGUGUNN
3756


 


NM_005080_1368-1386
CUUUUGACAUCCAGCAGUCNN
3757
GACUGCUGGAUGUCAAAAGNN
3758


 


NM_005080_1515-1533
UAGACAAAUGUCUUGAAGUNN
3759
ACUUCAAGACAUUUGUCUANN
3760


 


NM_005080_1541-1559
GAAUUUAUGAAUGGUUCUUNN
3761
AAGAACCAUUCAUAAAUUCNN
3762


 


NM_005080_1542-1560
AAUUUAUGAAUGGUUCUUUNN
3763
AAAGAACCAUUCAUAAAUUNN
3764


 


NM_005080_1571-1589
UUCCCCCUUUUUGGCAUCCNN
3765
GGAUGCCAAAAAGGGGGAANN
3766


 


NM_005080_151-169
GCCCUGCCGCUCAUGGUGCNN
3767
GCACCAUGAGCGGCAGGGCNN
3768


 


NM_005080_160-178
CUCAUGGUGCCAGCCCAGANN
3769
UCUGGGCUGGCACCAUGAGNN
3770


 


NM_005080_326-344
CUCGAAUGAGUGAGCUGGANN
3771
UCCAGCUCACUCAUUCGAGNN
3772


 


NM_005080_327-345
UCGAAUGAGUGAGCUGGAANN
3773
UUCCAGCUCACUCAUUCGANN
3774


 


NM_005080_331-349
AUGAGUGAGCUGGAACAGCNN
3775
GCUGUUCCAGCUCACUCAUNN
3776


 


NM_005080_424-442
CUUGUAGUUGAGAACCAGGNN
3777
CCUGGUUCUCAACUACAAGNN
3778


 


NM_005080_483-501
AGAGGAGGCGGAAGCCAAGNN
3779
CTTGGCTTCCGCCTCCTCTNN
3780


 


NM_005080_579-597
GGCCCAGUUGUCACCCCUCNN
3781
GAGGGGUGACAACUGGGCCNN
3782


 


NM_005080_745-763
UCUACCCAGAAGGACCCAGNN
3783
CUGGGUCCUUCUGGGUAGANN
3784


 


NM_005080_746-764
CUACCCAGAAGGACCCAGUNN
3785
ACUGGGUCCUUCUGGGUAGNN
3786


 


NM_005080_812-830
GCUGGAAGCCAUUAAUGAANN
3787
UUCAUUAAUGGCUUCCAGCNN
3788


 


NM_005080_871-889
UAGAGAUACCCUCUGAGACNN
3789
GUCUCAGAGGGUAUCUCUANN
3790


 


NM_005080_892-910
AGAGCCAAGCUAAUGUGGUNN
3791
ACCACAUUAGCUUGGCUCUNN
3792


 


NM_005080_978-996
AAGGAAGAACCUGUAGAAGNN
3793
CUUCUACAGGUUCUUCCUUNN
3794


 


NM_005080_982-1000
AAGAACCUGUAGAAGAUGANN
3795
UCAUCUUCUACAGGUUCUUNN
3796


 


NM_005080_257-275
AGGAGAAGGCGCUGAGGAGNN
3797
CUCCUCAGCGCCUUCUCCUNN
3798


 


NM_005080_364-382
GAAGAAGAGAACCAAAAACNN
3799
GTTTTTGGTTCTCTTCTTCNN
3800


 


NM_005080_816-834
GAAGCCAUUAAUGAACUAANN
3801
UUAGUUCAUUAAUGGCUUCNN
3802


 


NM_005080_884-902
UGAGACAGAGAGCCAAGCUNN
3803
AGCUUGGCUCUCUGUCUCANN
3804


 


NM_005080_925-943
AAGCACCUCUCAGCCCCUCNN
3805
GAGGGGCUGAGAGGUGCUUNN
3806


 


NM_005080_1440-1458
UACAGCUUUUAAGAUUGUANN
3807
UACAAUCUUAAAAGCUGUANN
3808


 


NM_005080_784-802
CUCUGUCAGUGGGGACGUCNN
3809
GACGUCCCCACUGACAGAGNN
3810


 


NM_005080_1593-1611
CUUGCCUCCAGUUUUAGGUNN
3811
ACCUAAAACUGGAGGCAAGNN
3812


 


NM_005080_301-319
CAGACUGCCAGAGAUCGAANN
3813
UUCGAUCUCUGGCAGUCUGNN
3814


 


NM_005080_674-692
CAACUUGGACCCAGUCAUGNN
3815
CAUGACUGGGUCCAAGUUGNN
3816


 


NM_005080_783-801
UCUCUGUCAGUGGGGACGUNN
3817
ACGUCCCCACUGACAGAGANN
3818


 


NM_005080_921-939
GAGGAAGCACCUCUCAGCCNN
3819
GGCUGAGAGGUGCUUCCUCNN
3820


 


NM_005080_1226-1244
CCCUUUUCCUUGACUAUUANN
3821
UAAUAGUCAAGGAAAAGGGNN
3822


 


NM_005080_1283-1301
CAUUCAAAAAGCCAAAAUANN
3823
UAUUUUGGCUUUUUGAAUGNN
3824


 


NM_005080_1416-1434
AGAAAUAUUACUAUAAUUGNN
3825
CAAUUAUAGUAAUAUUUCUNN
3826


 


NM_005080_1420-1438
AUAUUACUAUAAUUGAGAANN
3827
UUCUCAAUUAUAGUAAUAUNN
3828


 


NM_005080_1488-1506
CUAAAAUACUUAUUAUGUANN
3829
UACAUAAUAAGUAUUUUAGNN
3830


 


NM_005080_1492-1510
AAUACUUAUUAUGUAAGGGNN
3831
CCCUUACAUAAUAAGUAUUNN
3832


 


NM_005080_111-129
GGGGCAGCCCGCCUCCGCCNN
3833
GGCGGAGGCGGGCUGCCCCNN
3834


 


NM_005080_1639-1657
GAACACCUGCUGAGGGGGCNN
3835
GCCCCCUCAGCAGGUGUUCNN
3836


 


NM_005080_1685-1703
GAUCAAGAAUCUUUUGUGANN
3837
UCACAAAAGAUUCUUGAUCNN
3838


 


NM_005080_1733-1751
GAUGGAAUUUUUUCCUGCUNN
3839
AGCAGGAAAAAAUUCCAUCNN
3840


 


NM_005080_1734-1752
AUGGAAUUUUUUCCUGCUANN
3841
UAGCAGGAAAAAAUUCCAUNN
3842


 


NM_005080_1737-1755
GAAUUUUUUCCUGCUAGUGNN
3843
CACUAGCAGGAAAAAAUUCNN
3844


 


NM_005080_1756-1774
UAGCUUCUGAAAGGUGCUUNN
3845
AAGCACCUUUCAGAAGCUANN
3846


 


NM_005080_1757-1775
AGCUUCUGAAAGGUGCUUUNN
3847
AAAGCACCUUUCAGAAGCUNN
3848


 


NM_005080_152-170
CCCUGCCGCUCAUGGUGCCNN
3849
GGCACCAUGAGCGGCAGGGNN
3850


 


NM_005080_153-171
CCUGCCGCUCAUGGUGCCANN
3851
UGGCACCAUGAGCGGCAGGNN
3852


 


NM_005080_163-181
AUGGUGCCAGCCCAGAGAGNN
3853
CUCUCUGGGCUGGCACCAUNN
3854


 


NM_005080_167-185
UGCCAGCCCAGAGAGGGGCNN
3855
GCCCCUCUCUGGGCUGGCANN
3856


 


NM_005080_200-218
CGAGCGGGGGGCUGCCCCANN
3857
UGGGGCAGCCCCCCGCUCGNN
3858


 


NM_005080_252-270
CCCCGAGGAGAAGGCGCUGNN
3859
CAGCGCCUUCUCCUCGGGGNN
3860


 


NM_005080_255-273
CGAGGAGAAGGCGCUGAGGNN
3861
CCUCAGCGCCUUCUCCUCGNN
3862


 


NM_005080_260-278
AGAAGGCGCUGAGGAGGAANN
3863
UUCCUCCUCAGCGCCUUCUNN
3864


 


NM_005080_271-289
AGGAGGAAACUGAAAAACANN
3865
UGUUUUUCAGUUUCCUCCUNN
3866


 


NM_005080_297-315
AGCUCAGACUGCCAGAGAUNN
3867
AUCUCUGGCAGUCUGAGCUNN
3868


 


NM_005080_300-318
UCAGACUGCCAGAGAUCGANN
3869
UCGAUCUCUGGCAGUCUGANN
3870


 


NM_005080_335-353
GUGAGCUGGAACAGCAAGUNN
3871
ACUUGCUGUUCCAGCUCACNN
3872


 


NM_005080_368-386
AAGAGAACCAAAAACUUUUNN
3873
AAAAGUUUUUGGUUCUCUUNN
3874


 


NM_005080_378-396
AAAACUUUUGCUAGAAAAUNN
3875
AUUUUCUAGCAAAAGUUUUNN
3876


 


NM_005080_379-397
AAACUUUUGCUAGAAAAUCNN
3877
GAUUUUCUAGCAAAAGUUUNN
3878


 


NM_005080_380-398
AACUUUUGCUAGAAAAUCANN
3879
UGAUUUUCUAGCAAAAGUUNN
3880


 


NM_005080_389-407
UAGAAAAUCAGCUUUUACGNN
3881
CGUAAAAGCUGAUUUUCUANN
3882


 


NM_005080_426-444
UGUAGUUGAGAACCAGGAGNN
3883
CUCCUGGUUCUCAACUACANN
3884


 


NM_005080_427-445
GUAGUUGAGAACCAGGAGUNN
3885
ACUCCUGGUUCUCAACUACNN
3886


 


NM_005080_485-503
AGGAGGCGGAAGCCAAGGGNN
3887
CCCTTGGCTTCCGCCTCCTNN
3888


 


NM_005080_487-505
GAGGCGGAAGCCAAGGGGANN
3889
TCCCCTTGGCTTCCGCCTCNN
3890


 


NM_005080_488-506
AGGCGGAAGCCAAGGGGAANN
3891
TTCCCCTTGGCTTCCGCCTNN
3892


 


NM_005080_511-529
GUGAGGCCAGUGGCCGGGUNN
3893
ACCCGGCCACUGGCCUCACNN
3894


 


NM_005080_526-544
GGGUCUGCUGAGUCCGCAGNN
3895
CUGCGGACUCAGCAGACCCNN
3896


 


NM_005080_575-593
UGCAGGCCCAGUUGUCACCNN
3897
GGUGACAACUGGGCCUGCANN
3898


 


NM_005080_593-611
CCCUCCAGAACAUCUCCCCNN
3899
GGGGAGAUGUUCUGGAGGGNN
3900


 


NM_005080_595-613
CUCCAGAACAUCUCCCCAUNN
3901
AUGGGGAGAUGUUCUGGAGNN
3902


 


NM_005080_654-672
AUCCUGUUGGGCAUUCUGGNN
3903
CCAGAAUGCCCAACAGGAUNN
3904


 


NM_005080_675-693
AACUUGGACCCAGUCAUGUNN
3905
ACAUGACUGGGUCCAAGUUNN
3906


 


NM_005080_683-701
CCCAGUCAUGUUCUUCAAANN
3907
UUUGAAGAACAUGACUGGGNN
3908


 


NM_005080_684-702
CCAGUCAUGUUCUUCAAAUNN
3909
AUUUGAAGAACAUGACUGGNN
3910


 


NM_005080_693-711
UUCUUCAAAUGCCCUUCCCNN
3911
GGGAAGGGCAUUUGAAGAANN
3912


 


NM_005080_694-712
UCUUCAAAUGCCCUUCCCCNN
3913
GGGGAAGGGCAUUUGAAGANN
3914


 


NM_005080_726-744
CUGGAGGAGCUCCCAGAGGNN
3915
CCUCUGGGAGCUCCUCCAGNN
3916


 


NM_005080_744-762
GUCUACCCAGAAGGACCCANN
3917
UGGGUCCUUCUGGGUAGACNN
3918


 


NM_005080_765-783
UCCUUACCAGCCUCCCUUUNN
3919
AAAGGGAGGCUGGUAAGGANN
3920


 


NM_005080_768-786
UUACCAGCCUCCCUUUCUCNN
3921
GAGAAAGGGAGGCUGGUAANN
3922


 


NM_005080_777-795
UCCCUUUCUCUGUCAGUGGNN
3923
CCACUGACAGAGAAAGGGANN
3924


 


NM_005080_802-820
CAUCAGCCAAGCUGGAAGCNN
3925
GCUUCCAGCUUGGCUGAUGNN
3926


 


NM_005080_877-895
UACCCUCUGAGACAGAGAGNN
3927
CUCUCUGUCUCAGAGGGUANN
3928


 


NM_005080_878-896
ACCCUCUGAGACAGAGAGCNN
3929
GCUCUCUGUCUCAGAGGGUNN
3930


 


NM_005080_885-903
GAGACAGAGAGCCAAGCUANN
3931
UAGCUUGGCUCUCUGUCUCNN
3932


 


NM_005080_886-904
AGACAGAGAGCCAAGCUAANN
3933
UUAGCUUGGCUCUCUGUCUNN
3934


 


NM_005080_966-984
AUUGUCUCAGUGAAGGAAGNN
3935
CUUCCUUCACUGAGACAAUNN
3936


 


NM_005080_969-987
GUCUCAGUGAAGGAAGAACNN
3937
GUUCUUCCUUCACUGAGACNN
3938


 


NM_005080_1245-1263
CACUGCCUGGAGGAUAGCANN
3939
UGCUAUCCUCCAGGCAGUGNN
3940


 


NM_005080_1738-1756
AAUUUUUUCCUGCUAGUGUNN
3941
ACACUAGCAGGAAAAAAUUNN
3942


 


NM_005080_194-212
AGGCAGCGAGCGGGGGGCUNN
3943
AGCCCCCCGCUCGCUGCCUNN
3944


 


NM_005080_209-227
GGCUGCCCCAGGCGCGCAANN
3945
UUGCGCGCCUGGGGCAGCCNN
3946


 


NM_005080_269-287
UGAGGAGGAAACUGAAAAANN
3947
UUUUUCAGUUUCCUCCUCANN
3948


 


NM_005080_902-920
UAAUGUGGUAGUGAAAAUCNN
3949
GAUUUUCACUACCACAUUANN
3950


 


NM_005080_50-68
UGGUGGUGGUGGCAGCCGCNN
3951
GCGGCUGCCACCACCACCANN
3952


 


NM_005080_1017-1035
GGUAUCUCAAAUCUGCUUUNN
3953
AAAGCAGAUUUGAGAUACCNN
3954


 


NM_005080_1021-1039
UCUCAAAUCUGCUUUCAUCNN
3955
GAUGAAAGCAGAUUUGAGANN
3956


 


NM_005080_1022-1040
CUCAAAUCUGCUUUCAUCCNN
3957
GGAUGAAAGCAGAUUUGAGNN
3958


 


NM_005080_1062-1080
UCCUGCCUACUGGAUGCUUNN
3959
AAGCAUCCAGUAGGCAGGANN
3960


 


NM_005080_1074-1092
GAUGCUUACAGUGACUGUGNN
3961
CACAGUCACUGUAAGCAUCNN
3962


 


NM_005080_1116-1134
UUCAGUGACAUGUCCUCUCNN
3963
GAGAGGACAUGUCACUGAANN
3964


 


NM_005080_1149-1167
CAUUCUUGGGAGGACACUUNN
3965
AAGUGUCCUCCCAAGAAUGNN
3966


 


NM_005080_1150-1168
AUUCUUGGGAGGACACUUUNN
3967
AAAGUGUCCUCCCAAGAAUNN
3968


 


NM_005080_1161-1179
GACACUUUUGCCAAUGAACNN
3969
GUUCAUUGGCAAAAGUGUCNN
3970


 


NM_005080_1223-1241
UUGCCCUUUUCCUUGACUANN
3971
UAGUCAAGGAAAAGGGCAANN
3972


 


NM_005080_1280-1298
CUUCAUUCAAAAAGCCAAANN
3973
UUUGGCUUUUUGAAUGAAGNN
3974


 


NM_005080_1281-1299
UUCAUUCAAAAAGCCAAAANN
3975
UUUUGGCUUUUUGAAUGAANN
3976


 


NM_005080_1284-1302
AUUCAAAAAGCCAAAAUAGNN
3977
CUAUUUUGGCUUUUUGAAUNN
3978


 


NM_005080_1286-1304
UCAAAAAGCCAAAAUAGAGNN
3979
CUCUAUUUUGGCUUUUUGANN
3980


 


NM_005080_1288-1306
AAAAAGCCAAAAUAGAGAGNN
3981
CUCUCUAUUUUGGCUUUUUNN
3982


 


NM_005080_1365-1383
UGUCUUUUGACAUCCAGCANN
3983
UGCUGGAUGUCAAAAGACANN
3984


 


NM_005080_1417-1435
GAAAUAUUACUAUAAUUGANN
3985
UCAAUUAUAGUAAUAUUUCNN
3986


 


NM_005080_1421-1439
UAUUACUAUAAUUGAGAACNN
3987
GUUCUCAAUUAUAGUAAUANN
3988


 


NM_005080_1434-1452
GAGAACUACAGCUUUUAAGNN
3989
CUUAAAAGCUGUAGUUCUCNN
3990


 


NM_005080_1452-1470
GAUUGUACUUUUAUCUUAANN
3991
UUAAGAUAAAAGUACAAUCNN
3992


 


NM_005080_105-123
UCUGUCGGGGCAGCCCGCCNN
3993
GGCGGGCUGCCCCGACAGANN
3994


 


NM_005080_1455-1473
UGUACUUUUAUCUUAAAAGNN
3995
CUUUUAAGAUAAAAGUACANN
3996


 


NM_005080_112-130
GGGCAGCCCGCCUCCGCCGNN
3997
CGGCGGAGGCGGGCUGCCCNN
3998


 


NM_005080_113-131
GGCAGCCCGCCUCCGCCGCNN
3999
GCGGCGGAGGCGGGCUGCCNN
4000


 


NM_005080_1543-1561
AUUUAUGAAUGGUUCUUUANN
4001
UAAAGAACCAUUCAUAAAUNN
4002


 


NM_005080_1544-1562
UUUAUGAAUGGUUCUUUAUNN
4003
AUAAAGAACCAUUCAUAAANN
4004


 


NM_005080_1557-1575
CUUUAUCAUUUCUCUUCCCNN
4005
GGGAAGAGAAAUGAUAAAGNN
4006


 


NM_005080_115-133
CAGCCCGCCUCCGCCGCCGNN
4007
CGGCGGCGGAGGCGGGCUGNN
4008


 


NM_005080_1564-1582
AUUUCUCUUCCCCCUUUUUNN
4009
AAAAAGGGGGAAGAGAAAUNN
4010


 


NM_005080_1572-1590
UCCCCCUUUUUGGCAUCCUNN
4011
AGGAUGCCAAAAAGGGGGANN
4012


 


NM_005080_1575-1593
CCCUUUUUGGCAUCCUGGCNN
4013
GCCAGGAUGCCAAAAAGGGNN
4014


 


