MICRORNA COMPOUNDS AND METHODS FOR MODULATING MIR-122

摘要

Described herein are compositions and methods for the inhibition of miR-122 activity. The compositions have certain nucleoside modifications that yield potent inhibitors of miR-122 activity. The compounds may comprise conjugates to facilitate delivery to the liver. The compositions may be administered to subjects infected with hepatitis C virus, as a treatment for hepatitis C virus and related conditions.

主权项

1. A compound comprising a modified oligonucleotide consisting of 16 to 22 linked nucleosides, wherein the nucleobase sequence of the modified oligonucleotide is complementary to miR-122 (SEQ ID NO: 1) and wherein the modified oligonucleotide comprises at least 16 contiguous nucleosides of the following nucleoside pattern I in the 5′ to 3′ orientation:
(R)X—NQ—NQ—NB—NB—NQ—NB—NQ—NB—NQ—NB—NB—(NZ)Y wherein each R is, independently, a non-bicyclic nucleoside or a bicyclic nucleoside; X is from 4 to 10; each NB is, independently, a bicyclic nucleoside; each NQ is, independently, a non-bicyclic nucleoside; Y is 0 or 1; and NZ is a modified nucleoside or an unmodified nucleoside.