Oligomeric compounds and compositions for the use in modulation of micrornas

1. An oligomeric compound comprising a contiguous sequence of nucleotides having the formula:

5′-MMmmMmMMMmmmmMMMMmmmmm-3′ or

5′-MMmMMmMMmMMmMMmMMmMMmMM-3′, wherein

M and m are each 2′-modified nucleosides, wherein the 2′-modified nucleosides of M and m are not the same.

2. The oligomeric compound of claim 1 , wherein

M is a 2′-MOE modified nucleoside and

m is a bicyclic sugar modified nucleoside.

3. The oligomeric compound of claim 1 , wherein

M is a 2′-MOE modified nucleoside,

m is a bicyclic sugar modified nucleoside having a 4′-(CH 2 ) n —O-2′ bridge, and

n is 1 or 2.

4. The oligomeric compound of claim 1 , wherein

M is a 2′-MOE modified nucleoside and

m is a 2′-F modified nucleoside.

5. The oligomeric compound of claim 1 , wherein

M is a 2′-OMe modified nucleoside and

m is a 2′-F modified nucleoside.

6. The oligomeric compound of claim 1 , wherein M is a 2′-modified nucleoside that comprises a 2′-substituent group selected from O—C 1 -C 12 alkyl, substituted O—C 1 -C 12 alkyl, O—C 2 -C 12 alkenyl, substituted O—C 2 -C 12 alkenyl, O—C 2 -C 12 alkynyl, substituted O—C 2 -C 12 alkynyl, amino, substituted amino, amide, substituted amide, aralkyl, substituted aralkyl, O-aralkyl, substituted O-aralkyl, N 3 , SH, CN, OCN, CF 3 , OCF 3 , SOCH 3 , —SO 2 CH 3 , heterocycloalkyl, heterocycloalkaryl, aminoalkylamino and polyalkylamino; and

wherein each substituent group is, independently, halogen, C 1 -C 12 alkyl, substituted C 1 -C 12 alkyl, C 2 -C 12 alkenyl, substituted C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, substituted C 2 -C 12 alkynyl, O—C 1 -C 12 alkyl, substituted O—C 1 -C 12 alkyl, S—C 1 -C 12 alkyl, substituted S—C 1 -C 12 alkyl, acyl (C(═O)—H), substituted acyl, amino, substituted amino, amide, substituted amide, C 1 -C 12 alkylamino, substituted C 1 -C 12 alkylamino, C 1 -C 12 aminoalkoxy, substituted C 1 -C 12 aminoalkoxy, C 1 -C 12 alkylaminooxy, substituted C 1 -C 12 alkylaminooxy, guanidinyl, substituted guanidinyl or a protecting group.

7. The oligomeric compound of claim 6 wherein M is a 2′-modified nucleoside that independently comprises a 2′-substituent group selected from O(CH 2 ) 0-2 CH 3 , O(CH 2 ) 2 OCH 3 , O(CH 2 ) 2 SCH 3 , OCH 2 C(H)CH 2 , O(CH 2 ) 2 ON(CH 3 ) 2 and OCH 2 C(═O)N(H)CH 3 .

8. The oligomeric compound of claim 7 , wherein m is a bicyclic sugar modified nucleoside.

9. The oligomeric compound of claim 7 , wherein m is a 2′-F modified nucleoside.

10. The oligomeric compound of claim 1 wherein m is a bicyclic sugar modified nucleoside that independently comprises a bridge group between the 2′ and the 4′-carbon atoms comprising from 1 to 8 linked biradical groups independently selected from —O—, —S—, —N(R 1 )—, —C(R 1 )(R 2 )—, —C(R 1 )═C(R 1 )—, —C(═NR 1 )—, —S(═O) 2 —, —S(═O)—, —C(═O)— and —C(═S)—;

each R 1 and R 2 is, independently, H, hydroxyl, C 1 -C 12 alkyl, substituted C 1 -C 12 alkyl, C 2 -C 12 alkenyl, substituted C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, substituted C 2 -C 12 alkynyl, C 5 -C 20 aryl, substituted C 5 -C 20 aryl, a heterocycle radical, a substituted heterocycle radical, heteroaryl, substituted heteroaryl, C 5 -C 7 alicyclic radical, substituted C 5 -C 7 alicyclic radical, halogen, substituted oxy (—O—), amino, substituted amino, azido, carboxyl, substituted carboxyl, acyl, substituted acyl, CN, thiol, substituted thiol, sulfonyl (S(═O) 2 —H), substituted sulfonyl, sulfoxyl (S(═O)—H) or substituted sulfoxyl; and

wherein each substituent group is, independently, halogen, C 1 -C 12 alkyl, substituted C 1 -C 12 alkyl, C 2 -C 12 alkenyl, substituted C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, substituted C 2 -C 12 alkynyl, amino, substituted amino, acyl, substituted acyl, C 1 -C 12 aminoalkyl, C 1 -C 12 aminoalkoxy, substituted C 1 -C 12 aminoalkyl, substituted C 1 -C 12 aminoalkoxy or a protecting group.

11. The oligomeric compound of claim 10 , wherein M is a 2′-MOE modified nucleoside.

12. The oligomeric compound of claim 1 , wherein M is a 2′-F modified nucleoside.

13. The oligomeric compound of claim 12 , wherein M is a bicyclic sugar modified nucleoside.

14. The oligomeric compound of claim 1 , comprising at least one phosphorothioate internucleoside linkage group.

15. The oligomeric compound of claim 14 , wherein each internucleoside linkage group is a phosphorothioate internucleoside linkage group.