Methods and Compositions for RNAi Mediated Inhibition of Gene Expression in Mammals

Abstract

Methods and compositions are provided for modulating, e.g., reducing, coding sequence expression in mammals. In the subject methods, an effective amount of an RNAi agent, e.g., an interfering ribonucleic acid (such as an siRNA or shRNA) or a transcription template thereof, e.g., a DNA encoding an shRNA, is administered to a non-embryonic mammal, e.g., via a hydrodynamic administration protocol. 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 target RNA in a target cell of a non-embryonic mammal in vivo, said method comprising:
 administering to said mammal an effective amount of an RNAi agent specific for said target RNA to reduce expression of said target RNA in said target cell.   
     
     
         2 . The method according to  claim 1 , wherein said RNAi agent is a short hairpin RNA (shRNA). 
     
     
         3 - 7 . (canceled) 
     
     
         8 . The method according to  claim 1 , wherein said non-embryonic mammal is an adult. 
     
     
         9 . The method according to  claim 1 , wherein said non-embryonic mammal is a juvenile. 
     
     
         10 - 20 . (canceled) 
     
     
         21 . The method according to  claim 1 , wherein said target cell is a hepatic cell. 
     
     
         22 . The method according to  claim 1 , wherein said method further comprises administering an RNAse inhibitor. 
     
     
         23 - 37 . (canceled) 
     
     
         38 . The method according to  claim 1 , wherein the target RNA is an endogenous mRNA. 
     
     
         39 . The method according to  claim 1 , wherein the target RNA is pathogen RNA. 
     
     
         40 . The method according to  claim 39 , wherein the pathogen is a virus. 
     
     
         40 . The method according to  claim 1 , wherein the RNAi agent is chemically modified. 
     
     
         41 . The method according to  claim 40 , wherein the chemically modified RNAi agent comprises one or more backbone modifications selected from the group consisting of: a phosphorodiamidate, a methylphosphonate, a phosphorothioate, a phosphorodithioate, a phosphoroamidite, an alkyl phosphotriester, and a boranophosphate. 
     
     
         42 . The method according to  claim 41 , wherein the chemically modified RNAi agent comprises a sugar modification. 
     
     
         43 . The method according to  claim 42 , wherein the chemically modified RNAi agent comprises a 2′-O-methyl sugar modification.