Im interested to hear peoples thoughts on the issues generated from this recent highly publicised nature methods paper regarding off target effects of CRISPR editing. This follow up blog by Gaetan Burio of JCSMR in Australia has some interesting insights.
Thanks all.
Kenneth
Update: This paper is now being considered for retraction according to this editorial note. The Scientist has just reported criticisms of the paper also, and the article appears with a critical comment on pubmed.
That blog post you linked to really knocked the analysis out of the park. While there are certainly some off-target effects, the hoopla surrounding this seems to be mostly hype (not that anyone has EVER accused a Nature publication of seeking such a thing).
It is been always like this unless someone tries to really replicate the results or even increase the sample size and see what is the mutational burden. Tbh in era of NGS calling SNVs it will be a pity to not try to use a higher sample size to understand the mutational burden but without people even understanding the technique to its full application things come out as more ever promising revolution. I have seen the hype of this technology and still people do it (even in my lab) but no one wants to in fact understand why and how these off -target variations actually have an impact. To make such transforming tech into real-like applications these downstream bioinformatic analysis needs to be done but it all drains to the motivation of the group and the PI and also the person who does the CRISPR targeting to see if that person is really interested in doing it on large number of samples or not and then make a test of such mice to understand the off-target burdens and to what extent they can impact.
Considering the myriad of applications that CRISPR-Cas9 can and will be in employed I think research like this certainly is important. However, the sample size (N=2) is far too small to draw any conclusions. I'm surprised that a Nature paper think a sample size like that is sufficient, for any type of analysis. However, the observation of recurrent off target events is puzzling. The sensation around this paper is too much, definitely, but perhaps it's good to get everyone more alert about what possible side effects the "silver bullet" CRISPR-Cas9 might have. Follow-up of this work is required.
So the message of this paper is not appropriate, but so are Chinese scientists who already use this immature technology on human subjects. I guess this is just how science works - different findings (some more pronounced than others) after which a consensus is found.
That blog post you linked to really knocked the analysis out of the park. While there are certainly some off-target effects, the hoopla surrounding this seems to be mostly hype (not that anyone has EVER accused a Nature publication of seeking such a thing).
It is been always like this unless someone tries to really replicate the results or even increase the sample size and see what is the mutational burden. Tbh in era of NGS calling SNVs it will be a pity to not try to use a higher sample size to understand the mutational burden but without people even understanding the technique to its full application things come out as more ever promising revolution. I have seen the hype of this technology and still people do it (even in my lab) but no one wants to in fact understand why and how these off -target variations actually have an impact. To make such transforming tech into real-like applications these downstream bioinformatic analysis needs to be done but it all drains to the motivation of the group and the PI and also the person who does the CRISPR targeting to see if that person is really interested in doing it on large number of samples or not and then make a test of such mice to understand the off-target burdens and to what extent they can impact.