Making Universal Donor Type O Blood

 
An advance report that will soon be published in Nature Biotechnology describes progress toward artificially creating type O blood from A, AB, and B blood donors. The advantage is that type O blood can be given to any patient who needs a blood transfusion. If you can convert all donated blood to the universal donor then the blood supply becomes much more flexible.

The ABO blood types are determined by the presence or absence of sugar groups on proteins bound to the outer surface of red blood cells [ABO Blood Types]. A single gene is responsible for the different blood types [Human ABO Gene] and the genetics is well understood [Genetics of ABO Blood Types].

Liu et al. (2007) screened 2,500 fungus and bacterial species for enzymes that could remove the A antigens and B antigens from red blood cells.

The rationale is illustrated in this figure from their paper.

All red blood cells have H antigen. In people with type A blood the H antigen is converted to A antigen through the action of the enzyme α1,3-N- galactosaminyl transferase (GTA). GTA adds N-acetyl- galactosamine (GalNAc) to the H antigen structure. If you have blood type B then a different version of the enzyme (GTB) adds galactose (Gal) to make B antigen [see ABO Blood Types]. If neither version of the enzyme is present then H antigen will not be modified and you will have blood type O.

The authors discovered several enzymes (A-zyme) that remove GalNAc converting type A blood back to type O blood. They decided to characterize an enzyme from the flavobacterium Elizabethkingia meningoseptum that had previously been identified—and patented—in 2002. Liu et al. constucted recombinant versions of the E. meningoseptum gene and expressed it in Escherichia coli. They were able to make large quantities of active enzyme which led to crystallization and solving the structure.

A version of B-zyme was identified in the common gut bacterium Bacteroides fragilis. The gene for this enzyme was also cloned and expressed in E. coli. A modified version with high activity was selected for further study.

The two purified enzymes were used to treat blood from A, AB, and B donors. All traces of A- and B-antigens were removed as demonstrated by the lack of reactivity against anti-A and anti-B antibodies. Thus, the treated blood was effectively type O and was suitable to use as universal donor. The authors are confident that the process can be scaled up.

Accordingly, we believe that automated cost-effective processes can be developed for practical use in transfusion medicine.

Several of the authors are associated with ZymeQuest Inc. of Beverly MA (USA) and the project was funded, in part, by ZymeQuest. The authors declare their competing interest in a statement that can only be accessed from the full text version of the paper on the website. Here's the statement,

Declaration: Authors (except for G.S., J.M.N., W.S.L. and Y.V.) are employees, consultants and/or shareholders in Zymequest Inc., which holds patents covering the described technologies.

Liu, Q.P., Sulzenbacher, G., Yuan, H., Bennett, E.P., Pietz, G., Saunders, K., Spence, J., Nudelman, E., Levery, S.B., White, T., Neveu, J.M., Lane, W.S., Bourne, Y., Olsson, M.L., Henrissat, B. and Clausen, H. (2007) Bacterial glycosidases for the production of universal red blood cells. Nature Biotechnology Published online: 1 April 2007; | doi:10.1038/nbt1298.