What are the advances in CRISPR technology?

By Gloria Han, GenScript               February 11, 2020

On February 10, 2020, the pioneer of base editing technology, David R. Liu published two articles in Nature Biotechnology on the same day. In one paper, Liu and colleagues screened various enzymes and found a collection of enzymes that can convert C to T without causing many off-target mutations. In the other paper, Liu's team reported the development of new SpCas9 variants that can target regions of DNA that were previously unreachable. These improvements greatly expand the application scope of base editing.

In 2019, CRISPR pioneers all over the world, including Jennifer Doudna of U.C. Berkeley, Feng Zhang and David R. Liu of Broad Institute, all have very impressive results published. In this article, we will make an introduction of these newly developed gene editing tools and hopefully this collection could be a useful resource for those who employ CRISPR technology in their research work. Altogether, at the current growth rate, we have confidence in a future where CRISPR systems for every need will be available. Perfecting CRISPR technology and minimizing risks will open up the application of this method in therapeutics and diagnostics for humans.

PART I: CRISPR-Cas9 Alternatives

CRISPR-Cas9 is the most popular and widely used gene editing system. While its limitations, such as the off-target effects, difficult to be delivered inside cells, and the stringent requirement for the PAM sequence are forcing researchers to look for alternatives. Over the past years, new CRISPR systems such as Cas12 (Type V CRISPR-Cas system) and Cas13 (Type VI CRISPR-Cas systems) are being developed. Here we pick out a few outstanding articles published in 2019 that are focused on engineering more efficient CRISPR systems and make a brief introduction.

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PART II: Innovations

We have witnessed great progress in CRISPR genome editing technology during the past 2019. The "Prime Editing" genome editing approach developed by David Liu's team can make more precise and efficient edits to the genome. Feng Zhang's team from Broad Institute and Samuel h. Sternberg's team from Columbia University both reported a targeted DNA insertion system based on the CRISPR system and the transposon system. As all the approaches are so different from conventional CRISPR-Cas systems, we therefore identify them as innovative genome editing technologies and introduce them separately in this part.

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Doman, J. L., Raguram, A., Newby, G. A. & Liu, D.R. Nature Biotechnol. https://doi.org/10.1038/s41587-020-0414-6 (2020).

Miller, S. M. et al. Nature Biotechnol. https://doi.org/10.1038/s41587-020-0412-8 (2020).

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