Compositions and methods for inhibiting expression of Mylip/Idol gene

1. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of Mylip/Idol, wherein said dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to a Mylip/Idol transcript which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO: 21.

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 consisting of:

a 2′-O-methyl modified nucleotide; a nucleotide comprising a 5′-phosphorothioate group; a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group; 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.

4. The dsRNA of claim 1 , wherein the region of complementarity is at least 17 nucleotides in length.

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

6. The dsRNA of claim 5 , wherein the region of complementarity is 19 nucleotides in length.

7. The dsRNA of claim 1 , wherein each strand is no more than 30 nucleotides in length.

8. The dsRNA of claim 1 , wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide.

9. The dsRNA of claim 1 , further comprising a ligand.

10. The dsRNA of claim 9 , wherein the ligand is conjugated to the 3′ end of the sense strand of the dsRNA.

11. A dsRNA for inhibiting the expression of Mylip/Idol, wherein the dsRNA comprises a sense strand consisting of a nucleotide sequence selected from the group consisting of:

SEQ ID NOs: 20, 22, 24, 26, 28, 32, and 34 and an antisense strand consisting of a nucleotide sequence selected from the group consisting of:

SEQ ID NOs: 21, 23, 25, 27, 29, 33, and 35.

12. A pharmaceutical composition for inhibiting expression of a Mylip/Idol gene comprising a dsRNA comprising a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to a Mylip/Idol transcript which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the sequence of SEQ ID NO: 21.

13. The pharmaceutical composition of claim 12 , further comprising a lipid formulation.

14. The pharmaceutical composition of claim 13 , wherein the lipid formulation is a SNALP, or XTC formulation.

15. A method of treating a disorder mediated by Mylip/Idol expression comprising administering to a human in need of such treatment a therapeutically effective amount of a dsRNA comprising a sense strand and an antisense strand,

the antisense strand comprising a region of complementarity to a Mylip/Idol transcript which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the sequence of SEQ ID NO: 21;

or a pharmaceutical composition comprising a dsRNA comprising a sense strand and an antisense strand,

the antisense strand comprising a region of complementarity to a Mylip/Idol transcript which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from one of the sequence of SEQ ID NO: 21.

16. The method of claim 15 , wherein the human has a lipid disorder.

17. The method of claim 15 , wherein the human has a disorder associated with cholesterol metabolism.

18. The method of claim 15 , wherein the human has diabetes or atherosclerosis.

19. The method of claim 17 , wherein the administration of the dsRNA to the subject causes a decrease in Low Density Lipoprotein cholesterol (LDLc) in the serum of the subject by at least 10%.

20. The method of claim 15 , wherein the dsRNA is administered at a concentration of 0.01 mg/kg-5 mg/kg bodyweight of the subject.

21. The dsRNA of claim 1 , wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO: 20 and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the corresponding antisense nucleotide sequence of SEQ ID NO: 21.

22. The method of claim 15 , wherein said dsRNA comprises at least one modified nucleotide.

23. The method of claim 22 , wherein at least one of said modified nucleotides is chosen from the group consisting of:

a 2′-methyl modified nucleotide; a nucleotide comprising a 5′-phosphorothioate group; a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group; 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.

24. The method of claim 15 , wherein the region of complementarity is at least 17 nucleotides in length.

25. The method of claim 15 , wherein the region of complementarity is between 19 and 21 nucleotides in length.

26. The method of claim 15 , wherein the region of complementarity is 19 nucleotides in length.

27. The method of claim 15 , wherein each strand is no more than 30 nucleotides in length.

28. The method of claim 15 , wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide.

29. The method of claim 15 , wherein the dsRNA further comprises a ligand.

30. The method of claim 29 , wherein the ligand is conjugated to the 3′ end of the sense strand of the dsRNA.

31. A method of treating a disorder mediated by Mylip/Idol expression comprising administering to a human in need of such treatment a therapeutically effective amount of a dsRNA comprising a sense strand consisting of a nucleotide sequence selected from the group consisting of:

SEQ ID NOs: 20, 22, 24, 26, 28, 32, and 34 and an antisense strand consisting of a nucleotide sequence selected from the group consisting of:

SEQ ID NOs: 21, 23, 25, 27, 29, 33, and 35.