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A groundbreaking study published in Nature details the successful long-term function of genetically engineered porcine kidney grafts in nonhuman primates, marking a significant advancement in xenotransplantation research. Led by Ranjith P. Anand and a team of international researchers, the study focuses on the development of a humanized porcine donor with 69 genomic edits aimed at enhancing compatibility with human immune systems and reducing the risk of organ rejection.
The research involved the creation of a porcine donor from the Yucatan miniature pig breed, specifically engineered to lack three major glycan antigens (α-Gal, Neu5Gc, and Sd(a)) which are commonly targeted by the human immune response. Additionally, the pig’s genome was edited to inactivate porcine endogenous retrovirus sequences and to express human transgenes that regulate immune responses. These modifications were intended to minimize the risks associated with xenotransplantation, such as immune rejection and viral transmission.
In the study, kidney grafts from these engineered pigs were transplanted into cynomolgus monkeys, serving as a model to evaluate the grafts’ functionality and compatibility. The results showed that kidneys with both glycan antigen knockouts and human transgene expression demonstrated significantly improved survival times compared to those with only the glycan antigen knockouts.
The study’s findings suggest that the genetically modified pig kidneys could effectively function in a nonhuman primate model for up to two years, offering a potential solution to the organ shortage crisis. This success in nonhuman primates is a crucial step toward the possibility of clinical trials and the future use of porcine kidney grafts in human transplantation.
Xenotransplantation, the process of transplanting organs or tissues between different species, has been explored as a potential solution to the critical shortage of human organs for transplantation. Genetically engineered pigs are considered promising donors due to their physiological similarities with humans. This study’s success in modifying pigs to reduce immunological and viral risks addresses significant barriers in xenotransplantation, potentially paving the way for its clinical application and offering hope to thousands of patients waiting for organ transplants.