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Winning Solution: Genetically Engineered Pig Kidney Xenotransplantation

Genetically engineered pig kidneys that will reduce rejection possibility while providing more viable donor kidneys

David K.C. Cooper; Massachusetts General Hospital

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KidneyX Competition:

Artificial Kidney Prize, Phase 1

About the Solution

There is an urgent need for improved therapy for patients with kidney failure to provide them with a better quality of life than is possible on dialysis. If the complex ‘rejection’ response to a pig kidney could be prevented, transplantation of such a kidney is likely to fulfill all the essential functions of a human kidney. A genetically unmodified pig kidney transplanted into a nonhuman primate (e.g., a baboon, that has a similar rejection response to that of a human recipient) is rejected rapidly (usually within minutes or hours). However, if the pig is genetically modified by deleting the targets for the initial human rejection response, and by introducing human ‘protective’ genes, pig kidney graft survival in immunosuppressed nonhuman primates can currently be maintained for months or even more than a year.

To achieve this result requires the recipient to receive a slightly different form of immunosuppressive therapy than currently used in patients with human kidney transplants. My colleagues and I already have significant experience with this regimen. The US FDA will require evidence that a genetically engineered pig kidney transplanted into an immunosuppressed nonhuman primate can be fully life-supporting for at least 6 months (in the absence of rejection or serious complications) in at least 6 recipients. Further support would enable progression to a clinical trial within the next 12-18 months. If awarded this prize, I would hope to expand the number of pig kidney transplants we carry out to 10 per year, with the aim of obtaining the necessary results within the next 12 months.

About the Winner

David K. C. Cooper, MA, MS, MD, PhD, DSc (Med) studied medicine in the UK at Guy’s Hospital Medical School (now part of King’s College London), and trained in general and cardiothoracic surgery in Cambridge and London. Between 1972 and 1980, Dr. Cooper was a Fellow and Director of Studies in Medical Sciences at Magdalene College, Cambridge. In 1980, Dr. Cooper took up an appointment in cardiac surgery at the University of Cape Town where, under Professor Christiaan Barnard, he had responsibility for patients undergoing heart transplantation. In 1987, Dr. Cooper relocated to the Oklahoma Transplantation Institute where he continued to work in both the clinical and research fields.

After 17 years as a surgeon-scientist, Dr. Cooper decided to concentrate on research, initially at the Massachusetts General Hospital/Harvard Medical School in Boston (1996-2005, to which center he returned in 2021), and subsequently at the University of Pittsburgh (2005-2016), and the University of Alabama at Birmingham (2016-2021). Dr. Cooper’s major interest is in developing cross-species transplantation with the aim of using pigs as sources of organs, cells, and corneas for transplantation in humans.