[Recently,] a short communication came out in Nature methods on off targets (OT) effects following CRISPR/Cas9 editing into the mouse zygote. This paper has made few headlines in media outlets leading to a fall in stock market for biotechnology companies such as Editas Medicine or Caribou Biosciences.
One important question is this unusual OT rate was observed before? The simple answer is NO.
In general the number of OT reported in the literature after CRISPR/Cas9 editing is generally low and predictable as Cas9 is highly sensitive to mismatches.
[But then why does this] discrepancy [exist] between the report published in Nature Methods and previous observations?
From reading this report...in Nature Methods, it appears clear to me that 1) The methods of Cas9 delivery was unusual leading to the generation of an increase OT as normally reported 2) The low sample size...revealed a seriously underpowered study and meaningless results 3) The experimental design [was poor]...Therefore this led to an abnormal number of mutations reported. I would predict very few if not close to none of these variants are CRISPR related.
I find absolutely astonishing this paper got published in Nature Methods. This is a terrible paper and as a reviewer I would have dismissed it from the first round of review. This is a worrying trend from ‘high impact’ journals to promote the hype over good science.
[Read the full study here(behind paywall)]
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