Expanding the Kidney Donor Pool: Enzyme-Mediated ABO Conversion to Create Universal Donor Kidneys

In a potential breakthrough for organ transplantation, researchers have successfully altered the blood type of a human kidney prior to transplantation, marking a world first. Using enzyme technology developed at the University of British Columbia, the team converted a Type A kidney into a universal Type O, effectively removing one of the most significant compatibility barriers in transplantation. The converted organ was transplanted into a brain-dead recipient with family consent, allowing real-time monitoring of immune response without risking a living patient.

This technique hinges on the use of two bacterial enzymes—FpGalNAc deacetylase and FpGalactosaminidase—that selectively cleave the sugar molecules responsible for blood group A antigens on the surface of blood vessels in the kidney. When flushed through the organ during normothermic machine perfusion, the enzymes rapidly removed approximately 80 percent of the antigenic markers within just two hours. Once treated, the organ no longer carried the molecular flags that would normally trigger an immediate immune attack in a non-matching recipient.

After transplantation into the brain-dead recipient, the kidney showed no signs of hyperacute rejection for 48 hours. By the third day, traces of A antigens began to re-emerge, prompting a mild immune reaction—but the damage was far less severe than expected in a standard ABO-incompatible transplant. Notably, researchers observed signs of immune accommodation, suggesting that the host’s system was starting to accept the graft despite the antigen rebound.

This technique represents a significant shift from conventional approaches to ABO-incompatible transplantation, which typically require desensitizing the recipient through plasmapheresis, intravenous immunoglobulin, and immunosuppressants. These methods are labor-intensive, carry added risks, and are largely limited to living donor scenarios. In contrast, this enzyme-based approach alters the organ itself, potentially enabling broader use of mismatched deceased donor organs and reducing wait times—especially for patients with blood type O, who can only receive type O organs but whose universal compatibility often diverts O organs to others.

The proof-of-concept follows earlier preclinical studies demonstrating the feasibility of blood type conversion in human kidneys ex vivo. A 2022 study published in Nature Communications outlined how the same enzymes could strip A antigens from donor kidneys outside the body, providing the groundwork for this new human application. Other recent studies have similarly explored B-to-O conversion using different enzymatic approaches, though those efforts have yet to reach the point of actual transplantation.

Challenges remain. Because this conversion is phenotypic, not genotypic, the original blood group antigens can reappear over time. This rebound may provoke delayed immune responses or chronic rejection, particularly if the immune system reclassifies the graft as foreign after an initial period of acceptance. Researchers are now investigating strategies to suppress or slow this antigen re-expression, including potential re-dosing protocols and more durable enzyme formulations.

Long-term safety and efficacy data are also lacking, and further studies will be required before clinical use can be approved. The startup company Avivo Biomedical, which licensed the enzyme technology, is expected to lead the translational efforts needed to move this approach toward human trials. Regulatory pathways will likely require extensive documentation of graft survival, immune tolerance, and reproducibility across diverse donor-recipient scenarios.

Still, the implications are far-reaching. If perfected, blood type conversion could help equalize access to transplantation by freeing patients from the rigid constraints of ABO matching. In practice, this might allow for more equitable allocation of donor kidneys, reduce discard rates, and improve outcomes for patients currently at a disadvantage due to their blood type. The same strategy may eventually be extended to other organs, offering a broader solution to the chronic shortage and mismatch challenges in transplantation.