title: Virus-sized self-assembling lamellar complexes between plasmid DNA and cationic micelles promote gene transfer.
abstract: Gene therapy is based on the vectorization of genes to target cells and their subsequent expression. Cationic amphiphile-mediated delivery of plasmid DNA is the nonviral gene transfer method most often used. We examined the supramolecular structure of lipopolyamine/plasmid DNA complexes under various condensing conditions. Plasmid DNA complexation with lipopolyamine micelles whose mean diameter was 5 nm revealed three domains, depending on the lipopolyamine/plasmid DNA ratio. These domains respectively corresponded to negatively, neutrally, and positively charged complexes. Transmission electron microscopy and x-ray scattering experiments on complexes originating from these three domains showed that although their morphology depends on the lipopolyamine/plasmid DNA ratio, their particle structure consists of ordered domains characterized by even spacing of 80 A, irrespective of the lipid/DNA ratio. The most active lipopolyamine/DNA complexes for gene transfer were positively charged. They were characterized by fully condensed DNA inside spherical particles (diameter: 50 nm) sandwiched between lipid bilayers. These results show that supercoiled plasmid DNA is able to transform lipopolyamine micelles into a supramolecular organization characterized by ordered lamellar domains.
authors.affiliation: Vector Development, Rhône-Poulenc Rorer Gencell, 13 quai Jules Guesde, BP 14, 94403 Vitry-sur-seine Cedex, France. bruno.pitard@rp-rorer.fr
authors.forename: B
authors.initials: B
authors.lastname: Pitard
authors.forename: O
authors.initials: O
authors.lastname: Aguerre
authors.forename: M
authors.initials: M
authors.lastname: Airiau
authors.forename: A M
authors.initials: AM
authors.lastname: Lachagès
authors.forename: T
authors.initials: T
authors.lastname: Boukhnikachvili
authors.forename: G
authors.initials: G
authors.lastname: Byk
authors.forename: C
authors.initials: C
authors.lastname: Dubertret
authors.forename: C
authors.initials: C
authors.lastname: Herviou
authors.forename: D
authors.initials: D
authors.lastname: Scherman
authors.forename: J F
authors.initials: JF
authors.lastname: Mayaux
authors.forename: J
authors.initials: J
authors.lastname: Crouzet
mesh_terms: D004270:DNA, Circular / Q000235:genetics*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D010957:Plasmids / Q000235:genetics*; D011073:Polyamines; D014780:Viruses / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D004270:DNA, Circular; D011073:Polyamines