Plasmid DNA size does not affect the physicochemical properties of lipoplexes but modulates gene transfer efficiency

Clinical applications of gene therapy mainly depend on the development of e fficient gene transfer vectors. Large DNA molecules can only be transfected into cells by using synthetic vectors such as cationic lipids and polymers . The present investigation was therefore designed to explore the physicoch emical properties of cationic lipid-DNA particles, with plasmids ranging fr om 900 to 52 500 bp. The colloidal stability of the lipoplexes formed by co mplexing lipopolyamine micelles with plasmid DNA of various lengths, depend ing on the charge ratio, resulted in the formation of three domains, respec tively corresponding to negatively, neutrally and positively charged lipopl exes. Lipoplex morphology and structure were determined by the physicochemi cal characteristics of the DNA and of the cationic lipid. Thus, the lamella r spacing of the structure was determined by the cationic lipid and its sph erical morphology by the DNA. The main result of this study was that the mo rphological and structural features of the lipopolyamine-DNA complexes did not depend on plasmid DNA length. On the other hand, their gene transfer ca pacity was affected by the sire of plasmid DNA molecules which were sandwic hed between the lipid bilayers. The most effective lipopolyamine-DNA comple xes for gene transfer were those containing the shortest plasmid DNA.