Today is World CRISPR Day, let’s feel a bit of genomic vertigo by exploring CRISPR’s orders of magnitude with the help of the CRISPR Journal. The latest editorial (“Extreme Genome Editing”) goes from micro to macro, from phages to forests. Let’s give some numbers.
The size of edits spans from a single nucleotide to the removal of genomic islands greater than 100 kb (almost six orders of magnitude). The size of edited organisms varies between 10−7 m for submicroscopic viruses to over 10 m for trees (more than eight orders of magnitude). The range of genomes is tens of kilobases to tens of gigabases (seven orders of magnitude).
“Some of these theoretical combinations thus reach frightening orders of magnitude, from the modification of a single base in a 30 kb bacteriophage administered in a single 1 ml dose to 1 kb inserted in a 30 Gb tree genome scaled up to 100,000 hectares of a commercial forest” (here is the full text for more enjoyment of CRISPR vertigo).
The seminal paper by Doudna & Charpentier was published online at the end of June 2012. The printed issue came out a few weeks later, on August 17 (don’t try to buy it, Science VOLUME 337|ISSUE 6096 is out of stock). No wonder the gene-editing community is in the mood for celebration these days. If you are too, don’t miss the chance to read these articles on CRISPR’s ten-year anniversary!
Have you heard of GEN Biotechnology? Issue 3 is already out, but I’ve just got my free copy of the inaugural issue (thanks!). Same publisher (Mary Ann Liebert), same executive editor (Kevin Davies), and the same passion for biotech frontiers as The CRISPR Journal. See below some crispy starters from issue number 1:
The paper “Evolutionary Biology and Gene Editing of Cat Allergen Fel d 1” is a proof of principle but this is only the first step. About 15% of humans have allergic reactions to cats and the major allergen may be nonessential for those animals, given the apparent lack of evolutionary conservation. According to the bioinformatics analysis just published by Nicole Brackett et al. from the US company InBio “Fel d 1 is both a rational and viable candidate for gene deletion, which may profoundly benefit cat allergy sufferers by removing the major allergen at the source”.
The list of the latest additions since the beginning of September is impressive. They are called CasMINI (see Molecular Cell), Cas7-11 (see Nature), OMEGAs (see Science), and come respectively from Stanford University (Stanley Qi Lab), MIT (McGovern Institute), and the Broad Institute (Zhang Lab). CasMINI is half the size of Cas9 and could be much easier to deliver. Cas7-11 is the Cas9 of RNA. OMEGAs are a new class of widespread RNA-guided enzymes, thought to be the ancestors of CRISPR.
Modular design is the latest trend for developing new CRISPR tools. In The CRISPR Journal, Juan Carlos Collantes et al. present a base-editor system called Pin-point that recruits a DNA base-modifying enzyme through a hook (an RNA aptamer) within the guide-RNA molecule. In Nature Communicationsthe goal of Lacramioara Bintu and colleagues is not base editing but epigenomic editing, the effector is a chromatin regulator and the hook is an antibody. When the CRISPR-effector combo is big, delivery of individual modules is easier. Furthermore, if the effector is already present inside the cell it can be simply recruited by providing the right hook. One more potential advantage is the convenient reconfiguration of the system by the mix and match of individual components and simultaneous recruitment of different effectors to different target sites.
No wonder “Editing Humanity” by Kevin Davies is good reading. The executive editor of The CRISPR Journal (and the founding editor of Nature Genetics) is really in a great position to tell the CRISPR story so far. But the book deserves praise also for its aesthetic qualities, i.e., pictures and graphics. I’m totally in love with the typographical character marking the start of paragraphs – there is a sign representing Cas9 in place of the conventional pilcrow ¶.
Look at this map, from a detailed and up-to-date analysis published in the CRISPR Journal. It’s the global policy landscape on heritable human editing, i.e., modified embryos transferred to a uterus to initiate a pregnancy. Who would expect a catholic country like Italy to stand out as one of the very few countries not totally prohibiting such a controversial practice?
Researchers from all the life sciences are turning their attention to the pandemic, and the CRISPR community is no exception. The latest CRISPR Journal‘s editorial presents a few of the projects that are showing promise, and others are probably going on. Kevin Davies and Rodolphe Barrangou also comment on the cancellation or postponement of several key conferences in the next few months due to Covid-19, especially the CRISPR 2020 meeting in Paris. They applaud all the scientists who are battling this disease in myriad ways and promise: we’ll meet again.
The DNA double helix as a metaphor for the relationship between genetics and SciFi – novels and movies on the one strand and scientific breakthroughs on the other strand. It’s courtesy of graduated student Kartik Lakshmi Rallapalli, who examines the science and fiction timelines in a post for the Addgene blog.