Cochleate compositions directed against expression of proteins

Abstract

Disclosed herein are novel siRNA-cochleate and morpholino-cochleate compositions. Also disclosed are methods of making and using siRNA-cochleate and morpholino-cochleate compositions.

1 . An siRNA-cochleate composition comprising:
 a cochleate; and   an siRNA associated with the cochleate   
       wherein the siRNA is complexed with a transfection agent prior to contacting a liposome. 
     
     
         2 . The siRNA-cochleate composition of  claim 1 , wherein the siRNA comprises at least one mismatch. 
     
     
         3 . The siRNA-cochleate composition of  claim 1 , wherein the siRNA comprises at least one substitution. 
     
     
         4 . The siRNA-cochleate composition of  claim 1 , wherein the siRNA is about 21-23 nucleotides long. 
     
     
         5 . The siRNA-cochleate composition of  claim 1 , wherein the siRNA mediates RNA interference against a target mRNA. 
     
     
         6 . The siRNA-cochleate composition of  claim 5 , wherein the target mRNA expresses a protein selected from the group consisting of: a cancer protein, a virus protein, an HIV protein, a fungus protein, a bacterial protein, an abnormal cellular protein, a normal cellular protein. 
     
     
         7 . The siRNA-cochleate composition of  claim 1 , further comprising a second siRNA directed against a second target mRNA. 
     
     
         8 . The siRNA-cochleate composition of  claim 1 , wherein the cochleate comprises a negatively charged lipid component and a multivalent cation component. 
     
     
         9 . (canceled) 
     
     
         10 . The siRNA-cochleate composition of  claim 1 , wherein the transfection agent is a polycationic transfection agent. 
     
     
         11 . The siRNA-cochleate composition of  claim 1 , wherein the transfection agent is polyethylenimine (PEI) or a derivative thereof. 
     
     
         12 . The siRNA-cochleate composition of  claim 1 , further comprising at least one additional cargo moiety. 
     
     
         13 . The siRNA-cochleate composition of  claim 1 , further comprising an aggregation inhibitor. 
     
     
         14 - 24 . (canceled) 
     
     
         25 . A method of forming an siRNA-cochleate composition comprising: precipitating a liposome and an siRNA to form an siRNA-cochleate, wherein the siRNA is complexed with a transfection agent prior to precipitating. 
     
     
         26 . The method of  claim 25 , comprising adjusting the pH of a liposomal suspension of the siRNA. 
     
     
         27 . The method of  claim 25 , comprising charging the base pairs of the siRNA. 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 25 , wherein the transfection agent is mixed with the liposomes prior to adding the siRNA. 
     
     
         30 . The method of  claim 25 , wherein the transfection agent is PEI or a derivative thereof or other polyvalent cation. 
     
     
         31 . The method of  claim 25 , comprising using an elevated amount of calcium for precipitating the liposome and the siRNA. 
     
     
         32 . The method of  claim 25 , comprising the step of extruding the liposome an the siRNA prior to precipitation. 
     
     
         33 . The method of  claim 25 , wherein the siRNA-liposome is prepared by adding a chelating agent to a cochleate to form a liposome in the presence of siRNA. 
     
     
         34 - 63 . (canceled)