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 forma tion of liposome-plasmid complexes, These preparations were stable for months at 4 degrees C and gave reproducible high transfection activit y for in vivo gene delivery after intravenous injection in mice. Under these conditions, the expression of marker gene (luciferase) was prim arily in the lungs (reaching values up to 3 ng expression per mg tissu e protein), but also in other tissues to a lesser extent. Non-stabiliz ed formulations lost all their transfection activity in 4 days. In the se formulations cholesterol, not dioleoylphosphatidylethanolamine, was the helper lipid effective for sustaining high transfection activity in vivo. These new developments in formulation technology should enhan ce the potential for liposome-mediated gene therapy.