Enzymatic Removal of A- and B-Blood Group Antigenic Determinants To Generate Universal Blood May Be Feasible

Matching ABO antigens for RBC transfusions is time consuming and limits inventory. Research now shows how this barrier could be eliminated by generating universal blood. Type O RBCs lack the terminal antigenic sugar.Removal of the terminal sugars of the A- and B-antigens yield O-type cells.

A- and B-antigens are linked to the glycan via type 1, type 2, type 3 or type 4 chains. In order to make A- and B-cells non-antigenic like type-O cells, researchers started with a glycoside hydrolase from Streptococcus pneumonia that cleaves type 2 linkages on both A-and B-antigens.   After screening libraries of mutants from 5 rounds of directed mutagenesis, they identified a mutant with 170-fold improved activity to cleave type 1 chains while retaining wild-type cleavage of type 2 linkages. Since this enzyme cleaves the entire terminal trisaccharide of the A- and B-antigens, additional research is needed to confirm safety of the cells. Further enzyme mutagenesis will be necessary to broaden cleavage of linkages to type 3 and 4; however, this bodes well for the potential to engineer an enzyme that can convert A- and B-cells to O-cells.

Reference

1. Kwan DH, Constantinescu I, Chapanian R, Higgins MA, Kotzler MP, Samain E, Boraston AB, Kizhakkedathu JN, Withers SG. Toward Efficient Enzymes for the Generation of Universal Blood through Structure-Guided Directed Evolution. J Am Chem Soc 2015 May 6;137(17):5695-705.