NM_005080_1576-1594
CCUUUUUGGCAUCCUGGCUNN
4015
AGCCAGGAUGCCAAAAAGGNN
4016


 


NM_005080_117-135
GCCCGCCUCCGCCGCCGGANN
4017
UCCGGCGGCGGAGGCGGGCNN
4018


 


NM_005080_1582-1600
UGGCAUCCUGGCUUGCCUCNN
4019
GAGGCAAGCCAGGAUGCCANN
4020


 


NM_005080_1587-1605
UCCUGGCUUGCCUCCAGUUNN
4021
AACUGGAGGCAAGCCAGGANN
4022


 


NM_005080_118-136
CCCGCCUCCGCCGCCGGAGNN
4023
CUCCGGCGGCGGAGGCGGGNN
4024


 


NM_005080_119-137
CCGCCUCCGCCGCCGGAGCNN
4025
GCUCCGGCGGCGGAGGCGGNN
4026


 


NM_005080_120-138
CGCCUCCGCCGCCGGAGCCNN
4027
GGCUCCGGCGGCGGAGGCGNN
4028


 


NM_005080_124-142
UCCGCCGCCGGAGCCCCGGNN
4029
CCGGGGCUCCGGCGGCGGANN
4030


 


NM_005080_126-144
CGCCGCCGGAGCCCCGGCCNN
4031
GGCCGGGGCTCCGGCGGCGNN
4032


 


NM_005080_1676-1694
UUCAAGUAAGAUCAAGAAUNN
4033
AUUCUUGAUCUUACUUGAANN
4034


 


NM_005080_127-145
GCCGCCGGAGCCCCGGCCGNN
4035
CGGCCGGGGCTCCGGCGGCNN
4036


 


NM_005080_129-147
CGCCGGAGCCCCGGCCGGCNN
4037
GCCGGCCGGGGCTCCGGCGNN
4038


 


NM_005080_130-148
GCCGGAGCCCCGGCCGGCCNN
4039
GGCCGGCCGGGGCTCCGGCNN
4040


 


NM_005080_131-149
CCGGAGCCCCGGCCGGCCANN
4041
TGGCCGGCCGGGGCTCCGGNN
4042


 


NM_005080_1720-1738
UAUGUAAAUGCUUGAUGGANN
4043
UCCAUCAAGCAUUUACAUANN
4044


 


NM_005080_1724-1742
UAAAUGCUUGAUGGAAUUUNN
4045
AAAUUCCAUCAAGCAUUUANN
4046


 


NM_005080_132-150
CGGAGCCCCGGCCGGCCAGNN
4047
CTGGCCGGCCGGGGCTCCGNN
4048


 


NM_005080_133-151
GGAGCCCCGGCCGGCCAGGNN
4049
CCTGGCCGGCCGGGGCTCCNN
4050


 


NM_005080_134-152
GAGCCCCGGCCGGCCAGGCNN
4051
GCCTGGCCGGCCGGGGCTCNN
4052


 


NM_005080_136-154
GCCCCGGCCGGCCAGGCCCNN
4053
GGGCCTGGCCGGCCGGGGCNN
4054


 


NM_005080_1777-1795
UCCAUUUAUUUAAAACUACNN
4055
GUAGUUUUAAAUAAAUGGANN
4056


 


NM_005080_137-155
CCCCGGCCGGCCAGGCCCUNN
4057
AGGGCCUGGCCGGCCGGGGNN
4058


 


NM_005080_139-157
CCGGCCGGCCAGGCCCUGCNN
4059
GCAGGGCCUGGCCGGCCGGNN
4060


 


NM_005080_140-158
CGGCCGGCCAGGCCCUGCCNN
4061
GGCAGGGCCUGGCCGGCCGNN
4062


 


NM_005080_141-159
GGCCGGCCAGGCCCUGCCGNN
4063
CGGCAGGGCCUGGCCGGCCNN
4064


 


NM_005080_142-160
GCCGGCCAGGCCCUGCCGCNN
4065
GCGGCAGGGCCUGGCCGGCNN
4066


 


NM_005080_143-161
CCGGCCAGGCCCUGCCGCUNN
4067
AGCGGCAGGGCCUGGCCGGNN
4068


 


NM_005080_144-162
CGGCCAGGCCCUGCCGCUCNN
4069
GAGCGGCAGGGCCUGGCCGNN
4070


 


NM_005080_161-179
UCAUGGUGCCAGCCCAGAGNN
4071
CUCUGGGCUGGCACCAUGANN
4072


 


NM_005080_162-180
CAUGGUGCCAGCCCAGAGANN
4073
UCUCUGGGCUGGCACCAUGNN
4074


 


NM_005080_164-182
UGGUGCCAGCCCAGAGAGGNN
4075
CCUCUCUGGGCUGGCACCANN
4076


 


NM_005080_165-183
GGUGCCAGCCCAGAGAGGGNN
4077
CCCUCUCUGGGCUGGCACCNN
4078


 


NM_005080_166-184
GUGCCAGCCCAGAGAGGGGNN
4079
CCCCUCUCUGGGCUGGCACNN
4080


 


NM_005080_201-219
GAGCGGGGGGCUGCCCCAGNN
4081
CUGGGGCAGCCCCCCGCUCNN
4082


 


NM_005080_202-220
AGCGGGGGGCUGCCCCAGGNN
4083
CCUGGGGCAGCCCCCCGCUNN
4084


 


NM_005080_203-221
GCGGGGGGCUGCCCCAGGCNN
4085
GCCUGGGGCAGCCCCCCGCNN
4086


 


NM_005080_204-222
CGGGGGGCUGCCCCAGGCGNN
4087
CGCCUGGGGCAGCCCCCCGNN
4088


 


NM_005080_208-226
GGGCUGCCCCAGGCGCGCANN
4089
UGCGCGCCUGGGGCAGCCCNN
4090


 


NM_005080_212-230
UGCCCCAGGCGCGCAAGCGNN
4091
CGCUUGCGCGCCUGGGGCANN
4092


 


NM_005080_248-266
UGAGCCCCGAGGAGAAGGCNN
4093
GCCUUCUCCUCGGGGCUCANN
4094


 


NM_005080_251-269
GCCCCGAGGAGAAGGCGCUNN
4095
AGCGCCUUCUCCUCGGGGCNN
4096


 


NM_005080_258-276
GGAGAAGGCGCUGAGGAGGNN
4097
CCUCCUCAGCGCCUUCUCCNN
4098


 


NM_005080_262-280
AAGGCGCUGAGGAGGAAACNN
4099
GUUUCCUCCUCAGCGCCUUNN
4100


 


NM_005080_265-283
GCGCUGAGGAGGAAACUGANN
4101
UCAGUUUCCUCCUCAGCGCNN
4102


 


NM_005080_266-284
CGCUGAGGAGGAAACUGAANN
4103
UUCAGUUUCCUCCUCAGCGNN
4104


 


NM_005080_267-285
GCUGAGGAGGAAACUGAAANN
4105
UUUCAGUUUCCUCCUCAGCNN
4106


 


NM_005080_268-286
CUGAGGAGGAAACUGAAAANN
4107
UUUUCAGUUUCCUCCUCAGNN
4108


 


NM_005080_270-288
GAGGAGGAAACUGAAAAACNN
4109
GUUUUUCAGUUUCCUCCUCNN
4110


 


NM_005080_272-290
GGAGGAAACUGAAAAACAGNN
4111
CUGUUUUUCAGUUUCCUCCNN
4112


 


NM_005080_273-291
GAGGAAACUGAAAAACAGANN
4113
UCUGUUUUUCAGUUUCCUCNN
4114


 


NM_005080_277-295
AAACUGAAAAACAGAGUAGNN
4115
CUACUCUGUUUUUCAGUUUNN
4116


 


NM_005080_328-346
CGAAUGAGUGAGCUGGAACNN
4117
GUUCCAGCUCACUCAUUCGNN
4118


 


NM_005080_329-347
GAAUGAGUGAGCUGGAACANN
4119
UGUUCCAGCUCACUCAUUCNN
4120


 


NM_005080_334-352
AGUGAGCUGGAACAGCAAGNN
4121
CUUGCUGUUCCAGCUCACUNN
4122


 


NM_005080_336-354
UGAGCUGGAACAGCAAGUGNN
4123
CACUUGCUGUUCCAGCUCANN
4124


 


NM_005080_337-355
GAGCUGGAACAGCAAGUGGNN
4125
CCACUUGCUGUUCCAGCUCNN
4126


 


NM_005080_338-356
AGCUGGAACAGCAAGUGGUNN
4127
ACCACUUGCUGUUCCAGCUNN
4128


 


NM_005080_356-374
UAGAUUUAGAAGAAGAGAANN
4129
UUCUCUUCUUCUAAAUCUANN
4130


 


NM_005080_357-375
AGAUUUAGAAGAAGAGAACNN
4131
GUUCUCUUCUUCUAAAUCUNN
4132


 


NM_005080_359-377
AUUUAGAAGAAGAGAACCANN
4133
UGGUUCUCUUCUUCUAAAUNN
4134


 


NM_005080_360-378
UUUAGAAGAAGAGAACCAANN
4135
UUGGUUCUCUUCUUCUAAANN
4136


 


NM_005080_362-380
UAGAAGAAGAGAACCAAAANN
4137
UUUUGGUUCUCUUCUUCUANN
4138


 


NM_005080_367-385
GAAGAGAACCAAAAACUUUNN
4139
AAAGUUUUUGGUUCUCUUCNN
4140


 


NM_005080_382-400
CUUUUGCUAGAAAAUCAGCNN
4141
GCUGAUUUUCUAGCAAAAGNN
4142


 


NM_005080_386-404
UGCUAGAAAAUCAGCUUUUNN
4143
AAAAGCUGAUUUUCUAGCANN
4144


 


NM_005080_401-419
UUUUACGAGAGAAAACUCANN
4145
UGAGUUUUCUCUCGUAAAANN
4146


 


NM_005080_458-476
UGGGGAUGGAUGCCCUGGUNN
4147
ACCAGGGCAUCCAUCCCCANN
4148


 


NM_005080_484-502
GAGGAGGCGGAAGCCAAGGNN
4149
CCTTGGCTTCCGCCTCCTCNN
4150


 


NM_005080_489-507
GGCGGAAGCCAAGGGGAAUNN
4151
AUUCCCCUUGGCUUCCGCCNN
4152


 


NM_005080_574-592
GUGCAGGCCCAGUUGUCACNN
4153
GUGACAACUGGGCCUGCACNN
4154


 


NM_005080_594-612
CCUCCAGAACAUCUCCCCANN
4155
UGGGGAGAUGUUCUGGAGGNN
4156


 


NM_005080_604-622
AUCUCCCCAUGGAUUCUGGNN
4157
CCAGAAUCCAUGGGGAGAUNN
4158


 


NM_005080_627-645
AUUGACUCUUCAGAUUCAGNN
4159
CUGAAUCUGAAGAGUCAAUNN
4160


 


NM_005080_635-653
UUCAGAUUCAGAGUCUGAUNN
4161
AUCAGACUCUGAAUCUGAANN
4162


 


NM_005080_636-654
UCAGAUUCAGAGUCUGAUANN
4163
UAUCAGACUCUGAAUCUGANN
4164


 


NM_005080_666-684
AUUCUGGACAACUUGGACCNN
4165
GGUCCAAGUUGUCCAGAAUNN
4166


 


NM_005080_667-685
UUCUGGACAACUUGGACCCNN
4167
GGGUCCAAGUUGUCCAGAANN
4168


 


NM_005080_669-687
CUGGACAACUUGGACCCAGNN
4169
CUGGGUCCAAGUUGUCCAGNN
4170


 


NM_005080_681-699
GACCCAGUCAUGUUCUUCANN
4171
UGAAGAACAUGACUGGGUCNN
4172


 


NM_005080_690-708
AUGUUCUUCAAAUGCCCUUNN
4173
AAGGGCAUUUGAAGAACAUNN
4174


 


NM_005080_718-736
CUGCCAGCCUGGAGGAGCUNN
4175
AGCUCCUCCAGGCUGGCAGNN
4176


 


NM_005080_722-740
CAGCCUGGAGGAGCUCCCANN
4177
UGGGAGCUCCUCCAGGCUGNN
4178


 


NM_005080_723-741
AGCCUGGAGGAGCUCCCAGNN
4179
CUGGGAGCUCCUCCAGGCUNN
4180


 


NM_005080_724-742
GCCUGGAGGAGCUCCCAGANN
4181
UCUGGGAGCUCCUCCAGGCNN
4182


 


NM_005080_725-743
CCUGGAGGAGCUCCCAGAGNN
4183
CUCUGGGAGCUCCUCCAGGNN
4184


 


NM_005080_727-745
UGGAGGAGCUCCCAGAGGUNN
4185
ACCUCUGGGAGCUCCUCCANN
4186


 


NM_005080_728-746
GGAGGAGCUCCCAGAGGUCNN
4187
GACCUCUGGGAGCUCCUCCNN
4188


 


NM_005080_739-757
CAGAGGUCUACCCAGAAGGNN
4189
CCUUCUGGGUAGACCUCUGNN
4190


 


NM_005080_747-765
UACCCAGAAGGACCCAGUUNN
4191
AACUGGGUCCUUCUGGGUANN
4192


 


NM_005080_763-781
GUUCCUUACCAGCCUCCCUNN
4193
AGGGAGGCUGGUAAGGAACNN
4194


 


NM_005080_764-782
UUCCUUACCAGCCUCCCUUNN
4195
AAGGGAGGCUGGUAAGGAANN
4196


 


NM_005080_766-784
CCUUACCAGCCUCCCUUUCNN
4197
GAAAGGGAGGCUGGUAAGGNN
4198


 


NM_005080_770-788
ACCAGCCUCCCUUUCUCUGNN
4199
CAGAGAAAGGGAGGCUGGUNN
4200


 


NM_005080_774-792
GCCUCCCUUUCUCUGUCAGNN
4201
CUGACAGAGAAAGGGAGGCNN
4202


 


NM_005080_780-798
CUUUCUCUGUCAGUGGGGANN
4203
UCCCCACUGACAGAGAAAGNN
4204


 


NM_005080_781-799
UUUCUCUGUCAGUGGGGACNN
4205
GUCCCCACUGACAGAGAAANN
4206


 


NM_005080_805-823
CAGCCAAGCUGGAAGCCAUNN
4207
AUGGCUUCCAGCUUGGCUGNN
4208


 


NM_005080_44-62
GAGCUAUGGUGGUGGUGGCNN
4209
GCCACCACCACCAUAGCUCNN
4210


 


NM_005080_45-63
AGCUAUGGUGGUGGUGGCANN
4211
UGCCACCACCACCAUAGCUNN
4212


 


NM_005080_868-886
UCUUAGAGAUACCCUCUGANN
4213
UCAGAGGGUAUCUCUAAGANN
4214


 


NM_005080_875-893
GAUACCCUCUGAGACAGAGNN
4215
CUCUGUCUCAGAGGGUAUCNN
4216


 


NM_005080_47-65
CUAUGGUGGUGGUGGCAGCNN
4217
GCUGCCACCACCACCAUAGNN
4218


 


NM_005080_879-897
CCCUCUGAGACAGAGAGCCNN
4219
GGCUCUCUGUCUCAGAGGGNN
4220


 


NM_005080_880-898
CCUCUGAGACAGAGAGCCANN
4221
UGGCUCUCUGUCUCAGAGGNN
4222


 


NM_005080_881-899
CUCUGAGACAGAGAGCCAANN
4223
UUGGCUCUCUGUCUCAGAGNN
4224


 


NM_005080_882-900
UCUGAGACAGAGAGCCAAGNN
4225
CUUGGCUCUCUGUCUCAGANN
4226


 


NM_005080_883-901
CUGAGACAGAGAGCCAAGCNN
4227
GCUUGGCUCUCUGUCUCAGNN
4228


 


NM_005080_49-67
AUGGUGGUGGUGGCAGCCGNN
4229
CGGCUGCCACCACCACCAUNN
4230


 


NM_005080_914-932
GAAAAUCGAGGAAGCACCUNN
4231
AGGUGCUUCCUCGAUUUUCNN
4232


 


NM_005080_915-933
AAAAUCGAGGAAGCACCUCNN
4233
GAGGUGCUUCCUCGAUUUUNN
4234


 


NM_005080_926-944
AGCACCUCUCAGCCCCUCANN
4235
UGAGGGGCUGAGAGGUGCUNN
4236


 


NM_005080_945-963
GAGAAUGAUCACCCUGAAUNN
4237
AUUCAGGGUGAUCAUUCUCNN
4238


 


NM_005080_958-976
CUGAAUUCAUUGUCUCAGUNN
4239
ACUGAGACAAUGAAUUCAGNN
4240


 


NM_005080_959-977
UGAAUUCAUUGUCUCAGUGNN
4241
CACUGAGACAAUGAAUUCANN
4242


 


NM_005080_962-980
AUUCAUUGUCUCAGUGAAGNN
4243
CUUCACUGAGACAAUGAAUNN
4244


 


NM_005080_975-993
GUGAAGGAAGAACCUGUAGNN
4245
CUACAGGUUCUUCCUUCACNN
4246


 


NM_005080_983-1001
AGAACCUGUAGAAGAUGACNN
4247
GUCAUCUUCUACAGGUUCUNN
4248


 


NM_005080_128-146
CCGCCGGAGCCCCGGCCGGNN
4249
CCGGCCGGGGCTCCGGCGGNN
4250


 


NM_005080_249-267
GAGCCCCGAGGAGAAGGCGNN
4251
CGCCTTCTCCTCGGGGCTCNN
4252


 


NM_005080_697-715
UCAAAUGCCCUUCCCCAGANN
4253
UCUGGGGAAGGGCAUUUGANN
4254


 


NM_005080_729-747
GAGGAGCUCCCAGAGGUCUNN
4255
AGACCUCUGGGAGCUCCUCNN
4256


 


NM_005080_776-794
CUCCCUUUCUCUGUCAGUGNN
4257
CACUGACAGAGAAAGGGAGNN
4258


 


NM_005080_803-821
AUCAGCCAAGCUGGAAGCCNN
4259
GGCUUCCAGCUUGGCUGAUNN
4260


 


NM_005080_254-272
CCGAGGAGAAGGCGCUGAGNN
4261
CUCAGCGCCUUCUCCUCGGNN
4262


 


NM_005080_383-401
UUUUGCUAGAAAAUCAGCUNN
4263
AGCUGAUUUUCUAGCAAAANN
4264


 


NM_005080_116-134
AGCCCGCCUCCGCCGCCGGNN
4265
CCGGCGGCGGAGGCGGGCUNN
4266


 


NM_005080_123-141
CUCCGCCGCCGGAGCCCCGNN
4267
CGGGGCUCCGGCGGCGGAGNN
4268


 


NM_005080_125-143
CCGCCGCCGGAGCCCCGGCNN
4269
GCCGGGGCTCCGGCGGCGGNN
4270


 


NM_005080_135-153
AGCCCCGGCCGGCCAGGCCNN
4271
GGCCTGGCCGGCCGGGGCTNN
4272


 


NM_005080_253-271
CCCGAGGAGAAGGCGCUGANN
4273
UCAGCGCCUUCUCCUCGGGNN
4274


 


NM_005080_274-292
AGGAAACUGAAAAACAGAGNN
4275
CUCUGUUUUUCAGUUUCCUNN
4276


 


