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Research Article

Locked nucleic acids based DNA circuits with ultra-low leakage

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.

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Graphical Abstract

Leak becomes a bottleneck preventing further complications and practical application of the DNA circuit. Here, we have successfully demonstrated the validity and simplicity of locked nucleic acid (LNA) assisted leak prevention on four of the most common DNA circuits.

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 circuitsleakagelocked nucleic acidDNA strand displacementDNA nanotechnology

Electronic Supplementary Material

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Nano Research
Volume 16 Issue 1,
January 2023
Pages 865-872
DOI: 10.1007/s12274-022-4761-0
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
Topics:
Biomaterials

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Received: 09 May 2022
Revised: 08 July 2022
Accepted: 10 July 2022
Published: 17 August 2022
© Tsinghua University Press 2022
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