The version of CRISPR whose selling point has been its precision suffers, ironically, from the same shortcoming that has dogged other forms of the genome editor — that it makes a lot of unintended, off-target DNA changes. In two studies published on Thursday, one in mice embryos and one in rice plants, scientists find that this “base editing,” a form of CRISPR invented in 2016, can cause hundreds of unintended mutations, potentially making its clinical use a genetic crapshoot.

Fears about off-target mutations from CRISPR have waxed and waned even as clinical development of CRISPR, for severe genetic diseases ranging from sickle cell and inherited blindness to progeria and genetic epilepsy, marches on. In one episode, a 2017 paper reporting sky-high off-target edits in mice briefly tanked the stocks of three CRISPR companies. The paper was retracted last year after the authors conceded that they’d probably made a rookie mistake, but concerns about unintended edits haven’t disappeared.

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