Genetically Engineered Porcine Organs for Human Xenotransplantation.

Abstract

Xenotransplantation holds a promising future for many patients, especially those with end-stage renal disease or uncontrollable serum glucose levels. Porcine organs are viewed as the perfect candidate for a source of xenografts. However, the recipient's immunity, incompatibility of biologic systems, and transfer of new pathogenic organisms are all obstacles to clinical xenotransplantation, in addition to the risk of zoonosis and xenoantigens. Genetic modification of pigs using clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein 9 (Cas9) resulted in the production of porcine endogenous retrovirus (PERV)-free offsprings with the consequent removal of many clinical complications post-transplantation. Such as minimizing both acute and chronic inflammation, in addition to suppressing rejection reactions, which may prolong graft survival. To build on these recent successes, it is important to look at the limits of genetic engineering and develop ways to advance the field of xenotransplantation and reverse xenotransplantation clinical applications forward. Still, significant problems remain with clinical human xenotransplantation; future work should focus on developing an ideal genetically engineered swine donor source that can improve long-term graft survival and suppress the immune system in a clinically useful way.