A gene-edited pig liver was attached to a person and worked for 3 days.

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This has led researchers to genetically alter pigs' organs in an effort to make them a better match. Egenesis of Cambridge, Massachusetts, the biotech company breeding the pigs for the Penn study, aims to do the same with gene editing. Company scientists used Crispr to make a total of 69 genetic edits in animals. These included eliminating three pig genes to prevent immediate immune rejection and inserting seven human genes involved in inflammation, immunity and blood clotting. The remaining edits inactivate innate viruses found in the pig genome that could hypothetically infect people. In October, eGenesis was reported in the journal Nature That a kidney from a pig continued to function for more than two years in a monkey with the same editing.

The idea of ​​supporting patients with a pig liver outside the body is not new. In the 1960s and 1970s, more than 100 such procedures were attempted to help patients with liver failure. This method was abandoned once liver transplantation from deceased human donors became established.

In the 1990s, researchers at Duke University carried out a series of similar experiments on people with liver failure, but the process lasted only two to five hours before the pig's liver failed.

“It didn't work that well,” says Mike Curtis, CEO of eGenesis. In previous attempts with unmodified pig liver, swelling would occur and blood flow would stop within hours. In the Penn study, researchers observed stable blood flow and pressure. There were no signs of swelling either. “The simple question was, would our organs perform better? And now the answer is yes,” he says.

Whether all 69 edits are necessary is still debated. A study published in 2000 showed that organs from pigs with only two genetic modifications were able to support two liver failure patients for 10 hours before they were able to receive a transplant from a human donor. Curtis believes additional changes will ultimately help patients in the long run.

The Penn team plans to refine the procedure on an additional three brain-dead people. Curtis says Egenesis is also meeting with the FDA this month to discuss plans for an early-stage trial to use its pig system on patients with liver failure. In lieu of formal testing, the company is also considering one-off experiments in sick patients through the FDA's “compassionate use” program, which allows an experimental medical product to be used when it is used by someone with a life-threatening condition. The only option available for. Situation

In 2022 and 2023, surgeons at the University of Maryland used this route to perform two separate transplants on patients using hearts from genetically engineered pigs. Both recipients had suffered heart failure, but were not eligible for a traditional transplant with a human organ. The first patient, David Bennett, survived for two months before passing away in March 2022. The second, Lawrence Fawcett, died in October last year, six weeks after his transplant.

“When you're talking about long-term organ replacement, there are a lot of complex immune responses that occur,” Shaked says. “Here, it's a very different way of thinking.”

He says the Egenesis pig livers can probably keep working for up to five days, but beyond that, he's not so sure. Human liver can usually be preserved outside the body for only nine or more hours. The machine used in the study, made by the British company Organox, has been approved by the U.S. Food and Drug Administration and extended that window to several hours. No one knows how long a pig's liver will last on a machine while attached to a person.

Parsia Vagefi, a professor of surgery at the University of Texas Southwestern Medical Center, who was not involved in the Penn study, says it remains to be seen whether the combination of genetic modifications and the perfusion device will help survive patients.

“There has been an emphasis on innovation to help address the organ shortage,” Wegefi says. “But I think we have to be cognizant of the fact that more research is needed.”