AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Nano Research Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
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.

Show Author Information

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 nanotechnologyleakageDNA circuitslocked nucleic acidDNA strand displacement

Electronic Supplementary Material

Download File(s)
12274_2022_4761_MOESM1_ESM.pdf (3 MB)

References

[1]

Wang, B. Y.; Thachuk, C.; Ellington, A. D.; Winfree, E.; Soloveichik, D. Effective design principles for leakless strand displacement systems. Proc. Natl. Acad. Sci. USA 2018, 115, E12182–E12191.
Crossref Google Scholar
[2]

Hu, Y.; Niemeyer, C. M. From DNA nanotechnology to material systems engineering. Adv. Mater. 2019, 31, 1806294.
Crossref Google Scholar
[3]

Madsen, M.; Gothelf, K. V. Chemistries for DNA nanotechnology. Chem. Rev. 2019, 119, 6384–6458.
Crossref Google Scholar
[4]

Seelig, G.; Soloveichik, D.; Zhang, D. Y.; Winfree, E. Enzyme-free nucleic acid logic circuits. Science 2006, 314, 1585–1588.
Crossref Google Scholar
[5]

Woods, D.; Doty, D.; Myhrvold, C.; Hui, J.; Zhou, F.; Yin, P.; Winfree, E. Diverse and robust molecular algorithms using reprogrammable DNA self-assembly. Nature 2019, 567, 366–372.
Crossref Google Scholar
[6]

Liu, L. Q.; Hu, Q. Y.; Zhang, W. K.; Li, W. H.; Zhang, W.; Ming, Z. H.; Li, L. J.; Chen, N.; Wang, H. B.; Xiao, X. J. Multifunctional clip strand for the regulation of DNA strand displacement and construction of complex DNA Nanodevices. ACS Nano 2021, 15, 11573–11584.
Crossref Google Scholar
[7]

Zhu, D.; Lu, B.; Zhu, Y.; Ma, Z. H.; Wei, Y. Q.; Su, S.; Wang, L. H.; Song, S. P.; Zhu, Y.; Wang, L. H. et al. Cancer-specific microRNA analysis with a nonenzymatic nucleic acid circuit. ACS Appl. Mater. Interfaces 2019, 11, 11220–11226.
Crossref Google Scholar
[8]

Kim, K. T.; Angerani, S.; Chang, D. L.; Winssinger, N. Coupling of DNA circuit and templated reactions for quadratic amplification and release of functional molecules. J. Am. Chem. Soc. 2019, 141, 16288–16295.
Crossref Google Scholar
[9]

Cherry, K. M.; Qian, L. L. Scaling up molecular pattern recognition with DNA-based winner-take-all neural networks. Nature 2018, 559, 370–376.
Crossref Google Scholar
[10]

Wang, H. H.; Peng, P.; Wang, Q. W.; Du, Y.; Tian, Z. J.; Li, T. Environment-recognizing DNA-computation circuits for the intracellular transport of molecular payloads for mRNA imaging. Angew. Chem., Int. Ed. 2020, 59, 6099–6107.
Crossref Google Scholar
[11]

Bai, H. J.; Yan, Y. R.; Li, D. D.; Fan, N. K.; Cheng, W. Q.; Yang, W.; Ju, H. X.; Li, X. M.; Ding, S. J. Dispersion-to-localization of catalytic hairpin assembly for sensitive sensing and imaging microRNAs in living cells from whole blood. Biosens. Bioelectron. 2022, 198, 113821.
Crossref Google Scholar
[12]

Chen, Y. J.; Groves, B.; Muscat, R. A.; Seelig, G. DNA nanotechnology from the test tube to the cell. Nat. Nanotechnol. 2015, 10, 748–760.
Crossref Google Scholar
[13]

Ouyang, C. H.; Zhang, S. B.; Xue, C.; Yu, X.; Xu, H.; Wang, Z. M.; Lu, Y.; Wu, Z. S. Precision-guided missile-like DNA nanostructure containing warhead and guidance control for aptamer-based targeted drug delivery into cancer cells in vitro and in vivo. J. Am. Chem. Soc. 2020, 142, 1265–1277.
Crossref Google Scholar
[14]

Chen, X.; Briggs, N.; McLain, J. R.; Ellington, A. D. Stacking nonenzymatic circuits for high signal gain. Proc. Natl. Acad. Sci. USA 2013, 110, 5386–5391.
Crossref Google Scholar
[15]

Zimmers, Z. A.; Adams, N. M.; Haselton, F. R. Addition of mirror-image L-DNA elements to DNA amplification circuits to distinguish leakage from target signal. Biosens. Bioelectron. 2021, 188, 113354.
Crossref Google Scholar
[16]

Qian, L. L.; Winfree, E. Scaling up digital circuit computation with DNA strand displacement cascades. Science 2011, 332, 1196–1201.
Crossref Google Scholar
[17]

Jiang, Y. S.; Bhadra, S.; Li, B. L.; Ellington, A. D. Mismatches improve the performance of strand-displacement nucleic acid circuits. Angew. Chem., Int. Ed. 2014, 53, 1845–1848.
Crossref Google Scholar
[18]

Song, T. Q.; Gopalkrishnan, N.; Eshra, A.; Garg, S.; Mokhtar, R.; Bui, H.; Chandran, H.; Reif, J. Improving the performance of DNA strand displacement circuits by shadow cancellation. ACS Nano 2018, 12, 11689–11697.
Crossref Google Scholar
[19]

Koshkin, A. A.; Singh, S. K.; Nielsen, P.; Rajwanshi, V. K.; Kumar, R.; Meldgaard, M.; Olsen, C. E.; Wengel, J. LNA (locked nucleic acids): Synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition. Tetrahedron 1998, 54, 3607–3630.
Crossref Google Scholar
[20]

Arora, A.; Kaur, H.; Wengel, J.; Maiti, S. Effect of locked nucleic acid (LNA) modification on hybridization kinetics of DNA duplex. Nucleic Acids Symp. Ser. 2008, 52, 417–418.
Crossref Google Scholar
[21]

Campbell, M. A.; Wengel, J. Locked vs. unlocked nucleic acids (LNA vs. UNA):Contrasting structures work towards common therapeutic goals. Chem. Soc. Rev. 2011, 40, 5680–5689.
Crossref Google Scholar
[22]

Dai, W. H.; Zhang, J.; Meng, X. D.; He, J.; Zhang, K.; Cao, Y.; Wang, D. D.; Dong, H. F.; Zhang, X. J. Catalytic hairpin assembly gel assay for multiple and sensitive microRNA detection. Theranostics 2018, 8, 2646–2656.
Crossref Google Scholar
[23]

Liu, J. M.; Zhang, Y.; Xie, H. B.; Zhao, L.; