CRISPR Digest #10

Goodness gracious. It’s been almost two months since the last CRISPR update. Shame on me. I wonder how we all coped. So here is a concise Christmas CRISPR compendium.

In November, Michael Specter wrote a lengthy article on CRISPR in The New Yorker, which is well written and informative for a wide audience. There was one quote by Eric Lander, the director of the Broad Institute at MIT in Massachusetts, that I found particularly good:

There will be an enormous chart. Well, it will be electronic, and it will contain the therapeutic road map of every trick that cancer cells have—how they form, all the ways you can defeat them, and all the ways they can escape and defeat a treatment. And when we have that we win. Because every cancer cell starts naïve. It doesn’t know what we have waiting in the freezer for it. Infectious diseases are a different story; they share their knowledge as they spread. They learn from us as they move from person to person. But every person’s cancer starts naïve. And this is why we will beat it.

Although I hesitate to use martial words and phrases like “defeat” or “beat” cancer and find it difficult to believe that we will ever completely understand and be able to chart out “every trick that cancer cells have”, I do like the comparison with infectious diseases. Until now I have often tried to explain why I don’t think we can ever cure cancer by likening it to infectious disease agents such as viruses and bacteria: they mutate and evolve in response to changing environmental conditions and drug treatments. And so do cancer cells, but they are not passed between different cancer patients. It’s an obvious difference but I shall take care not to make cancer, a non-communicable disease, seem too similar to communicable diseases in the future.

On a more technical note, earlier this month a paper from Feng Zhang’s lab demonstrated an engineered Cas9 enzyme with reduced off-target effects (Slaymaker et al, 2015). One of the main impediments of using CRISPR/Cas9 for therapeutic applications is that the endonuclease, Cas9, creates DNA double-strand breaks not only at the intended site but also at distant sites, so called off-target sites. In this paper, with a comment here, they study the structure of the enzyme and make changes to the active site that “make sense” to increase the enzyme’s stringency. In everyday laboratory use, however, this more specific Cas9 probably isn’t necessary.

Lastly, Science has picked its scientific breakthrough of the year. Guess what it was:

Interestingly, the People’s Choice for Breakthrough of the Year was the pictures sent back from Pluto by the New Horizons probe. I find it much more fascinating to look deep down into our cells than far out into space, but to each his or her own, I suppose.

[EDIT] Not only did Science choose its Breakthrough, but Nature chose its top ten science influencers of the year – read the article here. Among them is Junjiu Huang who was the first to edit supernumerary human embryos using CRISPR earlier this year (Liang et al, 2015).

References:

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

Slaymaker IM, Gao L, Zetsche B, Scott DA, Yan WX, Zhang F (2015) Rationally engineered Cas9 nucleases with improved specificity. Science