Trouble with CRISPR Maybe, But Maybe Not. All pipelines showed that F0. SNVs 6. 3 and 8. F0. SNVs 5. 1 and 8. The System for Award Management SAM is an official website of the U. S. government. There is no cost to use SAM. You can use this site for FREE to. Free project manager papers, essays, and research papers. Breaking the biggest stories in celebrity and entertainment news. Get exclusive access to the latest stories, photos, and video as only TMZ can. Download Free Antivirus Software For Windows Xp Kaspersky Antivirus there. Derek Software Toxicology' title='Derek Software Toxicology' />Based near Edinburgh in Scotland, UK, ForthTox Ltd is a dynamic and proactive consultancy firm, with a broad range of toxicological expertise in Pharmaceutical. The same 1. 17 indels and 1,3. SNVs were detected in both of the CRISPR treated mice, which indicated nonrandom targeting. The mutation rate detected in CRISPR treated mice was substantially higher than that generated by spontaneous germline mutations 3 to 4 indels and 9. SNVs, de novo, per generation. Oh dear. If that holds up, thats clearly going to be a major difficulty in bringing CRISPR based therapeutics forward, at least with the current state of the art. Example+4.%3A+Drug+bioactivation+and+hepatotoxicity.jpg' alt='Derek Software Toxicology' title='Derek Software Toxicology' />Just as worrisome, if not more, is that fact that software predictions of the fifty most likely off target sites of action did not match any of the variants that were actually seen. So it would appear that we have no idea of whats going on here. As the paper says, with great restraint, The unpredictable generation of these variants is of concern. Now we get to the arguing, though, because the big question is whether these results are correct. They do not match up well with whats already in the literature on the subject, thats for sure. On Twitter, Nicolas Bray brought up one of the concerns. His question is a simple one, but it needs to be answered the two treated mice were siblings, while the control was apparently more distantly related. How many of these variations, then, can be ascribed to what the mice started out with The control animal was from the same inbred strain, but still the number of variations seen in this paper is way off what others have reported. Sam Sternberg noted that the paper and its supplementary information is not very clear about the relationship between the mice, and also suspects that many of these mutations are from the founders and not the CRISPR treatment per se. Meanwhile, Gaetan Burgio pointed out that the experimental details say that Briefly, an sg. RNA expressing plasmid had been coinjected, into FVBNJ zygotes, with the single stranded oligodeoxynucleotide ss. ODN donor template and Cas. F0 founders. Plasmids themselves, he notes, are known to cause mutations, since they have much longer half lives than RNA or protein, and he says his own labs work with direct injection of sg. RNA and Cas. 9 protein showed far fewer mutations, in keeping with the rest of the literature. Another potential problem has been brought up by many observers this study has an n of 2, with one control animal. Thats a pretty thin platform on which to build the CRISPR Is Doomed monument. So there are a number of reasons to wonder if these results are real. If they are, other questions arise about the newer Cas. RNA designs, but Im not even going to think about those, to be honest, until this result has been replicated and given a thorough going over. The implications are too big to start running around in circles just yet. There will be time for that, if needed. Derek Software Toxicology' title='Derek Software Toxicology' />Update, in the interests of full disclosure after publishing this post and looking at the moves in the stock prices of both EDIT and CRSP yesterday and today, I found my own doubts convincing enough to have bought some of both as a short term trade. I have no idea what their long term prospects are, but their sudden drops due to this news may not be justified. On the rare occasions that Ive taken a position in any sort of individual biopharma stock, Ive noted it on the blog, and will continue to do so. Now you all can watch me lose money in real time.