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

机译:基因疗法预防器官移植中的缺血/再灌注损伤

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摘要

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.
机译:将基因治疗引入分子医学已引起越来越多的兴趣。虽然治疗各种疾病例如利用基因转移技术对单基因缺陷或癌症进行了广泛研究,临床成功受到了限制。但是,最近的实验数据表明,基因治疗可能是预防移植受者缺血/再灌注损伤以及器官排斥的一种有吸引力且强大的方法。容易且选择性地接近供体器官有助于减少基因治疗载体的潜在有害全身性副作用。通过引入抗凋亡或细胞保护性基因,这些研究集中于保护移植物免于凋亡细胞死亡。另外,移植物自身中粘附分子的下调和/或基因表达的阻断也改善了缺血/再灌注损伤。这篇综述总结了基因疗法在对抗器官移植中的缺血-再灌注损伤中的最新进展。尽管强调了病毒载体的使用,但也讨论了非病毒基因转移技术。新型,低免疫原性载体的未来发展应进一步有助于将缺血/再灌注损伤降至最低,从而有助于器官移植的总体成功。

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