Novel lipid formulations for nucleic acid delivery

Abstract

The present invention provides novel, stable lipid particles comprising one or more active agents or therapeutic agents, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles. More particularly, the present invention provides stable nucleic acid-lipid particles (SNALP) comprising a nucleic acid (such as one or more interfering RNA), methods of making the SNALP, and methods of delivering and/or administering the SNALP.

What is claimed is: 
     
         1 . A nucleic acid-lipid particle comprising:
 (a) a nucleic acid;   (b) a cationic lipid;   (c) a non-cationic lipid comprising up to 55 mol % of the total lipid present in the particle, wherein the non-cationic lipid comprises a neutral lipid component comprising a phospholipid of from 3 mol % to 15 mol % of the total lipid present in the particle; and   (d) a conjugated lipid that inhibits aggregation of particles comprising from 0.1 mol % to 2 mol % of the total lipid present in the particle.   
     
     
         2 . The nucleic acid-lipid particle of  claim 1 , wherein the nucleic acid comprises an RNA. 
     
     
         3 . The nucleic acid-lipid particle of  claim 2 , wherein the RNA comprises an mRNA. 
     
     
         4 . The nucleic acid-lipid particle of  claim 1 , wherein the phospholipid comprises from 4 mol % to 12 mol % of the total lipid present in the particle. 
     
     
         5 . The nucleic acid-lipid particle of  claim 1 , wherein the phospholipid comprises from 6 mol % to 12 mol % of the total lipid present in the particle. 
     
     
         6 . The nucleic acid-lipid particle of  claim 1 , wherein the neutral lipid component further comprises cholesterol or a derivative thereof. 
     
     
         7 . The nucleic acid-lipid particle of  claim 6 , wherein the cholesterol or derivative thereof comprises from 25 mol % to 45 mol % of the total lipid present in the particle. 
     
     
         8 . The nucleic acid-lipid particle of  claim 6 , wherein the cholesterol or derivative thereof comprises from 40 mol % to 45 mol % of the total lipid present in the particle. 
     
     
         9 . The nucleic acid-lipid particle of  claim 1 , wherein the conjugated lipid that inhibits aggregation of particles comprises a polyethyleneglycol (PEG)-lipid conjugate. 
     
     
         10 . The nucleic acid-lipid particle of  claim 9 , wherein the PEG-lipid conjugate comprises a PEG-diacylglycerol (PEG-DAG) conjugate, a PEG-dialkyloxypropyl (PEG-DAA) conjugate, or a mixture thereof. 
     
     
         11 . The nucleic acid-lipid particle of  claim 1 , wherein the conjugated lipid that inhibits aggregation of particles comprises from 0.5 mol % to 2 mol % of the total lipid present in the particle. 
     
     
         12 . The nucleic acid-lipid particle of  claim 1 , wherein the conjugated lipid that inhibits aggregation of particles comprises from 1 mol % to 2 mol % of the total lipid present in the particle. 
     
     
         13 . The nucleic acid-lipid particle of  claim 1 , wherein the nucleic acid is fully encapsulated in the nucleic acid-lipid particle. 
     
     
         14 . A pharmaceutical composition comprising a nucleic acid-lipid particle of  claim 1  and a pharmaceutically acceptable carrier.