Facilitating crRNA Design by Integrating DNA Interaction Features of CRISPR-Cas12a System

文献类型： 外文期刊

第一作者： Yao, Zhihao

作者： Yao, Zhihao;Xu, Yan;Wu, Qun;Nie, Yao;Yao, Zhihao;Li, Wanglu;He, Kaiyu;Wang, Hongmei;Wang, Liu;Wang, Liu

作者机构：

关键词： activity prediction; CRISPR-Cas12a; deep learning; molecular dynamics simulation; trans-cleavage

期刊名称：ADVANCED SCIENCE （ 影响因子：14.1； 五年影响因子：15.6 ）

ISSN：

年卷期： 2025 年

页码：

收录情况： SCI

摘要： The CRISPR-Cas12a system has gained significant attention as a rapid nucleic acid diagnostic tool due to its crRNA-guided trans-cleavage activity. Accurately predicting the activity of different targets is significant to facilitate the crRNA availability but remains challenging. In this study, a novel approach is presented that combines molecular dynamics simulations and neural network modeling to predict the trans-cleavage activity. Unlike conventional tools that rely solely on the base sequences, our method integrated sequence features and molecular interaction features of DNA in the CRISPR-Cas12a system, significantly improving prediction accuracy. Through feature importance analysis, key sequence features that influence Cas12a trans-cleavage activity are identified. Additionally, a crRNA-DNA library with over 23 456 feature sequences from representative viruses and bacteria is established, and validated the high predictive accuracy of the model (Pearson's r = 0.9328) by screening crRNAs from reference targets. This study offers new insights into the molecular interactions of Cas12a/crRNA-DNA and provides a reliable framework for optimizing crRNA design, facilitating the application of the CRISPR-Cas12a in rapid nucleic acid diagnostics.

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