NM_005080_655-673
UCCUGUUGGGCAUUCUGGANN
4277
UCCAGAAUGCCCAACAGGANN
4278


 


NM_005080_775-793
CCUCCCUUUCUCUGUCAGUNN
4279
ACUGACAGAGAAAGGGAGGNN
4280


 


NM_005080_46-64
GCUAUGGUGGUGGUGGCAGNN
4281
CUGCCACCACCACCAUAGCNN
4282


 


NM_005080_1456-1474
GUACUUUUAUCUUAAAAGGNN
4283
CCUUUUAAGAUAAAAGUACNN
4284


 


NM_005080_1545-1563
UUAUGAAUGGUUCUUUAUCNN
4285
GAUAAAGAACCAUUCAUAANN
4286


 


NM_005080_1558-1576
UUUAUCAUUUCUCUUCCCCNN
4287
GGGGAAGAGAAAUGAUAAANN
4288


 


NM_005080_121-139
GCCUCCGCCGCCGGAGCCCNN
4289
GGGCUCCGGCGGCGGAGGCNN
4290


 


NM_005080_122-140
CCUCCGCCGCCGGAGCCCCNN
4291
GGGGCUCCGGCGGCGGAGGNN
4292


 


NM_005080_247-265
CUGAGCCCCGAGGAGAAGGNN
4293
CCUUCUCCUCGGGGCUCAGNN
4294


 


NM_005080_275-293
GGAAACUGAAAAACAGAGUNN
4295
ACUCUGUUUUUCAGUUUCCNN
4296


 


NM_005080_276-294
GAAACUGAAAAACAGAGUANN
4297
UACUCUGUUUUUCAGUUUCNN
4298


 


NM_005080_358-376
GAUUUAGAAGAAGAGAACCNN
4299
GGUUCUCUUCUUCUAAAUCNN
4300


 


NM_005080_387-405
GCUAGAAAAUCAGCUUUUANN
4301
UAAAAGCUGAUUUUCUAGCNN
4302


 


NM_005080_628-646
UUGACUCUUCAGAUUCAGANN
4303
UCUGAAUCUGAAGAGUCAANN
4304


 


NM_005080_656-674
CCUGUUGGGCAUUCUGGACNN
4305
GUCCAGAAUGCCCAACAGGNN
4306


 


NM_005080_719-737
UGCCAGCCUGGAGGAGCUCNN
4307
GAGCUCCUCCAGGCUGGCANN
4308


 


NM_005080_720-738
GCCAGCCUGGAGGAGCUCCNN
4309
GGAGCUCCUCCAGGCUGGCNN
4310


 


NM_005080_721-739
CCAGCCUGGAGGAGCUCCCNN
4311
GGGAGCUCCUCCAGGCUGGNN
4312


 


NM_005080_782-800
UUCUCUGUCAGUGGGGACGNN
4313
CGUCCCCACUGACAGAGAANN
4314


 


NM_005080_867-885
GUCUUAGAGAUACCCUCUGNN
4315
CAGAGGGUAUCUCUAAGACNN
4316


 


NM_005080_48-66
UAUGGUGGUGGUGGCAGCCNN
4317
GGCUGCCACCACCACCAUANN
4318


 


NM_005080_963-981
UUCAUUGUCUCAGUGAAGGNN
4319
CCUUCACUGAGACAAUGAANN
4320





Gene XBP1


reference transcript NM_005080 (human XBP 1 mRNA, FIG. 2)


