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A CRISPR spin-off causes unintended typos in DNA

Author: Tina Hesman Saey / Source: Science News

DNA editing
TOUCHING BASES A molecular tool that alters one DNA letter at a time may be overzealous, editing spots in the DNA it was never intended to change.

Even the best editor sometimes introduces typos. That’s true whether the editor is human or a version of the much-heralded gene-editing tool CRISPR.

One type of CRISPR gene editor that changes individual DNA bases, rather than cutting DNA, introduces more unwanted mutations than expected in mouse embryos and rice plants, researchers report. Those mistakes occurred in places where the tool wasn’t supposed to make changes. Another tested base editor, however, didn’t make the undesirable edits. The results were described in two studies published online February 28 in Science.

Researchers hope to use CRISPR base editors to make improvements to crops or correct genetic diseases in people one day. But the new findings suggest that some base editors still have challenges to overcome before being safe for use.

It is necessary to rigorously put the editors through their paces, says chemical biologist David Liu, a Howard Hughes Medical Institute investigator at Harvard University. His team originally created the base editors tested in the two studies, but he was not involved in either study. “The community needs these worst-case scenario pressure tests so we can make sure there’s a good margin of safety when these agents do enter clinical trials,” he says.

CRISPR/Cas9 is a molecular scissors that cuts DNA at precise locations. Researchers have used the gene-editing tool, introduced in 2012, to squash mosquito populations in the lab, tame ground cherries into easier-to-grow crops and alter countless other animals and plants. And last year, a scientist in China reported that he had edited DNA in two babies using CRISPR (SN: 12/22/18, p. 20). But researchers are concerned that the tool is still not safe enough to use in people.

In recent years, scientists have devised versions of CRISPR/Cas9 that don’t cut DNA, but can chemically alter individual DNA bases (SN: 11/25/17, p. 7), like a pencil erasing and correcting a mistake. DNA bases — represented by the letters A, C, G and T —carry genetic information about building an organism. Changes, or mutations, in just one of…

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