Human serum albumin enhances DNA transfection by lipoplexes and confers resistance to inhibition by serum

Cationic liposome-DNA complexes ('lipoplexes') are used as gene delivery ve hicles and may overcome some of the limitations of viral vectors for gene t herapy applications. The interaction of highly positively charged lipoplexe s with biological macromolecules in blood and tissues is one of the drawbac ks of this system. We examined whether coating cationic liposomes with huma n serum albumin (HSA) could generate complexes that maintained transfection activity. The association of HSA with liposomes composed of 1,2-dioleoyl-3 -(trimethylammonium) propane and dioleoylphosphatidylethanolamine, and subs equent complexation with the plasmid pCMVluc greatly increased luciferase e xpression in epithelial and lymphocytic cell lines above that obtained with plain lipoplexes. The percentage of cells transfected also increased by an order of magnitude. The zeta potential of the ternary complexes was lower than that of the lipoplexes. Transfection activity by HSA-lipoplexes was no t inhibited by up to 30% serum. The combined use of HSA and a pH-sensitive peptide resulted in significant gene expression in human primary macrophage s. HSA-lipoplexes mediated significantly higher gene expression than plain lipoplexes or naked DNA in the lungs and spleen of mice. Our results indica te that negatively charged HSA-lipoplexes can facilitate efficient transfec tion of cultured cells, and that they may overcome some of the problems ass ociated with the use of highly positively charged complexes for gene delive ry in vivo. (C) 2000 Elsevier Science B.V. All rights reserved.