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EGEN-2784 is a genetically modified porcine kidney developed by eGenesis for xenotransplantation into patients with end-stage renal disease. The organ is engineered with 69 genomic edits, including the knockout of three porcine carbohydrate antigens—GGTA1, CMAH, and B4GALNT2—to prevent hyperacute rejection by the human immune system (Kim et al., 2023). It also features the inactivation of 62 porcine endogenous retroviruses (PERVs) to mitigate the risk of zoonotic infection (eGenesis, 2024). To ensure physiological compatibility, EGEN-2784 expresses seven human transgenes (CD46, CD55, CD59, THBD, PROZ, TFPI, and TNFAIP3) that regulate the complement system, coagulation cascade, and inflammatory pathways (Massachusetts General Hospital, 2024). This complex engineering allows the porcine organ to function as a replacement for human kidneys while resisting the aggressive immune responses typically associated with cross-species transplantation. EGEN-2784 represents a pioneering approach in regenerative medicine aimed at addressing the critical shortage of human donor organs.
EGEN-2784 functions by providing renal filtration while utilizing 69 genetic edits to evade the human immune system. It knocks out three porcine antigens (GGTA1, CMAH, B4GALNT2) to prevent hyperacute rejection and expresses seven human transgenes (CD46, CD55, CD59, THBD, PROZ, TFPI, TNFAIP3) to inhibit complement activation, prevent blood clotting, and reduce inflammation. Furthermore, it inactivates 62 porcine endogenous retroviruses (PERVs) to prevent potential zoonotic infection in the recipient (Kim et al., 2023; eGenesis, 2024).
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