Working in non-human primates for 758 days! Long term survival demonstrated by organ xenotransplantation

A paper published on the 11th in the journal Nature reported on the successful transplantation of genetically modified pig kidneys into non human primates. Modifying the pig's genome to knock out the antigen coding gene, incorporating human genes, and clearing the pig virus can provide monkeys with a long-term survival rate of about two years

A paper published on the 11th in the journal Nature reported on the successful transplantation of genetically modified pig kidneys into non human primates. Modifying the pig's genome to knock out the antigen coding gene, incorporating human genes, and clearing the pig virus can provide monkeys with a long-term survival rate of about two years. This preclinical study further promotes the clinical testing of genetically modified pig kidneys for human transplantation.

In an unfriendly internal environment for pig organ transplantation in non human primates, pig kidneys edited by CRISPR survived and maintained animal life for 758 days. Green represents CD31+endothelial cells, magenta represents human CD46, red C4D, and blue represents the nucleus. Image source: eGenesis website

Animal organ transplantation into the human body (xenotransplantation) is a solution to the global organ shortage. Pigs are very promising donor animals, but there are several obstacles to overcome before clinical feasibility, including organ rejection and the risk of zoonotic diseases (animal virus transmission to humans).

Previous studies have identified three glycan antigens expressed in pigs that can be recognized and attacked by human antibodies, which can lead to organ rejection. Endogenous retroviruses from pigs have also been identified as a major risk for human transplantation.

The eGenesis research team, a technology company specializing in xenograft transplantation in the United States, based on previous research and altered the genome of donor pigs, successfully transplanted a genetically engineered pig kidney into a crab eating monkey model (non human primates with multiple humanoid traits). The research team conducted 69 genome edits on donor pigs (Yucatan mini pigs), knocking out three glycan antigens believed to cause rejection, overexpressing seven human genes (to reduce primate immune system resistance), and inactivating all copies of porcine retrovirus genes.

These transplanted kidneys have a significantly longer survival time (176 days compared to 24 days) compared to those that only knock out glycan antigens, indicating that the expression of these human transgenes can to some extent prevent rejection. By combining immunosuppressive therapy, this transplant can provide a long-term survival time of up to 758 days for primates. The researchers concluded that the above results demonstrate the prospects for pig organ transplantation into humans in the future and promote further clinical testing of the technology.

Why do we need xenotransplantation? Because this may be the solution to the global organ shortage crisis. The advancement of gene editing technology is enabling scientists to overcome the virological and immunological barriers of xenotransplantation in history. This article is the largest and most comprehensive preclinical dataset released in this field to date, which significantly increases the likelihood of xenograft transplantation being applicable to the human body in the future. For hundreds of thousands of patients waiting for organ transplants to save their lives, this achievement is like a ray of dawn.

Source: Science and Technology Daily

Editor in Chief | Liang Shanyin Intern Liao Ximian

Editor: Liang Shanyin

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