Compositions and methods for inhibiting expression of XBP-1 gene

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.