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Nano Research 2023, 16(1): 865-872 https://doi.org/10.1007/s12274-022-4761-0
Research Article | Issue | Published: 17 August 2022

Locked nucleic acids based DNA circuits with ultra-low leakage

Show Author's Information Hao Hu1,§,  Liquan Liu1,2,§,  Lei Zhang1,  Wei Zhang1,2,  Kejun Dong1,2,  Bei Yan1,  Yaoqin Mu1,  Mengdi Shi3,  Longjie Li1,3,  Xianjin Xiao1,2( )
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
School of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, China

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

Keywords:
DNA nanotechnology, leakage, DNA circuits, locked nucleic acid, DNA strand displacement
Topics:
Biomaterials
Cite this article:
Hu H, Liu L, Zhang L, et al. Locked nucleic acids based DNA circuits with ultra-low leakage. Nano Research, 2023, 16(1): 865-872. https://doi.org/10.1007/s12274-022-4761-0
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Abstract Full text Electronic supplementary material About this article

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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Electronic supplementary material
About this article

Locked nucleic acids based DNA circuits with ultra-low leakage

Show Author's information Hao Hu1,§, Liquan Liu1,2,§, Lei Zhang1, Wei Zhang1,2, Kejun Dong1,2, Bei Yan1, Yaoqin Mu1, Mengdi Shi3, Longjie Li1,3, Xianjin Xiao1,2( )
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
School of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, China

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

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.

Keywords: DNA nanotechnology, leakage, DNA circuits, locked nucleic acid, DNA strand displacement

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Publication history
Copyright
Acknowledgements

Publication history

Received: 09 May 2022
Revised: 08 July 2022
Accepted: 10 July 2022
Published: 17 August 2022
Issue date: January 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

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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