Stabilization of cationic liposome-plasmid DNA complexes by polyamines and poly(ethylene glycol)-phospholipid conjugates for efficient in vivo gene delivery.
Stable complexes of cationic liposomes with plasmid DNA were prepared by (1) including a small amount of poly(ethylene glycol)-phospholipid conjugate or (2) condensing the DNA with polyamines prior to the formation of liposome-plasmid complexes. These preparations were stable for months at 4 degrees C and gave reproducible high transfection activity for in vivo gene delivery after intravenous injection in mice. Under these conditions, the expression of marker gene (luciferase) was primarily in the lungs (reaching values up to 3 ng expression per mg tissue protein), but also in other tissues to a lesser extent. Non-stabilized formulations lost all their transfection activity in 4 days. In these formulations cholesterol, not dioleoylphosphatidylethanolamine, was the helper lipid effective for sustaining high transfection activity in vivo. These new developments in formulation technology should enhance the potential for liposome-mediated gene therapy.
Hong
K
K
Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA. keelung@itsa.ucsf.edu
Zheng
W
W
Baker
A
A
Papahadjopoulos
D
D
D000818:Animals; D002412:Cations; D002784:Cholesterol / Q000737:chemistry; D004247:DNA; D004337:Drug Carriers; D005260:Female; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D006801:Humans; D008081:Liposomes; D008156:Luciferases / Q000235:genetics; D051379:Mice; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D010957:Plasmids; D011073:Polyamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011073:Polyamines; D000644:Quaternary Ammonium Compounds; C015831:dimethyldioctadecylammonium; D011092:Polyethylene Glycols; C020888:1,2-dielaidoylphosphatidylethanolamine; D004247:DNA; D002784:Cholesterol; D008156:Luciferases