Scientists have discovered an enzyme that may be able to change a person’s blood type by cutting away antigens in types A and B to make them more like Type O. Since Type O may be donated to anybody without a chance of eliciting an immune response, it is considered the ‘universal’ blood type. Lead author and professor at the University of British Columbia of Canada, Stephen Withers, said, “In the end I see that it will be used to pre-treat A or B type blood as needed when there is shortage of compatible blood.” The team published their results in the Journal of the American Chemical Society.
The difference between the A, B and O blood types is the presence of slightly different sugar structures on the surface of red blood cells. Therefore, being given the correct type of blood is important Compared to Type O, A and B each have one additional sugar attached to their surface called N-acetylgalactosamine and galactose, respectively. Blood Type O is free from both of these, which is why any patient may receive it. The notion of converting blood types has existed since the 1980’s, however as Withers explains, “A major limitation has always been the efficiency of the enzymes that can do this: impractically large amounts of enzyme were needed.” Withers’ lab has been focussed on increasing the rates of these enzymes through a technology called ‘directed evolution’. “It should be feasible to substantially improve the activities of enzymes to be used in antigen removal through methods of directed evolution, thereby decreasing the cost of the process,” according to Withers.
Directed evolution is a way for scientists to mimic natural selection in the lab towards a particular goal, typically with proteins or nucleic acids. Building on 30 years of research, the technology allowed Withers and his team to insert many different types of mutations into the genes that code for blood antigens. By selecting strains that proved most effective at snipping away the antigens from A and B blood types, the team were able to produce an enzyme 170 times more efficient than the original strain.
Withers and his team now intend to develop chemo-enzymatic synthetic routes to discover strains that might cleave the other two major sub-types of Type A blood that are currently only cleaved by slowly by even the best mutants available. Given the team’s success so far, Withers told The Positive that he feels optimistic that this may work. The lab will apparently also be searching metagenomic libraries for new bacterial enzymes that might do the job. “The route forward is clear and that involves the evolution of the enzyme further to better cleave the other major sub-types of A blood,” said Withers. The team is confident in their ability to improve the enzyme to 100% efficiency using directed evolution so they can try it out in clinical trials. “That’s going to be our challenge, pushing it to 100 percent. This paper shows that conceptually, it’s possible. There’s going to be a lot of work to do, however it’s doable.” This level of efficiency is important because even the smallest amount of the other antigens may set off an undesirable immune response in the patient.
Withers also explained that, “There is potential application towards organ transplants, since the antigens present on red blood cells are present on other tissue types as well.” However, living organ tissue may regenerate cell surface antigens – a challenge not faced with red blood cells – resulting in rejection. Withers believes that if the antigens of donor tissue were to be removed, the technique might also be used to help ABO-incompatible organ transplantation.
How might this concept apply to organ transplants?