Humans are one step closer to getting gene-edited pig kidneys after monkeys given the organs survived for more than two years with no health issues.
Scientists, led by experts from biotechnology company eGenesis and Harvard Medical School in the US, transplanted kidneys from genetically modified Yucatan miniature pigs into macaque monkeys.
The scientists made 69 genetic modifications to help prevent rejection of the transplanted organ and to help prolong survival.
These edits included adding human genes, eliminating pig viruses and removing three antigen-coding genes which play a role in “hyperacute rejection”.
Previous work identified that the three “glycan antigen genes” found in pigs are recognised by the human immune system and attacked, leading to rejection of the organ.
Scientists theorised that removing these genes would help prevent the monkeys’ bodies from rejecting the transplanted kidney.
Meanwhile, a significant proportion of the modifications were dedicated to removing the porcine endogenous retrovirus (PERV) gene.
While this gene does not cause disease in pigs, there is limited laboratory evidence that it can infect human cells. Adding human genes to the pigs helps prolong survival of the transplanted organs, the scientists found. Some 21 monkeys were given pig kidney transplants.
Among these, six were given kidneys which had been modified to remove the antigen genes and the PERV gene; eight received transplants which had removed the antigen genes and added the human genes; and seven of the donor kidneys had all three types of genetic modification.
Overall, the team found that the addition of human genes appeared to significantly improve survival rates.
The researchers said their work brings clinical testing of genetically modified pig kidneys for human transplantation a step closer.
Dr Michael Curtis, chief executive of eGenesis, said the study marks a “significant step forward in transplantation and medicine more broadly”.
“Our most recent publication outlines the achievement of an extraordinary milestone that provides hope and paves the way to better outcomes for countless individuals in need of life-saving organ transplants,” he said.
“The global burden of kidney disease is staggering. Cross-piece transplantation offers the most sustainable, scalable and feasible approach for delivering new sources of organs to patients.”
Figures from NHS Blood and Transplant show that 5,562 people are waiting for a kidney transplant in the UK, which is more than three-quarters of all people waiting for any kind of transplant in the UK.
When a human receives an organ, tissue or cells from an animal, it is known as a xenotransplant.
Pigs are the most promising donor animals due to the availability of pig, gene-editing technology, plus their size and similarities to human organs.
Overcoming the rejection of pig organs by the human immune system has been a complex challenge for more than four decades.
But gene-editing technology and new techniques to suppress the immune system have shown promise in several recent experiments.
Two humans have received pig heart transplants, the first, in 2022, was David Bennett who died two months after the surgery.
The second patient, a 58-year-old with end-stage heart disease, received his new heart on September 20.
University of Maryland Medical Centre in the US, which performed both of the pioneering heart surgeries, said the patient, Lawrence Faucette, “continues to recover and has commenced physical therapy”.
