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Makana Therapeutics (formerly Makana Holdings) is developing genetically modified pigs, known as Triple Knockout (TKO) pigs, specifically engineered for xenotransplantation. These pigs have three key xenoantigen genes inactivated: GGTA1 (alpha-1,3-galactosyltransferase), B4GALNT2 (beta-1,4-N-acetyl-galactosaminyl transferase 2), and CMAH (cytidine monophosphate-N-acetylneuraminic acid hydroxylase). The mechanism of action involves the elimination of these genes to remove immunogenic carbohydrate antigens (alpha-Gal, Neu5Gc, and Sda) from the surface of pig cells. This reduction in xenoantigens significantly lowers the risk of hyperacute and acute immune rejection when pig organs or tissues are transplanted into human recipients. The technology is intended to provide a sustainable source of organs for treating end-stage organ failure (including kidney, heart, lung, and liver), as well as for blood transfusions and pancreatic islet replacement for diabetes. Preclinical data for kidney transplantation has shown survival rates exceeding 400 days in non-human primate models.
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