UBC enzymes show progress toward universal organs
Every year, numerous transplants and transfusions save lives, yet blood type and compatibility often limit access to the organs patients need. New research from the University of British Columbia is exploring enzymes that can remove antigens from blood vessels, effectively making organs universally compatible. This approach not only increases organ availability but also reduces the risk of organ rejection.
Research on the first successful human transplantation of a kidney converted from blood group A to universal blood group O was published in the October issue of Nature Biomedical Engineering under the title “Enzyme-converted O kidneys allow ABO-incompatible transplantation without hyperacute rejection in a human decedent model.“
We spoke with the study authors, Dr. Stephen Withers, UBC professor emeritus of chemistry, who co-led the enzyme development, and Dr. Jayachandran Kizhakkedathu, a UBC professor in the department of pathology and laboratory medicine and the Centre for Blood Research.
The idea that led to significant change: a pair of enzymes that work together
More than 10 years ago, specifically in the early 2010s, Dr. Stephen Withers and his colleague, Dr. Jayachandran Kizhakkedathu, came up with an exciting idea. The goal was to create universal donor blood by removing the sugars that define blood types and cause complications, especially in organ transplantation. The sugars, or antigens, not only determine a person’s blood type but are also present on the surfaces of blood vessels in organs. When these antigens are unfamiliar to a recipient’s immune system, it can recognize them as threats and attack, which may result in rapid and severe organ rejection.
In 2019, a pair of enzymes that work together to convert the A antigen into the O blood group antigen was discovered. The study, “An enzymatic pathway in the human gut microbiome that converts A to universal O-type blood”, was published in Nature Microbiology. This discovery promised to simplify blood transfusions and broaden the blood supply.
Then, in 2024, the scientists published an article, “Enzymatic conversion of human blood group A kidneys to universal blood group O.” As they explained, if a kidney has antigens that the patient’s immune system does not recognize, antibodies immediately attack the organ, which can lead to organ rejection. People with blood types O and B have to wait much longer for a kidney because O patients can only receive an organ from an O donor. One of the rare options for these patients is ABO-incompatible transplantation (ABOi), but it requires pre-transplant desensitization and plasmapheresis and can only be performed with living donors, which does not help with most kidneys from deceased donors.
Therefore, researchers have developed a strategy to convert the organ to the universal blood type O. The organ is connected to a perfusion machine, and bacterial enzymes remove the A or B antigens from the blood vessels, making the organ non-immunogenic and ready for transplantation without the risk of rejection. Two enzymes from the bacterium Flavonifractor plautii were used in the study: FpGalNAc deacetylase removes the acetyl group from the A antigen, and FpGalactosaminidase removes the rest of the sugar, together turning the A antigen into the H antigen, which is characteristic of blood group O. The treated kidney acts as a universal organ, which enables greater organ availability and reduction of rejection, dramatically shortening the waiting time of patients and increasing the chance for transplantation.
This discovery provided a crucial foundation for the next, far more ambitious step: applying the same principle not only to blood but to whole organs. As mentioned earlier, after successful tests on blood, lungs, and kidneys, the question remained: Can an organ transformed by enzymes survive within the human immune system?
Both professors, Dr. Withers and Dr. Kizhakkedathu, were actively involved in this research.
The first human experiment
In the first human experiment, an enzyme-treated kidney was transplanted into a brain-dead recipient with the family’s consent. This allowed researchers to directly observe the immune response without putting a human life at risk. During the first two days, the kidney functioned without signs of hyperacute rejection, while on the third day, some antigens began to trigger a mild reaction. Researchers noted that the body was gradually beginning to tolerate the organ.
The first successful human transplant of a kidney converted from blood type A to universal blood type O used special enzymes developed at the University of British Columbia.
This method could increase the overall number of organs available
Could this method potentially be applied to other types of transplants, and if so, which ones might be relatively easier compared to others?
Dr. Stephen Withers: Yes, indeed. In fact, we have already shown that human lungs can be successfully converted, and work is ongoing on hearts. Kidneys are the safest option—since we have two of them and dialysis as a backup—so they are the best place to start.
Dr. Jayachandran Kizhakkedathu: Our collaborators have already demonstrated its application in the lungs. A UBC spin-off company, AVIVO Biomedical Inc., is developing this technology for other organs.
What amount of enzyme is required in this case, and does the patient’s age matter?
Dr. Jayachandran Kizhakkedathu: The important thing is that we need very little enzyme for blood group conversion due to the high activity of the enzyme. For example, in the current work, we used a concentration of 1 microgram/mL of enzymes. That means with less than 1 mg of enzyme, we can convert a human A kidney to universal O using approximately 1 L of perfusion solution containing the enzyme. Since the blood group conversion occurs outside the body, we believe age does not matter.
This is great news both for science and for patients… so I would like to ask, and I hope it’s not too early, but globally, how much could this method reduce the average waiting time for a kidney? What do you need most, and where would you most need support and help?
Dr. Jayachandran Kizhakkedathu: Currently, O blood type patients wait more than 2–3 years longer for organs than other blood types. We believe this technology will increase the availability of organs for transplantation and improve equity in transplantation. The technology will also be applicable to deceased donors, where organ conversion can now be applied. This was not possible before. Thus, it would increase the overall number of organs available for transplantation.
Dr. Stephen Withers: That is very hard to quantify, but we do know that a certain percentage of A and AB type organs go unused because a suitable match is not found in time. This method would convert those organs to universal O, since we also have enzymes for B conversion.
What do you need most, and where would you most need support and help?
Dr. Stephen Withers: Mostly, we need funding to carry out several more decedent studies. Success in these studies will hopefully allow us to gain permission for true clinical trials.
The potential to transform the field of organ transplantation
Since the early 2010s, the idea of using enzymes to create universal donor organs has progressed into tangible scientific advances, demonstrating the potential to transform the field of organ transplantation. Moreover, the method requires only small amounts of enzyme, works outside the body, and shows promising results for other organs such as lungs and potentially hearts, further expanding its impact. While additional studies are needed, the progress achieved over the past decade illustrates how a focused enzyme-based approach can address one of the most pressing challenges in transplantation: the gap between organ supply and patient demand. As research continues, the combination of scientific innovation and clinical application offers hope that thousands of patients currently on transplant waiting lists could gain faster access to lifesaving organs.
Image: Dr. Stephen Withers (left) and Dr. Jayachandran Kizhakkedathu (right), UBC
