Oligomeric compounds and compositions for use in modulation of small non-coding RNAs
Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.
1. A method for inhibiting miR-122 in a cell, comprising contacting the cell with an oligomeric compound comprising an oligonucleotide consisting of 17 to 25 linked nucleosides, wherein the oligonucleotide is at least 90% complementary to nucleotides 29 to 51 of SEQ ID NO: 30, and wherein each nucleoside comprises a 2′-O-methoxyethyl sugar modification; and thereby inhibiting miR-122 in the cell.
2. The method of claim 1 wherein at least one internucleoside linkage of said oligomeric compound is a phosphorothioate internucleotide linkage.
3. The method of claim 2 wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.
4. The method of claim 1 wherein the oligonucleotide is at least 95% complementary to nucleotides 29 to 51 of SEQ ID NO: 30.
5. The method of claim 1 wherein the oligonucleotide is 100% complementary to nucleotides 29 to 51 of SEQ ID NO: 30.
6. The method of claim 1 , wherein at least one cytidine of said oligomeric compound is a 5-methylcytidine.
7. The method of claim 6 , wherein each cytidine is a 5-methylcytidine.
8. The method of claim 1 , wherein the oligomeric compound is an oligonucleotide.
9. The method of claim 1 , wherein said oligomeric compound comprises at least one conjugate moiety.
10. The method of claim 9 , wherein the conjugate moiety is cholesterol.
11. A method for inhibiting miR-122 in a cell comprising contacting the cell with an oligonucleotide consisting of 23 linked nucleosides and having the sequence of nucleobases set forth in SEQ ID NO: 313, wherein each nucleoside comprises a 2′-O-methoxyethyl sugar modification, wherein each internucleoside linkage is a phosphorothioate internucleoside linkage, and wherein each cytidine is a 5-methylcytidine; and thereby inhibiting miR-122 in the cell.
12. The method of claim 11 , wherein said cell is contacted with a composition comprising the oligonucleotide and a pharmaceutically acceptable diluent.
13. The method of claim 1 , wherein the oligonucleotide consists of 19 to 23 linked nucleosides.
14. The method of claim 1 , wherein the oligonucleotide consists of 22 linked nucleosides.
15. The method of claim 1 , wherein the oligonucleotide consists of 23 linked nucleosides.
16. A method for inhibiting miR-122 in a cell comprising contacting the cell with oligomeric compound comprising an oligonucleotide consisting of 15 to 30 linked nucleosides, wherein the oligonucleotide is at least 90% complementary to nucleotides 29 to 51 of SEQ ID NO: 30, and wherein each nucleoside comprises a sugar modification; and thereby inhibiting miR-122 in the cell.
17. The method of claim 16 , wherein at least one sugar modification is a 2′-O-methoxyethyl sugar modification.
18. The method of claim 17 , wherein each sugar modification is a 2′-O-methoxyethyl sugar modification.
19. The method of claim 16 , wherein at least one sugar modification is a bicyclic sugar modification.
20. The method of claim 16 , wherein at least one internucleoside linkage of said oligomeric compound is a phosphorothioate internucleoside linkage.
21. The method of claim 20 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.
22. The method of claim 16 , wherein said oligomeric compound comprises at least one modified cytidine, wherein the modified cytidine is a 5-methylcytidine.
23. The method of claim 22 wherein each cytidine is a 5-methylcytidine.
24. The method of claim 16 wherein the oligonucleotide is at least 95% complementary to SEQ ID NO: 30.
25. The method of claim 16 wherein the oligonucleotide is 100% complementary to SEQ ID NO: 30.
26. The method of claim 16 wherein the oligonucleotide consists of 17 to 25 linked nucleosides.
27. The method of claim 16 wherein the oligonucleotide consists of 19 to 23 linked nucleosides.
28. The method of claim 16 wherein the oligonucleotide consists of 23 linked nucleosides.
29. The method oligomeric compound of claim 16 wherein the oligonucleotide consists of 22 linked nucleosides.
30. The method of claim 16 wherein the oligomeric compound consists of an oligonucleotide.
31. A method for inhibiting miR-122 in a cell comprising contacting the cell with an oligonucleotide consisting of 15 to 30 linked nucleosides, wherein each nucleoside comprises a sugar modification, wherein each internucleoside linkage is a phosphorothioate internucleoside linkage, and wherein the oligonucleotide is at least 90% complementary to nucleotides 29 to 51 of SEQ ID NO: 30 and thereby inhibiting miR-122 in the cell.
32. The method of claim 31 , wherein said oligonucleotide consists of 17 to 25 linked nucleosides.
33. The method of claim 31 , wherein said oligonucleotide consists of 19 to 23 linked nucleosides.
34. The method of claim 31 , wherein said oligonucleotide consists of 22 linked nucleosides.
35. The method of claim 31 , wherein said oligonucleotide consists of 23 linked nucleosides.
36. The method of claim 31 wherein at least one sugar modification of said oligonucleotide is a 2′-O-methoxyethyl sugar modification.
37. The method of claim 36 , wherein each sugar modification is a 2′-O-methoxyethyl sugar modification.
38. The method of claim 31 , wherein at least one sugar modification of said nucleotide is a bicyclic sugar modification.
39. The method of claim 31 , wherein the oligonucleotide is at least 95% complementary to SEQ ID NO: 30.
40. The method of claim 31 , wherein the oligonucleotide is 100% complementary to SEQ ID NO: 30.