Crack in CRISPR Facade After Unanticipated in Vivo Mutations Arise

&quot;Unanticipated?&quot;<p>CRISPR is believed to be, at its core a bacterial immune system designed to &#x27;knock out&#x27; problem viral genes by chopping them up at specific &#x27;remembered&#x27; loci and hoping that the lossy repair mechanisms cause mutations that prevent the gene from functioning. It also evolved to work on the fairly small genomes of single-celled organisms.<p>So we&#x27;ve known for awhile that it&#x27;s going to be quite tricky to get only the exact mutations that we want, at only the exact point that we want them.<p>It&#x27;s not <i>magic</i>.

Pre-publication press release. Full text of article not available. How good was their control group? The press release says they used mice that had previously been edited with CRISPR&#x2F;Cas9 and found off-target mutations, most of which were single nucleotides. Did they have a good control group so as to exclude random point mutations? Who knows? What is the theory on how CRISPR&#x2F;Cas9 causes single nucleotide off-target mutations? No idea.<p>This is academic publishing at its absolute worst. Put out a sensational press release and whip up a fervour before the article is available. Those diving into the scrum to comment have not read the article.<p>Also, it&#x27;s research by MDs. Just sayin&#x27;.

Most of the DNA that suffers random mutations is non-coding DNA. It&#x27;s completely unknown what effects, if any, modifying non-coding DNA might have as its use is unknown.<p>I find it interesting that although anyone can experiment with CRISPR in their living room using something like this <a href="http:&#x2F;&#x2F;www.the-odin.com&#x2F;" rel="nofollow">http:&#x2F;&#x2F;www.the-odin.com&#x2F;</a> that no one has just tried modifying the non-coding DNA a lot and then observed any changes (or lack thereof) in the specimen.

Off target effects from CRISPR is not new. The method leverages DNA repair mechanisms in the cell to do the recombination. All errors involved in those DNA repair mechanisms (there are distinct ones) would apply here。

I seem to recall that in prior HN stories about CRISPR some poster was saying he believed CRISPR didn&#x27;t work the way people thought it worked. He said it was simply killing cells that didn&#x27;t have the desired mutation and biologists weren&#x27;t realising that because of design errors in the experiments (or rather, sometimes mass cell dieoffs were being reported but not dwelled upon).<p>If CRISPR isn&#x27;t actually editing the DNA but rather just selecting natural mutants that happen to have the desired edit, would that cause what&#x27;s seen here?

I believe George Church published some work several years ago now using whole genome sequencing after CRISPR, saying they had neglible off-site integration or other mutations.<p>But going back,the findings were much more measured than that- they still saw off-site integration.

the article headline kinda belies a bias before you even read it

Title is a bit dramatic. People just need to choose their gRNAs better based on available genomes.

Unanticipated<p>I&#x27;m just a normal person with nothing to do with this, and I expected such &quot;surprises&quot; from the beginning.<p>I remain convinced mankind should not mess with this.

I couldn&#x27;t be the only one worried about an &quot;I Am Legend&quot; type problem with this stuff. Obviously, that movie is an extreme, but the underlying problem of unintended mutation exists.

i am sick of all the CRISPR; hype this is the cure being worse than the disease.