Gene-edited pig kidney keeps monkey alive for 2 years, trial finds, a step toward longer-lasting human transplants

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About 13 people die every day People are waiting for kidney transplants due to a shortage of organ donors, but some scientists think pigs could be the solution. In a new clinical trial that researchers say is the largest of its kind, researchers transplanted genetically engineered pig kidneys into monkeys that lived for record lengths of time.

These scientists believe that proof-of-concept research journal nature This week, it could soon lead to human trials.

In the United States, more than 90,000 people You are on the waiting list for a new kidney because one or both kidneys are malfunctioning. Globally, approximately 8% to 16% of people have kidney problems, and kidneys are the leading cause of death. kill In 2019, more than 250,000 people, Research shows. Dialysis helps remove waste and excess water from the blood, but it only does 10% to 15% of the work a healthy person does. kidneyAnd people on dialysis have a 50% chance of dying within five years of starting treatment. Research shows.

Approximately 170 million people in the United States are registered to donate their organs, but only 3 in 1,000 people die before their organs are suitable for transplantation. According to US government figures.

Scientists are looking for alternatives, and several research teams have been experimenting with whether anatomically pig organs might be an option. similar to human organsand the pigs breed quickly.

For the new study, scientists selected Yucatan varieties That’s because a pig weighs about 150 pounds, the same as the average American woman. The kidneys are also about the same size as humans.

Scientists have genetically modified pigs to allow their kidneys to be transplanted into another species, increasing the chances that the organs will not be rejected. Even when a human donates an organ to another human, the recipient must take medication for the rest of his life to suppress his immune system so that his body does not reject the donor organ.

Previous pig-to-primate delivery experiments, even those involving genetically modified pigs, have required scientists to use a significant number of immunosuppressive drugs, and this experiment has The researchers said this means they cannot be used for organ donation experiments. However, in this test, the genetic modification was sufficiently effective, and the amount of drug required was only as much as humans could tolerate.

The researchers said three genetic modifications in the pigs were important. One researcher knocked out part of the gene that makes glycol antigens, chain structures made of sugar molecules that trigger the recipient’s body to reject the kidney. Other teams have also used this type of gene editing, but the recipient animals didn’t live as long.

The researchers behind the new study say two additional gene edits appear to have been key to extending the monkeys’ lifespans.

The second edit was to insert seven human genes that control kidney rejection pathways. The researchers also inactivated hermaphrodite retroviruses (remnants of ancient viral infections that are latent or inactive in pigs) so that they do not become active after the organ is transplanted into another species. I made it.

The complete combination of gene editing combined with immunosuppressive drugs appeared to support what researchers thought was long-term survival.

The research team transplanted pig kidneys into more than 20 monkeys, but not all of the pigs had undergone all the gene editing.

None of the monkeys that received kidneys from pigs that lacked the seven human genes survived more than 50 days. The monkeys given the complete combination lived much longer, with five living for more than a year and one for more than two years. Tests showed that her one donated kidney functioned similarly to her two natural kidneys.

“We are the only group in the field to comprehensively address donor organ safety and efficacy with these compilations,” said study co-author Dr. Mike Curtis. Organ transplantation.

Curtis said the study authors will work with the U.S. Food and Drug Administration in the coming months to pave the way for human clinical trials to begin.

Dr. Robert Montgomery, director of the New York University Langone Transplant Institute, believes the new trial is “an important contribution demonstrating improved survival of extensively gene-edited pig kidneys in non-human primates.” .

Montgomery was not involved in the new study, but in July he led the team that Genetically modified pig kidneys were transplanted into humans. The organ functioned for about two months before being removed on the scheduled day. This was the longest recorded xenotransplantation of this type, or transplantation between two species.

Montgomery wrote in an email that the study is a good push to move into human clinical trials “sooner rather than later.” However, he cautioned that there were theoretical risks from a safety perspective in implementing the “huge number of gene edits” the authors performed on donor pigs.

“Unintended off-target effects of these edits and variation in transgene expression levels between pigs will be difficult to assess and pose a formidable regulatory challenge,” he wrote.

Montgomery added that non-human primate models continue to be controversial in terms of how well their results translate to pig-to-human transplantation.

Other recent pig-to-human transplants have also had some success.

In January 2022, researchers at the University of Maryland transplanted a genetically modified pig heart into a 57-year-old Maryland man. The man had terminal heart disease, and his medical history made him ineligible for a heart from a human donor. Doctors announced that the transplant was successful, but the man died two months later.

During Septembera 58-year-old man with terminal heart disease received a donor heart from a genetically modified pig and is still alive.