Gene therapy in transplantation in the year 2000: moving towards clinical applications?

Transplantation faces several major obstacles that could be overcome by exp ression of immunomodulatory proteins through application of gene therapy te chniques. Gene therapy strategies to prolong graft survival involve gene tr ansfer of immunosuppressive or graft-protecting molecules. Very promising r esults have been obtained in small animal experimental models with inhibito rs of co-stimulatory signals on T cells, immunosuppressive cytokines, donor major histocompatibility antigens and regulators of cell apoptosis or oxid ative stress. The application of gene therapy techniques to transplantation offers a great experimental and therapeutic potential. Local production of immunosuppressive molecules may increase their therapeutic efficiency and reduce their systemic effects. When compared with other clinical situations , gene therapy in transplantation offers several potential advantages. Gene transfer into the graft can be performed ex vivo, during the transit betwe en the donor and the recipient, thus avoiding many of the hurdles encounter ed with in vivo gene transfer. Furthermore, the difficulties associated wit h immune responses to the gene transfer vectors and transient gene expressi on may be easier to overcome when gene therapy protocols are applied to tra nsplantation than when applied to other clinical situations. The next centu ry should witness a rapid increase in the application of gene therapy techn iques to large animal pre-clinical models of transplantation and later to c linical trials.