Blood-type incompatibility has long been one of the greatest obstacles in organ transplantation, forcing thousands of patients—particularly those with type O blood—to wait years longer for compatible donors. In a landmark achievement, scientists have now successfully converted a kidney from blood type A to universal type O and transplanted it into a human recipient. This breakthrough, using special enzymes, could help reduce transplant wait times and lower the risk of organ rejection worldwide.

Research on this began in the early 2010s when scientists at the University of British Columbia (Vancouver, BC, Canada) began focusing on developing universal donor blood by removing the sugar molecules that define blood types. These same sugars, or antigens, also coat the blood vessels of organs and trigger immune attacks when mismatched during transplantation. Type O patients—who make up over half of kidney transplant waitlists—can receive organs only from type O donors, often waiting up to four years longer and facing higher mortality risk.

The UBC team’s key discovery in 2019 of two highly efficient enzymes capable of stripping away the sugars defining type-A blood marked a turning point. These enzymes function as molecular scissors, precisely removing the antigen “nametags” that signal blood type A, effectively revealing universal type O beneath. The result is an organ that can be accepted by recipients of any blood type without triggering an aggressive immune response.

To test this in a human model, the research team performed a first-in-human transplant of an enzyme-converted kidney into a brain-dead recipient with family consent. The findings, published in Nature Biomedical Engineering, show that for two days, the organ functioned without signs of hyperacute rejection—the rapid immune reaction that typically destroys incompatible organs within minutes. By the third day, only mild immune activity was detected, indicating that the organ was beginning to show tolerance.

Traditional approaches to overcoming blood-type incompatibility rely on suppressing the recipient’s immune system or stripping antibodies over several days, typically requiring organs from living donors. The UBC method takes a reverse approach by changing the organ itself instead of the patient, enabling faster transplants and reducing complications.

This enzyme-based technology has also been applied successfully to blood and lungs, where lungs and kidneys were converted outside the body. The 2023 human study confirmed that the same method could be used safely inside the human immune system, providing crucial proof of concept. Regulatory approval for clinical trials is the next step, with efforts underway to advance the technology for use in both organ transplants and universal donor blood production.

“This is the first time we’ve seen this play out in a human model,” said Dr. Stephen Withers, UBC professor emeritus of chemistry who co-led the enzyme development. “It gives us invaluable insight into how to improve long-term outcomes.”

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