CRISPR Digest #6

Exams are over and the real, adult world is about to begin. My first taste of it has come in the form of flat hunting in London and let me tell you that this is, in many ways, more stressful than sitting exams. In any case, I thought I would have far more time to read and write after term finished but I was clearly wrong. So here is just a brief CRISPR update, including some recent reviews.

Firstly, in response to the paper earlier this year (Liang et al, 2015), which reported the first use of CRISRP/Cas9 genome-editing in human embryos, several influential members of the scientific community, including Emmanuelle Charpentier, Jennifer Doudna and Craig Venter (the first to sequence a human genome using the “shotgun” sequencing method), have commented on this development. When asked whether they thought human germline engineering was inevitable, Venter, for example, answered that he was convinced it would happen and would be difficult, if not impossible, to control. Charpentier and Doudna, on the other hand, were careful to reiterate that there are considerable risks, including ethical issues, that need to be dealt with before undertaking such experiments. In particular, Doudna and her colleagues argue that off-target effects still occur at non-insignificant rates and that even successful gene-editing could lead to unexpected effects due to genetic interactions with other, normal DNA variations in a human’s genome. Lastly, reference is made to the 1975 conference on recombinant DNA held in Asilomar (California) at which scientists decided that for 16 months work using recombinant DNA would be put on hold so that stricter, international guidelines could be implemented. Would such a “moratorium” (Baltimore et al, 2015) be applicable to CRISPR/Cas9 human genome-editing too?

Secondly, a new CRISPR review (Sternberg & Doudna, 2015) was published in Molecular Cell last month. It includes some of the latest research articles and another one of these handy overview spider diagrams:

Screen Shot 2015-06-12 at 15.48.07

Lastly, a new review (for which I can’t yet find the full online reference; Mou et al Genome Medicine (2015) 7:53) discusses CRISPR/Cas9 in the context of generating mouse models of cancer. Since CRISPR can be used to specifically alter single DNA bases, cause chromosomal translocations or completely knock-out gene function one can use the system to mimic the mutations that are normally acquired during tumourigenesis. For example, by using mice which inducibly express the Cas9 nuclease one can then provide the guide RNAs by injecting them directly into mouse livers to initiate cancer formation. Alternatively, groups have manipulated haematopoietic stem cells ex vivo using CRISPR and then re-introduced these cells into mice to model certain leukaemias such as acute myeloid leukaemia. Who knows, maybe I’ll even be using one of these models during my PhD on pancreatic cancer, starting in September?

References:

Baltimore D, Berg P, Botchan M, Carroll D, Charo RA, Church G, Corn JE, Daley GQ, Doudna JA, Fenner M, Greely HT, Jinek M, Martin GS, Penhoet E, Puck J, Sternberg SH, Weissman JS, Yamamoto KR (2015) Biotechnology. A prudent path forward for genomic engineering and germline gene modification. Science 348: 36-38

Bosley KS, Botchan M, Bredenoord AL, Carroll D, Charo RA, Charpentier E, Cohen R, Corn J, Doudna J, Feng G, Greely HT, Isasi R, Ji W, Kim J-S, Knoppers B, Lanphier E, Li J, Lovell-Badge R, Martin GS, Moreno J, Naldini L, Pera M, Perry ACF, Venter JC, Zhang F, Zhou Q (2015) CRISPR germline engineering – the community speaks. Nat Biotech 33: 478-486

Liang P, Xu Y, Zhang X, Ding C, Huang R, Zhang Z, Lv J, Xie X, Chen Y, Li Y, Sun Y, Bai Y, Songyang Z, Ma W, Zhou C, Huang J (2015) CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell: 1-10

Sternberg Samuel H, Doudna Jennifer A (2015) Expanding the Biologist’s Toolkit with CRISPR-Cas9. Molecular Cell 58: 568-574

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