Division of Transplantation, Department of Surgery, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Artif Organs. 2022 Feb;46(2):180-190. doi: 10.1111/aor.14151.
Organ transplantation is the definitive treatment for end-stage solid organ diseases, yet biological and logistical barriers reduce the rate of successful organ transplants. As such, there is a need for gene therapy and gene modulation strategies in the organ transplantation setting to prevent rejection, expand the donor pool of available organs, and attenuate ischemia-reperfusion damage. As we are entering an era of "precision medicine," the organ transplant field is becoming equipped with the tools necessary to personalize and optimize organs designed specifically to withstand injurious pathways that occur during transplantation, such that the concept of "designer organs" will be a reality in the near future. In this review, we highlight the recent progress using gene knockout and knock-in strategies used mainly in the context of xenotransplantation. We also discuss advancements in CRISPR-Cas9 gene editing and RNA interference in relation to organ transplantation. Lastly, we discuss the exciting future implications of customized gene therapy in the transplantation setting, and its ability to potentially create a future where organs intended for transplant are personalized to maximize both graft and patient survival.
器官移植是治疗终末期实体器官疾病的有效方法，但生物和物流方面的障碍降低了成功器官移植的比例。因此，需要在器官移植领域采用基因治疗和基因调节策略，以预防排斥反应、扩大可用器官的供体池，并减轻缺血再灌注损伤。随着我们进入“精准医学”时代，器官移植领域正在配备必要的工具，以对专门设计用于承受移植过程中发生的损伤途径的器官进行个性化和优化，从而使“设计器官”的概念在不久的将来成为现实。在这篇综述中，我们主要介绍了在异种移植背景下使用基因敲除和基因敲入策略的最新进展。我们还讨论了 CRISPR-Cas9 基因编辑和 RNA 干扰在器官移植方面的进展。最后，我们讨论了定制基因治疗在移植领域的令人兴奋的未来意义，以及它有可能创造一个未来，即用于移植的器官被个性化，以最大限度地提高移植物和患者的存活率。
