Companies Produce First Genetically Engineered Porcine Donors

On February 13, 2024, eGenesis, a United States-based biotechnology company, and PorMedTec, a Japanese porcine embryology organization, announced positive results of their collaboration, which produced the first successful genetically engineered porcine donors for xenotransplantation.

“Production of our first donors outside the United States is a critical milestone for eGenesis. This demonstrates the potential of broadening our reach and the promise of our platform to additional geographies and patient populations in need,” said Mike Curtis, PhD, Chief Executive Officer of eGenesis, in the press release. “We are thrilled to partner with PorMedTec, a global leader in porcine cloning and production, to advance our organ products to end waitlist mortality, extend lives, and ultimately transform the treatment of organ failure.”

According to the press release from both companies, eGenesis provided PorMedTec with genetically engineered, humanized porcine cells developed using the eGenesis Genome Engineering and Production (EGEN) platform, which addresses cross-species molecular incompatibilities and viral risk. PorMedTec used the cells and somatic cell nuclear transferring to develop these genetically engineered porcine donors.

The cells delivered by eGenesis had three primary edits, including the following:

1. Researchers knocked out three genes responsible for glycan antigen synthesis, which has been linked to hyperacute rejection.
2. eGenesis inserted seven human transgenes that help regulate inflammation, innate immunity, and coagulation, modulating rejection.
3. The company also inactivated viruses in the porcine genome, including the endogenous retroviruses.

The FDA defines xenotransplantation as a transplant, implant, or infusion procedure that delivers live cells, tissues, or organs from animals or human fluids, cells, tissues, or organs that have had “ex vivo contact with live nonhuman animal cells, tissues or organs” to human recipients. This process has been used as an alternative to human organ transplants since the number of available human organs does not meet the demand for organs by the healthcare system.

By developing genetically engineered and humanized porcine donors, researchers may be able to offer a xenotransplantation alternative to the increasing number of people on the organ transplant list, reducing the number of patients who die while waiting for an organ.

Domestically, 10 people die each day waiting for an organ transplant; however, the press announcement from eGenesis and PorMedTec notes that, in Japan, the risk is much greater, with only 3% of waitlist candidates receiving a transplant and an average wait time of 15 years.

“Very few patients on the waiting list with end-stage organ failure can undergo transplantation in Japan due to the lack of organ donors. Dialysis burdens patients and their families and generally results in a decreased quality of life. The medical costs are enormous — in Japan, 2 trillion yen is spent annually on renal dialysis, constituting 4% of the total medical expenditure of the country,” said Hiroshi Nagashima, Founder & Chief Scientist and CEO, PorMedTec and Professor, Meiji University, in the release. “Cloning technology will enable the use of an alternative organ supply using genetically engineered porcine donors. Our goal is to provide a sustainable supply of organs to all patients in need of transplant.”

The development of these genetically engineered organisms in Japan implies that porcine xenotransplantation will likely advance faster there than in the US — addressing a more dire need. However, international scientific advancements and cross-national collaborations could have significant implications and improvements for the US organ transplant system.