Notes


19mers found in both human and rhesus













TABLE 10







XBP-1 Human/Rhesus siRNA analysis









off target









Oligo Name/
human












Location of Target
Anti-
Anti-

rhesus















sequence from
sense
sense
Sense
Sense
Antisense
Antisense
Sense
Sense


5′ to 3′
Count
Score
Count
Score
Count
Score
Count
Score


















NM_005080_390-408
1
4
6
3
2
3.4
2
2


NM_005080_1184-1202
2
4
3
2
1
3.2
1
2


NM_005080_1494-1512
1
4
3
3.2
12
3
2
3


NM_005080_1463-1481
6
3.2
5
2
4
3.2
1
2


NM_005080_610-628
3
3.2
6
3
6
3.2
2
2


NM_005080_823-841
4
3.2
1
2
1
3.2
4
2


NM_005080_1507-1525
3
3.2
2
2
3
3
2
2


NM_005080_827-845
3
3.2
1
2.2
1
3
1
2


NM_005080_1503-1521
5
3.2
2
2.8
1
2
1
1


NM_005080_829-847
12
3.2
1
3
1
2
2
3


NM_005080_1783-1801
12
3.2
3
2.2
2
1
1
2.2


NM_005080_1183-1201
2
3
4
2
1
3.2
1
2


NM_005080_1501-1519
4
3
2
2.8
2
3.2
1
2.2


NM_005080_1504-1522
2
3
1
2
8
3.2
1
1


NM_005080_734-752
6
3
1
2
1
3.2
3
2


NM_005080_893-911
9
3
1
3
13
3.2
5
3


NM_005080_1064-1082
6
3
5
3
1
3
3
2.2


NM_005080_1066-1084
1
3
1
2
2
3
1
2.2


NM_005080_1136-1154
7
3
1
0
5
3
1
2


NM_005080_1137-1155
5
3
1
2
9
3
1
0


NM_005080_1182-1200
1
3
1
2.8
1
3
2
2


NM_005080_1186-1204
3
3
2
2
2
3
1
1.2


NM_005080_1189-1207
1
3
3
2
5
3
3
2


NM_005080_1224-1242
6
3
11
2
3
3
21
2


NM_005080_1229-1247
4
3
6
2
1
3
3
2


NM_005080_1235-1253
7
3
3
3
5
3
2
2.2


NM_005080_1236-1254
8
3
2
3
7
3
1
3


NM_005080_1438-1456
10
3
2
2.2
9
3
2
2.2


NM_005080_1441-1459
3
3
3
2
11
3
4
2


NM_005080_1442-1460
6
3
9
3.2
9
3
1
2


NM_005080_1493-1511
1
3
2
3
1
3
1
2


NM_005080_1502-1520
3
3
2
2
1
3
1
2


NM_005080_1506-1524
4
3
6
2
6
3
6
2


NM_005080_1594-1612
2
3
6
2
2
3
3
2


NM_005080_1790-1808
12
3
1
2
9
3
4
3


NM_005080_304-322
3
3
9
3
1
3
16
3


NM_005080_305-323
1
3
1
2
3
3
3
2.2


NM_005080_395-413
3
3
9
2
3
3
2
2


NM_005080_609-627
3
3
3
3
7
3
1
2


NM_005080_611-629
2
3
2
2
1
3
2
2


NM_005080_617-635
3
3
1
3
4
3
1
2.2


NM_005080_621-639
1
3
1
2.2
1
3
1
2.2


NM_005080_641-659
1
3
3
2
2
3
4
2


NM_005080_648-666
5
3
2
2
4
3
1
2


NM_005080_651-669
4
3
1
2
5
3
10
3


NM_005080_735-753
1
3
1
2
4
3
2
2


NM_005080_753-771
3
3
2
2
10
3
4
2


NM_005080_794-812
3
3
2
2
6
3
1
2


NM_005080_826-844
1
3
1
2.2
4
3
13
3


NM_005080_836-854
2
3
1
3
8
3
2
3


NM_005080_840-858
2
3
1
2.2
3
3
7
3


NM_005080_841-859
8
3
1
1
6
3
1
2


NM_005080_847-865
10
3
1
2
5
3
1
2


NM_005080_894-912
2
3
4
3
1
3
1
3


NM_005080_895-913
2
3
1
3
8
3
2
2.2


NM_005080_896-914
3
3
2
2
7
3
2
2


NM_005080_899-917
3
3
1
2
7
3
6
2


NM_005080_908-926
2
3
2
2
1
3
2
3.2


NM_005080_917-935
4
3
6
3.2
8
3
1
3.2


NM_005080_937-955
2
3
2
2
9
3
1
2


NM_005080_950-968
7
3
1
2
12
3
1
2.8


NM_005080_1185-1203
1
3
1
2
1
2.8
1
2


NM_005080_1187-1205
2
3
1
2.2
2
2.8
2
2.2


NM_005080_1153-1171
6
3
2
2
1
2.4
3
2


NM_005080_1787-1805
1
3
1
2
1
2.4
1
2


NM_005080_606-624
4
3
2
2.2
1
2.4
1
1


NM_005080_1019-1037
12
3
1
1
1
2.2
2
1


NM_005080_1072-1090
14
3
8
2
2
2.2
9
2


NM_005080_1228-1246
1
3
6
2
1
2.2
4
2


NM_005080_1461-1479
12
3
2
1
1
2.2
1
2.2


NM_005080_1495-1513
2
3
4
3
1
2.2
1
3


NM_005080_1496-1514
2
3
2
2.8
1
2.2
1
2.8


NM_005080_1500-1518
1
3
1
1.2
1
2.2
1
2.2


NM_005080_1644-1662
9
3
7
2
1
2.2
3
2


NM_005080_1708-1726
3
3
1
1
1
2.2
1
2


NM_005080_302-320
1
3
5
3
1
2.2
1
2


NM_005080_607-625
2
3
1
2
1
2.2
3
2.2


NM_005080_824-842
4
3
1
2
1
2.2
4
2


NM_005080_953-971
8
3
4
2
2
2.2
5
2


NM_005080_1011-1029
2
3
4
2
1
2
1
2.4


NM_005080_1230-1248
2
3
1
2
3
2
2
2.2


NM_005080_1231-1249
4
3
1
2
1
2
4
3


NM_005080_1290-1308
7
3
1
2
1
2
1
2


NM_005080_1331-1349
4
3
5
2
2
2
11
2


NM_005080_1460-1478
16
3
15
3
2
2
1
2.8


NM_005080_1670-1688
1
3
24
3
2
2
1
2


NM_005080_1671-1689
2
3
1
2.2
1
2
2
2.2


NM_005080_1735-1753
21
3
3
2
2
2
4
2


NM_005080_1744-1762
1
3
1
2
1
2
2
2


NM_005080_1796-1814
12
3
2
0
1
2
1
0


NM_005080_343-361
7
3
7
2
1
2
1
2


NM_005080_374-392
1
3
3
2
1
2
2
2


NM_005080_375-393
6
3
1
1
3
2
7
1


NM_005080_608-626
1
3
1
2
2
2
1
2.4


NM_005080_652-670
7
3
1
2
1
2
1
2


NM_005080_686-704
9
3
1
2
9
2
1
2


NM_005080_909-927
3
3
2
2
2
2
1
2


NM_005080_951-969
3
3
1
2.8
6
2
4
2


NM_005080_952-970
8
3
3
2
1
2
5
2


NM_005080_825-843
3
3
2
2.2
1
1.2
6
2.2


NM_005080_1194-1212
4
3
1
2.2
2
1
2
3


NM_005080_831-849
3
3
1
2
1
1
3
3.2


NM_005080_835-853
1
3
1
3
1
1
2
3


NM_005080_869-887
2
3
1
2.2
1
1
3
3.2


NM_005080_1246-1264
3
2.8
1
2.2
1
2.8
2
2.2


NM_005080_1453-1471
2
2.8
8
2
3
2.8
4
2


NM_005080_1512-1530
5
2.8
10
2.2
2
2.8
11
3


NM_005080_1546-1564
1
2.8
1
2
1
2.8
3
2


NM_005080_1789-1807
1
2.8
1
3
1
2.8
1
3


NM_005080_325-343
1
2.8
3
3
1
2.8
1
3


NM_005080_393-411
2
2.8
4
3
1
2.8
8
3


NM_005080_788-806
1
2.8
2
2
1
2.8
4
2


NM_005080_821-839
1
2.8
11
3
1
2.8
1
2


NM_005080_1514-1532
6
2.8
1
1
1
2.2
9
3


NM_005080_1797-1815
1
2.8
2
1
11
2.2
1
1


NM_005080_833-851
1
2.8
3
4
2
2.2
4
4


NM_005080_1509-1527
1
2.8
1
2
2
2
1
2


NM_005080_1802-1820
1
2.8
1
1.2
1
1.2
1
1.2


NM_005080_391-409
1
2.4
1
2
1
3
1
2


NM_005080_843-861
1
2.4
1
1
4
2.4
6
3


NM_005080_1508-1526
1
2.4
7
3
1
2
1
2


NM_005080_1754-1772
1
2.4
4
2
1
2
1
2


NM_005080_430-448
4
2.4
1
2
1
2
3
2


NM_005080_437-455
1
2.4
5
2.2
1
2
4
2.2


NM_005080_1465-1483
1
2.2
2
2.2
2
3.2
7
3


NM_005080_1742-1760
1
2.2
2
2
13
3.2
5
3


NM_005080_438-456
1
2.2
1
1
12
3.2
1
2.2


NM_005080_1060-1078
1
2.2
2
2
12
3
5
2


NM_005080_1067-1085
1
2.2
2
2
6
3
1
3


NM_005080_1197-1215
2
2.2
1
3
2
3
1
3


NM_005080_1198-1216
1
2.2
3
3
9
3
2
3


NM_005080_1424-1442
1
2.2
1
2.4
7
3
1
2.4


NM_005080_1464-1482
2
2.2
4
2
1
3
6
2


NM_005080_616-634
1
2.2
1
3
4
3
2
3


NM_005080_757-775
1
2.2
1
2
12
3
1
2.2


NM_005080_785-803
2
2.2
1
1.2
3
3
1
1


NM_005080_819-837
1
2.2
2
1
4
3
12
2


NM_005080_842-860
1
2.2
1
1
2
3
6
3


NM_005080_845-863
1
2.2
4
3
1
3
11
3


NM_005080_1013-1031
1
2.2
1
1
1
2.8
2
1


NM_005080_1431-1449
6
2.2
1
1.2
1
2.8
1
1.2


NM_005080_1673-1691
3
2.2
3
2.2
1
2.8
5
2.2


NM_005080_283-301
2
2.2
2
2
5
2.8
1
2.2


NM_005080_838-856
1
2.2
1
2
1
2.8
1
2


NM_005080_279-297
2
2.2
7
2
1
2.4
2
1


NM_005080_633-651
1
2.2
2
0
1
2.4
9
2


NM_005080_1024-1042
2
2.2
9
2
1
2.2
4
2


NM_005080_1147-1165
2
2.2
4
1
1
2.2
1
1


NM_005080_1154-1172
1
2.2
4
2
4
2.2
5
2


NM_005080_1188-1206
2
2.2
1
1
4
2.2
3
1


NM_005080_1192-1210
2
2.2
4
2
1
2.2
2
2


NM_005080_1195-1213
2
2.2
1
2.2
3
2.2
2
3


NM_005080_1238-1256
2
2.2
2
3
2
2.2
1
3


NM_005080_1548-1566
1
2.2
1
2.2
1
2.2
2
2.2


NM_005080_1549-1567
3
2.2
1
2
9
2.2
3
2


NM_005080_1677-1695
1
2.2
1
2.8
2
2.2
2
2


NM_005080_1707-1725
1
2.2
4
2
1
2.2
2
2


NM_005080_1713-1731
1
2.2
1
1
3
2.2
2
2


NM_005080_1786-1804
6
2.2
1
2
6
2.2
3
2


NM_005080_210-228
1
2.2
10
2
5
2.2
12
2


NM_005080_278-296
1
2.2
6
1
2
2.2
14
1


NM_005080_284-302
4
2.2
1
2
8
2.2
9
2


NM_005080_290-308
2
2.2
1
2
3
2.2
1
2


NM_005080_342-360
3
2.2
1
2
4
2.2
5
3


NM_005080_431-449
8
2.2
1
1
4
2.2
1
1


NM_005080_576-594
1
2.2
3
2
7
2.2
1
2


NM_005080_602-620
3
2.2
2
2
2
2.2
4
2


NM_005080_618-636
2
2.2
1
3
1
2.2
1
3


NM_005080_678-696
1
2.2
1
1
6
2.2
1
2


NM_005080_796-814
4
2.2
1
3
1
2.2
2
2.2


NM_005080_940-958
1
2.2
9
3
3
2.2
1
2


NM_005080_954-972
5
2.2
9
2
3
2.2
1
1


NM_005080_977-995
2
2.2
1
2
1
2.2
1
1.2


NM_005080_1018-1036
1
2.2
1
1
2
2
1
1


NM_005080_1026-1044
2
2.2
8
2
1
2
2
2


NM_005080_1138-1156
1
2.2
1
2
1
2
1
0


NM_005080_1141-1159
1
2.2
3
2
1
2
8
2


NM_005080_1142-1160
2
2.2
2
2.2
2
2
1
2.8


NM_005080_1155-1173
1
2.2
3
2
2
2
3
2


NM_005080_1158-1176
1
2.2
1
2.2
1
2
1
2


NM_005080_1193-1211
2
2.2
1
2
2
2
1
2


NM_005080_1196-1214
2
2.2
2
3
5
2
2
2.8


NM_005080_1219-1237
2
2.2
3
2
3
2
7
2.2


NM_005080_107-125
3
2.2
1
0
1
2
2
0


NM_005080_108-126
4
2.2
1
0
1
2
2
0


NM_005080_1505-1523
1
2.2
1
2
5
2
1
2


NM_005080_1567-1585
4
2.2
1
1.2
1
2
1
2


NM_005080_1672-1690
2
2.2
2
2.2
1
2
6
3


NM_005080_1678-1696
4
2.2
1
2.8
1
2
2
2.8


NM_005080_1778-1796
4
2.2
7
2
2
2
9
2


NM_005080_1779-1797
1
2.2
9
2
4
2
1
1


NM_005080_280-298
5
2.2
7
2
1
2
2
1


NM_005080_282-300
2
2.2
2
2
1
2
2
2


NM_005080_288-306
1
2.2
1
1
2
2
1
1


NM_005080_291-309
3
2.2
2
2
5
2
1
2


NM_005080_347-365
3
2.2
2
2.4
1
2
4
3


NM_005080_397-415
4
2.2
20
3
1
2
1
2.2


NM_005080_398-416
1
2.2
1
2.2
2
2
1
2.2


NM_005080_399-417
2
2.2
1
2
2
2
3
2.2


NM_005080_512-530
2
2.2
1
2
1
2
9
2


NM_005080_517-535
2
2.2
1
0
1
2
1
0


NM_005080_596-614
1
2.2
5
2
3
2
4
2


NM_005080_598-616
1
2.2
4
2
3
2
7
2


NM_005080_601-619
2
2.2
8
3
1
2
1
2.2


NM_005080_605-623
2
2.2
5
2
5
2
9
2


NM_005080_661-679
2
2.2
8
2
1
2
1
1


NM_005080_688-706
1
2.2
2
0
2
2
2
1


NM_005080_691-709
2
2.2
8
2
2
2
15
2


NM_005080_828-846
1
2.2
3
3.2
1
2
1
2


NM_005080_830-848
8
2.2
1
2.8
2
2
2
3


NM_005080_834-852
2
2.2
6
3
3
2
3
3


NM_005080_846-864
2
2.2
1
2
1
2
1
2


NM_005080_870-888
4
2.2
1
2.2
1
2
7
3.2


NM_005080_891-909
2
2.2
6
2
2
2
5
2


NM_005080_900-918
2
2.2
1
2
2
2
1
2.2


NM_005080_911-929
3
2.2
2
3
1
2
1
2.2


NM_005080_912-930
3
2.2
7
3.2
1
2
1
2.2


NM_005080_979-997
5
2.2
2
2
1
2
5
2.2


NM_005080_1366-1384
5
2.2
2
1.2
1
1.2
1
1.2


NM_005080_150-168
4
2.2
8
1
1
1.2
1
2


NM_005080_1437-1455
1
2.2
2
2.2
1
1
1
2


NM_005080_482-500
5
2.2
4
2
6
1
4
2


NM_005080_580-598
1
2.2
1
2
1
1
3
2


NM_005080_613-631
1
2
6
3
2
4.2
2
3


NM_005080_1065-1083
4
2
1
3.4
3
4
3
2.2


NM_005080_614-632
1
2
1
2
8
3.2
1
2


NM_005080_640-658
1
2
3
2
3
3.2
1
2


NM_005080_1014-1032
2
2
1
2
16
3
2
2


NM_005080_1015-1033
3
2
2
1.2
1
3
1
2.2


NM_005080_1146-1164
1
2
3
2
28
3
2
2


NM_005080_1232-1250
1
2
1
2
5
3
1
3


NM_005080_1234-1252
1
2
1
2
1
3
1
2.2


NM_005080_1237-1255
1
2
4
3
10
3
5
3


NM_005080_1443-1461
1
2
2
2
9
3
6
2.2


NM_005080_1462-1480
2
2
2
2
4
3
3
3


NM_005080_1510-1528
1
2
1
2
4
3
1
2


NM_005080_1591-1609
3
2
1
1
4
3
2
1.2


NM_005080_1615-1633
1
2
1
2
2
3
8
2


NM_005080_1716-1734
4
2
6
3
9
3
1
1


NM_005080_1718-1736
1
2
7
3
20
3
1
2.2


NM_005080_1725-1743
1
2
1
2.2
16
3
2
2


NM_005080_1748-1766
1
2
1
4
7
3
2
3.2


NM_005080_1780-1798
2
2
4
2
5
3
9
2


NM_005080_1794-1812
2
2
1
2
6
3
2
2


NM_005080_156-174
2
2
4
2
21
3
2
1


NM_005080_299-317
1
2
2
2
10
3
2
2


NM_005080_344-362
1
2
5
2.2
7
3
1
2.2


NM_005080_371-389
3
2
6
3
20
3
1
2.2


NM_005080_373-391
1
2
3
2
5
3
1
2


NM_005080_524-542
4
2
2
2
3
3
4
3


NM_005080_525-543
3
2
6
2
6
3
3
2


NM_005080_612-630
1
2
3
2
1
3
8
3


NM_005080_615-633
1
2
1
2
1
3
1
2


NM_005080_645-663
1
2
1
1
6
3
3
1


NM_005080_792-810
1
2
2
2.2
10
3
2
2


NM_005080_905-923
2
2
1
2.2
1
3
4
3


NM_005080_976-994
1
2
4
2
4
3
4
2


NM_005080_1244-1262
3
2
7
2
1
2.8
5
2


NM_005080_1791-1809
5
2
4
2
1
2.8
2
2.8


NM_005080_755-773
5
2
4
2
1
2.8
4
2


NM_005080_799-817
3
2
2
2
1
2.8
16
2


NM_005080_832-850
3
2
3
3
1
2.8
4
3


NM_005080_839-857
1
2
2
2.2
1
2.8
3
2


NM_005080_100-118
3
2
6
2
1
2.4
2
1


NM_005080_281-299
7
2
3
2
1
2.4
10
2


NM_005080_822-840
1
2
5
2.2
1
2.4
1
2.2


NM_005080_1152-1170
1
2
3
2
3
2.2
2
2.2


NM_005080_1191-1209
3
2
4
1
1
2.2
3
2


NM_005080_1225-1243
2
2
5
2
2
2.2
1
1


NM_005080_1227-1245
3
2
1
1
1
2.2
1
1


NM_005080_1239-1257
2
2
1
2
5
2.2
1
2


NM_005080_1430-1448
2
2
2
2
4
2.2
2
2.2


NM_005080_1499-1517
1
2
4
2.2
4
2.2
10
2.2


NM_005080_1553-1571
1
2
2
2.2
2
2.2
8
2


NM_005080_1585-1603
1
2
1
2
5
2.2
1
1


NM_005080_1592-1610
3
2
2
2
2
2.2
3
2


NM_005080_1743-1761
1
2
2
2
1
2.2
4
2


NM_005080_154-172
1
2
1
2.2
2
2.2
5
3


NM_005080_193-211
1
2
1
1
10
2.2
1
1


NM_005080_199-217
10
2
3
2
5
2.2
4
3


NM_005080_292-310
5
2
3
2
1
2.2
2
2


NM_005080_341-359
1
2
1
2
2
2.2
1
2.2


NM_005080_377-395
4
2
1
1
5
2.2
7
2


NM_005080_519-537
1
2
3
1
12
2.2
4
2


NM_005080_522-540
2
2
8
2
1
2.2
5
2


NM_005080_577-595
2
2
6
2
8
2.2
3
2


NM_005080_599-617
4
2
5
2
7
2.2
5
2


NM_005080_754-772
2
2
5
3
1
2.2
1
2


NM_005080_888-906
1
2
1
2.2
4
2.2
1
2


NM_005080_939-957
1
2
1
2.8
2
2.2
1
2


NM_005080_964-982
1
2
1
1
1
2.2
4
2


NM_005080_1012-1030
6
2
4
3
4
2
3
3.2


NM_005080_1016-1034
4
2
2
1.2
1
2
10
3


NM_005080_1020-1038
7
2
2
2
2
2
4
2


NM_005080_1025-1043
2
2
9
2
3
2
2
2.2


NM_005080_1027-1045
1
2
1
2
1
2
1
2


NM_005080_1028-1046
1
2
5
2
3
2
8
2


NM_005080_1030-1048
1
2
2
2
1
2
1
2


NM_005080_1031-1049
16
2
2
2
4
2
1
2


NM_005080_1032-1050
3
2
21
3
2
2
4
2.8


NM_005080_1033-1051
11
2
1
2
7
2
2
2.2


NM_005080_1056-1074
1
2
6
2
2
2
13
2


NM_005080_1057-1075
3
2
2
2.2
2
2
1
2


NM_005080_1058-1076
4
2
2
1
5
2
2
1


NM_005080_1059-1077
5
2
2
2
13
2
3
2


NM_005080_1061-1079
4
2
3
2
16
2
1
1.2


NM_005080_1063-1081
11
2
3
2
1
2
4
2


NM_005080_1069-1087
2
2
10
3
1
2
1
2


NM_005080_1071-1089
2
2
2
3
1
2
2
3


NM_005080_1073-1091
4
2
12
3
4
2
3
2


NM_005080_1075-1093
6
2
2
2.2
6
2
3
2.2


NM_005080_1076-1094
7
2
4
3
7
2
1
3


NM_005080_1078-1096
4
2
3
2
3
2
12
2


NM_005080_1139-1157
1
2
2
2
2
2
1
0


NM_005080_1140-1158
4
2
3
2
2
2
1
2


NM_005080_1143-1161
2
2
2
2.2
3
2
1
3


NM_005080_1144-1162
1
2
2
2
1
2
3
2


NM_005080_1145-1163
1
2
1
2.2
1
2
2
2


NM_005080_1148-1166
2
2
4
2
1
2
2
2


NM_005080_1156-1174
12
2
1
2.2
6
2
1
2


NM_005080_1157-1175
1
2
2
2
1
2
1
1


NM_005080_1159-1177
1
2
1
2
4
2
3
2


NM_005080_1160-1178
1
2
1
1.2
3
2
2
2


NM_005080_1190-1208
1
2
2
2.2
5
2
2
2


NM_005080_1218-1236
2
2
1
2
16
2
4
2.2


NM_005080_1220-1238
5
2
1
1
4
2
1
1


NM_005080_1221-1239
5
2
1
1
10
2
1
1


NM_005080_1233-1251
1
2
3
3
1
2
1
3


NM_005080_1240-1258
6
2
1
2
4
2
1
2


NM_005080_1241-1259
13
2
2
2
13
2
1
2


NM_005080_1242-1260
3
2
3
2
4
2
3
2


NM_005080_1243-1261
1
2
2
2
2
2
1
2.8


NM_005080_1282-1300
12
2
5
2
8
2
2
1


NM_005080_1287-1305
6
2
3
2
10
2
1
2


NM_005080_1289-1307
2
2
21
3
1
2
4
2.2


NM_005080_1310-1328
1
2
3
2
3
2
1
2.2


NM_005080_1330-1348
6
2
2
2
4
2
7
2


NM_005080_1332-1350
2
2
8
3
1
2
12
3


NM_005080_1333-1351
2
2
1
2
1
2
1
2


NM_005080_1369-1387
4
2
3
2
4
2
4
2


NM_005080_1370-1388
1
2
7
2
1
2
5
2


NM_005080_1371-1389
4
2
2
2
8
2
1
1


NM_005080_101-119
1
2
2
2
2
2
2
1


NM_005080_1418-1436
2
2
1
1
3
2
11
2


NM_005080_1419-1437
3
2
3
2
9
2
8
2.2


NM_005080_1422-1440
6
2
11
3
1
2
6
3


NM_005080_102-120
3
2
1
2
5
2
8
2


NM_005080_1423-1441
6
2
4
3
4
2
6
3


NM_005080_1425-1443
1
2
2
2
1
2
1
2


NM_005080_1427-1445
5
2
1
2
11
2
1
2


NM_005080_1428-1446
6
2
1
2.2
7
2
1
2


NM_005080_1429-1447
1
2
5
3
1
2
3
3


NM_005080_1432-1450
3
2
3
2
2
2
1
2.8


NM_005080_1433-1451
3
2
4
2
4
2
6
2


NM_005080_1435-1453
1
2
1
2
2
2
4
2


NM_005080_1439-1457
1
2
1
2
2
2
4
2


NM_005080_104-122
1
2
5
3
4
2
7
2


NM_005080_1444-1462
3
2
4
2
1
2
2
2


NM_005080_1445-1463
10
2
3
2
17
2
3
2


