This natural defense strategy could help some genes fend off CRISPR edits

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Nucleosome. Image credit: Journal of Cell Science

Sowbugs, armadillos, hedgehogs… and DNA? The same strategy that some animals use to avoid being attacked — roll into a ball and keep your vulnerable bits beyond predators’ reach — turns out to let genes avoid being sliced up by the genome-editing molecules of CRISPR, scientists reported on [September 10]. When a segment of DNA wraps itself around a protein into what’s called a nucleosome, CRISPR-Cas9 can no more cut it than a hungry hawk can bite a rolled-up hedgehog.

If CRISPR “can’t see DNA when it’s wrapped around a nucleosome,” said biochemist Dana Carroll of the University of Utah, who led the study, “it could be an issue.”

Nucleosomes exist because fitting the 6-foot-long human genome into a cell nucleus is akin to packing 30 miles of yarn into a basketball: It needs to be rolled up. When a cell doesn’t need a particular gene at a particular moment, that gene rolls around a protein, becoming inaccessible to the cell’s gene-activating machinery.

The nucleosome issue is only the latest in an expanding list of challenges, including genomic havoc and concerns about cancer, to using CRISPR to treat diseases. As with those others, it’s too early to know whether rolled-up DNA will be an impediment to the use of CRISPR to repair disease genes in people.

Read full, original post: CRISPR’s hedgehog problem: Rolled-up genes can’t be edited, study finds

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