When you’re rushed into the hospital for a blood transfusion, what happens if they don’t have your blood type? It’s a problem that scientists have been trying to solve for decades, and they might have finally made a breakthrough. By modifying an enzyme to snip off the antigens from types A and B blood, they’ve managed to make it more like the universal donor type O. The study is published in the Journal of the American Chemical Society.
The A and B antigens are sugars that are carried on the surface of red blood cells. It is the combination of these antigens—with blood cells having one, all, or none of these antigens—that give rise to the four principal blood types: A, B, AB, and O. This is what determines which blood you can accept and who you can give blood to. So whilst type O can be given to anyone as the blood cells have neither antigen, all other types can cause life-threatening immune reactions if given to the wrong patient.
The idea of converting blood types has existed since the 1980s, when a team in New York was able to demonstrate that an enzyme extracted from green coffee beans was able to remove B antigens from red blood cells. Clinical trials showed that the blood could be safely transfused to people of a different blood group. However, the enzyme reaction was simply far too inefficient, requiring too large a volume at too high a temperature to convert all the blood cells to make the process practical.
However, scientists from the University of British Columbia have created an enzyme that could potentially solve this problem. It works in exactly the same way, by snipping off the problem antigens, and effectively turning A and B blood into type O. As Steve Withers, one of the researchers explains, “The concept is not new but until now we needed so much of the enzyme to make it work that it was impractical. Now I'm confident that we can take this a whole lot further.”
The team created the enzyme through a process known as "directed evolution." This is a method of protein engineering that is based on natural selection and allows a user to evolve a protein, such as an enzyme, towards a desired goal. Starting with an original enzyme, the scientist inserted mutations into the gene that codes for it. By selecting the mutants that were most efficient in removing the antigens, and repeating the process again and again, the researchers were able to make the enzyme 170 times more effective over just five generations.
“We produced a mutant enzyme that is very efficient at cutting off the sugars in A and B blood, and is much more proficient at removing the subtypes of the A-antigen that the parent enzyme struggles with,” said David Kwan, the lead author of the study and a postdoctoral fellow in the Department of Chemistry.
Their job, however, is not yet done. Whilst the enzyme was able to remove the vast majority of antigens from type A and B blood, they were not able to remove all of them. As the immune system is incredibly sensitive to blood groups—so much so that even small amounts of residual antigen can trigger an immune response—the scientists must first be certain that all antigens are absent.