Tag Archives: tools

The ever-expanding CRISPR toolbox

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Credit: Mon Oo Yee/Innovative Genomics Institute

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.

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Toward an NIH-validated CRISPR toolkit

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The Somatic Cell Genome Editing (SCGE) Consortium is working to accelerate the development of better methods of editing. Seventy-two principal investigators from 38 institutions are pursuing 45 distinct but well-integrated projects, funded by the US National Institutes of Health with US$190 million over 6 years. A perspective published in Nature details their plans:

“New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled—along with validated datasets—into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit—and the knowledge generated by its applications—as a means to accelerate the clinical development of new therapies for a wide range of conditions”.

CRISPR Ikea-style

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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 Communications the 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.

TALEN vs CRISPR

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Soon after the arrival of CRISPR, a report from Harvard compared the new gene-editing technique and its older sister side by side. As reported by Kevin Davies in the book “Editing Humanity,” CRISPR won convincingly, and this paper helped boost CRISPR’s popularity. This video shows that nowadays CRISPR is considered the best in terms of ease of design, ease of experimental setup, and flexibility. TALEN, however, is more precise. What about efficiency? Well, it depends. CRISPR works better in the less-tightly wound regions of the genome, but according to a recent Nature Communications paper, TALEN can access the heterochromatin region better than CRISPR. The study by Huimin Zhao and colleagues at the University of Illinois Urbana-Champaign adds to the evidence that the more (tools), the better.