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  • Title: Cationic and anionic lipoplexes inhibit gene transfection by electroporation in vivo.
    Author: Mignet N, Vandermeulen G, Pembouong G, Largeau C, Thompson B, Spanedda MV, Wasungu L, Rols MP, Bessodes M, Bureau MF, Préat V, Scherman D.
    Journal: J Gene Med; 2010 Jun; 12(6):491-500. PubMed ID: 20527042.
    Abstract:
    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.
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