In DepthBiology

Genome editor gets more versatile and precise

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Science  02 Mar 2018:
Vol. 359, Issue 6379, pp. 967
DOI: 10.1126/science.359.6379.967

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CRISPR, the genome editing tool, makes it easier to target and cut DNA than ever before, but one of its shortcomings is that it can't cut just anywhere. New research has discovered a way to improve the tool and make it more versatile. The human genome has 3.2 billion bases of DNA. The most common form of CRISPR relies on a stretch of RNA to guide its molecular scissors—an enzyme called Cas9 in shorthand—to cut a specific one of those 3.2 billion bases. But Cas9 can't latch onto the genome unless there is a specific sequence flanking the cut site, which amounts to something of a landing pad. Harvard University chemist David Liu and colleagues, as they report online in the 28 February issue of Nature, have engineered a new version of Cas9 that has a more commonly found DNA sequence and can land in four times as many places. Dubbed xCas9, it has only been tested on a few dozen sites so far, but it holds the promise of making the remarkably powerful CRISPR even more muscular. And, to the astonishment of Liu, the more promiscuous xCas9 in his lab's experiments also had fewer off-target cuts than Cas9, which means it was less likely to introduce mistakes that could be dangerous when CRISPR is used for medicine.