How is gene editing being applied to enable xenotransplantation?

Xenotransplantation requires extensive genetic modification of pig organs to prevent rejection and pathogen transmission. Key edits include: knocking out alpha-Gal (GGTA1), Neu5Gc (CMAH), and SD(a) (B4GALNT2) antigens that trigger hyperacute rejection; adding human complement regulatory proteins (CD46, CD55, CD59); expressing human coagulation regulators (thrombomodulin, EPCR); and inactivating porcine endogenous retroviruses (PERVs) - CRISPR enabled inactivation of 62 PERV copies. Additional modifications address cellular and chronic rejection. Challenges include balancing modification number with animal viability, achieving sufficient expression of human transgenes, and ensuring long-term graft function. Recent pig kidney and heart xenotransplants in humans demonstrated feasibility. Regulatory frameworks are evolving for this emerging therapy.