The gene-editing tool CRISPR is everywhere these days. Scientists are using it to try and fight cancer and treat muscular dystrophy, companies are using it in agriculture, and TV executives are even writing it into shows.

And it's ubiquity isn't surprising because CRISPR is one of the biggest scientific discoveries of our time. It tremendously improves upon earlier gene-editing techniques because it's fast, cheap, and accurate. Or so we thought. A new study published last week in Nature Methods found that CRISPR might not be as precise as researchers believed it to be. But not everyone agrees.

In the study, researchers were using a strain of mice that had mutations causing early onset retinal degenerationa disorder that blinded the mice. Using CRISPR, the researchers were able to snip out and correct a mutation in a particular gene to restore the mice's vision.

But the scientists were curious about what are known as "off-target" effects, or secondary mutations caused by CRISPR that occur away from the intended genetic target. So, they compared the DNA from two CRISPR-treated mice to that of a mouse which hadn't received the gene editing. They found a surprisingly large number of differences. Namely, the CRISPR-treated mice had around 1400 small off-target mutations and over 100 more considerable genetic alterations.

"When you read about CRISPR, the focus is on the amazing ability of this system to go in and fix a single nucleotide out of the three billion in a genome. People have been looking at off-targeting, but generally you get the sense that it's not that bad, or it's not consequential. So this definitely came as a surprise," Vinit Mahajan, a Stanford University ophthalmology professor and researcher on the project, told Seeker.

According to the paper, the researchers didn't observe any physical effects of the off-target mutations at the time. But they warned that such effects could show up later in the CRISPR-treated mice or even in their offspring.

Off-target mutations are definitely something researchers need to pay attention to. Particularly those involved in clinical studies and the ongoing human trials. But not everyone thinks the study's findings are as valid as the authors present.

"CRISPR isn't ready to be used in human gene editing."

Cara Moravec is a postdoctoral researcher at the University of Wisconsin - Madison and she uses CRISPR in her research all the time. She found a few anomalies in the study that raised some concerns for her in regards to the interpretations of the findings. She says off-target effects are a known issue with CRISPR but that this study isn't the best representation of those problems.

"I think this paper does bring to light that CRISPR isn't ready to be used in human gene editing," Moravec told Motherboard, "And there are concerns about off-target effects, but in this study they're overestimating those off-target effects because of some of the choices they made in their methods."

Moravec points to a comment left on Pubmed's listing of the article, which claims that a number of the off-targets listed in the paper are actually on-target, meaning the mutations happened on the gene the researchers were shooting for, not elsewhere. And other concerns, many shared by Moravec, are raised on UC Davis professor Paul Knoepfler's blog.

While this study brings some CRISPR limitations to the forefront, all of its claims may not stand up under scrutiny. We're definitely going to need more research to really figure out the extent of off-target mutations, when they happen, and why.

Read more:

CRISPR Is Not Accurate Enough to Save Us Yet - Motherboard - Motherboard

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