1. J Gene Med. 2010 Jun;12(6):491-500.

Cationic and anionic lipoplexes inhibit gene transfection by electroporation in
vivo.

Mignet N, Vandermeulen G, Pembouong G, Largeau C, Thompson B, Spanedda MV,
Wasungu L, Rols MP, Bessodes M, Bureau MF, Préat V, Scherman D.

Inserm U1022- CNRS UMR8151, Paristech, Unité de Pharmacologie Chimique et
Génétique et d'Imagerie, Université Paris Descartes, Paris, France.
nathalie.mignet@parisdescartes.fr

BACKGROUND: Nonviral gene therapy still suffers from low efficiency. Methods that
would lead to higher gene expression level of longer duration would be a major
advance in this field. Lipidic vectors and physical methods have been
investigated separately, and both induced gene expression improvement. METHODS:
We sought to combine both chemical and physical methods. Cationic or anionic
lipids can potentially destabilize the cell membrane and could consequently
enhance gene delivery by a physical method such as electrotransfer. A plasmid
model encoding luciferase was used, either free or associated with
differently-charged lipoplexes before electrotransfer. RESULTS: Electrotransfer
alone strongly enhanced gene expression after intramuscular and intradermal
injection of naked DNA. On the other hand, cationic and anionic lipoplex
formulations decreased gene expression after electrotransfer, whereas
poorly-charged thiourea-based complexes, brought no benefit. Pre-injection of the
lipids, followed by administration of naked DNA, did not modified gene expression
induced by electroporation in the skin. CONCLUSIONS: The results obtained in the 
present study suggest that packing of DNA plasmid in lipoplexes strongly
decreases the efficiency of gene electrotransfer, independently of the lipoplex
charge. Non-aggregating complexes, such as poorly-charged thiourea-based
complexes, should be preferred to increase DNA release.

PMID: 20527042 [PubMed - in process]