CRISPR-Cas9-Mediated Genetic Modifications in Pig-to-Human Xenotransplantation

Donor shortage remained a major challenge in organ transplantation that may continue to deteriorate as life expectancy increases. Therefore, xenotransplantation is a promising and effective alternative approach to narrow the imbalance of organ supply and demand. Pigs are the major xenograft donor. While organs without genetic modifications may trigger several immune rejection and PERV infection, CRISPR-Cas9 has brought unprecedented progress to recent xenotransplant research with high efficiency and broad applications. This paper analyzes the principal mechanism and components of CRISPR-Cas9. In addition, this paper analyzes recent achievements of CRISPR-Cas9 in gene modification, including inactivating three major glycan absent in human from porcine cells to prevent immune rejection, insertion of a human gene, and inactivating PERVs completely from the porcine primary cell line. Finally, this paper analyzes recent pig-to-human xenotransplant and summarizes their shared commonalities. Most pig-to-human transplantations succeed without acute rejection or PERV infection after gene modification on the donor. This paper is intended to analyse achievements and progress of CRISPR-Cas9 in pig-to-human xenotransplantation. Though current xenotransplantation has just entered the clinical stage and is more suitable for bridge therapy instead of complete substitution for human organs. Future research can improve xenotransplantation for temporary treatment for patients who suffer from severe organ dysfunction, and use more living human recipients for more valuable data to continue editing xenografts for long-term survival.