Surgeons at Massachusetts General Hospital will transplant the world’s first genetically modified pig kidney into a living human.
Massachusetts General Hospital
Biotech startup eGenesis has developed a gene-edited kidney that was successfully transplanted into a living patient last week. According to the CEO, the company is just getting started.
by alex knappForbes staff
LOn Thursday, surgeons at Massachusetts General Hospital announced that the first living human patient received a kidney transplant from a pig. Jolene Masden, the hospital’s transplant director, said at a press conference after the announcement that this scientific advance represents hope for the dozens of people who die every day waiting for an organ transplant. “The holy grail, the dream of transplant researchers, was to use pig organs to replace human organs to solve the problem of organ shortage,” he said.
Of course, it wasn’t as simple as just going to the farm. The kidney was developed by EGenesis, a Massachusetts-based startup that has been working for nearly a decade to genetically edit pig organs so they can be safely transplanted into humans. But CEO Mike Curtis told Forbes this week’s milestone is just the beginning. His company, which has raised $291 million in venture backing to date, will bring its gene-editing technology for kidney, liver and heart transplants into clinical trials over the next two years, a market Grandview Research is focusing on. We aim to become a disruptive player. Estimate Approximately $15 billion
“We showed that we actually have something that can help patients,” he said. “For me, it’s all about being able to enter this new era of science and help people who have few treatment options.”
There are currently more than 100,000 people in the United States on transplant waiting lists, but fewer than half of them will receive a transplant that year due to limited donor organ availability. Scientists have thought for decades that animal organs could help some patients, even as a way to keep them alive long enough to receive human organ transplants. Pigs are ideal candidates for donor organs because they grow rapidly and have organs comparable in size and function to humans.
As scientists learn more about how pig organs function within the human body, they are developing pigs so that they require less or no immunosuppressive drugs compared to human organs. It may become possible to genetically manipulate organs.
Massachusetts General Hospital
The patient in this case is a 62-year-old man whose previously transplanted kidney had failed and who underwent surgery under the Food and Drug Administration’s Expanded Access program, which is made available to patients with life-threatening conditions. allowed to proceed. Refers to experimental drugs and experimental procedures. The surgery followed several different experiments with pig kidneys from brain-dead donors, and two surgeries in which gene-edited pig hearts were transplanted into living patients.
Jamil Azzi, a transplant surgeon at Brigham and Women’s Hospital who was not involved in Thursday’s surgery, praised the procedure. “This is an incredible advance that has been decades in the making,” he said. forbes. That said, he cautioned that more data will be needed before this type of surgery is routinely performed on human patients. A key question is how long a donated pig kidney will last in a human patient. “If it fails within a few months, we’re way behind,” he says. In 2023, two patients who received pig heart transplants developed by United Therapeutics subsidiary Livivicore died within weeks of the surgery, for reasons that are still not entirely clear.
One of the biggest challenges in animal-human transplants is ensuring that the recipient’s body does not completely reject the animal’s organs. This is already a problem with kidneys donated from humans, and skeptics say such transplants are impossible because there are many differences between pigs and humans. This is where gene editing comes into play. Last week’s surgery involved genetically modifying the donor pig’s kidney with seven different human genes, removing three pig genes and 59 additional DNA, Curtis explained. These edits ensure that the kidneys are not attacked by the patient’s own immune system to the point of rejection, although they require immunosuppressive drugs like human organs.
These edits were made in a single pig cell, which was then incorporated into an embryo and cloned. The cloned embryos were then implanted into sows, resulting in piglets with genetic changes.
Curtis explains that making so many changes increases the risk of unintentional changes to other parts of the animal’s genome, so-called “off-target” editing. However, advances in genome sequencing in recent years have made it possible to detect whether off-target editing has occurred. In the case of this particular pig, the company was able to determine that such edits were minimal and would not affect the results.
in Paper published in Nature Last fall, the company demonstrated cases in which monkeys who received pig kidney transplants survived for more than a year, and in one case for more than two years. Between this data and the success of this year’s kidney transplants, EGenesis has officially submitted an application to the FDA to begin full-scale clinical trials to transplant more pig kidneys into humans as early as 2025. Curtis said that progress is being made. But Curtis said the agency wants to see more primate data before giving the company the green light. More data is needed, but what has been demonstrated so far is a “good indicator” that the company is on the right track, Azzi added.
Curtis said one of the things the company needs to do to scale is get to the point where it can raise pigs using readily available organs without the need for cloning or transplantation. he said. George Church, co-founder of eGenesis and a genetics researcher at Harvard Medical School, told Forbes that this could offer the opportunity for a single pig donor to donate multiple organs to a patient. he said.
“The ultimate vision is to create organs in pigs that do not require immunosuppression.”
Curtis said his company’s program to edit pig livers and hearts for transplantation into humans using a process similar to kidneys is nearing fruition. In January, the company announced the success of the operation Gene-edited pig livers were used in brain-dead patients and the organs were connected outside the body. This procedure could help patients with liver failure survive a few days long enough to receive a full transplant from a human donor.
Because of this success, Curtis said his company intends to submit its gene-edited liver to the FDA and aims to begin clinical trials by the end of this year. The company ultimately aims to completely transplant its livers into living patients.
The goal for eGenesis kidneys and livers is permanent transplantation. But as for the heart program, EGenesis is primarily aimed at pediatric patients, and pig hearts could serve as a bridge until human organs can be transplanted, he said. Currently, more than 50% of children who need a new heart die while waiting for a transplant, he said. The company has so far seen baboons with gene-edited hearts survive for more than 200 days, which Curtis said “could lead to advances in pediatric heart transplants later this year or early next year.” He said he was looking forward to it.
In the long term, the company has even bigger ambitions. “The ultimate vision is to create organs in pigs that don’t require immunosuppression,” Curtis said. That could mean transplant patients no longer need to be given drugs that lower their immune systems to prevent rejection. While this preserves life, it also increases the risk of infection and cancer. “We know it will require additional engineering, but we will need human data to know what that engineering looks like.”
Genetics researcher George Church, co-founder of eGenesis, says that in addition to organs that don’t require transplant patients to take drugs, the company hopes to one day create “enhanced organs” through the power of genetic engineering. He added that it was even a possibility. For example, it might be possible to edit a pig’s genome to create “organs that are resistant to multiple pathogens” or organs that age more slowly, he said. As a proof of concept, he pointed to his research in his lab at Harvard Medical School, whose peer-reviewed results were: was announced on Nature, a simple genetic change made a bacterial species resistant to all known viruses. “Now I want to do it with pigs,” he said.
Curtis said the company will need to expand in the near term, which will also require more capital. The company says it has enough runway to run through the end of 2026 and is already in the process of raising further funding. Curtis hopes the success of the business will show potential investors that the company is on track.
“What this first kidney transplant into a living human does is validate our entire approach,” he said. “And not only can you bring the kidneys forward, but you can also bring the liver and heart forward in parallel.”
