Cas9 protein structure from Staphylococcus aureus WIKICOMMONS, THOMAS SPLETTSTOESSER A team of scientists that previously identified genes within bacteriophage genomes that code for anti-CRISPR proteins has now discovered phages that harbor an antidote to the Cas9 enzyme that is a key component of the predominant CRISPR system that is today used as a gene-editing tool. The team, led by the University of Toronto’s Alan Davidson, described three bacteriophage-encoded, anti–Cas9 genes and showed that the corresponding proteins are able to block the activity of CRISPR-Cas9—derived from bacterial type II CRISPR-Cas systems—in human cells. in a paper. The team’s work, published last week (December 8) in Cell, could help researchers better understand naturally occurring CRISPR systems and better modulate the activity of CRISPR-based gene-editing tools for research and clinical applications.
Notably, the work is “going specifically after Cas9 and then applying the discoveries in human cells,” Harvard’s George Church, who was not involved in the study, wrote in an email to The Scientist.
“The identification of those much awaited anti-CRISPR proteins for type II systems started by classical in silico searches based on sequence similarity with already known anti-CRISPR proteins,” Philippe Horvath, a senior scientist at DuPont in France who first showed that the CRISPR system provides resistance to phages in prokaryotes and who was also not involved in the study, wrote in an email to The Scientist. “What is less trivial in this work, and really crafty, is the iterative combination of sequence similarity searches and genetic context analyses, prophesizing that type II anti-CRISPR ...
