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Applications of gene therapy in transplantation

机译：基因治疗在移植中的应用

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The success of organ transplantation is limited by the availability of donor organs and the requirement for long-term immunosuppression. Use of animal organs would circumvent the organ shortage, and the swine is the most likely candidate to serve as donor for xenotransplantation. Establishing specific tolerance to donor organs would eliminate the need for chronic immunosuppression. Specific tolerance to transplantation antigens across major histocompatibility complex (MHC) barriers has been demonstrated by establishing mixed bone marrow chimerism in the recipient. An alternative approach to establishing chimerism is the use of gene therapy to transduce autologous bone marrow cells with a vector containing one or more MHC antigens. Previous studies in miniature swine have shown that tolerance can be established across allogeneic barriers when a single MHC antigen is shared between donor and recipient. A gene therapy approach is particularly attractive in xenotransplantation since the availability of MHC-inbred miniature swine as donors allows the use of a single vector for transferring swine MHC genes into recipient progenitor cells. In this article, we review the basics for using a gene therapy approach to achieve specific immune tolerance and describe the models being used to evaluate its efficacy in allogeneic as well as in xenogeneic organ transplantation.
机译：器官移植的成功受到供体器官的可用性和长期免疫抑制的要求的限制。使用动物器官可以避免器官短缺，而猪是最有可能成为异种移植供体的候选者。建立对供体器官的特异性耐受将消除对慢性免疫抑制的需要。跨主要组织相容性复合物（MHC）屏障对移植抗原的特异性耐受性已通过在受体中建立混合的骨髓嵌合体得到证实。建立嵌合体的另一种方法是使用基因疗法通过含有一种或多种MHC抗原的载体转导自体骨髓细胞。先前在小型猪中的研究表明，当供体和受体之间共享单个MHC抗原时，可以跨同种异体屏障建立耐受性。基因治疗方法在异种移植中特别有吸引力，因为作为供体的MHC自交微型猪的可用性允许使用单个载体将猪MHC基因转移到受体祖细胞中。在本文中，我们回顾了使用基因治疗方法实现特定免疫耐受的基础知识，并描述了用于评估其在同种异体以及异种器官移植中的功效的模型。

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