MicroRNA Compounds and Methods for Modulating MIR-122

Abstract

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.

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 -N Q -N Q -N B -N B -N Q -N B -N Q -N B -N Q -N B -N B -(N Z ) Y   
                 
             
                
               
            
           
         
         wherein each R is, independently, a non-bicyclic nucleoside or a bicyclic nucleoside; 
         X is from 4 to 10; 
         each N B  is, independently, a bicyclic nucleoside; 
         each N Q  is, independently, a non-bicyclic nucleoside; 
         Y is 0 or 1; and 
         N Z  is a modified nucleoside or an unmodified nucleoside. 
       
     
     
         2 .- 114 . (canceled)