Correlation between structure and transfection efficiency: a study of DC-Chol-DOPE/DNA complexes

The supramolecular structural nature of some cationic liposomes-DNA complexes, currently used as vehicles in non-viral gene delivery, has been elucidated by recent X-ray diffraction experiments. The relationship between the chemico-physical properties of these self-assembled structures and their transfection efficiency is extensively studied. Here we report a first comprehensive structural study by using energy dispersive X-ray diffraction, of the complex DC-Chol-DOPE/DNA (3beta[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol dioleoylphosphatidylethanolamine/DNA), which has been classified as one of the most effective in in-vivo experiments. Our results show that DC-Chol-DOPE/DNA lipoplexes have a columnar inverted hexagonal structure, which is not influenced by the cationic liposome/DNA charge ratio. The transfection efficiency of C6 rat glioma cells by DC-Chol-DOPE/DNA lipoplexes and the toxicity of lipoplexes to cells are dramatically affected by cationic liposome/DNA weight ratio. It seems therefore that the lipoplex structures have not any influence on transfection efficiency and toxicity in our experimental system. (C) 2004 Elsevier B.V. All rights reserved.