ISTOCK, RATSANALNatural differences in our DNA may cut into CRISPR’s ability to precision-edit the human genome, by thwarting Cas9’s ability to hit the right genetic target—or any target at all. An analysis of the extent of this problem, described today (July 31) in Nature Medicine, could have implications for how genome-editing technologies are tested in clinical trials and whether they could become broadly available.
“Precision editing technologies like CRISPR/Cas9 are incredibly promising as therapies,” geneticist Daniel MacArthur of the Broad Institute of Harvard and MIT tells The Scientist in an email. “They’re also exquisitely sensitive to the precise genetic changes present in a patient's genome.”
In 2014, researchers first started to see how genetic variation could disrupt CRISPR-Cas9 from reaching its targets. But to what extent such variation could confound the ability of the Cas9 enzyme to recognize its intended editing site wasn’t well understood.
In the new study, David Scott and Feng Zhang, both of MIT and the Broad Institute, analyzed data from the Exome Aggregation Consortium and the 1,000 Genomes database, projects that catalogue human genetic variation, and found that differences in DNA substantially impact the efficacy ...
