Genetic Engineering in Allotransplantation of Vascularized Organs

P.      Mathieu; C.      Chauveau; D.      Bouchet; C.      Guillot; L.      Tesson; I.      Anegon

Abstract

Transplantation offers a unique opportunity for gene transfer into allografts before grafting. After organ retrieval, the cold ischemic period renders organs available for manipulation and gene transfer. Local expression of protective or immunomodulatory molecules within the graft environment offers a better local bioavailability of bioreagents and potentially less systemic side effects. Protection against ischemia-reperfusion injury, acute and / or chronic rejection without significant side effects would be a major breakthrough in transplant research. However, protocols of transfection adapted to the transplant setting and control of gene expression must be clearly evaluated before going to clinical trials. The first part of this review deals with gene transfer techniques into the allograft, emphasizing particular transplant conditions that are encountered and that must be respected when designing protocols for gene transfer experiments. The second part deals with specific therapeutic strategies to protect and prolong allograft survival.

Keywords: Allotransplantation, immunomodulatory molecules, hypercholesterolemia, Cationic Polymers, hyperbaric administration, Costimulatory Signals, Immunosuppressive Cytokines, Anti-Oxidative Molecules