Blood-Type-Altering Enzyme Could Make Anyone a Universal Donor

You need a blood transfusion, but the blood bank reports that it has run out of blood matching your type. You try to absorb the news. You feel a pat on your shoulder. Is it a doctor? A nurse? You’re not really paying attention. The lights seem dim. And the incessant beeping of the medical equipment … odd. Muffled now. Still, a voice comes through. Almost a sigh. “Sorry …”

A grim scenario. But it could happen. Blood of an incompatible type, no matter how abundant, would help you not at all. If it were to be transfused into you, you would suffer a severe, potentially fatal, immune response. But what if blood of one type could be changed into blood of another type?

This possibility has intrigued scientists for a long time. And in recent years they have even made some progress. They have come up with an enzyme that snips off the sugars, or antigens, that sprout from red blood cells. When the enzyme acts on the red blood cells from Type A and Type B blood, they become more like the blood cells from Type O blood. And Type O blood is “universal”—it does not cause an immune response when it is given to people with Type A, Type B, or Type AB blood.

To date, this approach—the use of an antigen-cleaving enzyme—has been inefficient and uneconomical. A recent study, however, shows that a greatly improved version of the enzyme can be developed. This study, undertaken by scientists at the University of British Columbia and the Centre for Blood Research, was described April 14 in the Journal of the American Chemical Society (JACS), in an article entitled, “Toward Efficient Enzymes for the Generation of Universal Blood through Structure-Guided Directed Evolution.”

To create a high-powered version of the antigen-snipping enzyme, researchers used a technology called directed evolution that involves inserting mutations into the gene that codes for the enzyme, and selecting mutants that are more effective at cutting the antigens. In just five generations, the enzyme became 170 times more effective.

“Enzymatic removal of the terminal N-acetylgalactosamine or galactose of A- or B-antigens, respectively, yields universal O-type blood, but is inefficient,” the authors of the JACS study wrote. “Starting with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A- and B-antigens from some of the linkages on RBC surface glycans, through several rounds of evolution, we developed variants with vastly improved activity toward some of the linkages that are resistant to cleavage by the wild-type enzyme.”

With this improved enzyme, the scientists were able to remove the wide majority of the antigens in Type A and B blood. But before any such enzyme could be used in clinical settings, it would have to be capable of removing all of the antigens. The immune system is highly sensitive to blood groups, and even small amounts of residual antigens could trigger an immune response.

“The concept is not new, but until now we needed so much of the enzyme to make it work that it was impractical,” said Steve Withers, Ph.D., the study’s senior author and a professor of chemistry at the University of British Columbia. “Now I’m confident that we can take this a whole lot further.”

More details in http://www.genengnews.com/gen-news-highlights/blood-type-altering-enzyme-could-make-anyone-a-universal-donor/81251215/

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s