Solving blood supply shortage with glycomics

Posted: June 14, 2021

GlycoNet Investigators study the sugars on red blood cells to find ways to make universal donor blood

GlycoNet Investigator Dr. Stephen Withers from the University of British Columbia.

Blood shortage is a big problem in many countries while blood donation and transfusion is its main solution. Especially during the ongoing coronavirus pandemic, blood, and plasma donations have managed to save many lives and have given hope to people suffering from the virus.

For blood transfusions to be safe, the donor and patient blood types must match. Now GlycoNet researchers at the University of British Columbia (UBC) have identified a new, more powerful group of enzymes that can turn any type of blood into the universally usable type O—expanding the pool of potential blood donors and making blood matching safer and easier. 

“Blood type is determined by the presence of antigens on the surface of red blood cells; type A blood has the A antigen, B has the B antigen, AB blood has both antigens and O blood has none,” said Dr. Stephen Withers, Lead Investigator and Professors of chemistry at UBC. “Antigens can trigger an immune response if they are foreign to the body, so transfusion patients should receive either their own blood type, or type O to avoid a reaction. That’s why O blood is so important.”

Removing antigens from blood effectively transforms the blood type into type O.

“We have been particularly interested in enzymes that allow us to remove the A or B antigens from red blood cells,” Wither explains. “If you can remove or cleave those antigens, which are just simple sugars, then you can convert A or B to O blood.” He says scientists have pursued the idea of adjusting donated blood to a common type for a while, but they have yet to find efficient, selective enzymes that are also safe and economical.

Previously, the team developed a new group of enzymes using a metagenomics approach, where the researchers sampled the genes of millions of microorganisms without the need for individual cultures. The researchers then used E. coli to select for genes that code for enzymes that can cleave sugar residues. “This is a way of getting that genetic information out of the environment and into the laboratory setting and then screening for the activity we are interested in,” says Withers.

Ultimately, the team found successful candidate enzymes in the human gut microbiome. Glycosylated proteins called mucins line the gut wall, providing sugars that serve as attachment points for gut bacteria while also feeding them as they assist in digestion. Some of the mucin sugars are similar in structure to the antigens on A- and B-type blood. The researchers homed in on the enzymes the bacteria use to pluck the sugars off mucin and found a new family of enzymes that are 30 times more effective at removing red blood cell antigens than previously reported candidates.

“Expanding global blood supply is critical in light of growing populations and the frequency of natural disasters,” said Withers, pointing out that both the U.S. Red Cross and Canadian Blood Services have recently made emergency appeals for blood donations. “Our hope is that one day we can eventually render any type of donated blood, tissues or organs, safe for use by anyone regardless of their native blood type.”

The technology has now evolved into a proprietary platform and a Vancouver start-up company ABOzymes Biomedical Inc. Founded in 2020, the company’s first product is an enzyme additive for a standard blood bag that first primes and then eliminates a marker on the red blood cell that determines blood group A, rendering it group O. This enables the conversion of A-negative blood to O-negative blood—the universal donor blood. The company has recently closed a pre-seed round of financing, raising approximately $1.3M in equity investment.

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