This has led researchers to genetically modify pigs to make their organs more compatible. EGenesis, the Cambridge, Mass.-based biotechnology company that bred the pigs for Penn’s research, aims to do just that with gene editing. The company’s scientists used Crispr to perform a total of 69 gene edits on the animal. These include knocking out her three pig genes to prevent immediate immune rejection and inserting her seven human genes involved in inflammation, immunity, and blood clotting. The remaining edits disabled a congenital virus found in the pig genome and hypothesized to infect humans. In October, eGenesis reported in the journal Nature It turns out that pig kidneys with the same edits also functioned for more than two years in monkeys.
The idea of transplanting pig livers outside the body to support patients is not new. In the 1960s and his 1970s, More than 100 such procedures have been attempted To help patients with liver failure. This method was abandoned once liver transplantation from deceased human donors was established.
In the 1990s, researchers at Duke University A series of similar experiments Although effective in people with liver failure, the treatment lasted only two to five hours before the pigs’ livers began to fail.
“It didn’t go very well,” says eGenesis CEO Mike Curtis. Previous attempts using unmodified pig liver caused swelling and blood flow to stop within a few hours. In Penn’s study, researchers observed steady blood flow and pressure. There were no signs of inflammation. “The simple question was, would our organs function better? And now the answer is yes,” he says.
Whether all 69 edits are necessary is still debatable.a Research published in 2000 Pig organs with just two genetic modifications have been shown to be able to support two patients with liver failure for up to 10 hours before receiving a transplant from a human donor. Curtis believes the additional changes will ultimately allow patients to be supported for longer periods of time.
The Penn State team plans to refine the procedure on three additional brain-dead patients. Curtis said EGenesis is also meeting with the FDA this month to discuss plans for an early-stage clinical trial of its pig system in patients with liver failure. The company is also considering one-time trials on sick patients through the FDA’s “compassionate use” program in lieu of formal clinical trials. This allows the use of experimental drugs when they are the only option available to people with life-threatening illnesses. situation.
In 2022 and 2023, University of Maryland surgeons used this route to perform two separate transplants on patients using genetically modified pig hearts. Although both recipients had heart failure, they were not eligible for a traditional human organ transplant. The first patient, David Bennett, lived for two months before his death in March 2022. The second patient, Lawrence Fawcett, died in October last year, six weeks after the transplant.
“When you’re talking about long-term organ replacement, there are many complex immune responses,” Shaked says. “We have a completely different mindset here.”
He says eGenesis’ pork liver could probably continue working for five days, but he’s not sure beyond that. Human livers can usually only be stored for about 9 hours outside the body. The machine used in the study was made by the British company OrganOx and has been approved by the US Food and Drug Administration and has been shown to extend that period by several hours. No one knows how long a pig’s liver will last on a machine while attached to a human.
Parthia Vagefi, a professor of surgery at the University of Texas Southwestern Medical Center who was not involved in the Penn study, said it remains to be seen whether the combination of genetic modification and perfusion devices will help support living patients. Ta.
“There is a push for innovation to address the organ shortage,” Vagefi said. “But I think we need to recognize the fact that more research is needed.”
