Open AccessGene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides
Author(s) -
Sérgio Simões,
Vladimir Slepushkin,
Rogério Gaspar,
M.P. Lima,
Nejat Düzgüneş
Publication year - 1998
Publication title -
gene therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.332
H-Index - 159
eISSN - 1476-5462
pISSN - 0969-7128
DOI - 10.1038/sj.gt.3300674
Subject(s) - transferrin , transfection , liposome , cationic liposome , gene delivery , microbiology and biotechnology , lipofectamine , transferrin receptor , cationic polymerization , chemistry , peptide , dna , biology , biochemistry , gene , vector (molecular biology) , recombinant dna , organic chemistry
Potential problems with the use of viral vectors for gene therapy necessitate the development of efficient nonviral vectors. The association of transferrin, or the pH-sensitive peptide GALA, with cationic liposomes composed of 1,2-dioleoyl-3-(trimethylammonium) propane and its equimolar mixture with dioleoylphosphatidylethanolamine, under conditions where the liposome/DNA complex is negatively charged, drastically increased luciferase expression from pCMVluc. The percentage of cells transfected, measured by beta-galactosidase expression, was also increased by about 10-fold. The zeta potential of the ternary complexes was lower than that of the liposome/DNA complexes. Transfection activity of positively charged complexes was also enhanced by association with transferrin, GALA or the influenza hemagglutinin N terminal peptide HA-2, but to a smaller extent compared with the negatively charged complexes. The enhancement of gene delivery by transferrin or GALA was not affected significantly by the presence of serum and did not cause significant cytotoxicity. Our results indicate that negatively charged ternary complexes of cationic liposomes, DNA and transferrin, or fusigenic peptides, can facilitate efficient transfection of cultured cells, and that they may alleviate the drawbacks of the use of highly positively charged complexes for gene delivery in vivo.