Tapping evolution to improve biotech products

Scientists can improve protein-based drugs by reaching into the evolutionary past, a paper published in Nature Biotechnology proposes.

As a proof of concept for this approach, the research team from Emory, Children’s Healthcare of Atlanta and Georgia Tech showed how “ancestral sequence reconstruction” or ASR can guide engineering of the blood clotting protein known as factor VIII, which is deficient in the inherited disorder hemophilia A.

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Structure of Factor VIII

Other common protein-based drugs include monoclonal antibodies, insulin, human growth hormone and white blood cell stimulating factors given to cancer patients. The authors say that ASR-based engineering could be applied to other recombinant proteins produced outside the human body, as well as gene therapy.

Experimental hematologist and gene therapist Chris Doering, PhD and his colleagues already had some success in addressing these challenges by filling in some of the sequence of human factor VIII with the same protein from pigs.

“We hypothesized that human factor VIII has evolved to be short lived in the blood to reduce the risk of thrombosis,” Doering says. “And we reasoned that by going even farther back in evolutionary history, it should be possible to find more stable, potent relatives.”

Doering is associate professor of pediatrics at Emory University School of Medicine and Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta. He is also a faculty member in the MSP program. The first author of the paper is former MSP graduate student Philip Zakas, PhD.

Doering’s lab teamed up with Trent Spencer, PhD, director of cell and gene therapy for the Aflac Cancer and Blood Disorders Center and MSP faculty member, and Eric Gaucher, PhD, associate professor of biological sciences at Georgia Tech, who specializes in ASR.

Doering and co-author H. Trent Spencer are co-founders and stockholders of Expression Therapeutics, which owns the intellectual property for the part-porcine factor VIII.

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