Abstract

The CRISPR-Cas nickase system for genome editing has attracted considerable attention owing to its safety, efficiency, and versatility. Although alternative effectors to Cas9 have the potential to expand the scope of genome editing, their application has not been optimized. Herein, we used an enhanced CRISPR-Cas12a nickase system to induce mutations by targeting genes in a human-derived cell line. The optimized CRISPR-Cas12a nickase system effectively introduced mutations into target genes under a specific directionality and distance between nickases. In particular, the single-mode Cas12a nickase system can induce the target-specific mutations with less DNA double-strand breaks. By inducing mutations in the Thymine-rich target genes in single- or dual-mode, Cas12a nickase compensates the limitations of Cas9 nickase and is expected to contribute to the development of future genome editing technologies.

Details

Title
Utilization of nicking properties of CRISPR-Cas12a effector for genome editing
Author
Kim, Chan Hyoung 1 ; Lee, Wi-jae 2 ; Oh, Yeounsun 2 ; Lee, Youngjeon 3 ; Lee, Hyomin K. 4 ; Seong, Jung Bae 5 ; Lim, Kyung-Seob 6 ; Park, Sang Je 5 ; Huh, Jae-Won 3 ; Kim, Young-Hyun 5 ; Kim, Kyoung Mi 7 ; Hur, Junho K. 8 ; Lee, Seung Hwan 2 

 Korea Research Institute of Bioscience and Biotechnology (KRIBB), National Primate Research Center (NPRC), Cheongju, Republic of Korea (GRID:grid.249967.7) (ISNI:0000 0004 0636 3099); Chungnam National University, Department of Biological Sciences, Daejeon, Republic of Korea (GRID:grid.254230.2) (ISNI:0000 0001 0722 6377) 
 Chung-Ang University, Department of Life Science, Seoul, Republic of Korea (GRID:grid.254224.7) (ISNI:0000 0001 0789 9563) 
 Korea Research Institute of Bioscience and Biotechnology (KRIBB), National Primate Research Center (NPRC), Cheongju, Republic of Korea (GRID:grid.249967.7) (ISNI:0000 0004 0636 3099); Korea University of Science and Technology (UST), Department of Functional Genomics, KRIBB School of Bioscience, Daejeon, Republic of Korea (GRID:grid.412786.e) (ISNI:0000 0004 1791 8264) 
 Hanyang University, Department of Medicine, Major in Medical Genetics, Graduate School, Seoul, Republic of Korea (GRID:grid.49606.3d) (ISNI:0000 0001 1364 9317) 
 Korea Research Institute of Bioscience and Biotechnology (KRIBB), National Primate Research Center (NPRC), Cheongju, Republic of Korea (GRID:grid.249967.7) (ISNI:0000 0004 0636 3099) 
 Korea Research Institute of Bioscience and Biotechnology (KRIBB), Futuristic Animal Resource and Research Center (FARRC), Cheongju, Republic of Korea (GRID:grid.249967.7) (ISNI:0000 0004 0636 3099) 
 Chungnam National University, Department of Biological Sciences, Daejeon, Republic of Korea (GRID:grid.254230.2) (ISNI:0000 0001 0722 6377) 
 Hanyang University, Department of Genetics, College of Medicine, Seoul, Republic of Korea (GRID:grid.49606.3d) (ISNI:0000 0001 1364 9317); Hanyang University, Graduate School of Biomedical Science and Engineering, Seoul, Republic of Korea (GRID:grid.49606.3d) (ISNI:0000 0001 1364 9317) 
Pages
3352
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2924108399
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.