This is good news, to be celebrated with caution. The first patient with a CRISPR-edited pig kidney has left the hospital. A little over two weeks have passed since the surgery at Massachusetts General Hospital, but according to U.S. press reports, Richard Slayman is well enough to have been discharged. Fingers crossed, then, for this 62-year-old man who, thanks to a xeno-rene, no longer needs dialysis.
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David Bennett, the first patient transplanted with a genetically edited pig heart, died on March 8 last year, two months after the surgery, presumably from a latent pig virus (a problem that does not seem hard to solve with more stringent protocols and screening, as Linda Scobie explained to me a few months ago). Since then, experimental transplants have continued in brain-dead patients who had donated their bodies to research. After xenokidneys with a single genetic modification transplanted in late 2021, in the summer of 2022 it was the turn of ten edits xenohearts. The state of the art now is that the potential of the approach still appears high, as does the morale of specialists.
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As you probably know, the first patient with a pig heart died two months after the transplant surgery. You probably heard also that a porcine cytomegalovirus (PCMV) may have contributed to the death. However, if you are still wondering how bad is the news for the future of xentransplantation, Linda Scobie from Glasgow Caledonian University is the one to listen to. She leads a research group interested in viral zoonoses in the context of novel technologies such as xenotransplantation, and the contribution and/or reactivation of viruses in chronic disease conditions. Professor Scobie is a member of the World Health Organisation committee for the global consultation on regulatory requirements for xenotransplantation trials. I reached her by email for a feature just published in Le Scienze, the Italian edition of Scientific American. Below you can read her answers.
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The first paper on a CRISPR xenotransplant is out in the American Journal of Transplantation. It’s about two swine kidneys with 10 modified genes transplanted into a dead brain man as a proof of concept. The surgery was performed on September 30 by Jayme Locke and colleagues from the University of Alabama at Birmingham.
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As you probably know, on January 7 at the University of Maryland Medical Center in Baltimore a 57 years old man named David Bennett became the first human to have his heart replaced with that of a CRISPRed pig. But what does make a xenoheart suitable for transplantation?
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And so it happened. “In a first, surgeons attached a pig kidney to a human, and it worked,” as the New York Times puts it. Data are scarce, however, and all the info we have is from the general media. The kidney came from a GalSafe pig, which is the only one FDA approved so far. But scientists from several companies have already developed pigs much more engineered than that (with three or four porcine genes knocked-out instead of one, and human gene additions). To get an updated picture, we highly recommend this article published in Nature Biotechnology last April.
It’s mid-August, but CRISPR never goes on vacation. Not to be missed this week is the Science paper by George Church’s team. They have cloned 15 PERV-free piglets, meaning porcine retrovirus sequences have been edited out. The animals can now “serve as a foundation pig strain, which can be further engineered to provide safe and effective organ and tissue resources for xenotransplantation,” researchers write. According to the Harvard geneticist, the first pig-to-human transplants could occur within two years. Another article in the same journal feels the pulse of public perception of human genome editing, concluding that opinions are nuanced and the challenge is to find the best way to engage people in discussions about genome-editing regulation.
CRISPeR FRENZY 