A research group in Denmark has found proteins in intestinal and soil microbes that can inhibit the action of cutting CRISPR-Cas9 genes, a finding that could help to control the technology with more precision and less risk.
Bacteria and viruses have been fighting an evolutionary arms race for millions of years. Bacteria developed CRISPR systems to combat invading viruses called bacteriophages by removing the viral DNA from the bacterial genome. These systems formed the basis of pioneering tools for processing genes of today CRISPR-Cas9. Less well studied, however, is the viral way to disarm the immune system, anti-CRISPR proteins.
"Anti-CRISPRs are found in phages, their genomes usually miss annotations and we do not know the function of most of their genes,"Morten Sommer, the main researcher who carries out the work at the Novo Nordisk Foundation Center for Biosustainability, told me."Therefore, it makes it difficult to identify these proteins without any prior knowledge or test to test for their function."
In a study published in Cell Host & Microbe, the researchers obtained DNA from the gut microbiomes of people, pigs and cows, as well as the soil. They introduced random sections of the collected DNA into a specially designed strain of Streptococcus pyogenes bacteria to identify genes that were able to bypass the bacteria's CRISPR-Cas9 system.
From this approach, the researchers identified four new viral anti-CRISPR genes that could one day help refine CRISPR-Cas9 gene processing, off-target operations that can damage cells.
"Today, most researchers using CRISPR-Cas9 have difficulty checking the system and activities outside the target area, " Sommer said in a statement. "Anti-CRISPR systems are very important because you want to turn your system on and off to test the activity, so these new proteins could become very useful."
The researchers investigate the commercialization of this discovery, but have not given any details. All tools for improving CRISPR systems can be attractive for companies that want to use the technology in medical applications. As an example from last year, the Swiss company CRISPR Therapeutics and its American partner Vertex Pharmaceuticals launched it first try of CRISPR-Cas9 in Europe, for the treatment of genetic diseases.
In addition to medical use, anti-CRISPR proteins can also improve the accuracy of CRISPR for genetically modified animals, crops and microbes, a route that the German company BASF takes.
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