NM_005080_1446-1464
8
2
2
2
18
2
1
1


NM_005080_1447-1465
1
2
2
2.2
3
2
3
2


NM_005080_1448-1466
2
2
1
2
2
2
5
2


NM_005080_1451-1469
2
2
1
1
1
2
1
1


NM_005080_1454-1472
2
2
4
2
4
2
4
2


NM_005080_1458-1476
6
2
3
2
4
2
10
2


NM_005080_1459-1477
1
2
3
2
3
2
1
1.2


NM_005080_106-124
2
2
1
1.2
1
2
9
2.2


NM_005080_1466-1484
1
2
2
2
2
2
2
2


NM_005080_1486-1504
2
2
3
2
2
2
1
0


NM_005080_1487-1505
2
2
3
2
2
2
1
1


NM_005080_1489-1507
4
2
5
2
1
2
1
1


NM_005080_1490-1508
3
2
2
2
6
2
4
2


NM_005080_1491-1509
3
2
2
2
2
2
2
2.2


NM_005080_109-127
5
2
1
1
4
2
2
1


NM_005080_1497-1515
1
2
2
3.2
1
2
2
3


NM_005080_1498-1516
2
2
2
2.2
4
2
1
2


NM_005080_110-128
3
2
2
1
4
2
1
1


NM_005080_1511-1529
2
2
10
2
3
2
8
2


NM_005080_1513-1531
5
2
1
1
3
2
1
2.8


NM_005080_1516-1534
1
2
1
2
1
2
2
2.2


NM_005080_1517-1535
2
2
1
1
2
2
2
1


NM_005080_1518-1536
4
2
2
2
2
2
3
2


NM_005080_1547-1565
2
2
1
2
4
2
2
2


NM_005080_1550-1568
5
2
2
2
4
2
5
2


NM_005080_1551-1569
1
2
2
1.2
1
2
1
1.2


NM_005080_1552-1570
4
2
1
1.2
4
2
1
1.2


NM_005080_1554-1572
3
2
1
1
7
2
1
1.2


NM_005080_1559-1577
5
2
1
2
7
2
1
2


NM_005080_1560-1578
5
2
1
1
5
2
1
1


NM_005080_1563-1581
5
2
1
1.2
18
2
1
1


NM_005080_1565-1583
7
2
2
1.2
11
2
3
1.2


NM_005080_1566-1584
6
2
1
1.2
9
2
9
1.2


NM_005080_1570-1588
2
2
1
2
5
2
1
2.2


NM_005080_1573-1591
2
2
9
2
1
2
5
2


NM_005080_1578-1596
2
2
1
2
5
2
3
2


NM_005080_1579-1597
3
2
4
2
4
2
3
2


NM_005080_1580-1598
3
2
2
2
4
2
5
2


NM_005080_1581-1599
3
2
5
2
2
2
5
2


NM_005080_1583-1601
4
2
4
2
4
2
1
1


NM_005080_1584-1602
7
2
7
2
9
2
1
0


NM_005080_1586-1604
4
2
1
1
3
2
2
1


NM_005080_1589-1607
1
2
3
2
1
2
1
2


NM_005080_1590-1608
4
2
9
3
4
2
1
2


NM_005080_1595-1613
1
2
10
2
1
2
6
2


NM_005080_1616-1634
3
2
1
2
1
2
2
2


NM_005080_1617-1635
2
2
1
1
1
2
3
1


NM_005080_1643-1661
2
2
5
2
3
2
1
1.2


NM_005080_1645-1663
1
2
2
1
1
2
1
1


NM_005080_1646-1664
3
2
5
1
3
2
1
1


NM_005080_1647-1665
4
2
7
2
1
2
4
2


NM_005080_1648-1666
7
2
4
2
5
2
10
2


NM_005080_1649-1667
2
2
9
2
5
2
14
2


NM_005080_1679-1697
5
2
2
2.2
5
2
2
2.2


NM_005080_1680-1698
2
2
1
2.2
3
2
1
2.2


NM_005080_1681-1699
7
2
1
2
7
2
1
3


NM_005080_1682-1700
12
2
1
2
19
2
1
2.2


NM_005080_1683-1701
6
2
15
3
7
2
3
3


NM_005080_1684-1702
5
2
3
3
6
2
1
3


NM_005080_1687-1705
4
2
4
1
2
2
1
1


NM_005080_1709-1727
1
2
6
2
1
2
5
2


NM_005080_1710-1728
3
2
6
2
2
2
5
2


NM_005080_1711-1729
1
2
1
1
2
2
1
1.2


NM_005080_1712-1730
10
2
1
2
10
2
1
2.2


NM_005080_1714-1732
1
2
1
2
1
2
2
1


NM_005080_1715-1733
2
2
1
2
3
2
1
1


NM_005080_1717-1735
4
2
4
3
2
2
1
2.2


NM_005080_1719-1737
7
2
1
2
13
2
2
2


NM_005080_1721-1739
1
2
8
3
1
2
5
3


NM_005080_1722-1740
4
2
10
3
2
2
6
3


NM_005080_1723-1741
1
2
1
2
3
2
4
2.2


NM_005080_1726-1744
2
2
1
2.8
11
2
1
2.2


NM_005080_1727-1745
3
2
1
2
10
2
17
3


NM_005080_1728-1746
10
2
2
2
3
2
1
2


NM_005080_1729-1747
7
2
1
1
4
2
3
1


NM_005080_1736-1754
10
2
1
2
2
2
4
2


NM_005080_1739-1757
1
2
8
2
1
2
8
2


NM_005080_1746-1764
2
2
4
2.2
1
2
1
2


NM_005080_1747-1765
3
2
3
3
1
2
1
2.2


NM_005080_1749-1767
3
2
1
2.2
3
2
2
3


NM_005080_1750-1768
6
2
1
2
13
2
2
2


NM_005080_1751-1769
5
2
3
2
14
2
2
2


NM_005080_1752-1770
3
2
6
2
1
2
1
2


NM_005080_1753-1771
1
2
7
2
3
2
1
2


NM_005080_1755-1773
7
2
2
2
1
2
1
2


NM_005080_1758-1776
7
2
7
2
12
2
3
2


NM_005080_1781-1799
1
2
1
1.2
1
2
7
2


NM_005080_1782-1800
1
2
1
2
3
2
2
2


NM_005080_1784-1802
2
2
3
3
1
2
1
2


NM_005080_1785-1803
4
2
1
2.2
2
2
1
2.2


NM_005080_1788-1806
1
2
3
3
7
2
3
2.2


NM_005080_1792-1810
2
2
1
2.8
1
2
2
2.8


NM_005080_1793-1811
3
2
2
2
1
2
1
2.8


NM_005080_1795-1813
5
2
1
2.4
1
2
2
2


NM_005080_1798-1816
1
2
7
2
1
2
5
2


NM_005080_1799-1817
1
2
4
2
1
2
5
2


NM_005080_1800-1818
5
2
3
2
4
2
1
2


NM_005080_1801-1819
2
2
3
2.2
4
2
2
1


NM_005080_146-164
4
2
2
1
1
2
1
1


NM_005080_147-165
2
2
2
1
1
2
23
2


NM_005080_148-166
1
2
3
2
1
2
4
2


NM_005080_149-167
1
2
1
1.2
2
2
1
1.2


NM_005080_155-173
5
2
3
2
2
2
3
1


NM_005080_157-175
7
2
7
2
5
2
11
2


NM_005080_158-176
4
2
7
2
6
2
1
1


NM_005080_159-177
4
2
5
2.2
3
2
1
1.2


NM_005080_188-206
4
2
1
1
8
2
2
1


NM_005080_189-207
1
2
1
1
2
2
3
1


NM_005080_195-213
4
2
2
1
5
2
6
2


NM_005080_196-214
4
2
2
1
2
2
2
2.2


NM_005080_197-215
2
2
3
2
1
2
1
2.2


NM_005080_198-216
4
2
1
2
4
2
2
2


NM_005080_205-223
5
2
6
1
6
2
1
0


NM_005080_206-224
7
2
8
1
1
2
10
1


NM_005080_207-225
5
2
3
1
4
2
3
1


NM_005080_211-229
2
2
15
2
2
2
3
2


NM_005080_250-268
16
2
8
2
6
2
1
0


NM_005080_256-274
11
2
1
0
7
2
2
0


NM_005080_263-281
6
2
4
2.2
4
2
2
1


NM_005080_264-282
5
2
1
2.2
4
2
2
2


NM_005080_285-303
2
2
3
3
3
2
14
3


NM_005080_286-304
8
2
1
2
9
2
2
2


NM_005080_287-305
8
2
1
0
5
2
1
0


NM_005080_294-312
5
2
2
2
1
2
1
2


NM_005080_295-313
1
2
1
0
1
2
3
2


NM_005080_296-314
1
2
2
1.2
1
2
2
2.2


NM_005080_298-316
1
2
1
2.2
4
2
3
2


NM_005080_303-321
1
2
1
2
1
2
1
2


NM_005080_332-350
8
2
1
2
11
2
1
2


NM_005080_339-357
3
2
1
1
1
2
1
1


NM_005080_340-358
3
2
2
2
2
2
1
2


NM_005080_345-363
1
2
5
2.2
6
2
1
2.2


NM_005080_346-364
2
2
5
3
1
2
1
3


NM_005080_348-366
1
2
3
2
1
2
2
2


NM_005080_349-367
4
2
5
2
1
2
8
2


NM_005080_352-370
3
2
3
2.2
6
2
3
2.2


NM_005080_353-371
3
2
1
2.2
2
2
1
2.2


NM_005080_354-372
8
2
7
2
12
2
4
2


NM_005080_355-373
6
2
1
2
3
2
1
3


NM_005080_361-379
2
2
2
1
5
2
1
1


NM_005080_366-384
2
2
2
2
4
2
12
2.2


NM_005080_369-387
9
2
3
2.2
4
2
6
2


NM_005080_370-388
9
2
2
2
13
2
6
2


NM_005080_372-390
3
2
1
2
1
2
1
2.2


NM_005080_376-394
2
2
1
1
2
2
1
1


NM_005080_381-399
8
2
2
2.2
5
2
1
1


NM_005080_384-402
2
2
4
2.2
3
2
8
2


NM_005080_388-406
1
2
1
1
1
2
1
1


NM_005080_392-410
1
2
1
2.2
1
2
1
2.2


NM_005080_394-412
1
2
2
3
1
2
9
3


NM_005080_396-414
1
2
2
2
2
2
2
3


NM_005080_400-418
6
2
3
0
18
2
1
0


NM_005080_421-439
2
2
9
2.2
1
2
9
1.2


NM_005080_422-440
1
2
1
2
1
2
1
1


NM_005080_423-441
1
2
1
2
1
2
1
1


NM_005080_425-443
3
2
6
3
7
2
2
2


NM_005080_428-446
4
2
1
2.2
4
2
2
2.2


NM_005080_429-447
3
2
4
2.8
3
2
1
2


NM_005080_432-450
4
2
5
2
1
2
1
2


NM_005080_433-451
10
2
5
2
5
2
1
2


NM_005080_434-452
5
2
3
2.2
3
2
4
1


NM_005080_435-453
6
2
2
3
4
2
4
1


NM_005080_436-454
4
2
1
2
7
2
4
2.2


NM_005080_459-477
2
2
2
2.2
3
2
4
2.2


NM_005080_460-478
1
2
5
3
2
2
4
2


NM_005080_462-480
1
2
1
2
2
2
2
2


NM_005080_486-504
5
2
1
1
3
2
1
1


NM_005080_510-528
3
2
1
1
4
2
9
2


NM_005080_513-531
2
2
2
2
1
2
1
2


NM_005080_514-532
3
2
10
2
8
2
1
0


NM_005080_515-533
1
2
7
2
3
2
1
0


NM_005080_516-534
4
2
1
0
7
2
1
0


NM_005080_520-538
1
2
3
1
13
2
3
2


NM_005080_521-539
2
2
1
1
11
2
2
2


NM_005080_523-541
6
2
2
2
2
2
2
2


NM_005080_578-596
2
2
2
2
6
2
1
2


NM_005080_581-599
4
2
1
1
2
2
1
1


NM_005080_582-600
3
2
1
2
4
2
1
2


NM_005080_583-601
4
2
2
2
17
2
1
2


NM_005080_584-602
5
2
2
2
17
2
1
2


NM_005080_585-603
3
2
2
2
4
2
2
2


NM_005080_586-604
1
2
2
2
1
2
1
2.2


NM_005080_587-605
3
2
6
3
4
2
1
2.2


NM_005080_588-606
3
2
1
2
3
2
24
3


NM_005080_589-607
2
2
1
1
3
2
1
1


NM_005080_590-608
1
2
1
2
3
2
1
2


NM_005080_591-609
3
2
1
2.2
5
2
7
2.2


NM_005080_597-615
2
2
1
2.2
1
2
5
2.2


NM_005080_600-618
1
2
1
2.2
3
2
9
2


NM_005080_603-621
4
2
3
2
4
2
3
2


NM_005080_619-637
3
2
4
3.2
1
2
7
3.2


NM_005080_620-638
5
2
2
4.2
1
2
1
3


NM_005080_622-640
1
2
1
2.2
2
2
1
2.2


NM_005080_623-641
3
2
1
3
1
2
2
3


NM_005080_624-642
2
2
1
3
1
2
1
2


NM_005080_625-643
8
2
4
2.8
19
2
2
2


NM_005080_626-644
9
2
1
2.8
5
2
1
2


NM_005080_629-647
2
2
4
1
1
2
4
1


NM_005080_632-650
1
2
2
0
3
2
7
1


NM_005080_634-652
6
2
2
1
4
2
7
2


NM_005080_637-655
2
2
2
2
2
2
1
2


NM_005080_638-656
2
2
5
3
8
2
3
3


NM_005080_639-657
1
2
1
2
1
2
1
2


NM_005080_642-660
2
2
1
1
2
2
2
2


NM_005080_643-661
1
2
3
2
3
2
4
3


NM_005080_644-662
2
2
4
3
3
2
6
2.2


NM_005080_646-664
2
2
2
1
5
2
1
1


NM_005080_649-667
1
2
2
2
1
2
1
2


NM_005080_650-668
1
2
1
2
1
2
1
3


NM_005080_653-671
2
2
2
2
2
2
2
2


NM_005080_658-676
2
2
2
1
1
2
1
1


NM_005080_659-677
2
2
2
2
2
2
1
2


NM_005080_660-678
1
2
6
2
2
2
1
1


NM_005080_663-681
6
2
5
2
2
2
2
2


NM_005080_664-682
4
2
4
2
1
2
9
2.2


NM_005080_668-686
6
2
2
2.2
3
2
4
2.2


NM_005080_671-689
1
2
2
1
10
2
11
2


NM_005080_676-694
3
2
1
2
4
2
9
3


NM_005080_677-695
2
2
1
2
1
2
2
2


NM_005080_679-697
1
2
1
2
1
2
1
2


NM_005080_680-698
2
2
5
3
1
2
19
3.2


NM_005080_682-700
7
2
2
2
4
2
1
2


NM_005080_687-705
1
2
3
1
2
2
6
1


NM_005080_689-707
2
2
1
2
3
2
2
2


NM_005080_695-713
2
2
1
2
1
2
1
2


NM_005080_696-714
3
2
1
1
1
2
1
2


NM_005080_698-716
11
2
1
2
11
2
1
2


NM_005080_731-749
1
2
1
1
1
2
1
2.2


NM_005080_732-750
1
2
2
2
1
2
1
2


NM_005080_733-751
1
2
1
2.8
1
2
1
2


NM_005080_736-754
1
2
2
2
4
2
4
2


NM_005080_737-755
1
2
6
3
4
2
1
2


NM_005080_738-756
2
2
2
2.2
7
2
3
2.2


NM_005080_740-758
4
2
7
3
5
2
1
3


NM_005080_741-759
3
2
5
3
1
2
1
3


NM_005080_742-760
1
2
4
3
3
2
1
3


NM_005080_743-761
4
2
2
2
6
2
5
3


NM_005080_748-766
6
2
1
1.2
4
2
2
2


NM_005080_749-767
5
2
2
2
2
2
2
2


NM_005080_750-768
4
2
3
2
2
2
2
2


NM_005080_751-769
4
2
1
2
1
2
1
2.2


NM_005080_752-770
7
2
2
2
3
2
1
2


NM_005080_756-774
3
2
2
2
3
2
8
3


NM_005080_758-776
1
2
1
2
1
2
1
1


NM_005080_759-777
4
2
2
2
4
2
2
2


NM_005080_760-778
1
2
1
2
3
2
1
2


NM_005080_761-779
5
2
1
2.2
3
2
1
2


NM_005080_762-780
7
2
2
2.2
1
2
1
2.2


NM_005080_767-785
5
2
4
2
5
2
1
1


NM_005080_769-787
4
2
1
1.2
7
2
5
2


NM_005080_773-791
14
2
2
1
7
2
3
1


NM_005080_779-797
6
2
6
2
21
2
9
2


NM_005080_786-804
1
2
1
1.2
1
2
1
1


NM_005080_787-805
2
2
2
2
1
2
2
2


NM_005080_789-807
1
2
4
2.2
1
2
6
2.2


NM_005080_793-811
4
2
1
2
11
2
1
2


NM_005080_795-813
1
2
4
3
1
2
1
3


NM_005080_797-815
3
2
5
3.2
3
2
1
2


NM_005080_798-816
4
2
2
2.8
1
2
1
1


NM_005080_800-818
5
2
2
1
3
2
1
1


NM_005080_804-822
9
2
2
1
8
2
2
0


NM_005080_806-824
11
2
3
2
11
2
5
2


NM_005080_807-825
2
2
4
2.2
1
2
2
2


NM_005080_808-826
2
2
1
2.2
1
2
1
2.2


NM_005080_809-827
3
2
7
2
4
2
10
2


NM_005080_810-828
1
2
5
2
3
2
2
2


NM_005080_811-829
1
2
1
1
1
2
1
1


NM_005080_813-831
6
2
2
2
7
2
2
2


NM_005080_814-832
1
2
1
2
1
2
1
2


NM_005080_818-836
4
2
1
2.2
2
2
1
2.2


NM_005080_820-838
1
2
5
2
1
2
1
2


NM_005080_837-855
1
2
3
2.8
6
2
1
2.2


NM_005080_844-862
4
2
3
2
13
2
1
2.2


NM_005080_872-890
2
2
1
3
4
2
1
3


NM_005080_873-891
1
2
4
2
3
2
1
2


NM_005080_874-892
4
2
7
3.2
2
2
1
2.4


NM_005080_876-894
6
2
1
2.2
4
2
4
2.2


NM_005080_889-907
1
2
2
2.2
1
2
2
2


NM_005080_890-908
2
2
1
3
3
2
1
2


NM_005080_897-915
1
2
2
3
5
2
4
3


NM_005080_898-916
1
2
2
3
1
2
7
3


NM_005080_901-919
4
2
3
2.2
3
2
2
2.2


NM_005080_903-921
1
2
2
2
4
2
1
1


NM_005080_904-922
1
2
3
2.2
4
2
1
2


NM_005080_906-924
2
2
4
3
2
2
5
3


NM_005080_907-925
1
2
4
3
2
2
3
3


NM_005080_910-928
5
2
2
2
4
2
1
1


NM_005080_913-931
4
2
1
3.2
3
2
3
3.2


NM_005080_916-934
3
2
7
3
3
2
4
3


NM_005080_918-936
1
2
2
3
1
2
3
3


NM_005080_919-937
3
2
3
3
1
2
4
3


NM_005080_920-938
2
2
2
2
2
2
2
2


NM_005080_922-940
5
2
4
2
9
2
3
2.2


NM_005080_923-941
3
2
3
2
14
2
1
2


NM_005080_929-947
8
2
8
2
5
2
5
2


NM_005080_930-948
6
2
4
2
5
2
1
2


NM_005080_931-949
3
2
1
2.2
2
2
10
3


NM_005080_932-950
1
2
3
2
4
2
2
2


NM_005080_933-951
5
2
10
3
2
2
4
2


NM_005080_934-952
1
2
2
2.2
6
2
5
2


NM_005080_935-953
2
2
3
2
7
2
1
2


NM_005080_936-954
4
2
8
3
2
2
7
3


NM_005080_938-956
1
2
1
2
1
2
1
2


NM_005080_941-959
3
2
2
2
5
2
2
2


NM_005080_942-960
1
2
1
2
1
2
1
1.2


NM_005080_943-961
2
2
1
2
2
2
1
2


NM_005080_944-962
3
2
3
3
6
2
1
2.2


NM_005080_946-964
1
2
2
3
2
2
9
3


NM_005080_947-965
1
2
2
2
2
2
4
2


NM_005080_948-966
3
2
1
2.2
4
2
4
2.2


NM_005080_949-967
1
2
1
2
3
2
4
2


NM_005080_955-973
5
2
2
2
4
2
3
2


NM_005080_956-974
2
2
9
2
2
2
4
2


NM_005080_957-975
2
2
3
2
1
2
2
2.2


NM_005080_960-978
7
2
2
1
2
2
1
1


NM_005080_961-979
2
2
2
2
1
2
3
2


NM_005080_965-983
2
2
1
1
2
2
3
2


NM_005080_967-985
8
2
1
2
3
2
1
2


NM_005080_968-986
12
2
1
2.2
13
2
2
2.2


NM_005080_971-989
3
2
12
3
7
2
1
2


NM_005080_972-990
8
2
3
2
23
2
2
2


NM_005080_973-991
6
2
1
1
8
2
1
2


NM_005080_980-998
8
2
3
2.2
7
2
1
2


NM_005080_984-1002
14
2
3
2
18
2
1
2


NM_005080_986-1004
1
2
2
2
5
2
2
2


NM_005080_1023-1041
1
2
1
1.2
1
1.2
1
1.2


NM_005080_1151-1169
2
2
3
2
6
1.2
5
2


NM_005080_1367-1385
9
2
1
2.2
1
1.2
4
2.8


NM_005080_1414-1432
2
2
1
1
1
1.2
7
2


NM_005080_1415-1433
7
2
1
1
1
1.2
4
1


NM_005080_1674-1692
3
2
8
3
1
1.2
3
2


NM_005080_1675-1693
1
2
2
2
1
1.2
6
2


NM_005080_330-348
4
2
6
2
1
1.2
2
2


NM_005080_333-351
8
2
2
1
2
1.2
4
2


NM_005080_592-610
3
2
3
2
1
1.2
1
2.2


NM_005080_665-683
3
2
2
2
3
1.2
1
2.8


NM_005080_815-833
3
2
2
2
2
1.2
1
2


NM_005080_1029-1047
1
2
3
2.2
2
1
9
3


NM_005080_1077-1095
9
2
1
3
1
1
1
3.2


NM_005080_1222-1240
3
2
2
1
1
1
4
1


NM_005080_1285-1303
13
2
1
2
1
1
1
2


NM_005080_1334-1352
2
2
1
3
1
1
1
2


NM_005080_1335-1353
4
2
1
2.2
1
1
6
3


NM_005080_1436-1454
3
2
4
2
1
1
2
2


NM_005080_1449-1467
3
2
3
3
1
1
9
3


NM_005080_1450-1468
1
2
1
2.2
1
1
4
2.2


NM_005080_114-132
13
2
1
0
1
1
7
2


NM_005080_1555-1573
2
2
2
1
1
1
1
1


NM_005080_1556-1574
5
2
1
1
1
1
2
2


NM_005080_1561-1579
5
2
2
1
1
1
7
1


NM_005080_1562-1580
7
2
1
1
1
1
1
1


NM_005080_1569-1587
1
2
2
2
5
1
4
2.2


NM_005080_1588-1606
2
2
2
1
1
1
1
1


NM_005080_1640-1658
1
2
2
2
1
1
3
2


NM_005080_1641-1659
2
2
1
2
1
1
1
2


NM_005080_1642-1660
5
2
2
2
2
1
1
2


NM_005080_1650-1668
1
2
4
2
1
1
4
2


NM_005080_1686-1704
6
2
1
2.2
1
1
2
2.2


NM_005080_1745-1763
1
2
1
2
1
1
1
2


NM_005080_138-156
21
2
2
1
1
1
1
1


NM_005080_145-163
10
2
5
1
1
1
3
1


NM_005080_190-208
4
2
3
2
1
1
2
1


NM_005080_191-209
13
2
3
1
2
1
5
1


NM_005080_192-210
5
2
1
1
1
1
1
1


NM_005080_259-277
6
2
1
1
3
1
3
1


NM_005080_261-279
19
2
1
1
2
1
1
0


NM_005080_289-307
1
2
1
1
2
1
1
1


NM_005080_363-381
15
2
5
2
2
1
6
2


NM_005080_365-383
5
2
2
2
2
1
3
1.2


NM_005080_385-403
4
2
3
2
1
1
9
2


NM_005080_461-479
1
2
1
1.2
2
1
5
2.2


NM_005080_490-508
3
2
1
3
1
1
3
3


NM_005080_518-536
3
2
1
1
2
1
1
1


NM_005080_673-691
6
2
3
2.2
2
1
2
2.2


NM_005080_685-703
1
2
3
2
1
1
3
2


NM_005080_730-748
3
2
4
2
1
1
1
2


NM_005080_772-790
3
2
1
2
1
1
7
2


NM_005080_801-819
5
2
1
1
1
1
2
1


NM_005080_817-835
2
2
1
2
1
1
3
2


NM_005080_887-905
3
2
1
2.2
1
1
2
2


NM_005080_924-942
7
2
2
1
4
1
1
1


NM_005080_927-945
13
2
3
2
4
1
6
2


NM_005080_928-946
1
2
3
2
1
1
2
2.8


NM_005080_974-992
4
2
1
1
2
1
1
2


NM_005080_985-1003
13
2
2
2
1
1
3
3


NM_005080_187-205
4
2
8
2
1
0
1
0


