The FDA's approval of the first CRISPR-Cas9–based gene therapy marked a major milestone in biomedicine, validating genome ...

Anti-CRISPR proteins in biotechnological applications Certain phages have evolved small inhibitor proteins known as anti-CRISPRs to inactivate bacteria’s use of CRISPR effectors for immune defense.

Anti-CRISPR proteins were first characterized by Joseph Bondy-Denomy in a paper published in 2012, when he was a doctoral student in Davidson’s lab (Nature, 2012 DOI: 10.1038/nature11723).

Aca proteins act as regulators of the phage's counter-defense. They make sure the initial burst of anti-CRISPR production that inactivates CRISPR is then rapidly dampened to low levels.

Caption The anti-CRISPR protein (red on right) mimics DNA, binding in the site where the cutting enzyme Cas9 typically grips the target DNA (left) before it cuts. But the anti-CRISPR protein doesn ...

Along with anti-CRISPR proteins previously discovered, the hope is that scientists can design phages carrying these CRISPR-Cas inhibiting Racrs, and thereby block the immune defenses of bacteria.

These proteins “are the phages’ answers to bacterial CRISPR systems which are a form of aggression by the bacteria,” he added. “The discovery of anti-CRISPR proteins is not surprising in the sense ...

Finally, the Zhang team provided key proof-of-concept evidence that each of these anti-CRISPR protein can serve as an off-switch for CRISPR-Cas3 in human cells.

In their paper the authors concluded, “Our comparison of ‘safeguard sgRNAs’, anti-CRISPR proteins and small-molecule inhibitors suggests that [C] extension is a convenient and safe tool.” ...