Issue 40, 2021

Element coding based accurate evaluation of CRISPR/Cas9 initial cleavage

Abstract

As a powerful gene editing tool, the kinetic mechanism of CRISPR/Cas9 has been the focus for its further application. Initial cleavage events as the first domino followed by nuclease end trimming significantly affect the final on-target rate. Here we propose EC-CRISPR, element coding CRISPR, an accurate evaluation platform for initial cleavage that directly characterizes the cleavage efficiency and breaking sites. We benchmarked the influence of 19 single mismatch and 3 multiple mismatch positions of DNA-sgRNA on initial cleavage, as well as various reaction conditions. Results from EC-CRISPR demonstrate that the PAM-distal single mismatch is relatively acceptable compared to the proximal one. And multiple mismatches will not only affect the cleavage efficiency, but also generate more non-site #3 cleavage. Through in-depth research of kinetic behavior, we uncovered an abnormally higher non-#3 proportion at the initial stage of cleavage by using EC-CRISPR. Together, our results provided insights into cleavage efficiency and breaking sites, demonstrating that EC-CRISPR as a novel quantitative platform for initial cleavage enables accurate comparison of efficiencies and specificities among multiple CRISPR/Cas enzymes.

Graphical abstract: Element coding based accurate evaluation of CRISPR/Cas9 initial cleavage

Supplementary files

Article information

Article type
Edge Article
Submitted
02 Jul 2021
Accepted
06 Sep 2021
First published
07 Sep 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021,12, 13404-13412

Element coding based accurate evaluation of CRISPR/Cas9 initial cleavage

J. Hu, R. Liu, J. Zhou and Y. Lv, Chem. Sci., 2021, 12, 13404 DOI: 10.1039/D1SC03599A

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