American surgeons have transplanted a pig kidney with an edited genome into a man with end-stage renal failure, the Massachusetts General Hospital press service reported. He became the fourth living recipient and the second to receive an organ with 69 modifications.
Transplantation of organs from animals (xenotransplantation) is one way to fill the donor shortage. To increase the compatibility of such organs with the human body and remove viruses embedded in the genome, various modifications are made to the genetic material of the animal (usually a pig). Several companies are developing this technique, with United Therapeutics and eGenesis leading the way. The first pig GM kidney was connected to the vessels of a brain-dead patient in 2021, and completely transplanted in the same situation in 2023.
The first fully living recipient was 62-year-old Richard Slayman in March 2024. Tatsuo Kawai, Nahel Elias and colleagues at Massachusetts General Hospital transplanted him with eGenesis's EGEN-2784 GM pig kidney, which contained three types of modifications affecting 69 genes. It took root and began producing urine, but the patient died two months later, apparently unrelated to the surgery.
The second transplant was a single-modified UThymoKidney kidney from United Therapeutics, implanted with animal thymus tissue. Surgeons at NYU Langone Transplant Institute, led by its director Robert Montgomery, transplanted it in April 2024 into 54-year-old Lisa Pisano, who had just days earlier been fitted with a left ventricular assist device (LVAD). The organ also took root, but the patient died of heart failure less than three months later. The same team of doctors transplanted a UKidney pig GM kidney (also from United Therapeutics) with 10 modifications into 53-year-old Towana Looney, who had previously donated a kidney to her mother, in December 2024. At the time of writing, the organ is functioning and the patient is alive.
The fourth recipient was Timothy Andrews, 66, from New Hampshire. He suffered from terminal kidney disease and had been on hemodialysis for two and a half years. Because of this, he was constantly tired and could not cope with everyday tasks. In July 2023, the man suffered a myocardial infarction. An additional complication was his blood type O - according to statistics, the wait for a donor kidney with it takes 5-10 years, compared to the average of 3-5 years. A team of specialists from Massachusetts General Hospital led by Kawai, Elias, Leonardo Riella and Shimul Shah transplanted a pig GM kidney into him on January 25. The procedure took 2.5 hours.
Andrews received the EGEN-2784 pig kidney created by eGenesis (the same as the first recipient). Three types of modifications were made to the donor animal’s genome using CRISPR-Cas and RMCE technologies: knockout of three glycan antigen synthesis genes that cause subacute rejection; addition of seven human transgenes that regulate inflammation, innate immunity, blood clotting, and the complement system, thereby modulating the rejection reaction; inactivation of 59 endogenous porcine retroviruses. The organ immediately began producing urine and functions normally. The patient’s condition has improved dramatically, he no longer needs dialysis, and on February 1, he was discharged from the hospital. He noted that he feels “reborn.”
As with previous recipients, the procedure was performed under the FDA’s expanded access protocol, which allows experimental technology to be used for compassionate reasons. Massachusetts General Hospital and eGenesis are planning two more such transplants this year. Meanwhile, United Therapeutics, which is collaborating with transplant surgeons at NYU Langone, has received a license to begin clinical trials of its GM organs, with six patients expected to participate in the first phase.
In addition to genetic modifications, experiments are being conducted to grow a real human kidney in a pig's body. You can read about these technologies in detail in the article "About Pigs and People".