Gene editing system has universal "brakes"

the latest work by team Jennifer Dondner, co-discoverer of crispr-Cas9 gene editing tools, published in
, a leading journal: They found two proteins, ACRII., that inhibit Cas9 activity through X-diffraction crystallization. C1 and ACRII.C3 have completely different mechanisms of action, and ACRII.C1 has broad-spectrum inhibition, that is, can play the role of "brake device" in different gene editing systems, so that the gene editing process at the appropriate time to terminate, reduce off-target effect.
CRISPR-Cas9 system is simple and efficient, there is a major security risk: it cannot stop shearing after the wrong gene has been repaired, but may continue to modify normal genes, resulting in off-target effects. Scientists have been hoping to find a "safe gate" in the bacterial natural system that can shut down the gene editing process in time.
at least seven Cas9 inhibitors (ACR proteins) have been found before, with the ability to stop cells from cutting and editing. This time, the Dondner team compared two proteins that had been shown to inhibit Cas9 in human cells and found that they worked in completely different ways. ACRII.C1 binds closely to two important amino acids that bind DNA in Cas9, making Cas9 lose the ability to cut DNA, while ACRII.C3 changes its structure by allowing two Cas9 molecules to form a two-polymer, making Cas9 no longer binding to DNA. Based on two different processes, ACRII.C1 inhibits many different Cas9 proteins and has a broad spectrum, while ACRII.C3 inhibits only one protein called NmeCas9.
Huang Zhiwei, a professor at Harbin University of Technology's School of Life Sciences and Technology, published a weighty paper in the journal Nature in April, the first study of the mechanism of effect of another Cas9 inhibitory protein, ACRII.C4, to prove that it can effectively inhibit the gene editing activity of SpyCas9. Professor Huang told Science and Technology Daily that their findings predated the Dondner team's report that there was no evidence that ACRII.C1 and ACRII.C3 had a better inhibitory effect than ACRII.C4, but that comparative studies showed that the most effective inhibitors could be found, adding them to the gene editing system, allowing Cas9 to "turn off" the function on time after completing the gene editing task and avoid the off-target effect. (Source: Science and Technology Daily