CRISPR-Cas9 has been hailed as a revolutionary way to edit imperfections out of DNA, but the technique has raised concerns about the potential for unwanted changes to be made in genes. Now a team of researchers at the University of Toronto and the University of Massachusetts Medical School believe they’ve fingered three families of proteins that can temporarily suspend CRISPR, thereby preventing those unintentional edits.
Their work, which appears in the journal Cell, may make it possible to dictate where CRISPR is used within an individual cell and to turn it on and off at will, said lead author Alan Davidson of the University of Toronto in a press release. "The three anti-CRISPR proteins we've isolated seem to bind to different parts of the Cas9, and there are surely more out there."
CRISPR inhibitors actually occur naturally in the body when bacteria and viruses interact. Bacteria use CRISPR-Cas complexes to process genetic material made by viruses, which then respond by producing proteins that bind to those complexes, in essence halting the bacterial response.
The ability to harness that process and use it in gene editing could prevent off-target effects of CRISPR-Cas9, the researchers believe. “CRISPR-Cas9 in ancillary cells, tissues, or organs is at best useless and at worst a safety risk," says co-author Erik Sontheimer of the University of Massachusetts in the release. "But if you could build an off-switch that keeps Cas9 inactive everywhere except the intended target tissue, then the tissue specificity will be improved."
CRISPR-Cas9 is being investigated as a way to treat a range of diseases, from blindness to HIV to sickle cell, but gene editing is still far from a perfect process. That has made the quest to improve CRISPR a priority around the world. In September, researchers at Christiana Care Health System in Delaware said they figured out how to perfect CRISPR’s gene editing using segments of synthetic single-stranded DNA. And earlier this year, scientists at Texas Tech University Health Sciences Center said they improved the efficiency of the process by 50 percent by tweaking RNA.