First ‘off-switches’ discovered for CRISPR/Cas9 technique

Researchers have discovered three naturally occurring proteins that can modulate the gene editing system CRISPR/Cas9, making it more precise.

CRIPSR/Cas9 editing is becoming used in biotechnology as it is quicker and relatively easier than other existing techniques. However, it is not always error free - off target mutations caused by unnecessary changes to the genome as a result of this have limited its role in therapeutic applications.

Dr Alan Davidson, also from the Medical School, said: “CRISPR is very powerful, but we have to be able to turn it off. This is a very fundamental addition to the toolbox, which should give researchers more confidence to use gene editing.”

CRISPR/Cas9 consists of two separate molecules — one that cuts DNA (Cas9) and a RNA guide that consists of clustered regularly interspaced short palindromic repeats (CRISPR). First seen in bacteria, this system allowed them to nullify viral infections by cutting almost any DNA sequence. Uses for CRISPR/Cas9 include editing of cell lines for research and simplifying the creation of animal disease models.

Professor Erik J. Sontheimer, from the University of Massachusetts Medical School, said: “CRISPR/Cas9 is a good thing because it introduces specific chromosome breaks that can be exploited to create genome edits, but because chromosome breakage can be hazardous, it is possible to have too much of a good thing, or to have it go on for too long. There is a current shortage of reliable ways to turn off Cas9 once it has already been delivered to a cell. If you can trip an off-switch after the correct editing is done, then the problem is relieved."

The study was published in Cell.