Cationic liposome-mediated gene delivery via systemic administration

Cationic liposomes have been studied as a potential carrier for delivering genes to cells for the purpose of gene therapy. This report summarizes our efforts to characterize the in vivo expression of transgene delivered by cationic liposomes via intravenous administrtion. Using a CMV driven gene expression system containing cDNA of luciferase or green fluorescence protein gene as a reporter and two commonly used cationic lipids, 2, 3-dioleoyloxypropyl-1-trimethyl ammonium chloride (DOTMA) and 2, 3-dioleoyloxyl-1-trimethylammonium propanyl chloride (DOTAP), we demonstrate that a significant level of gene expression can be obtained in different organs including the lung, heart, spleen, liver and kidneys following intravenous administration in the mouse. Our finding show that the transfection efficiency of cationic liposomes is determined by the structure of the cationic lipids, the lipid composition of liposomes and cationic lipid to DNA ratio. Furthermore, gene expression was short in duration, peaked between 4-24 hours post injection, and dropped to less than 1% of the peak level within a 4 day period. Experiments with repeated injections revealed that cells initially transfected by the first transfection were not fully responsive to the subsequent second transfection for approximately 14 days.