Highly parallel profiling of the activities and specificities of Cas12a variants in human cells

Several Cas12a variants have been developed to broaden its targeting range, improve the gene editing specificity or the efficiency. However, selecting the appropriate Cas12a among the many orthologs for a given target sequence remains difficult. Here, we perform high-throughput analyses to evaluate the activity and compatibility with specific PAMs of 24 Cas12a variants and develop deep learning models for these Cas12a variants to predict gene editing activities at target sequences of interest. Furthermore, we reveal and enhance the truncation in the integrated tag sequence that may hinder off-targeting detection for Cas12a by GUIDE-seq. This enhanced system, which we term enGUIDE-seq, is used to evaluate and compare the off-targeting and translocations of these Cas12a variants.

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Publication Details

Journal
Nature Communications
Published
2025-03-28
DOI
https://doi.org/10.1038/s41467-025-57150-9
Citations
6
Primary Topic
CRISPR and Genetic Engineering
Type
article
Field-Weighted Citation Impact
4.84

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article

Highly parallel profiling of the activities and specificities of Cas12a variants in human cells

Chonil Paek, Peng Chen, Hongjian Wang, Lei Yin et al.
6 citations
Nature Communications
CRISPR and Genetic Engineering
4.84
article

Highly parallel profiling of the activities and specificities of Cas12a variants in human cells

Chonil Paek, Peng Chen, Hongjian Wang, Lei Yin, Huan Liu, Jun Lei, Jin Zhou, Zaiqiao Sun, Jingli Chen, Yankang Wu
article en
6 citations

Abstract

Several Cas12a variants have been developed to broaden its targeting range, improve the gene editing specificity or the efficiency. However, selecting the appropriate Cas12a among the many orthologs for a given target sequence remains difficult. Here, we perform high-throughput analyses to evaluate the activity and compatibility with specific PAMs of 24 Cas12a variants and develop deep learning models for these Cas12a variants to predict gene editing activities at target sequences of interest. Furthermore, we reveal and enhance the truncation in the integrated tag sequence that may hinder off-targeting detection for Cas12a by GUIDE-seq. This enhanced system, which we term enGUIDE-seq, is used to evaluate and compare the off-targeting and translocations of these Cas12a variants.

Nature CommunicationsVol. 16(1)
Wuhan University (CN), China International Science and Technology Cooperation (CN), Wuhan YZY Biopharma (China) (CN), Children's Hospital of Chongqing Medical University (CN), State Key Laboratory of Virology, Wuhan University of Science and Technology (CN), Chongqing Medical University (CN)
National Natural Science Foundation of China, China Postdoctoral Science Foundation
Zero hunger
Openalex Percentile: Top 5%
CRISPR and Genetic Engineering
4.84
DOIOpen Access PDFOpenAlex
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Highly parallel profiling of the activities and specificities of Cas12a variants in human cells — Chonil Paek, Peng Chen, et al. · Nature Communications (2025) | TGRS Research Map | TGRS