Methods and compositions for rnai mediated inhibition of gene expression in mammals

Abstract

Methods and compositions are provided for modulating, e.g., reducing, expression of a target sequence in mammals and mammalian cells in vivo. In the subject methods, an effective amount of an RNAi agent, e.g., an interfering ribonucleic acid (such as an siRNA or shRNA) is introduced into a target cell, e.g., by being administered to a mammal that includes the target cell, e.g., via intravascular injection. Also provided are RNAi agent pharmaceutical preparations for use in the subject methods. The subject methods and compositions find use in a variety of different applications, including academic and therapeutic applications.

1 . A method of reducing expression of a pathogenic viral nucleic acid sequence in target cell in a non-embryonic mammal, said method comprising:
 administering to said mammal, in vivo, an effective amount of an RNAi agent, said RNAi agent being specific for said pathogenic viral nucleic acid sequence present in said target cell in the non-embryonic mammal after viral infection thereof and having a duplex structure of about 15-29 nucleotides.   
     
     
         2 . The method according to  claim 1 , wherein said RNAi agent is an shRNA. 
     
     
         3 . The method according to  claim 1 , wherein said RNAi agent is an siRNA. 
     
     
         4 . The method according to  claim 2  or  3 , wherein said RNAi agent comprises a duplex structure about 15-25 base pairs in length. 
     
     
         5 . The method according to  claim 1 , wherein said non-embryonic mammal is an adult. 
     
     
         6 . The method according to  claim 1 , wherein said non-embryonic mammal is a juvenile. 
     
     
         7 . The method according to  claim 1 , wherein said RNAi agent is intravascularly administered to said non-embryonic mammal. 
     
     
         8 . The method according to  claim 7 , wherein the RNAi agent is administered to a peripheral vein of the mammal. 
     
     
         9 . The method of  claim 1 , wherein the pathogenic viral nucleic acid sequence present in the target cell is a genomic viral RNA sequence. 
     
     
         10 . The method of  claim 1 , wherein the pathogenic viral nucleic acid sequence present in the target cell is a transcript encoded by an RNA or DNA virus. 
     
     
         11 . The method of  claim 1 , wherein the pathogenic viral nucleic acid sequence present in the target cell is from an RNA viral infection. 
     
     
         12 . The method of  claim 1 , wherein the pathogenic viral nucleic acid sequence present in the target cell is from an DNA viral infection. 
     
     
         13 . The method of  claim 11  or  claim 12 , wherein the viral infection is a hepatitis viral infection.