Gene Therapy for the Prevention of Ischemia / Reperfusion Injury in Organ Transplantation

T.      Ritter; J.   W.   Kupiec-Weglinski

Abstract

Introduction of gene therapy into molecular medicine has been gaining increasing interest. Although treatment of various diseases e.g. monogenetic defects or cancer by using gene transfer technologies has been extensively probed, the clinical success has been limited. However, recent experimental data suggest that gene therapy may represent an attractive and powerful approach in preventing ischemia / reperfusion injury as well as organ rejection in transplant recipients. Easy and selective access to the donor organ facilitates the reduction of potentially harmful systemic side effects of gene therapy vectors. By introducing anti-apoptotic or cytoprotective genes, these studies focused on the protection of the transplant from the apoptotic cell death. In addition, down-regulation of adhesion molecules and / or blockade of gene expression in the graft itself also ameliorated ischemia / reperfusion injury. This review summarizes the current progress on gene therapy application in combating ischemia-reperfusion injury in organ transplantation. Although the use of viral vectors is emphasized, non-viral gene transfer techniques are also discussed. Future development of novel, low-immunogenic vectors should further contribute to the minimization of ischemia / reperfusion injury, and thus to the overall success of organ transplantation.

Keywords: gene therapy, transplantation, ischemia/reperfusion injury, viral vectors, anti-apoptotic genes, cytoprotective genes

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