Enzymatic Production of O-Type Blood

Everyone knows that blood for transfusions is always in short supply.  Qiyong Liu and colleagues report in Nature Biotechnology the conversion of type A and B blood to type O.  Liu, et al, screened 2500 fungal and bacterial samples to find exoglycosidases that efficiently cleave carbohydrate groups from donor erythrocytes, thereby providing a route to "universal red blood cells".

In a short news piece by Peter Aldhous, The New Scientist notes that:

The A and B antigens, which give blood groups their name, are sugars carried on the surface of red blood cells. Human red blood cells can carry one of these antigens, both, or neither; giving four blood groups: A, B, AB and O, respectively. Receiving mismatched blood can cause a life-threatening reaction, and errors are made in 1 in every 15,000 transfusions, on average.

From Liu, et al., (jargon warning):

The enzymes are expressed with high yields in E. coli and because they have similar properties, a single common conversion buffer system and process can be used to remove A and B antigens and produce ECO RBCs from A, B and AB RBCs that type as blood group O with routine licensed typing reagents and methods. Extensive FACS and biochemical analyses confirm the efficient removal of the immunodominant A and B antigens and exposure of the underlying H antigens. The current process, which is performed manually at neutral pH, is scalable to automated full-unit conversions, and ECO cells produced by this method are predicted to survive and function in a manner equivalent to native group O RBCs in non-ABO matched individuals as reported previously for B-ECO RBCs . The process has a projected consumption of approx60 mg (A-ECO) and 2 mg (B-ECO) recombinant enzyme with 60-min enzyme treatment per unit RBCs. This is approx30- (A-ECO) and 1,000-fold less (B-ECO) enzyme than the conversion protocol developed for group B RBCs with the Coffee bean alpha-galactosidase . Accordingly, we believe that automated cost-effective processes can be developed for practical use in transfusion medicine.

...Preferred properties of an exoglycosidase suitable for enzymatic conversion of RBCs include the following parameters: (i) high substrate specificity for the blood group antigens to restrict the reaction to the immunodominant blood group A and B antigens; (ii) reaction conditions suitable for maintenance of RBC integrity and functions; (iii) high efficiency in cleavage of antigens on the RBC surface to minimize residual antigens and enzyme consumption; and (iv) properties to facilitate enzyme removal from the RBCs by routine cell-washing techniques. The glycosidases presented in this study offer all of these characteristics.

The two enzyme families described here perform efficiently in conversion of RBCs; ECO cells type as group O with all licensed reagents; and sensitive FACS and glycolipid analyses confirm efficient removal of A and B antigens. Finally, enzymes from both families are slightly basic and associate with the negatively charged RBCs through ionic interactions, thereby enabling efficient removal with isotonic buffer solutions, such as PBS, used for cell washing.

The availability of enzymes from these glycosidase families has resulted in the development of a simple and efficient process for producing universal RBCs that type as blood group O. Clinical translation of this approach may allow improvement of the blood supply and enhancement of patient safety in transfusion medicine.

In principle, this is an excellent set of new parts for the toolbox, to be sure.  Though the New Scientist reports that the technology, with obvious monetary value, is being commercialized by ZymeQuest.

Given that mammalian erythrocytes, notably from cows, can be used in emergency transfusions, I wonder if there are set of enzymes that could be more generally used to strip carbohydrates from animal blood cells, thereby providing an even bigger pool of universal donor cells.