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posted by martyb on Saturday July 08 2017, @01:17PM   Printer-friendly
from the of-mice-and-mien dept.

A new study has contradicted a finding of CRISPR-Cas9 off-target activity, instead finding that "unexpected mutations" were due to two closely related mice:

In May, a study claimed that the revolutionary CRISPR gene editing technique can cause thousands of unwanted and potentially dangerous mutations. The authors called for regulators to reassess the safety of the technique. But doubts were raised about these claims from the very beginning, not least because it was a tiny study involving just three mice. Some critics have called for the paper to be withdrawn. Now a paper posted online on 5 July has proposed a simple and more plausible explanation for the controversial results. If it's right, the authors of the original study were wrong.

[...] When Stephen Tsang of Columbia University Medical Center and colleagues compared the entire genomes of two CRISPR-edited mice with a third one, they found thousands of shared mutations in the two edited mice. Tsang and co attributed to these mutations to CRISPR, and issued a widely-covered press release that suggested CRISPR is far riskier than dozens of other studies had suggested.

[...] But there is a much simpler explanation, says the latest study: the two CRISPR-edited mice just happened to be more closely related and thus shared more mutations. [...] "I agree the two mice are indeed more likely to be closely related," says geneticist Gaetan Burgio of the Australian National University, one of the many critics of the original paper. He says its publication in a prominent journal was a failure of peer review.

"Unexpected mutations after CRISPR-Cas9 editing in vivo" are most likely pre-existing sequence variants and not nuclease-induced mutations (open, DOI: 10.1101/159707) (DX)

The disputed press release from May, and the study it was based on:

Unexpected mutations after CRISPR–Cas9 editing in vivo (DOI: 10.1038/nmeth.4293) (DX)


Original Submission

 
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  • (Score: 4, Informative) by takyon on Saturday July 08 2017, @02:31PM (2 children)

    by takyon (881) <reversethis-{gro ... s} {ta} {noykat}> on Saturday July 08 2017, @02:31PM (#536540) Journal

    Off-target activity refers to random splices or mutations caused by an imperfect CRISPR method. It's as if you used Find and Replace on a document but it would add your replacement string in places you don't want it to go, change single characters, delete characters, etc.

    There are already some ways to make CRISPR more precise. What this new study suggests is that at least one alarmist perspective of the accuracy/precision of CRISPR was very flawed.

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  • (Score: 1, Interesting) by Anonymous Coward on Saturday July 08 2017, @04:16PM (1 child)

    by Anonymous Coward on Saturday July 08 2017, @04:16PM (#536558)

    What this new study suggests is that at least one alarmist perspective of the accuracy/precision of CRISPR was very flawed.

    Not really, it is more that their understanding of how CRISPR works is wrong:

    However, our attempt to find a consensus DNA sequence at or near the locations of these sequence variants failed to reveal any consistent motif (Supplementary Fig. 3; Supplementary Note 4), a result that makes it hard to envision any reasonable mechanism for how CRISPR-Cas9 could direct alterations to the same genomic loci in the two mice.

    It seems to primarily work by selecting for pre-existing mutants... this is something I have been saying since the hype started. The critique paper is just as clueless but at least now people are starting to recognize the existence of these pre-existing variants. Once they get around to looking closer at their data and quantifying this they will "discover" about 1/100 to 1/10k cells are mutants already *anywhere* they look.

    • (Score: 0) by Anonymous Coward on Sunday July 09 2017, @04:07PM

      by Anonymous Coward on Sunday July 09 2017, @04:07PM (#536846)

      they will "discover" about 1/100 to 1/10k cells are mutants already *anywhere* they look.

      Bullshit.
      Your explanation is inconsistent with just about any genomic sequencing result. If what you are saying were true, then all the studies reporting the fidelity of DNA and RNA polymerases are wrong as well as just about every study involving quantitative sequencing.