HDL particles for delivery of nucleic acids

A high density lipoprotein-nucleic acid particle comprising:

• a) an apolipoprotein;
• b) a nucleic acid component comprising a therapeutic nucleic acid segment;
• and
• c) a polypeptide of 2 to 500 consecutive amino acids, wherein the polypeptide comprises a positively-charged region associated with the nucleic acid component;
• wherein the particle comprises a neutral phospholipid, and the neutral phospholipid is 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), egg phosphatidylcholine (“EPC”), dilauryloylphosphatidylcholine (“DLPC”), dimyristoylphosphatidylcholine (“DMPC”), dipalmitoylphosphatidylcholine (“DPPC”), distearoylphosphatidylcholine (“DSPC”), 1-myristoyl-2-palmitoyl phosphatidylcholine (“MPPC”), 1-palmitoyl-2-myristoyl phosphatidylcholine (“PMPC”), 1-palmitoyl-2-stearoyl phosphatidylcholine (“PSPC”), 1-stearoyl-2-palmitoyl phosphatidylcholine (“SPPC”), dimyristyl phosphatidylcholine (“DMPC”), 1,2-distearoyl-sn-glycero-3-phosphocholine (“DAPC”), 1,2-diarachidoyl-sn-glycero-3-phosphocholine (“DBPC”), 1,2-dieicosenoyl- sn-glycero-3-phosphocholine (“DEPC”), palmitoyloleoyl phosphatidylcholine (“POPC”), lysophosphatidylcholine, dilinoleoylphosphatidylcholine, distearoylphosphatidylethanolamine (“DSPE”), dimyristoyl phosphatidylethanolamine (“DMPE”), dipalmitoyl phosphatidylethanolamine (“DPPE”), palmitoyloleoyl phosphatidylethanolamine (“POPE”), or lysophosphatidylethanolamine.