Gene therapy in transplantation.
Gene transfer and gene therapy represent a relatively new field that has grown and expanded enormously in the last 5-10 years. The application of gene transfer and gene medicines to transplantation is currently in its infancy. Consideration for gene medicines in transplantation requires delivery of vectors, either to the graft or to the immune system. Delivery of vectors to the graft provides a choice of potential immunologic targets including: costimulatory signals; inhibitory cytokines; adhesion molecules; and molecules relating to apoptosis. In addition, non-immunologic targets, that increase graft protective mechanisms by reducing ischemic and immunologic damage, represent significant targets for gene transfer. Delivery of vectors to the immune system includes potential targets to modify the immune system, and results in tolerance. Other considerations for gene therapy include the development of additional technologies, such as gene conversion or transgenesis coupled with xenotransplantation, which may provide genetically modified organs. Another important aspect of gene transfer relates to regulation of the transgene expression. A variety of issues concerning innate immunity, adaptive immunity, response to vector components, response to transgene products, and entry of vectors into the antigen presentation and processing pathway require further investigation and refinement of approaches. Lastly, regulatable promoters and the understanding of their interaction with individual cells, tissues and organs, and their interaction with innate and adaptive immunity, are of paramount importance to improving the efficacy and utility of gene transfer. There is no doubt that there is much exciting basic and translational science to be accomplished in the next decade in order to solve these potential barriers and advance gene medicines into the clinical realm in transplantation.
Carl C. Icahn Institute for Gene Therapy and Molecular Medicine and the Recanati/Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
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D000069594:Abatacept; D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis; D003713:Dendritic Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D018014:Gene Transfer Techniques; D005805:Genes, MHC Class I; D015316:Genetic Therapy; D006801:Humans; D018796:Immunoconjugates / Q000235:genetics; D007165:Immunosuppression Therapy / Q000379:methods*; D016753:Interleukin-10 / Q000235:genetics; D016328:NF-kappa B / Q000502:physiology; D016377:Organ Transplantation; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D014183:Transplantation, Heterologous / Q000276:immunology
D018796:Immunoconjugates; D016328:NF-kappa B; D016753:Interleukin-10; D000069594:Abatacept