Porcine genome engineering for xenotransplantation

The extreme shortage of human donor organs for treatment of patients with end-stage organ failures is well known. Xenotransplantation, which might provide unlimited organ supply, is a most promising strategy to solve this problem. Domestic pigs are regarded as ideal organ-source animals owing to similarity in anatomy, physiology and organ size to humans as well as high reproductive capacity and low maintenance cost. However, several barriers, which include immune rejection, inflammation and coagulative dysfunctions, as well as the cross-species transmission risk of porcine endogenous retrovirus, blocked the pig-tohuman xenotransplantation. With the rapid development of genome engineering technologies and the potent immunosuppressive medications in recent years, these barriers could be eliminated through genetic modification of pig genome together with the administration of effective immunosuppressants. A number of candidate genes involved in the regulation of immune response, inflammation and coagulation have been explored to optimize porcine xenograft survival in non-human primate recipients. PERV inactivation in pigs has also been accomplished to firmly address the safety issue in pig-to-human xenotransplantation. Many encouraging preclinical milestones have been achieved with some organs surviving for years. Therefore, the clinical trials of some promising organs, such as islet, kidney and heart, are aimed to be launched in the near future. (c) 2020 Published by Elsevier B.V.

Automated summary

Xenotransplantation of pig organs offers a potential solution to the shortage of donor organs for human patients but faces challenges such as immune rejection and the risk of porcine endogenous retrovirus transmission. Advances in genome engineering and immunosuppressive medications have the potential to overcome these barriers, leading to promising preclinical results and upcoming clinical trials for organs like islet, kidney, and heart transplantation.