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New CRISPR 'Off-Switch' Provides Greater Control on Gene Editing Method

Dec 14, 2016 05:58 AM EST

CRISPR/Cas9 or CRISPR has been a revolution method of gene editing that has been discovered quite recently by scientists. Its rather simple method has revolutionized the field of genetics for a lot of researchers. 

However, the new technology is not an exact science yet. Dangers include excessive or unwanted changes in the genome that can create off-target mutations. This can limit safety and efficacy in therapeutic applications, until now at least.

According to Medical News, researchers at the UMass Medical School and the University of Toronto have discovered the first known "off-switch" for the CRISPR, allowing scientists more accuracy in their genetic editing.

A new study published in Cell from Erik Sontheimer, Alan Davidson, and Karen Maxwell identified three naturally occurring proteins that inhibit the Cas9 enzyme. These anti-CRISPRs have the ability to block DNA cleavage by the Cas9 nuclease.

According to GEN News, Sontheimer said the off-switch can relieve potential problems in the system. This includes the fact that while CRISPR/Cas9 can introduce specific chromosome breaks to create genome edits, chromosome breakage can be hazardous.

Davidson added that the off-switch is a good indication that the CRISPR can be turned off, as this allows researchers to have better confidence in using gene editing.

CRISPR9 uses a molecular scalpel (Cas9) that cuts DNA efficiently but is muzzled in its native state. An RNA guide complex unlocks the scalpel when a matching genetic sequence is found and is cut. The RNA guides are produced from "clustered regularly interspaced short palindromic repeats" or CRISPR arrays that contain remnants of the genomes of past viral infections.

The CRISPR/Cas9 system can then be an adaptive immune defense for bacterial cells. But this also means scientists can reprogram the system with artificial guide RNAs to cleave sequences and enable the insertion of new fragments of genetic information.

This simple method is changing biomedical research by making it vastly easier to inactivate and edit genes. 

Sadly, this also means the power of the system is not exact. There is a potential to mismatch because the RNA cannot be guided to the right position. This can occur as many as 100 times across the six billion nucleotides that make up the human genome and can cause damage. The off-switch allows the Cas9 to be inactive everywhere except the target tissue.  

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