NM_005080_672-690
8
2
2
2
1
0
1
2


NM_005080_771-789
3
2
10
2
1
0
6
1


NM_005080_1740-1758
1
1.2
5
2
1
3.2
1
2.2


NM_005080_1741-1759
1
1.2
2
1
3
3.2
1
2.2


NM_005080_662-680
1
1.2
2
1
1
2.4
2
1


NM_005080_1070-1088
1
1.2
6
2
4
2.2
14
2


NM_005080_631-649
1
1.2
2
0
2
2.2
1
1


NM_005080_647-665
2
1.2
2
2
2
2.2
1
2


NM_005080_791-809
1
1.2
2
2.2
1
2.2
1
2.2


NM_005080_981-999
2
1.2
1
2
14
2.2
1
2


NM_005080_1068-1086
1
1.2
1
2
1
2
1
2


NM_005080_1391-1409
1
1.2
1
1
1
2
1
1


NM_005080_1426-1444
2
1.2
2
2.4
1
2
9
3


NM_005080_103-121
1
1.2
6
3
8
2
9
3


NM_005080_1457-1475
1
1.2
2
2.2
2
2
1
2


NM_005080_1568-1586
2
1.2
1
2
5
2
10
2


NM_005080_1574-1592
1
1.2
13
3
7
2
2
2


NM_005080_1577-1595
1
1.2
1
1
5
2
3
1


NM_005080_1730-1748
2
1.2
1
1
4
2
3
1


NM_005080_1731-1749
4
1.2
1
1.2
4
2
3
1.2


NM_005080_1732-1750
2
1.2
3
2
3
2
5
2


NM_005080_293-311
2
1.2
4
2
3
2
5
2


NM_005080_350-368
1
1.2
3
2.2
1
2
1
1.2


NM_005080_351-369
1
1.2
1
2.2
5
2
1
2.2


NM_005080_630-648
1
1.2
2
2
1
2
2
2


NM_005080_657-675
2
1.2
1
1
2
2
1
1


NM_005080_670-688
1
1.2
4
2
2
2
2
3


NM_005080_692-710
2
1.2
1
1
1
2
6
1


NM_005080_778-796
1
1.2
8
3
4
2
2
2


NM_005080_790-808
1
1.2
8
2.2
1
2
3
3


NM_005080_970-988
1
1.2
2
2
6
2
2
2


NM_005080_1162-1180
1
1.2
7
3
3
1.2
1
2.2


NM_005080_1368-1386
1
1.2
3
2.8
1
1.2
5
3


NM_005080_1515-1533
1
1.2
1
2
2
1.2
2
2.2


NM_005080_1541-1559
1
1.2
4
2
1
1.2
1
2


NM_005080_1542-1560
1
1.2
1
2
1
1.2
2
2


NM_005080_1571-1589
1
1.2
2
2
1
1.2
4
2


NM_005080_151-169
1
1.2
11
2
1
1.2
8
3


NM_005080_160-178
2
1.2
3
2
1
1.2
5
2


NM_005080_326-344
1
1.2
1
3.2
1
1.2
1
3


NM_005080_327-345
1
1.2
2
3.2
1
1.2
1
3


NM_005080_331-349
2
1.2
4
2
2
1.2
1
1


NM_005080_424-442
1
1.2
1
2.2
1
1.2
2
2


NM_005080_483-501
3
1.2
1
1.2
3
1.2
1
1.2


NM_005080_579-597
2
1.2
1
2.2
2
1.2
1
2


NM_005080_745-763
1
1.2
1
2
1
1.2
1
2.2


NM_005080_746-764
1
1.2
2
2
1
1.2
1
2


NM_005080_812-830
2
1.2
5
2
1
1.2
4
2


NM_005080_871-889
1
1.2
2
3
7
1.2
3
3


NM_005080_892-910
2
1.2
3
3
8
1.2
1
2


NM_005080_978-996
1
1.2
2
2
1
1.2
1
1.2


NM_005080_982-1000
1
1.2
4
2.8
8
1.2
4
2.8


NM_005080_257-275
1
1.2
2
1
1
1
3
1


NM_005080_364-382
2
1.2
7
2
2
1
3
1


NM_005080_816-834
1
1.2
2
2
2
1
2
2


NM_005080_884-902
1
1.2
6
2
1
1
1
2


NM_005080_925-943
1
1.2
6
2.2
4
1
1
2


NM_005080_1440-1458
1
1
2
2
1
2.8
5
2


NM_005080_784-802
1
1
2
2
20
2.8
1
1


NM_005080_1593-1611
2
1
1
2
2
2.2
1
2


NM_005080_301-319
1
1
10
3
2
2.2
9
3


NM_005080_674-692
2
1
2
2.4
1
2.2
1
1.2


NM_005080_783-801
1
1
2
2
2
2.2
3
1


NM_005080_921-939
1
1
4
2
10
2.2
2
2


NM_005080_1226-1244
2
1
3
1
4
2
1
1


NM_005080_1283-1301
2
1
1
2
5
2
2
1.2


NM_005080_1416-1434
1
1
1
1
9
2
10
2


NM_005080_1420-1438
1
1
1
1
5
2
1
1


NM_005080_1488-1506
1
1
3
2
1
2
2
1


NM_005080_1492-1510
1
1
1
2.2
1
2
3
3


NM_005080_111-129
1
1
3
1
10
2
1
1


NM_005080_1639-1657
1
1
4
2
1
2
2
2


NM_005080_1685-1703
1
1
2
2
8
2
1
2


NM_005080_1733-1751
2
1
1
1
7
2
1
1


NM_005080_1734-1752
1
1
5
2
7
2
1
1


NM_005080_1737-1755
1
1
2
1
2
2
2
1


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7
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2


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4
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7
2
3
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6
2
5
2
4
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1
3
2
1
2
4
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1
3
2
1
2
4
2


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1
2
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2
2
1
1


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1
1
2
9
2
1
2


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1
5
2
6
2
7
2


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1
1
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3
2
1
1.2


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1
1
1
34
2
1
0


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1
3
2
8
2
4
2


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1
1
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9
2
1
1.2


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1
2
2
1
2
1
2


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1
2
1
4
2
1
1


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1
1
2
1
2
6
2


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1
2
1
6
2
1
1


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5
1
4
2
7
2
3
2


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4
1
4
2
5
2
1
1


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1
3
2
1
2
1
1


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1
1
1
2
4
2
1
1


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1
4
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3
2
1
1


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1
1
1.2
12
2
1
1


NM_005080_487-505
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1
2
1
6
2
1
1


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1
2
2
1
2
3
2


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1
1
1
1.2
4
2
21
2


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3
1
1
2
1
2
5
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1
1
2
2
2
2
1
2


NM_005080_593-611
2
1
3
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16
2
1
2


NM_005080_595-613
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1
8
2
4
2
4
2


NM_005080_654-672
2
1
3
2
3
2
2
2


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3
1
1
2
1
2
4
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1
1
1
2
3
2
1
1


NM_005080_684-702
1
1
2
2
3
2
4
2


NM_005080_693-711
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1
8
1
3
2
1
1


NM_005080_694-712
3
1
12
2
2
2
8
2


NM_005080_726-744
2
1
1
1.2
14
2
1
1.2


NM_005080_744-762
2
1
2
2
2
2
3
2


NM_005080_765-783
1
1
2
3
2
2
1
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NM_005080_768-786
3
1
2
2
2
2
3
2


NM_005080_777-795
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1
4
2
2
2
5
2


NM_005080_802-820
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1
2
1
7
2
3
2


NM_005080_877-895
1
1
2
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5
2
2
1


NM_005080_878-896
1
1
2
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2
2
1
2


NM_005080_885-903
1
1
3
2
2
2
2
2


NM_005080_886-904
1
1
3
2
2
2
2
2


NM_005080_966-984
1
1
2
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2
2
1
2.4


NM_005080_969-987
1
1
5
2
12
2
2
2


NM_005080_1245-1263
1
1
1
2
1
1.2
2
2


NM_005080_1738-1756
1
1
9
2
2
1.2
1
1


NM_005080_194-212
1
1
1
1
1
1.2
2
1


NM_005080_209-227
1
1
1
1
1
1.2
1
1


NM_005080_269-287
2
1
21
2
3
1.2
17
2


NM_005080_902-920
1
1
1
1.2
5
1.2
1
2.2


NM_005080_50-68
2
1
8
1
1
1.2
8
1


NM_005080_1017-1035
1
1
1
2.2
1
1
4
3


NM_005080_1021-1039
2
1
1
2
1
1
1
2


NM_005080_1022-1040
2
1
1
1
1
1
2
2


NM_005080_1062-1080
2
1
3
2
3
1
1
2


NM_005080_1074-1092
1
1
1
2
2
1
2
2.2


NM_005080_1116-1134
5
1
2
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2
1
12
3


NM_005080_1149-1167
1
1
1
2
1
1
10
3


NM_005080_1150-1168
2
1
1
2
8
1
1
1.2


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1
1
1
2
1
1
1
2


NM_005080_1223-1241
2
1
2
1
5
1
25
2


NM_005080_1280-1298
1
1
1
1
1
1
1
1


NM_005080_1281-1299
1
1
1
1
1
1
3
1


NM_005080_1284-1302
4
1
1
1
1
1
1
1


NM_005080_1286-1304
1
1
3
2
2
1
2
2


NM_005080_1288-1306
2
1
5
2
3
1
1
2


NM_005080_1365-1383
1
1
1
2.2
1
1
10
3


NM_005080_1417-1435
2
1
4
2
1
1
5
2


NM_005080_1421-1439
1
1
2
2
1
1
1
2


NM_005080_1434-1452
3
1
1
2
1
1
1
2.2


NM_005080_1452-1470
1
1
4
2
1
1
4
2


NM_005080_105-123
1
1
1
1
2
1
3
2


NM_005080_1455-1473
1
1
5
2
2
1
3
2


NM_005080_112-130
1
1
2
1
1
1
1
1.2


NM_005080_113-131
2
1
3
1
2
1
1
1


NM_005080_1543-1561
3
1
3
2.2
2
1
1
2.2


NM_005080_1544-1562
2
1
6
3
2
1
1
2


NM_005080_1557-1575
1
1
6
2
4
1
6
1


NM_005080_115-133
2
1
1
0
1
1
1
1.2


NM_005080_1564-1582
1
1
3
1
4
1
4
1


NM_005080_1572-1590
1
1
3
2
1
1
4
2


NM_005080_1575-1593
1
1
5
2
1
1
4
2


NM_005080_1576-1594
1
1
1
2
1
1
1
2


NM_005080_117-135
4
1
3
1
14
1
10
1


NM_005080_1582-1600
1
1
9
2
1
1
1
1


NM_005080_1587-1605
1
1
5
2
3
1
12
2


NM_005080_118-136
8
1
5
1
10
1
3
1


NM_005080_119-137
7
1
2
1
4
1
1
1


NM_005080_120-138
6
1
47
2
7
1
35
2


NM_005080_124-142
6
1
1
0
1
1
1
0


NM_005080_126-144
1
1
3
1
2
1
1
1


NM_005080_1676-1694
1
1
2
2
1
1
5
2


NM_005080_127-145
7
1
2
1
3
1
1
1


NM_005080_129-147
3
1
18
2
2
1
2
1


NM_005080_130-148
4
1
7
1
1
1
5
1


NM_005080_131-149
1
1
1
0
1
1
6
1


NM_005080_1720-1738
1
1
1
3
4
1
1
3


NM_005080_1724-1742
1
1
2
2
2
1
2
2


NM_005080_132-150
3
1
3
1
1
1
3
1


NM_005080_133-151
5
1
1
1
3
1
3
1


NM_005080_134-152
2
1
1
1.2
1
1
1
1


NM_005080_136-154
3
1
1
1
2
1
7
1


NM_005080_1777-1795
1
1
1
1
1
1
4
2


NM_005080_137-155
4
1
4
1
4
1
7
1


NM_005080_139-157
10
1
1
1.2
2
1
7
2


NM_005080_140-158
1
1
1
1.2
2
1
1
1.2


NM_005080_141-159
7
1
1
0
7
1
1
0


NM_005080_142-160
4
1
1
0
1
1
1
0


NM_005080_143-161
6
1
1
0
2
1
3
1


NM_005080_144-162
1
1
5
1
4
1
9
1


NM_005080_161-179
2
1
4
2
1
1
1
2


NM_005080_162-180
4
1
6
2
2
1
6
3


NM_005080_164-182
2
1
2
2
1
1
4
2


NM_005080_165-183
1
1
7
2
4
1
1
1


NM_005080_166-184
3
1
2
1
2
1
7
1


NM_005080_201-219
4
1
4
2
1
1
1
2


NM_005080_202-220
5
1
3
1
4
1
1
1


NM_005080_203-221
3
1
6
1
3
1
1
1


NM_005080_204-222
3
1
9
1
2
1
1
1


NM_005080_208-226
3
1
2
1
2
1
4
1


NM_005080_212-230
2
1
2
1
1
1
5
2


NM_005080_248-266
4
1
1
1
5
1
11
1


NM_005080_251-269
1
1
9
2
2
1
1
1


NM_005080_258-276
2
1
2
2
1
1
12
2


NM_005080_262-280
2
1
4
2
1
1
1
0


NM_005080_265-283
2
1
2
2
3
1
4
2.2


NM_005080_266-284
2
1
7
2
2
1
1
1


NM_005080_267-285
4
1
2
1
1
1
1
1


NM_005080_268-286
3
1
6
2
1
1
1
1


NM_005080_270-288
3
1
4
2
1
1
6
2


NM_005080_272-290
2
1
1
2
1
1
2
2


NM_005080_273-291
2
1
4
1
3
1
1
2


NM_005080_277-295
4
1
3
1
2
1
1
1


NM_005080_328-346
1
1
2
2
1
1
8
3


NM_005080_329-347
1
1
1
2
1
1
11
3


NM_005080_334-352
1
1
4
1
1
1
2
1


NM_005080_336-354
1
1
1
1
1
1
1
1


NM_005080_337-355
4
1
1
1
2
1
1
1


NM_005080_338-356
5
1
1
1
3
1
1
1.2


NM_005080_356-374
1
1
1
1
1
1
1
2


NM_005080_357-375
2
1
2
2
2
1
2
2


NM_005080_359-377
1
1
1
2
1
1
2
2.8


NM_005080_360-378
1
1
1
2
1
1
1
2


NM_005080_362-380
4
1
1
1
4
1
1
1


NM_005080_367-385
1
1
3
2
1
1
2
2


NM_005080_382-400
6
1
8
2.2
2
1
5
1.2


NM_005080_386-404
1
1
2
2
1
1
2
2


NM_005080_401-419
2
1
3
1
1
1
1
1


NM_005080_458-476
3
1
1
2
1
1
3
2


NM_005080_484-502
3
1
6
2
2
1
1
1


NM_005080_489-507
2
1
1
2
1
1
1
1.2


NM_005080_574-592
1
1
3
2
5
1
4
2.2


NM_005080_594-612
6
1
7
2
13
1
12
2


NM_005080_604-622
4
1
2
2
3
1
3
2


NM_005080_627-645
2
1
2
1
3
1
3
1


NM_005080_635-653
1
1
4
2
3
1
2
2


NM_005080_636-654
1
1
8
1.2
2
1
1
1.2


NM_005080_666-684
2
1
4
2.2
7
1
9
3


NM_005080_667-685
1
1
1
2
1
1
1
2


NM_005080_669-687
1
1
8
3
1
1
4
3


NM_005080_681-699
2
1
4
2
1
1
2
2


NM_005080_690-708
5
1
5
2
1
1
6
2


NM_005080_718-736
4
1
1
1.2
5
1
1
1


NM_005080_722-740
3
1
1
1
3
1
2
1


NM_005080_723-741
3
1
1
1
3
1
1
1


NM_005080_724-742
6
1
2
1
4
1
3
0


NM_005080_725-743
5
1
2
1
2
1
7
1


NM_005080_727-745
1
1
1
1
1
1
2
1.2


NM_005080_728-746
1
1
2
1
3
1
4
1


NM_005080_739-757
1
1
5
2.2
4
1
1
2.2


NM_005080_747-765
1
1
1
2
7
1
8
3


NM_005080_763-781
1
1
2
2
6
1
1
2


NM_005080_764-782
3
1
1
2.8
3
1
1
2.2


NM_005080_766-784
1
1
13
2
1
1
1
1


NM_005080_770-788
1
1
2
1
1
1
4
2


NM_005080_774-792
2
1
2
1
4
1
1
1


NM_005080_780-798
5
1
1
1
20
1
1
1


NM_005080_781-799
5
1
4
2
20
1
8
2


NM_005080_805-823
1
1
1
1
1
1
3
1


NM_005080_44-62
30
1
4
2
42
1
5
2.8


NM_005080_45-63
2
1
3
0
5
1
5
0


NM_005080_868-886
1
1
1
2.2
1
1
16
3


NM_005080_875-893
1
1
1
3.2
1
1
3
3.2


NM_005080_47-65
5
1
6
2
10
1
1
1


NM_005080_879-897
1
1
3
2
2
1
1
1


NM_005080_880-898
1
1
3
2
1
1
3
2


NM_005080_881-899
1
1
15
2
1
1
18
2


NM_005080_882-900
1
1
2
2
1
1
1
2


NM_005080_883-901
1
1
1
2
4
1
1
2


NM_005080_49-67
3
1
1
0
1
1
13
1


NM_005080_914-932
1
1
1
3
1
1
2
4


NM_005080_915-933
1
1
1
2
1
1
4
3


NM_005080_926-944
10
1
1
2
7
1
1
2


NM_005080_945-963
2
1
3
2
3
1
7
2


NM_005080_958-976
2
1
1
0
1
1
1
1


NM_005080_959-977
2
1
1
0
1
1
1
2


NM_005080_962-980
1
1
1
1
1
1
1
1


NM_005080_975-993
1
1
4
2
1
1
2
2


NM_005080_983-1001
1
1
3
1
1
1
1
1


NM_005080_128-146
2
1
2
1
1
0
8
2


NM_005080_249-267
1
1
1
1
1
0
11
1


NM_005080_697-715
1
1
2
2
1
0
1
2.2


NM_005080_729-747
3
1
2
1
1
0
9
1.2


NM_005080_776-794
1
0
4
1.2
1
2.2
2
1.2


NM_005080_803-821
1
0
11
2
2
2.2
4
2


NM_005080_254-272
9
0
6
2
1
2
2
2


NM_005080_383-401
2
0
2
2
2
2
7
2


NM_005080_116-134
2
0
7
1
14
1
6
1


NM_005080_123-141
1
0
1
1
2
1
13
2


NM_005080_125-143
1
0
1
0
2
1
1
0


NM_005080_135-153
2
0
10
2
1
1
1
0


NM_005080_253-271
9
0
13
2
2
1
11
2


NM_005080_274-292
1
0
3
1
2
1
2
2


NM_005080_655-673
2
0
3
2.8
1
1
1
2


NM_005080_775-793
1
0
2
1.2
1
1
1
1


NM_005080_46-64
1
0
3
1
15
1
9
1


NM_005080_1456-1474
1
0
4
2
2
0
1
1.2


NM_005080_1545-1563
1
0
9
3
1
0
1
1


NM_005080_1558-1576
1
0
2
2
3
0
8
2


NM_005080_121-139
1
0
1
0
1
0
48
2


NM_005080_122-140
1
0
1
1
1
0
13
2


NM_005080_247-265
1
0
1
1
1
0
1
1


NM_005080_275-293
1
0
4
1
1
0
2
1


NM_005080_276-294
1
0
1
1
1
0
1
1


NM_005080_358-376
1
0
8
2.2
1
0
6
2.2


NM_005080_387-405
1
0
2
2
1
0
3
2


NM_005080_628-646
2
0
1
0
2
0
3
1


NM_005080_656-674
2
0
1
1
1
0
1
1


NM_005080_719-737
1
0
6
2
1
0
6
2


NM_005080_720-738
2
0
4
1
3
0
1
1


NM_005080_721-739
1
0
1
1.2
1
0
9
2


NM_005080_782-800
5
0
3
2
20
0
12
2


NM_005080_867-885
2
0
5
2
2
0
1
2.2


NM_005080_48-66
2
0
3
1
1
0
1
0


NM_005080_963-981
1
0
1
1
1
0
5
2





Gene XBP-1


reference transcript NM_005080 (human XBP-1 mRNA, FIG. 2)


Notes


19mers found in both human and rhesus













TABLE 11







XBP-1 mouse/Rhesus siRNAs











Target sequence on






rhesus mRNA

SEQ

SEQ


transcript

ID

ID


5′to 3′
sense (5′-3′)
NO:
antinsense (5′-3′)
NO:














NM_013842_369-387
AGAAAACUCACGGCCUUGU
2119
ACAAGGCCGUGAGUUUUCU
2120


 


NM_013842_237-255
AACUGAAAAACAGAGUAGC
321
GCUACUCUGUUUUUCAGUU
322


 


NM_013842_491-509
GGGUCUGCUGAGUCCGCAG
1693
CUGCGGACUCAGCAGACCC
1694


 


NM_013842_917-935
AUCACCCUGAAUUCAUUGU
197
ACAAUGAAUUCAGGGUGAU
198


 


NM_013842_923-941
CUGAAUUCAUUGUCUCAGU
2037
ACUGAGACAAUGAAUUCAG
2038


 


NM_013842_702-720
CCCAGAGGUCUACCCAGAA
1181
UUCUGGGUAGACCUCUGGG
1182


 


NM_013842_926-944
AAUUCAUUGUCUCAGUGAA
1349
UUCACUGAGACAAUGAAUU
1350


 


NM_013842_391-409
UGAGAACCAGGAGUUAAGA
1035
UCUUAACUCCUGGUUCUCA
1036


 


