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Locked nucleic acids based DNA circuits with ultra-low leakage

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Abstract

DNA circuits based on toehold-mediated DNA strand displacement reaction are powerful tools owing to their programmability and predictability. However, performance and practical application of the circuits are greatly restricted by leakage, which refers to the fact that there is no input (invading strand) in the circuit, and the output signal is still generated. Herein, we constructed locked nucleic acids-based DNA circuits with ultra-low leakage. High binding affinity of LNA (locked nucleic acid)-DNA/LNA suppressed the leakage by inhibiting the breathing effect. Based on the strategy, we have built various low-leakage DNA circuits, including translator circuit, catalytic hairpin assembly (CHA) circuit, entropy-driven circuit (EDC), and seesaw circuit. More importantly, our strategy would not affect the desired main reactions: The output signal remained above 85% for all tested circuits, and the signal-to-noise ratios were elevated to 148.8-fold at the most. We believe our strategy will greatly promote the development and application of DNA circuits-based DNA nanotechnology.

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Acknowledgements

This work was financially supported by the National Key Research and Development Program of China (No. 2021YFC2701402), the National Natural Science Foundation of China (No. 81871732), the Open Research Fund of State Key Laboratory of Bioelectronics, South-east University (No. Sklb2021-k06), the Open Project Fund from NHC Key Lab of Reproduction Regulation (No. KF2021-02), and the Open Research Fund of State Key Laboratory of Advanced Technology for Materials Synthesis and Processing (Wuhan University of Technology, No. 2022-KF-2).

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  1. Hao Hu and Liquan Liu contributed equally to this work.

Authors and Affiliations

  1. Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Hao Hu, Liquan Liu, Lei Zhang, Wei Zhang, Kejun Dong, Bei Yan, Yaoqin Mu, Longjie Li & Xianjin Xiao

  2. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Liquan Liu, Wei Zhang, Kejun Dong & Xianjin Xiao

  3. School of Life Science and Technology, Wuhan Polytechnic University, Wuhan, 430023, China

    Mengdi Shi & Longjie Li

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  1. Hao Hu
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  2. Liquan Liu
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  3. Lei Zhang
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  4. Wei Zhang
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Correspondence to Xianjin Xiao.

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Hu, H., Liu, L., Zhang, L. et al. Locked nucleic acids based DNA circuits with ultra-low leakage. Nano Res. 16, 865–872 (2023). https://doi.org/10.1007/s12274-022-4761-0

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