Researchers prove they can engineer proteins called proteases to find new targets with high selectivity, a critical advance toward potential new treatments for everything from neuro-regeneration to cytokine storm.
When people hear botulinum toxin, they often think one of two things: a cosmetic that makes frown lines disappear or a deadly poison. But the "miracle poison," as it's also known, has been approved by the F.D.A. to treat a suite of maladies like chronic migraines, uncontrolled blinking, and certain muscle spasms.
And now, a team of researchers from Harvard University and the Broad Institute have, for the first time, proved they could rapidly evolve the toxin in the laboratory to target a variety of different proteins, creating a suite of bespoke, super-selective proteins called proteases with the potential to aid in neuroregeneration, regulate growth hormones, calm rampant inflammation, or dampen the life-threatening immune response called cytokine storm.
"In theory, there is a really high ceiling for the number and type of conditions where you could intervene," said Travis Blum, a postdoctoral researcher in the Department of Chemistry and Chemical Biology and first author on the study published in Science. The study was the culmination of a collaboration with Min Dong, an associate professor at the Harvard Medical School, and David Liu, the Thomas Dudley Cabot Professor of the Natural Sciences, a Howard Hughes Medical Institute Investigator, and a core faculty member of the Broad Institute.
Together, the team achieved two firsts: They successfully reprogrammed proteases--enzymes that cut proteins to either activate or deactivate them--to cut entirely new protein targets, even some with little or no similarity to the native targets of the starting proteases, and to simultaneously avoid engaging their original targets.
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