GENE DELIVERY BY NEGATIVELY CHARGED TERNARY COMPLEXES OF DNA, CATIONIC LIPOSOMES AND TRANSFERRIN OR FUSIGENIC PEPTIDES

Potential problems with the use of viral vectors for gene therapy nece ssitate the development of efficient nonviral vectors. The association of transferrin, or the PH-sensitive peptide GALA, with cationic lipos omes composed of 1,2-dioleoyl-3-(trimethylammonium) propane and its eq uimolar mixture with dioleoylphosphatidylethanolamine, under condition s where the lipsosome/DNA complex is negatively charged, drastically i ncreased luciferase expression from pCMVluc. The percentage of cells t ransfected, measured by beta-galactosidase expression, was also increa sed by about 10-fold. The zeta potential of the ternary complexes was lower than that of the liposome/DNA complexes. Transfection activity o f positively charged complexes was also enhanced by association with t ransferrin, GALA lot the influenza hemagglutinin N terminal peptide HA -2, but to a smaller extent compared with the negatively charged compl exes. The enhancement of gene delivery by transferrin or GALA was not affected significantly by the presence of serum and did not cause sign ificant cytotoxicity. Our results indicate that negatively charged ter nary complexes of cationic liposomes, DNA and transferrin, or fusigeni c peptides, can facilitate efficient transfection of cultured cells, a nd that they may alleviate the drawbacks of the use of highly positive ly charged complexes for gene delivery in vivo.