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.
Keywords: CRISPR-Cas9; RNA interference; designer organs; ex situ perfusion; gene editing; gene modulation; gene therapy; graft treatment; machine perfusion; machine perfusion preservation; organ preservation; personalized medicine; precision medicine.
© 2022 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.