SHIN ET AL., SCIENCE ADVANCES Last December, two groups of scientists published their discoveries of several proteins that could block CRISPR-Cas9 activity. In a study published today (July 12) in Science Advances, researchers have now used one of those anti-CRISPR agents to reduce off-target effects in Cas9-mediated genome editing in human cells.
“CRISPRs have been recognized as bacterial immune systems for some time, and of course, one of the pretty common themes in biology is that if something develops a weapon, the target is going to develop a defense,” says study coauthor Jacob Corn, a professor of biochemistry and biophysics at the University of California, Berkeley. “It turns out that . . . the phages have evolved ways to fight off the CRISPR systems, and that’s these anti-CRISPR proteins.”
To study the mechanism behind one of these anti-CRISPR proteins, AcrIIA4, which was co-discovered by Corn’s collaborator, Joseph Bondy-Demony, a biologist at the University of California, San Francisco, the team used a variety of methods, including cryo-electron microscopy and human cell culture experiments.
Through a multi-lab effort, researchers ...