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A previous study has shown an efficient, systemic transinclusion of cholesterol as a helper lipid increased the in gene expression in mice via intravenous administration of vivo transfection efficiency of LPD and more importantly, a LPD formulation composed of DOTAP liposomes, protadecrease the amount of cationic lipid required for the maximine sulfate and plasmid DNA. In this study, factors affectmal level of gene expression. Studies on the interaction ing the in vivo performance of this formulation were further between mouse serum and LPD showed that LPD became evaluated. A protocol in which liposomes were mixed with negatively charged after exposure to serum, and LPDs protamine before the addition of plasmid DNA was shown containing different helper lipids varied in the amount of to produce small condensed particles with a diameter of associated serum proteins. LPD containing DOPE was about 135 nm. These particles were stable over time and more enriched in a protein corresponding to albumin in gave a high level of gene expression in all tissues exammolecular weight. These results suggest that the mechined including lung, heart, spleen, liver and kidney with the anism of LPD-mediated intravenous gene delivery might highest level of expression in the lung. Inclusion of dioleoylbe different from that of in vitro lipofection and that serum phosphatidylethanolamine (DOPE) as a helper lipid sigprotein association might be a major factor limiting the in nificantly decreased the in vivo activity of LPD. In contrast, vivo transfection by LPD.