First-ever CRISPR-edited pig kidney transplant

The procedure, known as xenotransplantation, was performed over the course of four hours on March 16 without any complications. The patient, 62-year-old Richard Slayman, is recovering well and is expected to be discharged soon, MGH said.

Slayman previously received a human kidney transplant, but after around five years, the organ failed, requiring him to resume kidney dialysis in 2023.

According to Slayman, he saw the surgery "not only as a way to help me, but a way to provide hope for the thousands of people who need a transplant to survive."

The kidney used in the surgery was provided by eGenesis, a pharmaceutical company that has pioneered the development of human-friendly pig organs using CRISPR gene-editing technology. The pig that produced the kidney was part of the company's EGEN-2784 flock, a breed of Yucatan minipig, that had 69 total DNA edits from CRISPR.

To ensure the kidney would be suitable for human use, scientists at eGenesis eliminated three pig genes for molecules that trigger the human immune system, removed dozens of potentially dangerous viruses from the pig genome, and added in seven human genes to make the organ more compatible with the human circulatory system.

According to Winfred Williams, the associate chief of the nephrology division at MGH, there have been no signs of Slayman's body rejecting the kidney so far.

"His blood pressure, his vital signs are very stable," Williams said. "He looks almost completely on the way to full recovery."

Discussion

There have been other pig-to-human transplants in the past, including two pig-to-human heart transplants in the United States. However, in both cases, the patients lived no more than two months after their surgery.

Experts hope that being able to transplant organs from animals could help the more than 100,000 people in the United States currently on the national transplant waiting list, but it could be years before the procedure is more widely used, as more data is required.

"What we really want to do is get to the initial clinical trials, where you have multiple patients that are receiving xenografts and several centers that are participating where you can really test a hypothesis and see how safe this is and how well it works," said Robert Montgomery, director of the NYU Langone Transplant Institute.

Tatsuo Kawai, a transplant surgeon at MGH who oversaw the kidney transplant, said his team hopes "that this transplant approach will offer a lifeline to millions of patients worldwide who are suffering from kidney failure."

"It really is a groundbreaking milestone," Williams said. "Should the kidney continue to work well and this is a success, I think it represents a breakthrough in a number of different areas."

Mike Curtis, CEO of eGenesis, said in a statement that the procedure "represents a new frontier in medicine and demonstrates the potential of genome engineering to change the lives of millions of patients."

The question still remains how long the kidney will last following the procedure.

"It will be really interesting to learn whether or not the xenograft is ultimately a bridge, meaning it lasts for a short period of time until a human allograft can be found, or if it's going to be what we call destination, meaning it will last this individual the rest of his life," said Jayme Locke, a transplant surgeon at the University of Alabama Birmingham Heersink School of Medicine.

Even so, the procedure is "game-changing," Locke added. (Molteni/Boodman, STAT+ [subscription required], 3/21; Lovelace Jr./Martin, NBC News, 3/21; Stein, "Shots," NPR, 3/21; Kekatos, ABC News, 3/21)

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