From the archive, originally posted by: [ spectre ],1,5159031.story?ctrack=2&cset=true

Universal blood is created from other types

The process is safe, efficient and cost-effective, researchers report.
By Thomas H. Maugh II  /  April 2, 2007

Researchers have perfected an inexpensive and efficient way to convert
types A, B and AB blood into type O, the universal-donor blood that
can be given to anyone – an achievement that promises to make
transfusions safer and to relieve shortages of type O blood.

The team reported Sunday in the journal Nature Biotechnology that it
isolated bacterial enzymes that safely remove from red blood cells the
sugar molecules that provoke an immune reaction in the recipient.

Previous studies of type O blood produced from type B by a different
method have shown it to be both safe and effective, and the
researchers are now conducting clinical trials with the new product.

Mismatching of blood causes at least half of all transfusion-related
deaths. And the need for precisely matched blood is behind the costly
and inefficient process of shuttling blood units back and forth
between regional blood banks and hospitals to match daily

“Those issues could be largely resolved if there were a universally
transfusible blood supply,” said Douglas L. Clibourn, chief executive
of ZymeQuest Inc. in Beverly, Mass., which is developing the

The problem involves sugar molecules on the surface of red blood
cells. Type A blood has one set of sugars and type B has another,
whereas type O has none. People with type A blood have antibodies
against the type B sugars, people with type B have antibodies against
type A, and people with type O have antibodies against both.

If a person receives mismatched blood, the antibodies attack red blood
cells, producing a potentially fatal breakdown of the cells.

In the 1980s, researchers isolated an enzyme from coffee beans that
could convert type B to type O. Clinical trials of the enzyme-produced
blood showed it behaved no differently from normal blood in
hospitalized patients.

But the enzymes involved were very expensive and had to be used under
highly acidic conditions that damaged the red cells. And the research
team could not able to find an enzyme that would convert type A to
type O. So development was halted.

ZymeQuest commissioned cellular biologist Henrik Clausen of the
University of Copenhagen to search for new enzymes to carry out the

Clausen and his team investigated more than 2,500 bacteria and fungi
before they identified the two candidates that were cited in the
Nature Biotechnology report.

The discovery could be a major breakthrough in improving the blood
supply, wrote Geoff Daniels of Britain’s Bristol Institute for
Transfusion Sciences in an editorial accompanying the article.

The new enzymes are 100 to 1,000 times more potent than previously
used ones and, more important, they work at room temperature and
neutral pH, which is very good for blood cells, said Dr. Martin L.
Olsson of Lund University in Sweden, who is overseeing the clinical
trials. In an hour, the enzymes remove all the sugar molecules from
the surface of red blood cells, after which they can be easily washed

The team initially isolated blood from healthy individuals, converted
the red cells to type O and injected them back into the donors, said

After that study showed no problems, they began a larger clinical
trial using donor blood. Olsson said there had been no adverse
reactions to the product; he would not comment further on the results.

Clibourn said he expected results from the trial to be available later
this year.

If the trials are successful, ZymeQuest will manufacture a system that
can be used by blood banks and hospitals to convert donor blood into
type O as necessary.

thomas [dot] maugh [at] latimes [dot] com

ZymeQuest, Inc.
Email:    contacts [at] zymequest [dot] com


Main activities: Molecular Diagnostics, including fetal genotyping for
red cell surface antigens and membrane biochemistry. The molecular
genetic basis of blood groups. The expression and function of
structures with blood group activity with particular emphasis on their
role in erythropoiesis.

e-mail: geoff [dot] daniels [at] nbs [dot] nhs [dot] uk


“Enzymatic removal of blood group ABO antigens to develop universal
red blood cells (RBCs) was a pioneering vision originally proposed
more than 25 years ago. Although the feasibility of this approach was
demonstrated in clinical trials for group B RBCs, a major obstacle in
translating this technology to clinical practice has been the lack of
efficient glycosidase enzymes. Here we report two bacterial
glycosidase gene families that provide enzymes capable of efficient
removal of A and B antigens at neutral pH with low consumption of
recombinant enzymes. The crystal structure of a member of the alpha-N-
acetylgalactosaminidase family reveals an unusual catalytic mechanism
involving NAD+. The enzymatic conversion processes we describe hold
promise for achieving the goal of producing universal RBCs, which
would improve the blood supply while enhancing the safety of clinical

Published online: 1 April 2007; | doi:10.1038/nbt1298
Bacterial glycosidases for the production of universal red blood cells

Qiyong P Liu1, 9, Gerlind Sulzenbacher2, 9, Huaiping Yuan1, Eric P
Bennett3, Greg Pietz1, 3, Kristen Saunders1, Jean Spence1, Edward
Nudelman1, Steven B Levery4, Thayer White1, John M Neveu5, William S
Lane5, Yves Bourne2, Martin L Olsson6, 7, Bernard Henrissat2 & Henrik
Clausen3, 8

Correspondence should be addressed to
Gerlind Sulzenbacher: gerlind [dot] sulzenbacher [at] afmb [dot]
or Henrik Clausen: hc [at] imbg [dot] ku [dot] dk

1  ZymeQuest Inc., 100 Cummings Center, Suite 436H, Beverly,
Massachusetts 01915, USA.

2  Architecture et Fonction des Macromolécules Biologiques, UMR6098,
CNRS, Universités Aix-Marseille I & II, Case 932, 163 Avenue de
Luminy, 13288 Marseille Cedex 9, France.

3  Departments of Cellular and Molecular Medicine and Oral
Diagnostics, University of Copenhagen, Blegdamsvej, DK-2200 Copenhagen
N, Denmark.

4  Department of Chemistry, University of New Hampshire, Durham, New
Hampshire 03824, USA.

5  Harvard Microchemistry and Proteomics Analysis Facility, Harvard
University, Cambridge, Massachusetts 02138, USA.

6  Division of Hematology and Transfusion Medicine, Department of
Laboratory Medicine, Lund University and University Hospital Blood
Center, SE-22185, Lund, Sweden.

7  Department of Pathology, Beth Israel Deaconess Medical Center and
Harvard Medical School, Boston, Massachusetts 02215, USA.

8  Hematology Division Brigham & Women’s Hospital and Harvard Medical
School, Boston, Massachusetts 02115, USA.

9  These authors contributed equally to this work.

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