Oligomeric compounds comprising bicyclic nucleosides and uses thereof
The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. In certain embodiments, the present invention provides compounds comprising oligonucleotides. In certain embodiments, such oligonucleotides comprise a region having a gapmer sugar motif. In certain embodiments, oligonucleotides comprise one or more type of modified sugar moieties and/or naturally occurring sugar moieties arranged along an oligonucleotide or region thereof in a defined pattern or sugar modification motif.
1. A compound comprising:
a modified oligonucleotide consisting of 10 to 20 linked nucleosides, wherein the modified oligonucleotide has a motif selected from: BBB-(D) 8 -BBBAA; BBB-(D) 7 -BBBAA; BBB-(D) 8 -BBBAAA; BBB-(D) 7 -BBBAAA; BABA-(D) 8 -ABAB; BABA-(D) 7 -ABAB; ABAB-(D) 8 -ABAB; ABAB-(D) 7 -ABAB; AABB-(D) 8 -BBAA; AABB-(D) 7 -BBAA; BBB-(D) 9 -BBA; BBB-(D) 8 -BBA; BBB-(D) 7 -BBA; ABBB-(D) 8 -BBBA; ABBB-(D) 7 -BBBA; ABBB-(D) 8 -BBBAA; ABBB-(D) 7 -BBBAA; AABBB-(D) 8 -BBB; AABBB-(D) 7 -BBB; AABBB-(D) 8 -BBBA; AABBB-(D) 7 -BBBA; ABBAABB-(D) 8 -BB; ABBAABB-(D) 7 -BB; ABBABB-(D) 8 -BBB; and ABBABB-(D) 7 -BBB;
wherein each B is a bicyclic nucleoside, each A is a non-bicyclic modified nucleoside, and each D is a 2′-deoxynucleoside.
2. The compound of claim 1 , wherein at least one B is a cEt nucleoside.
3. The compound of claim 2 , wherein each B is a cEt nucleoside.
4. The compound of claim 1 , wherein at least one B is a LNA nucleoside.
5. The compound of claim 4 , wherein each B is a LNA nucleoside.
6. The compound of claim 1 , wherein each B is either a cEt nucleoside or a LNA nucleoside.
7. The compound of claim 1 , wherein each B comprises the same bicyclic sugar moiety.
8. The compound of claim 1 , wherein at least one A is a 2′-MOE nucleoside.
9. The compound of claim 1 , wherein at least one A is a 2′-OMe nucleoside.
10. The compound of claim 1 , wherein each A comprises the same non-bicyclic modified sugar moiety.
11. The compound of claim 1 comprising at least one modified internucleoside linkage.
12. The compound of claim 11 comprising at least one phosphorothioate internucleoside linkage.
13. A method of modulating expression of a target nucleic acid in a cell comprising contacting the cell with a compound according to claim 1 .
14. The method of claim 13 , wherein the cell is in an animal.
15. The method of claim 14 , wherein the animal is a human.
16. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable diluent.
17. A method of modulating expression of a target nucleic acid in an animal comprising administering to the animal a pharmaceutical composition according to claim 16 .