In vivo delivery of nucleic acids to the liver or liver tissue

Abstract

The invention encompasses methods of delivering nucleic acids, including dsRNA, to mammalian target cells in vivo via intercellular transfer, wherein the dsRNA is delivered to or expressed in a first cell different from the target cell, wherein the first cell facilitates delivery of the dsRNA to the target cell.

What is claimed: 
     
         1 . A method of delivering at least one RNA to a target cell in an animal comprising: transfecting a first cell in vitro with a nucleic acid encoding said RNA, isolating at least one exovesicle from said first cell wherein said exovesicle contains said RNA, and contacting said target cell with said exovesicle. 
     
     
         2 . The method of  claim 1 , wherein said RNA is a dsRNA. 
     
     
         3 . The method of  claim 1 , wherein said first cell is a muscle cell or a skin cell. 
     
     
         4 . The method of  claim 1 , wherein a nucleic acid expressing a transmembrane or surface ligand specific for said target cell is co-transfected with said nucleic acid encoding said RNA. 
     
     
         5 . The method of  claim 4 , wherein said nucleic acid expressing said transmembrane or surface ligand and said nucleic acid encoding said dsRNA are encoded on a single plasmid. 
     
     
         6 . A method of delivering at least one RNA to a target organ or tissue in an animal comprising transfecting at least one first cell ex vivo with a nucleic acid encoding said RNA, and introducing said transfected cell into said animal, wherein said introduction results in said RNA being delivered to at least one second cell in said target organ or tissue, wherein said target organ or tissue is distal from the site of introduction of said transfected first cell. 
     
     
         7 . The method of  claim 6 , wherein said RNA is a dsRNA. 
     
     
         8 . The method of  claim 6 , wherein said first cell is a muscle cell or a skin cell. 
     
     
         9 . The method of  claim 6 , wherein a nucleic acid expressing a transmembrane or surface ligand specific for said target cell is co-transfected with said nucleic acid encoding said RNA. 
     
     
         10 . The method of  claim 9 , wherein said nucleic acid expressing said transmembrane or surface ligand and said nucleic acid encoding said dsRNA are encoded on a single plasmid.