In general, a major area of concern regarding technical obstacles to organ transplantation is the host immune rejection of the donor organ. When it comes to xenotransplantation of a donor pig heart to a human person, the complexities are even more so. The sugar moieties on the surface of the pig heart cells trigger a host immune reaction and rejection. Accordingly, some of the pig cell surface-specific antigen genes were CRISPR/Cas9 edited to remove those genes. One example is the alpha-1,3-galactosyltransferase gene that encodes for the gene product of a critical pig cell surface antigen.27,28
Another cohort of genes removed (knocked out) by CRISPR/Cas9 involves leukocyte antigens specific for pigs termed “Swine Leukocyte Antigen”.27,28 These pig-specific antigens would also induce severe human host rejection upon xenotransplantation. Hence, effective silencing of those genes helps enhance the host immune tolerance of the xeno organ.
27. Wang, W., He, W., Ruan, Y., & Geng, Q. (2022). First pig-to-human heart transplantation. Innovation(Cambridge (Mass.)), 3(2), 100223. https://doi.org/10.1016/j.xinn.2022.100223
28. Ryczek, N., Hryhorowicz, M., Zeyland, J., Lipinski, D., & Slomski, R. (2021). CRISPR/Cas Technology in Pig-to-Human Xenotransplantation Research. International journal of molecular sciences, 22(6), 3196. https://doi.org/10.3390/ijms22063196
