The Future Prospects of Xenotransplantation

Abstract

In the past era, gene manipulation techniques were slowly developed and inefficient, making them very difficult to experiment with xenotransplantation. But now it is possible to create genetically modified animals quickly and accurately with CRISPR-Cas9 system. This allows the development of GGTA1 or DKO or TKO to suppress the expression of certain glycan in pigs. Moreover, the expression of hCRPs can be added, thus curbing the HARs and AXHRs that appear by the glycans during the xenotransplantation. This technique enables studies of other barriers while preventing early immune responses as much as possible. They will be SLAs and other immune-related proteins. Suppressing SLAs will significantly reduce the immune response of pigs’ APCs. Also, using substances that suppress various proteins involved in the host immunity will enhance the organ viability after implantation. But simply inhibiting multiple molecules at once to transgenic pig organs is a very difficult task. Creation of GTKO pigs and CRISPR-Cas9-based genome-wide inactivation of PERVs allowed the future possibility for xenografts in clinical trials. In addition, immune modulatory drug design will open a new way for better outcome.