Structure-Guided design of Cas12a variants improves detection of nucleic acids

CRISPR-Cas12a holds promising potential for pathogen detection. However, its performance is not optimal when combined with isothermal amplification. Hence, we engineered a mutant of LbCas12a (K595A) with reduced cis-cleavage activity, to minimize interference with isothermal amplification. Compared...

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Bibliographic Details
Main Authors: Xiaohan Tong, Tianle Li, Kun Zhang, Dongming Zhao, Ying Zhang, Hao Yin
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Cell Insight
Online Access:http://www.sciencedirect.com/science/article/pii/S2772892725000021
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Summary:CRISPR-Cas12a holds promising potential for pathogen detection. However, its performance is not optimal when combined with isothermal amplification. Hence, we engineered a mutant of LbCas12a (K595A) with reduced cis-cleavage activity, to minimize interference with isothermal amplification. Compared to wild-type Cas12a, the K595A mutant exhibited a 2–3 times faster reaction speed and a 1,000–10,000 times increase in sensitivity in a one-pot reaction. We applied this mutant for detection of African Swine Fever Virus (ASFV). This K595A mutant successfully detected all 30 ASFV samples within 20 minutes. Our study suggests a universal approach to improve the performance of Cas12a for pathogen detection.
ISSN:2772-8927