Lipid encapsulated interfering rna

Abstract

The present invention provides compositions and methods for silencing gene expression by delivering nucleic acid-lipid particles comprising a siRNA molecule to a cell.

1 - 51 . (canceled) 
     
     
         52 . A nucleic acid-lipid particle, said nucleic acid-lipid particle comprising:
 an interfering RNA;   a cationic lipid;   a non-cationic lipid; and   a conjugated lipid that inhibits aggregation of particles.   
     
     
         53 . The nucleic acid-lipid particle of  claim 52 , wherein said interfering RNA is fully encapsulated in said nucleic acid-lipid particle. 
     
     
         54 . The nucleic acid-lipid particle of  claim 52 , wherein said interfering RNA silences the expression of a gene selected from the group consisting of a gene associated with viral infection and survival, a gene associated with a metabolic disease or disorder, and a gene associated with tumorigenesis and cell transformation. 
     
     
         55 . The nucleic acid-lipid particle of  claim 52 , wherein said interfering RNA comprises an siRNA. 
     
     
         56 . The nucleic acid-lipid particle of  claim 55 , wherein said siRNA is about 19 to about 25 base pairs in length. 
     
     
         57 . The nucleic acid-lipid particle of  claim 55 , wherein said siRNA comprises 3′ overhangs. 
     
     
         58 . The nucleic acid-lipid particle of  claim 55 , wherein said siRNA comprises 2′-O-methyl ribonucleotides. 
     
     
         59 . The nucleic acid-lipid particle of  claim 52 , wherein the conjugated lipid that inhibits aggregation of particles comprises a polyethyleneglycol (PEG)-lipid conjugate, a polyamide (ATTA)-lipid conjugate, or combinations thereof. 
     
     
         60 . The nucleic acid-lipid particle of  claim 52 , wherein the conjugated lipid that inhibits aggregation of particles comprises a PEG-diacylglycerol (DAG) conjugate, a PEG-dialkyloxypropyl (DAA) conjugate, a PEG-phospholipid conjugate, a PEG-ceramide conjugate, or combinations thereof. 
     
     
         61 . The nucleic acid-lipid particle of  claim 60 , wherein the PEG-DAA conjugate is selected from the group consisting of a PEG-dilauryloxypropyl (C 12 ), a PEG-dimyristyloxypropyl (C 14 ), a PEG-dipalmityloxypropyl (C 16 ), a PEG-distearyloxypropyl (C 18 ), and combinations thereof. 
     
     
         62 . The nucleic acid-lipid particle of  claim 52 , wherein said non-cationic lipid comprises a phospholipid and cholesterol. 
     
     
         63 . The nucleic acid-lipid particle of  claim 52 , wherein said particle has a median diameter of less than about 100 nm. 
     
     
         64 . A pharmaceutical composition comprising a nucleic acid-lipid particle of  claim 52  and a pharmaceutically acceptable carrier. 
     
     
         65 . A method of introducing an interfering RNA into a cell, said method comprising contacting said cell with a nucleic acid-lipid particle of  claim 52 . 
     
     
         66 . A method for silencing the expression of a target sequence, said method comprising administering to a mammalian subject a therapeutically effective amount of a nucleic acid-lipid particle of  claim 52 . 
     
     
         67 . A method for the in vivo delivery of an interfering RNA, said method comprising administering to a mammalian subject a nucleic acid-lipid particle of  claim 52 . 
     
     
         68 . A method for the in vivo delivery of an interfering RNA to a liver cell, said method comprising administering to a mammalian subject a nucleic acid-lipid particle of  claim 52 . 
     
     
         69 . A method for treating a disease in a mammalian subject, said method comprising administering to said mammalian subject a therapeutically effective amount of a nucleic acid-lipid particle of  claim 52 .