VIRUS-SIZED SELF-ASSEMBLING LAMELLAR COMPLEXES BETWEEN PLASMID DNA AND CATIONIC MICELLES PROMOTE GENE-TRANSFER

Gene therapy is based on the vectorization of genes to target cells an d their subsequent expression. Cationic amphiphile-mediated delivery o f plasmid DNA is the nonviral gene transfer method most often used, We examined the supramolecular structure of lipopolyamine/plasmid DNA co mplexes under various condensing conditions. Plasmid DNA complexation with lipopolyamine micelles whose mean diameter was 5 nm revealed thre e domains, depending on the lipopolyamine/plasmid DNA ratio. These dom ains respectively corresponded to negatively, neutrally, and positivel y charged complexes. Transmission electron microscopy and x-ray scatte ring experiments on complexes originating from these three domains she lved that although their morphology depends on the lipopolyamine/plasm id DNA ratio, their particle structure consists of ordered domains cha racterized by even spacing of 80 Angstrom, irrespective of the lipid/D NA ratio. The most active lipopolyamine/DNA complexes for gene transfe r were positively charged. They were characterized by fully condensed DNA inside spherical particles (diameter: 50 nm) sandwiched between li pid bilayers. These results show that supercoiled plasmid DNA is able to transform lipopolyamine micelles into a supramolecular organization characterized by ordered lamellar domains.