Transfection of human macrophages by lipoplexes via the combined use of transferrin and pH-sensitive peptides

The crucial function of macrophages hi a variety of biological processes an d pathologies render these cells important targets for gene therapeutic int erventions. Commonly used synthetic gene delivery vectors have not been suc cessful in transfecting these non-dividing cells. A combination strategy in volving cationic liposomes to condense and carry DNA, transferrin to facili tate cellular uptake, and the pa-sensitive peptide GALA to promote endosome destabilization, resulted in significant expression of a luciferase gene. Transfection of macrophages TI as dependent on the degree of differentiatio n of the cells. The quaternary complexes of cationic liposomes, DNA, transf errin, and GALA exhibited a net negative charge, which may obviate a limita tion of cationic synthetic vectors in vivo. The lack of cytotoxicity and th e expected lack of immunogenicity of these complexes may render them useful for gene delivery to macrophages in vivo.