NM_013842_775-793
AAGCUGGAAGCCAUUAAUG
1249
CAUUAAUGGCUUCCAGCUU
1250


 


NM_013842_1150-1168
CCCCAGCUGAUUAGUGUCU
123
AGACACUAAUCAGCUGGGG
124


 


NM_013842_776-794
AGCUGGAAGCCAUUAAUGA
1251
UCAUUAAUGGCUUCCAGCU
1252


 


NM_013842_921-939
CCCUGAAUUCAUUGUCUCA
1343
UGAGACAAUGAAUUCAGGG
1344


 


NM_013842_777-795
GCUGGAAGCCAUUAAUGAA
1585
UUCAUUAAUGGCUUCCAGC
1586


 


NM_013842_539-557
GUGCAGGCCCAGUUGUCAC
1951
GUGACAACUGGGCCUGCAC
1952


 


NM_013842_731-749
CCUUACCAGCCUCCCUUUC
1995
GAAAGGGAGGCUGGUAAGG
1996


 


NM_013842_924-942
UGAAUUCAUUGUCUCAGUG
2039
CACUGAGACAAUGAAUUCA
2040


 


NM_013842_1151-1169
CCCAGCUGAUUAGUGUCUA
43
UAGACACUAAUCAGCUGGG
44


 


NM_013842_1152-1170
CCAGCUGAUUAGUGUCUAA
125
UUAGACACUAAUCAGCUGG
126


 


NM_013842_1718-1736
ACUAUGUAAAUGCUUGAUG
479
CAUCAAGCAUUUACAUAGU
480


 


NM_013842_368-386
GAGAAAACUCACGGCCUUG
2121
CAAGGCCGUGAGUUUUCUC
2122


 


NM_013842_489-507
CCGGGUCUGCUGAGUCCGC
499
GCGGACUCAGCAGACCCGG
500


 


NM_013842_238-256
ACUGAAAAACAGAGUAGCA
289
UGCUACUCUGUUUUUCAGU
290


 


NM_013842_240-258
UGAAAAACAGAGUAGCAGC
529
GCUGCUACUCUGUUUUUCA
530


 


NM_013842_390-408
UUGAGAACCAGGAGUUAAG
329
CUUAACUCCUGGUUCUCAA
330


 


NM_013842_487-505
GGCCGGGUCUGCUGAGUCC
569
GGACUCAGCAGACCCGGCC
570


 


NM_013842_741-759
CUCCCUUUCUCUGUCAGUG
2055
CACUGACAGAGAAAGGGAG
2056


 


NM_013842_918-936
UCACCCUGAAUUCAUUGUC
157
GACAAUGAAUUCAGGGUGA
158


 


NM_013842_919-937
CACCCUGAAUUCAUUGUCU
343
AGACAAUGAAUUCAGGGUG
344


 


NM_013842_1130-1148
CUUUUGCCAAUGAACUUUU
2123
AAAAGUUCAUUGGCAAAAG
2124


 


NM_013842_1712-1730
AAAUUUACUAUGUAAAUGC
845
GCAUUUACAUAGUAAAUUU
846


 


NM_013842_1714-1732
AUUUACUAUGUAAAUGCUU
847
AAGCAUUUACAUAGUAAAU
848


 


NM_013842_1717-1735
UACUAUGUAAAUGCUUGAU
851
AUCAAGCAUUUACAUAGUA
852


 


NM_013842_1719-1737
CUAUGUAAAUGCUUGAUGG
853
CCAUCAAGCAUUUACAUAG
854


 


NM_013842_1775-1793
CCAUUUAUUUAAAACUACC
379
GGUAGUUUUAAAUAAAUGG
380


 


NM_013842_1776-1794
CAUUUAUUUAAAACUACCC
381
GGGUAGUUUUAAAUAAAUG
382


 


NM_013842_239-257
CUGAAAAACAGAGUAGCAG
383
CUGCUACUCUGUUUUUCAG
384


 


NM_013842_347-365
CUAGAAAAUCAGCUUUUAC
1013
GUAAAAGCUGAUUUUCUAG
1014


 


NM_013842_348-366
UAGAAAAUCAGCUUUUACG
1679
CGUAAAAGCUGAUUUUCUA
1680


 


NM_013842_485-503
GUGGCCGGGUCUGCUGAGU
1063
ACUCAGCAGACCCGGCCAC
1064


 


NM_013842_486-504
UGGCCGGGUCUGCUGAGUC
1065
GACUCAGCAGACCCGGCCA
1066


 


NM_013842_488-506
GCCGGGUCUGCUGAGUCCG
1067
CGGACUCAGCAGACCCGGC
1068


 


NM_013842_540-558
UGCAGGCCCAGUUGUCACC
1695
GGUGACAACUGGGCCUGCA
1696


 


NM_013842_703-721
CCAGAGGUCUACCCAGAAG
1183
CUUCUGGGUAGACCUCUGG
1184


 


NM_013842_705-723
AGAGGUCUACCCAGAAGGA
1185
UCCUUCUGGGUAGACCUCU
1186


 


NM_013842_730-748
UCCUUACCAGCCUCCCUUU
1717
AAAGGGAGGCUGGUAAGGA
1718


 


NM_013842_742-760
UCCCUUUCUCUGUCAGUGG
1721
CCACUGACAGAGAAAGGGA
1722


 


NM_013842_744-762
CCUUUCUCUGUCAGUGGGG
1221
CCCCACUGACAGAGAAAGG
1222


 


NM_013842_767-785
CAUCAGCCAAGCUGGAAGC
1723
GCUUCCAGCUUGGCUGAUG
1724


 


NM_013842_771-789
AGCCAAGCUGGAAGCCAUU
1241
AAUGGCUUCCAGCUUGGCU
1242


 


NM_013842_916-934
GAUCACCCUGAAUUCAUUG
195
CAAUGAAUUCAGGGUGAUC
196


 


NM_013842_920-938
ACCCUGAAUUCAUUGUCUC
1341
GAGACAAUGAAUUCAGGGU
1342


 


NM_013842_922-940
CCUGAAUUCAUUGUCUCAG
1345
CUGAGACAAUGAAUUCAGG
1346


 


NM_013842_925-943
GAAUUCAUUGUCUCAGUGA
1347
UCACUGAGACAAUGAAUUC
1348


 


NM_013842_1720-1738
UAUGUAAAUGCUUGAUGGA
1841
UCCAUCAAGCAUUUACAUA
1842


 


NM_013842_232-250
GAGGAAACUGAAAAACAGA
1911
UCUGUUUUUCAGUUUCCUC
1912


 


NM_013842_236-254
AAACUGAAAAACAGAGUAG
1913
CUACUCUGUUUUUCAGUUU
1914


 


NM_013842_728-746
GUUCCUUACCAGCCUCCCU
1991
AGGGAGGCUGGUAAGGAAC
1992


 


NM_013842_729-747
UUCCUUACCAGCCUCCCUU
1993
AAGGGAGGCUGGUAAGGAA
1994


 


NM_013842_745-763
CUUUCUCUGUCAGUGGGGA
2001
UCCCCACUGACAGAGAAAG
2002


 


NM_013842_766-784
UCAUCAGCCAAGCUGGAAG
1473
CUUCCAGCUUGGCUGAUGA
1474


 


NM_013842_927-945
AUUCAUUGUCUCAGUGAAG
2041
CUUCACUGAGACAAUGAAU
2042


 


NM_013842_234-252
GGAAACUGAAAAACAGAGU
2093
ACUCUGUUUUUCAGUUUCC
2094


 


NM_013842_235-253
GAAACUGAAAAACAGAGUA
2095
UACUCUGUUUUUCAGUUUC
2096


 


NM_013842_346-364
GCUAGAAAAUCAGCUUUUA
2099
UAAAAGCUGAUUUUCUAGC
2100


 


NM_013842_490-508
CGGGUCUGCUGAGUCCGCA
501
UGCGGACUCAGCAGACCCG
502


 


NM_013842_700-718
CUCCCAGAGGUCUACCCAG
91
CUGGGUAGACCUCUGGGAG
92


 


NM_013842_1715-1733
UUUACUAUGUAAAUGCUUG
849
CAAGCAUUUACAUAGUAAA
850


 


NM_013842_734-752
UACCAGCCUCCCUUUCUCU
1217
AGAGAAAGGGAGGCUGGUA
1218


 


NM_013842_773-791
CCAAGCUGGAAGCCAUUAA
1245
UUAAUGGCUUCCAGCUUGG
1246


 


NM_013842_778-796
CUGGAAGCCAUUAAUGAAC
1253
GUUCAUUAAUGGCUUCCAG
1254


 


NM_013842_779-797
UGGAAGCCAUUAAUGAACU
1255
AGUUCAUUAAUGGCUUCCA
1256


 


NM_013842_1774-1792
UCCAUUUAUUUAAAACUAC
1853
GUAGUUUUAAAUAAAUGGA
1854


 


NM_013842_704-722
CAGAGGUCUACCCAGAAGG
1987
CCUUCUGGGUAGACCUCUG
1988


 


NM_013842_1716-1734
UUACUAUGUAAAUGCUUGA
477
UCAAGCAUUUACAUAGUAA
478


 


NM_013842_1713-1731
AAUUUACUAUGUAAAUGCU
315
AGCAUUUACAUAGUAAAUU
316


 


NM_013842_768-786
AUCAGCCAAGCUGGAAGCC
2057
GGCUUCCAGCUUGGCUGAU
2058


 


NM_013842_1129-1147
ACUUUUGCCAAUGAACUUU
2125
AAAGUUCAUUGGCAAAAGU
2126


 


NM_013842_389-407
GUUGAGAACCAGGAGUUAA
245
UUAACUCCUGGUUCUCAAC
246


 


NM_013842_701-719
UCCCAGAGGUCUACCCAGA
1179
UCUGGGUAGACCUCUGGGA
1180


 


NM_013842_706-724
GAGGUCUACCCAGAAGGAC
1187
GUCCUUCUGGGUAGACCUC
1188


 


NM_013842_707-725
AGGUCUACCCAGAAGGACC
1189
GGUCCUUCUGGGUAGACCU
1190


 


NM_013842_727-745
AGUUCCUUACCAGCCUCCC
1213
GGGAGGCUGGUAAGGAACU
1214


 


NM_013842_733-751
UUACCAGCCUCCCUUUCUC
1719
GAGAAAGGGAGGCUGGUAA
1720


 


NM_013842_736-754
CCAGCCUCCCUUUCUCUGU
1493
ACAGAGAAAGGGAGGCUGG
1494


 


NM_013842_738-756
AGCCUCCCUUUCUCUGUCA
1219
UGACAGAGAAAGGGAGGCU
1220


 


NM_013842_743-761
CCCUUUCUCUGUCAGUGGG
1547
CCCACUGACAGAGAAAGGG
1548


 


NM_013842_769-787
UCAGCCAAGCUGGAAGCCA
1239
UGGCUUCCAGCUUGGCUGA
1240


 


NM_013842_772-790
GCCAAGCUGGAAGCCAUUA
1243
UAAUGGCUUCCAGCUUGGC
1244


 


NM_013842_774-792
CAAGCUGGAAGCCAUUAAU
1247
AUUAAUGGCUUCCAGCUUG
1248


 


NM_013842_231-249
GGAGGAAACUGAAAAACAG
1909
CUGUUUUUCAGUUUCCUCC
1910


 


NM_013842_233-251
AGGAAACUGAAAAACAGAG
2073
CUCUGUUUUUCAGUUUCCU
2074


 


NM_013842_735-753
ACCAGCCUCCCUUUCUCUG
1997
CAGAGAAAGGGAGGCUGGU
1998


 


NM_013842_737-755
CAGCCUCCCUUUCUCUGUC
1471
GACAGAGAAAGGGAGGCUG
1472


 


NM_013842_739-757
GCCUCCCUUUCUCUGUCAG
1999
CUGACAGAGAAAGGGAGGC
2000


 


NM_013842_740-758
CCUCCCUUUCUCUGUCAGU
2077
ACUGACAGAGAAAGGGAGG
2078


 


NM_013842_746-764
UUUCUCUGUCAGUGGGGAC
2003
GUCCCCACUGACAGAGAAA
2004


 


NM_013842_770-788
CAGCCAAGCUGGAAGCCAU
2005
AUGGCUUCCAGCUUGGCUG
2006


 


NM_013842_26-44
GCUAUGGUGGUGGUGGCAG
2079
CUGCCACCACCACCAUAGC
2080


 


NM_013842_27-45
CUAUGGUGGUGGUGGCAGC
2015
GCUGCCACCACCACCAUAG
2016


 


NM_013842_732-750
CUUACCAGCCUCCCUUUCU
1215
AGAAAGGGAGGCUGGUAAG
1216





Gene XBP-1


reference transcript NM_013842 (Mus musculis XPB 1 mRNA, FIG. 3)


Notes


100 siRNA sequences common to both mouse and rhesus













TABLE 12







XBP-1 mouse/Rhesus siRNAs with 3′dinucleotide overhangs











Target sequence on
sense (5′-3′)
SEQ
antisense (5′-3′)
SEQ


rhesus mRNA
with 3′ dinucleotide
ID
with 3′ dinucleotide
ID


transcript 5′ to 3′
overhand
NO:
overhang
NO:














NM_013842_369-387
AGAAAACUCACGGCCUUGUNN
4321
ACAAGGCCGUGAGUUUUCUNN
4322


 


NM_013842_237-255
AACUGAAAAACAGAGUAGCNN
2523
GCUACUCUGUUUUUCAGUUNN
2524


 


NM_013842_491-509
GGGUCUGCUGAGUCCGCAGNN
3895
CUGCGGACUCAGCAGACCCNN
3896


 


NM_013842_917-935
AUCACCCUGAAUUCAUUGUNN
2399
ACAAUGAAUUCAGGGUGAUNN
2400


 


NM_013842_923-941
CUGAAUUCAUUGUCUCAGUNN
4239
ACUGAGACAAUGAAUUCAGNN
4240


 


NM_013842_702-720
CCCAGAGGUCUACCCAGAANN
3383
UUCUGGGUAGACCUCUGGGNN
3384


 


NM_013842_926-944
AAUUCAUUGUCUCAGUGAANN
3551
UUCACUGAGACAAUGAAUUNN
3552


 


NM_013842_391-409
UGAGAACCAGGAGUUAAGANN
3237
UCUUAACUCCUGGUUCUCANN
3238


 


NM_013842_775-793
AAGCUGGAAGCCAUUAAUGNN
3451
CAUUAAUGGCUUCCAGCUUNN
3452


 


NM_013842_1150-1168
CCCCAGCUGAUUAGUGUCUNN
2325
AGACACUAAUCAGCUGGGGNN
2326


 


NM_013842_776-794
AGCUGGAAGCCAUUAAUGANN
3453
UCAUUAAUGGCUUCCAGCUNN
3454


 


NM_013842_921-939
CCCUGAAUUCAUUGUCUCANN
3545
UGAGACAAUGAAUUCAGGGNN
3546


 


NM_013842_777-795
GCUGGAAGCCAUUAAUGAANN
3787
UUCAUUAAUGGCUUCCAGCNN
3788


 


NM_013842_539-557
GUGCAGGCCCAGUUGUCACNN
4153
GUGACAACUGGGCCUGCACNN
4154


 


NM_013842_731-749
CCUUACCAGCCUCCCUUUCNN
4197
GAAAGGGAGGCUGGUAAGGNN
4198


 


NM_013842_924-942
UGAAUUCAUUGUCUCAGUGNN
4241
CACUGAGACAAUGAAUUCANN
4242


 


NM_013842_1151-1169
CCCAGCUGAUUAGUGUCUANN
2245
UAGACACUAAUCAGCUGGGNN
2246


 


NM_013842_1152-1170
CCAGCUGAUUAGUGUCUAANN
2327
UUAGACACUAAUCAGCUGGNN
2328


 


NM_013842_1718-1736
ACUAUGUAAAUGCUUGAUGNN
2681
CAUCAAGCAUUUACAUAGUNN
2682


 


NM_013842_368-386
GAGAAAACUCACGGCCUUGNN
4323
CAAGGCCGUGAGUUUUCUCNN
4324


 


NM_013842_489-507
CCGGGUCUGCUGAGUCCGCNN
2701
GCGGACUCAGCAGACCCGGNN
2702


 


NM_013842_238-256
ACUGAAAAACAGAGUAGCANN
2491
UGCUACUCUGUUUUUCAGUNN
2492


 


NM_013842_240-258
UGAAAAACAGAGUAGCAGCNN
2731
GCUGCUACUCUGUUUUUCANN
2732


 


NM_013842_390-408
UUGAGAACCAGGAGUUAAGNN
2531
CUUAACUCCUGGUUCUCAANN
2532


 


NM_013842_487-505
GGCCGGGUCUGCUGAGUCCNN
2771
GGACUCAGCAGACCCGGCCNN
2772


 


NM_013842_741-759
CUCCCUUUCUCUGUCAGUGNN
4257
CACUGACAGAGAAAGGGAGNN
4258


 


NM_013842_918-936
UCACCCUGAAUUCAUUGUCNN
2359
GACAAUGAAUUCAGGGUGANN
2360


 


NM_013842_919-937
CACCCUGAAUUCAUUGUCUNN
2545
AGACAAUGAAUUCAGGGUGNN
2546


 


NM_013842_1130-1148
CUUUUGCCAAUGAACUUUUNN
4325
AAAAGUUCAUUGGCAAAAGNN
4326


 


NM_013842_1712-1730
AAAUUUACUAUGUAAAUGCNN
3047
GCAUUUACAUAGUAAAUUUNN
3048


 


NM_013842_1714-1732
AUUUACUAUGUAAAUGCUUNN
3049
AAGCAUUUACAUAGUAAAUNN
3050


 


NM_013842_1717-1735
UACUAUGUAAAUGCUUGAUNN
3053
AUCAAGCAUUUACAUAGUANN
3054


 


NM_013842_1719-1737
CUAUGUAAAUGCUUGAUGGNN
3055
CCAUCAAGCAUUUACAUAGNN
3056


 


NM_013842_1775-1793
CCAUUUAUUUAAAACUACCNN
2581
GGUAGUUUUAAAUAAAUGGNN
2582


 


NM_013842_1776-1794
CAUUUAUUUAAAACUACCCNN
2583
GGGUAGUUUUAAAUAAAUGNN
2584


 


NM_013842_239-257
CUGAAAAACAGAGUAGCAGNN
2585
CUGCUACUCUGUUUUUCAGNN
2586


 


NM_013842_347-365
CUAGAAAAUCAGCUUUUACNN
3215
GUAAAAGCUGAUUUUCUAGNN
3216


 


NM_013842_348-366
UAGAAAAUCAGCUUUUACGNN
3881
CGUAAAAGCUGAUUUUCUANN
3882


 


NM_013842_485-503
GUGGCCGGGUCUGCUGAGUNN
3265
ACUCAGCAGACCCGGCCACNN
3266


 


NM_013842_486-504
UGGCCGGGUCUGCUGAGUCNN
3267
GACUCAGCAGACCCGGCCANN
3268


 


NM_013842_488-506
GCCGGGUCUGCUGAGUCCGNN
3269
CGGACUCAGCAGACCCGGCNN
3270


 


