IS THERE ANY PLACE FOR GENE-THERAPY IN OR GAN-TRANSPLANTATION

The major research objectives in organ transplantation are to palliate the lack of organs, to decrease the adverse effects of chronic immuno suppression and to improve medium-term and long-term graft survival. X enotransplantation and induction of a permanent and specific tolerance to an allograft therefore represent two main lines of research which could partly resolve the problems of organ transplantation. The object ive of this article is to evaluate the possible role of gene therapy i n the development of xenotransplantation and induction of allograft to lerance. They review the various gene vectors currently available as w ell as the routes of administration of these vectors specific to trans plantation. The place of gene therapy is then evaluated in the context of allo-and xenotransplantation. In allotransplantation, transfection of certain genes of interest into the transplant organ before implant ation or into the recipient's immune system is considered. Transfectio n into the transplant organ of-genes coding for immunomodulating cytok ines (TGF-beta, IL-4, IL-IO, etc.), molecules which block the secund s ignal (CTLA4-Ig) or molecules responsible for apoptosis (Fas/FasL) is discussed. The value of gene therapy in the recipient's immune system consists of transfection onto the recipient's bone marrow cells of gen es coding for major histocompatibility system molecules (HLA-DR, DQ, e tc.). In xenotransplantation gene therapy will certainly play a major role in the development of transgenic pigs expressing, on the surface endothelium of their organs, certain human molecules which regulate th e activity of complement (CD55, CD59, etc.) or which modify the expres sion of glycosylated xenoantigens (alpha-galactosyl) recognized by pre formed antibodies.