Cationic and anionic lipoplexes inhibit gene transfection by electroporation in vivo

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....

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Published in:The journal of gene medicine 2010-06, Vol.12 (6), p.491-500
Main Authors: Mignet, Nathalie, Vandermeulen, Gaëlle, Pembouong, Gaëlle, Largeau, Céline, Thompson, Betty, Spanedda, Maria-Vittoria, Wasungu, Luc, Rols, Marie-Pierre, Bessodes, Michel, Bureau, Michel F., Préat, Véronique, Scherman, Daniel
Format: Article
Language:English
Subjects:
Animals
Cations - chemistry
Cations - metabolism
CHO Cells
Cricetinae
Cricetulus
DNA - chemistry
Electroporation - methods
electrotransfer
Female
Gene therapy
Gene Transfer Techniques
lipoplexes
Liposomes - chemistry
Liposomes - metabolism
lyophilization
Mice
Mice, Inbred BALB C
Muscle, Skeletal - cytology
Muscle, Skeletal - physiology
nonviral vectors
Plasmids - chemistry
Plasmids - genetics
Skin - cytology
Skin - metabolism
Transfection
uptake of DNA complexes
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Summary: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. Copyright © 2010 John Wiley & Sons, Ltd.
ISSN:1099-498X
1521-2254
1521-2254
DOI:10.1002/jgm.1460