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 of inhibiting the activity, function, or amount of miR-21, comprising:
contacting a cell with a compound comprising a modified oligonucleotide consisting of 8, 9, 10, 11, or 12 monomeric subunits, wherein the modified oligonucleotide is 100% complementary to miR-21, and wherein each monomeric subunit of the modified oligonucleotide comprises a modified sugar moiety;
and thereby inhibiting the activity, function, or amount of miR-21.
2. The method of claim 1 wherein the modified oligonucleotide consists of 8 monomeric subunits.
3. The method of claim 1 wherein the modified oligonucleotide consists of 9 monomeric subunits.
4. The method of claim 1 wherein the modified oligonucleotide comprises one or more modifications selected from a modified internucleoside linkage and a modified nucleobase.
5. The method of claim 1 wherein each modified sugar moiety is independently selected from 2′-F, 2′-O-methyl, 2′-O-methoxyethyl, and a bicyclic sugar moiety.
6. The method of claim 4 wherein the modified internucleoside linkage is a phosphorothioate linkage.
7. The method of claim 1 wherein at least one modified sugar moiety is 2′-O-methoxyethyl.
8. The method of claim 1 wherein each internucleoside linkage of the modified oligonucleotide is a phosphorothioate internucleoside linkage.
9. The method of claim 1 wherein the modified oligonucleotide is attached to a conjugate group.
10. The method of claim 9 wherein the conjugate group is a cholesterol.
11. The method of claim 5 , wherein the bicyclic sugar moiety is has a 4′-CH 2 —O-2′bridge.
12. The method of claim 1 wherein the modified oligonucleotide consists of 10 monomeric subunits.
13. The method of claim 1 wherein the modified oligonucleotide consists of 11 monomeric subunits.
14. The method of claim 1 wherein the modified oligonucleotide consists of 12 monomeric subunits.
15. The method of claim 1 , wherein the miR-21 has the sequence of SEQ ID NO: 236.
16. The method of claim 9 , wherein the conjugate group comprises a carbohydrate.
17. The method of claim 1 , wherein each modified sugar moiety is a bicyclic sugar moiety having a 4′-CH 2 —O-2′bridge.
18. A method of inhibiting the activity, function, or amount of miR-21 in a subject, the method comprising administering to the subject a compound comprising a modified oligonucleotide, wherein:
the modified oligonucleotide is 100% complementary to miR-21;
the modified oligonucleotide consists of 8, 9, 10, 11, or 12 linked monomeric subunits; wherein each monomeric subunit of the modified oligonucleotide comprises a modified sugar moiety.
19. The method of claim 18 wherein the modified oligonucleotide consists of 8 monomeric subunits.
20. The method of claim 18 wherein the modified oligonucleotide consists of 9 monomeric subunits.
21. The method of claim 18 wherein each modified sugar moiety is independently selected from 2′-F, 2′-O-methyl, 2′-O-methoxyethyl, and a bicyclic sugar moiety.
22. The method of claim 18 wherein each internucleoside linkage of the modified oligonucleotide is a phosphorothioate internucleoside linkage.
23. The method of claim 18 wherein the modified oligonucleotide is attached to a conjugate group.
24. The method of claim 23 wherein the conjugate group is a cholesterol.
25. The method of claim 23 , wherein the conjugate group comprises a carbohydrate.
26. The method of claim 21 , wherein the bicyclic sugar moiety has a 4′-CH 2 —O-2′ bridge.
27. The method of claim 18 , wherein the miR-21 comprises the sequence of SEQ ID NO: 236.
28. The method of claim 18 , wherein each modified sugar moiety is a bicyclic sugar moiety having a 4′-CH 2 —O-2′bridge.