Virus-sized self-assembling lamellar complexes between plasmid DNA and cationic micelles promote gene transfer

Bruno Pitard, Olivier Aguerre, Marc Airiau, Anne Marie Lachagès, Tsiala Boukhnikachvili, Gérardo Byk, Catherine Dubertret, Christian Herviou, Daniel Scherman, Jean François Mayaux, Joël Crouzet

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

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 Å, 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.

Original languageEnglish
Pages (from-to)14412-14417
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number26
DOIs
StatePublished - 23 Dec 1997
Externally publishedYes

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