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Direct gene transfer into rat articular cartilage by in vivo electroporation

LAURENT GROSSIN¹, CHRISTEL COURNIL-HENRIONNET¹, LLUIS M. MIR, BERTRAND LIAGRE, DOMINIQUE DUMAS^*, STÉPHANIE ETIENNE, CORINNE GUINGAMP, PATRICK NETTER² and PIERRE GILLET

Unité Mixte de Recherches 7561, Centre National de la Recherche Scientifique-Université Henri Poincaré Nancy 1, Faculté de Médecine, BP184, F-54505 Vandoeuvre lès Nancy, France;
^* Unité Mixte de Recherches 7563 "Mécanique et Ingénierie Cellulaire et Tissulaire" (LEMTA), Centre National de la Recherche Scientifique, Université Henri Poincaré Nancy 1, Faculté de Médecine, BP184, F-54505 Vandoeuvre lès Nancy, France; and
Unité Mixte de Recherche 8121 "Vectorologie et transfert de gènes" Centre National de la Recherche Scientifique, Institut Gustave-Roussy, F-94805 Villejuif Cedex, France

²Correspondence: Unité Mixte de Recherches 7561, Centre National de la Recherche Scientifique-Université Henri Poincaré Nancy 1, Faculté de Médecine, Avenue de la Forêt de Haye, BP184, F-54505 Vandoeuvre lès Nancy, France. E-mail: Patrick.Netter{at}medecine.uhp-nancy.fr

To establish a system for efficient direct in vivo gene targeting into rat joint, we have evaluated a strategy of gene transfer by means of the delivery of external electric pulses (EP) to the knee after intra-articular injection of a reporter gene (GFP). Rats were killed at various times after the electro gene-therapy to analyze GFP gene expression by immunohistochemistry. GFP staining was detected in the superficial, middle, and deep zones of the patellar cartilage at days 2 and 9, and thereafter only in the deep zone (months 1 and 2). The average percentage of GFP-positive cells was estimated at 30% both one and 2 months after the gene transfer. Moreover, no pathologic change caused by the EP was detected in the cartilage. The level and stability of the long-term GFP expression found in this study demonstrate the feasibility of a treatment of joint disorders (inflammatory or degenerative, focal or diffuse) using electric gene transfer.—Grossin, L., Cournil-Henrionnet, C., Mir, L. M., Liagre, B., Dumas, D., Etienne, S., Guingamp, C., Netter, P., Gillet, P. Direct gene transfer into rat articular cartilage by in vivo electroporation.

Key Words: electropermeabilization • in vivo gene transfer • electro gene therapy • GFP • patellar cartilage

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