NM_013842_540-558
UGCAGGCCCAGUUGUCACCNN
3897
GGUGACAACUGGGCCUGCANN
3898


 


NM_013842_703-721
CCAGAGGUCUACCCAGAAGNN
3385
CUUCUGGGUAGACCUCUGGNN
3386


 


NM_013842_705-723
AGAGGUCUACCCAGAAGGANN
3387
UCCUUCUGGGUAGACCUCUNN
3388


 


NM_013842_730-748
UCCUUACCAGCCUCCCUUUNN
3919
AAAGGGAGGCUGGUAAGGANN
3920


 


NM_013842_742-760
UCCCUUUCUCUGUCAGUGGNN
3923
CCACUGACAGAGAAAGGGANN
3924


 


NM_013842_744-762
CCUUUCUCUGUCAGUGGGGNN
3423
CCCCACUGACAGAGAAAGGNN
3424


 


NM_013842_767-785
CAUCAGCCAAGCUGGAAGCNN
3925
GCUUCCAGCUUGGCUGAUGNN
3926


 


NM_013842_771-789
AGCCAAGCUGGAAGCCAUUNN
3443
AAUGGCUUCCAGCUUGGCUNN
3444


 


NM_013842_916-934
GAUCACCCUGAAUUCAUUGNN
2397
CAAUGAAUUCAGGGUGAUCNN
2398


 


NM_013842_920-938
ACCCUGAAUUCAUUGUCUCNN
3543
GAGACAAUGAAUUCAGGGUNN
3544


 


NM_013842_922-940
CCUGAAUUCAUUGUCUCAGNN
3547
CUGAGACAAUGAAUUCAGGNN
3548


 


NM_013842_925-943
GAAUUCAUUGUCUCAGUGANN
3549
UCACUGAGACAAUGAAUUCNN
3550


 


NM_013842_1720-1738
UAUGUAAAUGCUUGAUGGANN
4043
UCCAUCAAGCAUUUACAUANN
4044


 


NM_013842_232-250
GAGGAAACUGAAAAACAGANN
4113
UCUGUUUUUCAGUUUCCUCNN
4114


 


NM_013842_236-254
AAACUGAAAAACAGAGUAGNN
4115
CUACUCUGUUUUUCAGUUUNN
4116


 


NM_013842_728-746
GUUCCUUACCAGCCUCCCUNN
4193
AGGGAGGCUGGUAAGGAACNN
4194


 


NM_013842_729-747
UUCCUUACCAGCCUCCCUUNN
4195
AAGGGAGGCUGGUAAGGAANN
4196


 


NM_013842_745-763
CUUUCUCUGUCAGUGGGGANN
4203
UCCCCACUGACAGAGAAAGNN
4204


 


NM_013842_766-784
UCAUCAGCCAAGCUGGAAGNN
3675
CUUCCAGCUUGGCUGAUGANN
3676


 


NM_013842_927-945
AUUCAUUGUCUCAGUGAAGNN
4243
CUUCACUGAGACAAUGAAUNN
4244


 


NM_013842_234-252
GGAAACUGAAAAACAGAGUNN
4295
ACUCUGUUUUUCAGUUUCCNN
4296


 


NM_013842_235-253
GAAACUGAAAAACAGAGUANN
4297
UACUCUGUUUUUCAGUUUCNN
4298


 


NM_013842_346-364
GCUAGAAAAUCAGCUUUUANN
4301
UAAAAGCUGAUUUUCUAGCNN
4302


 


NM_013842_490-508
CGGGUCUGCUGAGUCCGCANN
2703
UGCGGACUCAGCAGACCCGNN
2704


 


NM_013842_700-718
CUCCCAGAGGUCUACCCAGNN
2293
CUGGGUAGACCUCUGGGAGNN
2294


 


NM_013842_1715-1733
UUUACUAUGUAAAUGCUUGNN
3051
CAAGCAUUUACAUAGUAAANN
3052


 


NM_013842_734-752
UACCAGCCUCCCUUUCUCUNN
3419
AGAGAAAGGGAGGCUGGUANN
3420


 


NM_013842_773-791
CCAAGCUGGAAGCCAUUAANN
3447
UUAAUGGCUUCCAGCUUGGNN
3448


 


NM_013842_778-796
CUGGAAGCCAUUAAUGAACNN
3455
GUUCAUUAAUGGCUUCCAGNN
3456


 


NM_013842_779-797
UGGAAGCCAUUAAUGAACUNN
3457
AGUUCAUUAAUGGCUUCCANN
3458


 


NM_013842_1774-1792
UCCAUUUAUUUAAAACUACNN
4055
GUAGUUUUAAAUAAAUGGANN
4056


 


NM_013842_704-722
CAGAGGUCUACCCAGAAGGNN
4189
CCUUCUGGGUAGACCUCUGNN
4190


 


NM_013842_1716-1734
UUACUAUGUAAAUGCUUGANN
2679
UCAAGCAUUUACAUAGUAANN
2680


 


NM_013842_1713-1731
AAUUUACUAUGUAAAUGCUNN
2517
AGCAUUUACAUAGUAAAUUNN
2518


 


NM_013842_768-786
AUCAGCCAAGCUGGAAGCCNN
4259
GGCUUCCAGCUUGGCUGAUNN
4260


 


NM_013842_1129-1147
ACUUUUGCCAAUGAACUUUNN
4327
AAAGUUCAUUGGCAAAAGUNN
4328


 


NM_013842_389-407
GUUGAGAACCAGGAGUUAANN
2447
UUAACUCCUGGUUCUCAACNN
2448


 


NM_013842_701-719
UCCCAGAGGUCUACCCAGANN
3381
UCUGGGUAGACCUCUGGGANN
3382


 


NM_013842_706-724
GAGGUCUACCCAGAAGGACNN
3389
GUCCUUCUGGGUAGACCUCNN
3390


 


NM_013842_707-725
AGGUCUACCCAGAAGGACCNN
3391
GGUCCUUCUGGGUAGACCUNN
3392


 


NM_013842_727-745
AGUUCCUUACCAGCCUCCCNN
3415
GGGAGGCUGGUAAGGAACUNN
3416


 


NM_013842_733-751
UUACCAGCCUCCCUUUCUCNN
3921
GAGAAAGGGAGGCUGGUAANN
3922


 


NM_013842_736-754
CCAGCCUCCCUUUCUCUGUNN
3695
ACAGAGAAAGGGAGGCUGGNN
3696


 


NM_013842_738-756
AGCCUCCCUUUCUCUGUCANN
3421
UGACAGAGAAAGGGAGGCUNN
3422


 


NM_013842_743-761
CCCUUUCUCUGUCAGUGGGNN
3749
CCCACUGACAGAGAAAGGGNN
3750


 


NM_013842_769-787
UCAGCCAAGCUGGAAGCCANN
3441
UGGCUUCCAGCUUGGCUGANN
3442


 


NM_013842_772-790
GCCAAGCUGGAAGCCAUUANN
3445
UAAUGGCUUCCAGCUUGGCNN
3446


 


NM_013842_774-792
CAAGCUGGAAGCCAUUAAUNN
3449
AUUAAUGGCUUCCAGCUUGNN
3450


 


NM_013842_231-249
GGAGGAAACUGAAAAACAGNN
4111
CUGUUUUUCAGUUUCCUCCNN
4112


 


NM_013842_233-251
AGGAAACUGAAAAACAGAGNN
4275
CUCUGUUUUUCAGUUUCCUNN
4276


 


NM_013842_735-753
ACCAGCCUCCCUUUCUCUGNN
4199
CAGAGAAAGGGAGGCUGGUNN
4200


 


NM_013842_737-755
CAGCCUCCCUUUCUCUGUCNN
3673
GACAGAGAAAGGGAGGCUGNN
3674


 


NM_013842_739-757
GCCUCCCUUUCUCUGUCAGNN
4201
CUGACAGAGAAAGGGAGGCNN
4202


 


NM_013842_740-758
CCUCCCUUUCUCUGUCAGUNN
4279
ACUGACAGAGAAAGGGAGGNN
4280


 


NM_013842_746-764
UUUCUCUGUCAGUGGGGACNN
4205
GUCCCCACUGACAGAGAAANN
4206


 


NM_013842_770-788
CAGCCAAGCUGGAAGCCAUNN
4207
AUGGCUUCCAGCUUGGCUGNN
4208


 


NM_013842_26-44
GCUAUGGUGGUGGUGGCAGNN
4281
CUGCCACCACCACCAUAGCNN
4282


 


NM_013842_27-45
CUAUGGUGGUGGUGGCAGCNN
4217
GCUGCCACCACCACCAUAGNN
4218


 


NM_013842_732-750
CUUACCAGCCUCCCUUUCUNN
3417
AGAAAGGGAGGCUGGUAAGNN
3418





Gene XBP-1


reference transcript NM_013842 (Mus musculis XPB 1 mRNA, FIG. 3)


Notes


100 siRNA sequences common to both mouse and rhesus













TABLE 13







XBP-1 mouse/Rhesus analysis of siRNAs









off target










mouse













Anti-
Anti-

rhesus
















sense
sense
Sense
Sense
Antisense
Antisense
Sense
Sense


Oligo Name
Count
Score
Count
Score
Count
Score
Count
Score


















NM_013842_369-387
4
3.2
2
2
1
2.8
1
2.4


NM_013842_237-255
3
3
1
2
2
2.2
14
1


NM_013842_491-509
1
3
1
2
1
2
5
2.2


NM_013842_917-935
9
3
1
2
1
2
5
2


NM_013842_923-941
7
3
2
1
1
1
1
1


NM_013842_702-720
2
2.8
8
2
4
2
1
2


NM_013842_926-944
2
2.8
1
1
1
2
3
2


NM_013842_391-409
2
2.4
7
3
1
2
1
2


NM_013842_775-793
2
2.4
5
2
3
2
2
2


NM_013842_1150-1168
3
2.2
1
2
1
2.8
1
2


NM_013842_776-794
3
2.2
6
2
1
2
1
1


NM_013842_921-939
1
2.2
1
2
2
2
4
2


NM_013842_777-795
6
2.2
3
2
1
1.2
4
2


NM_013842_539-557
2
2.2
4
2
5
1
4
2.2


NM_013842_731-749
3
2.2
4
2.8
1
1
1
1


NM_013842_924-942
2
2.2
3
2
1
1
1
2


NM_013842_1151-1169
1
2
1
2.2
2
3
1
1.2


NM_013842_1152-1170
1
2
1
2
2
3
2
2.2


NM_013842_1718-1736
1
2
5
3
20
3
1
2.2


NM_013842_368-386
1
2
2
2
1
3
1
2.2


NM_013842_489-507
1
2
1
2
3
3
4
3


NM_013842_238-256
1
2
10
3
1
2.4
2
1


NM_013842_240-258
1
2
4
2
1
2.4
10
2


NM_013842_390-408
2
2
18
3
4
2.2
1
1


NM_013842_487-505
1
2
3
2
1
2.2
5
2


NM_013842_741-759
3
2
2
1
1
2.2
2
1.2


NM_013842_918-936
1
2
1
2
2
2.2
5
2


NM_013842_919-937
2
2
2
2
3
2.2
1
1


NM_013842_1130-1148
1
2
2
2
12
2
1
1


NM_013842_1712-1730
4
2
1
2
10
2
1
2.2


NM_013842_1714-1732
2
2
1
2
1
2
2
1


NM_013842_1717-1735
4
2
6
3
2
2
1
2.2


NM_013842_1719-1737
1
2
1
2
13
2
2
2


NM_013842_1775-1793
2
2
4
2
2
2
9
2


NM_013842_1776-1794
1
2
4
2
4
2
1
1


NM_013842_239-257
9
2
3
2
1
2
2
1


NM_013842_347-365
2
2
3
2
1
2
1
1


NM_013842_348-366
3
2
5
2.2
1
2
1
1


NM_013842_485-503
2
2
1
2.2
13
2
3
2


NM_013842_486-504
2
2
1
2
11
2
2
2


NM_013842_488-506
5
2
5
3
2
2
2
2


NM_013842_540-558
6
2
4
2
2
2
1
2


NM_013842_703-721
2
2
8
2
7
2
3
2.2


NM_013842_705-723
6
2
5
2.8
5
2
1
3


NM_013842_730-748
2
2
1
2.8
2
2
1
2.8


NM_013842_742-760
3
2
1
1
2
2
5
2


NM_013842_744-762
3
2
1
1
21
2
9
2


NM_013842_767-785
6
2
6
2.2
7
2
3
2


NM_013842_771-789
7
2
3
1
11
2
5
2


NM_013842_916-934
1
2
4
2.2
6
2
4
2


NM_013842_920-938
1
2
3
2
4
2
3
2


NM_013842_922-940
3
2
2
1
1
2
2
2.2


NM_013842_925-943
1
2
1
2
2
2
1
1


NM_013842_1720-1738
1
2
1
2.2
4
1
1
3


NM_013842_232-250
7
2
1
1
3
1
1
2


NM_013842_236-254
1
2
2
2
2
1
1
1


NM_013842_728-746
22
2
2
2
6
1
1
2


NM_013842_729-747
13
2
1
2.2
3
1
1
2.2


NM_013842_745-763
4
2
2
1
20
1
1
1


NM_013842_766-784
2
2
8
2
1
1
2
1


NM_013842_927-945
2
2
5
2
1
1
1
1


NM_013842_234-252
6
2
1
1
1
0
2
1


NM_013842_235-253
2
2
1
1
1
0
1
1


NM_013842_346-364
2
2
1
1
1
0
3
2


NM_013842_490-508
1
1.2
12
3
6
3
3
2


NM_013842_700-718
1
1.2
3
2.2
4
3
2
2


NM_013842_1715-1733
1
1.2
6
3
3
2
1
1


NM_013842_734-752
1
1.2
1
1
7
2
5
2


NM_013842_773-791
2
1.2
1
2
1
2
1
2.2


NM_013842_778-796
1
1.2
3
2
7
2
2
2


NM_013842_779-797
1
1.2
5
3
1
2
1
2


NM_013842_1774-1792
1
1.2
1
1
1
1
4
2


NM_013842_704-722
2
1.2
1
2
4
1
1
2.2


NM_013842_1716-1734
1
1
5
3
9
3
1
1


NM_013842_1713-1731
1
1
1
2.2
3
2.2
2
2


NM_013842_768-786
1
1
2
2.2
2
2.2
4
2


NM_013842_1129-1147
1
1
2
2
1
2
1
1


NM_013842_389-407
1
1
2
2
1
2
3
2


NM_013842_701-719
2
1
1
1
4
2
4
2


NM_013842_706-724
3
1
6
2
1
2
1
3


NM_013842_707-725
2
1
1
1
3
2
1
3


NM_013842_727-745
1
1
1
2
1
2
1
2.2


NM_013842_733-751
2
1
1
2.2
2
2
3
2


NM_013842_736-754
1
1
3
2
3
2
6
1


NM_013842_738-756
2
1
7
2
7
2
3
1


NM_013842_743-761
1
1
2
2
4
2
2
2


NM_013842_769-787
1
1
2
2
8
2
2
0


NM_013842_772-790
3
1
4
2
1
2
2
2


NM_013842_774-792
2
1
2
2
4
2
10
2


NM_013842_231-249
2
1
1
1.2
1
1
2
2


NM_013842_233-251
4
1
4
2
2
1
2
2


NM_013842_735-753
3
1
2
1
1
1
4
2


NM_013842_737-755
4
1
3
2
1
1
7
2


NM_013842_739-757
2
1
6
2
4
1
1
1


NM_013842_740-758
1
1
9
2
1
1
1
1


NM_013842_746-764
2
1
1
1
20
1
8
2


NM_013842_770-788
2
1
4
1
1
1
3
1


NM_013842_26-44
4
1
1
1
15
1
9
1


NM_013842_27-45
2
1
2
2
10
1
1
1


NM_013842_732-750
1
0
2
2.8
5
2
1
1





Gene XBP-1


reference transcript NM_013842 (Mus musculis XPB1 mRNA, FIG. 3)


Notes


100 siRNA sequences common to both mouse and rhesus






Other embodiments are in the claims.

## Claims

1. A double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of an XBP-1 gene, wherein said dsRNA comprises a sense strand and an antisense strand that together form a region of complementarity less than 30 base pairs in length and wherein the antisense strand is complementary to at least 15 contiguous nucleotides of 5′ CACCCUGAAUUCAUUGUCU 3′ (SEQ ID NO:2149).

2. The dsRNA of claim 1, wherein said dsRNA comprises at least one modified nucleotide.

3. The dsRNA of claim 2, wherein at least one of said modified nucleotides is chosen from the group of: a 2′-O-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative, vitamin E, or dodecanoic acid bisdecylamide group.

4. The dsRNA of claim 2, wherein said modified nucleotide is chosen from the group of: a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide.

5. The dsRNA of claim 1, wherein the region of complementarity is at least 15 nucleotides in length.

6. The dsRNA of claim 1, wherein the region of complementarity is between 19 and 21 nucleotides in length.

7. A cell comprising the dsRNA of claim 1.

8. A pharmaceutical composition for inhibiting expression of an XBP-1 gene comprising the dsRNA of claim 1 and a pharmaceutically acceptable carrier.

9. A method of inhibiting XBP-1 expression in a cell, the method comprising:
(a) introducing into the cell the dsRNA of claim 1; and
(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of the XBP-1 gene, thereby inhibiting expression of the XBP-1 gene in the cell.

10. A vector comprising a regulatory sequence operably linked to a nucleotide sequence encoding at least one strand of the dsRNA of claim 1.

11. The vector of claim 10, wherein the region of complementarity is at least 15nucleotides in length.

12. The vector of claim 10, wherein the region of complementarity is 19 to 21nucleotides in length.

13. A cell comprising the vector of claim 10.

14. The dsRNA of claim 1, wherein the antisense strand comprises SEQ ID NO:2150.

15. The dsRNA of claim 1, wherein the antisense strand consists of SEQ ID NO:2150.

16. The dsRNA of claim 1, wherein the sense strand comprises SEQ ID NO:2149.

17. The dsRNA of claim 1, wherein the sense strand consists of SEQ ID NO:2149.

18. The dsRNA of claim 1, wherein the antisense strand consists of SEQ ID NO:2150and the sense strand consists of SEQ ID NO:2149.

19. The dsRNA of claim 2 comprising a 5′-phosphorothioate group or a 2′-O-methyl modified nucleotide.

20. The dsRNA of claim 2, wherein the antisense strand comprises SEQ ID NO:2178.

21. The dsRNA of claim 2, wherein the antisense strand consists of SEQ ID NO:2178.

22. The dsRNA of claim 2, wherein the sense strand comprises SEQ ID NO:2177.

23. The dsRNA of claim 2, wherein the sense strand consists of SEQ ID NO:2177.

24. The dsRNA of claim 2, wherein the antisense strand consists of SEQ ID NO:2178and the sense strand consists of SEQ ID NO:2177.

25. The dsRNA of claim 1 comprising one or more single-stranded nucleotide overhangs.

26. The dsRNA of claim 1 comprising a 3′ dinucleotide overhang on the sense strand and a 3′ dinucleotide overhang on the antisense strand.

27. The dsRNA of claim 1, wherein the region of complementarity is 19 nucleotides in length.

28. The dsRNA of claim 1, wherein each strand of the dsRNA is 21 nucleotides in length.