20. november 2020

Anti-CRISPRs pave the way for future biotechnological discoveries


Anti-CRISPR genes that encode CRISPR-Cas inhibitors could serve as marker genes for identifying new anti-defense systems with biotechnological potential

Like humans, bacteria are under constant threat of infection by viruses and, to protect themselves, they have evolved an arsenal of anti-viral defense mechanisms. One of these is CRISPR-Cas, an immune system that uses specialized molecular scissors to recognize and chop up the genes of invading viruses. In recent years, however, these gene-scissors have become popular for their application in genome engineering, a revolutionary development that was honored with the chemistry Nobel Prize this year.

In an international collaboration, researchers at the Department of Biology, University of Copenhagen, have shed light on the complex evolutionary battle between CRISPR-Cas systems and their viral targets and the results have recently been published in the renowned scientific journal Nature Communications.

- “We discovered 11 new Anti-CRISPR protein families. These are inhibitors that viruses have naturally developed to overcome CRISPR-Cas immunity”, states Rafael Pinilla-Redondo, a recent PhD graduate from the University of Copenhagen and co-lead author of this work.      

- “This is the largest number of Anti-CRISPRs reported in a single study, and it increases the number of described type I anti-CRISPRs by 45%”, continues co-first author Saadlee Shehreen, PhD candidate at the University of Otago.

CRISPR technologies are predicted to have far-reaching biotechnological, molecular and medical applications, but the methods to regulate them are currently limited. In recent years, there has been a growing interest in repurposing Anti-CRISPRs as off-switches for CRISPR-based technologies.

Interestingly, the researchers report that the genes encoding for the Anti-CRISPRs are not randomly scattered across viral genomes. Instead, they are located in defined genomic regions together with inhibitors of other bacterial defense functions.

- “It was fascinating to find that diverse anti-defense genes tend to organize in clusters within viral genomes. This is reminiscent of the co-location of defense systems in bacterial genomes, something that is known as “defense islands”, adds Prof. Søren J. Sørensen, head of the Microbiology Section at the University of Copenhagen and continues: “The anti-defense clustering phenomenon has not been described before and we propose to name these regions ‘anti-defense islands”.

Importantly, the concept of “defense islands” has allowed scientists to predict novel defense systems following a ‘guilt-by-association’ approach (i.e. using known defense systems as a guide post to find new ones). The researchers suggest that the same principle can be applied for the discovery of anti-defense genes. These new anti-defenses will likely exhibit novel inhibitory mechanisms, which could be exploitable in the development of various biotechnological applications.

The study is supported by: Innovation Fund Denmark and the Independent Research Fund Denmark