BioWorld International Correspondent

LONDON - The discovery of two enzymes that can cut off the A and B antigens from red blood cells, turning them into blood group O, which can be given to anyone, has the potential to relieve pressure on the blood supply and make transfusions safer.

Originally discovered in bacteria, and now available in purified recombinant form, the two enzymes can carry out their work at neutral pH. A final step washes away the enzymes and the antigen fragments from the red blood cells.

Henrik Clausen, professor in the Department of Cellular and Molecular Medicine at the University of Copenhagen in Denmark, told BioWorld International, "This technology could make it much easier and less costly to manage the blood supply, because group O blood is frequently shipped around to make sure it is available where it is needed most. It would also reduce the risk of being infused with the wrong blood type, which can be lethal."

Clausen is also a science consultant to ZymeQuest Inc., of Beverly, Mass., a private biotechnology company that has been developing modified blood products for use in transfusion medicine.

ZymeQuest has a partnership with Chiron, a business unit of Novartis Vaccines and Diagnostics, of Emeryville, Calif., to market blood treated with the enzymes, and currently is raising capital to finance forthcoming clinical trials.

Together with collaborators in France, Sweden and the U.S., Clausen reports the identification of the enzymes in a paper in the April 1 issue of Nature Biotechnology titled "Bacterial glycosidases for the production of universal red blood cells."

The four main blood groups are A, B, AB and O. People with group A blood have A antigens on their red blood cells and antibodies in their plasma to the B antigen, and those with group B blood have B antigens on their red blood cells and antibodies in their plasma to the A antigen. Those of group AB have both types of antigen on their red blood cells but neither type of antibody in their plasma. Blood group O has neither type of antigen on the cells but both types of antibodies in the plasma.

Red blood cells of people with group O blood therefore can be transfused into recipients of any other group, whether A, B or AB, without adverse reaction.

Group O therefore is known as the "universal donor," and is always in short supply. For that reason, researchers have tried for decades to find ways of converting blood of other groups into type O.

Blood group is determined by the presence of complex sugar chains, called H antigens, on the surface of the red cells. The type of monosaccharide on the end of the H antigen determines whether the blood group is A, B or AB; except in blood group O where there is no additional monosaccharide on the H antigen.

One initial strategy, tried by ZymeQuest with the New York Blood Center, using an enzyme derived from coffee beans, seemed to work for red blood cells of group B but was not sufficiently efficient or cost-effective for general use.

Clausen and his colleagues, working with scientists at ZymeQuest, screened a panel of 2,500 bacteria and fungi, looking for enzymes that were able to detach the A and B monosaccharide groups from the H antigens on red blood cells. They identified two enzymes that could efficiently cut off both the A and the B monosaccharides.

Working with ZymeQuest, Clausen and colleagues have now produced recombinant versions of the enzymes in Escherichia coli.

Clausen said: "Using standard blood typing and immunochemistry, we have shown that there is essentially no A or B antigen left on the cells after the treatment. Furthermore, instead of requiring 1 to 2 grams of enzyme per unit of group B red blood cells, as was necessary with earlier attempts, only 1 mg to 2 mg per unit are now needed. This brings the cost of the enzymes down to affordable levels per unit, and suddenly it becomes potentially economically feasible to apply this in practice."

ZymeQuest is planning to conduct clinical trials with the B enzyme. Clinical trials of the enzyme that cleaves the A antigen from red blood cells have begun recently in Europe, and results are expected within a year.

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