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Responsive MXene nanovehicles deliver CRISPR/Cas12a for boolean logic-controlled gene editing

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Abstract

Programmable and precise regulation of genetic information is crucial in bioengineering and biomedicine; however, it remains challenging to implement this objective. Here we deployed DNA-functionalized MXenes as a smart delivery system for spatiotemporally controllable genome editing. The MXene nanovehicles rationally integrated photothermal effect with nucleic acid strand displacement reaction, thereby allowing for the binary logic gate-controlled release of Cas ribonucleoprotein complexes in response to different input patterns of NIR light and nucleic acids. This system was highly programmable and could be harnessed to construct 2-input (AND, OR, and N-IMPLY) and 3-input (AND/OR and N-IMPLY/OR) logic gates for precise gene editing in mammalian cells. Moreover, an AND logic gate-controlled delivery system achieved selective induction of tumor cell death in a xenograft mice model using tissue-penetrating NIR light and cancer-relevant microRNA as the inputting cues. Therefore, the MXene nanovehicles adopted both the external and endogenous signals as the stimuli to precisely control gene editing under logic computation, presenting a helpful strategy for therapeutic genome editing.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2020YFA0907500), the National Natural Science Foundation of China (22034002, 21974038, 21725503, 22074034) and the Natural Science Foundation of Hunan Province (2022JJ20004).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha, 410082, China

    Song Wang, Zhenhua Zhang, Rui Tang, Fang He, Yan Huang, Zhou Nie & Chunyang Lei

  2. Hubei Yangtze Memory Laboratories, Wuhan, 430205, China

    Song Wang

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  1. Song Wang
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  2. Zhenhua Zhang
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Correspondence to Chunyang Lei.

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Supporting information The supporting information is available online at https://chem.scichina.com and https://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Wang, S., Zhang, Z., Tang, R. et al. Responsive MXene nanovehicles deliver CRISPR/Cas12a for boolean logic-controlled gene editing. Sci. China Chem. 65, 2318–2326 (2022). https://doi.org/10.1007/s11426-022-1376-1

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