Anti-CRISPR - an off-switch for genome editing

Scientists have discovered a new set of proteins that can block CRISPR/Cas9 , potentially acting as an 'off-switch' for the genome editing system.

'Researchers and the public are reasonably concerned about CRISPR being so powerful that it potentially gets put to dangerous uses,' said Dr Joseph Bondy-Denomy of the University of California, San Francisco, and a senior author of the study. He said that the newly discovered proteins could 'provide a mechanism to block nefarious or out-of-control CRISPR applications, making it safer to explore all the ways this technology can be used to help people'.

The team of researchers had been studying how viruses infect bacteria. They reasoned that in order to incorporate themselves into the genome of the bacteria, some viruses must be able to overcome the CRISPR/Cas9 defence mechanism of the bacteria.

They analysed the genomes of almost 300 strains of Listeria monocytogenes bacteria that had been infected by viruses. Such bacteria were likely to contain viral DNA encoding CRISPR/Cas9-blocking proteins. Dr Bondy-Denomy's team found that more than half of the strains they analysed contained at least one protein capable of blocking CRISPR/Cas9, suggesting that the CRISPR/Cas9 inactivation system is widespread.

Further experiments demonstrated that two of these proteins could inhibit the type of CRISPR/Cas9 system that is now widely used in labs for genome editing bacteria and animal cells.

Based on these findings, the researchers suggest that these inhibitory proteins could help make genome-editing technology safer. The proteins could also be used in newer techniques such as CRISPR interference and CRISPR activation, which are used to increase or decrease gene activity (rather than simply deleting genes).

'The next step is to show in human cells that using these inhibitors can actually improve the precision of genome editing by reducing off-target effects,' said team member Dr Benjamin Rauch, who was first author of the study published in Cell. 'We also want to understand exactly how the inhibitor proteins block Cas9's gene-targeting abilities, and continue the search for more and better CRISPR inhibitors in other bacteria.'

Dr David Edgell from Western University in London, Ontario, who was not involved in the study, told the National Post that it was important to first improve the accuracy of CRISPR/Cas9 before carrying out human genome-editing trials: 'Before you start tweaking the genome of a living person, you want to be assured the gene-editing technology is precise, accurate and not toxic'.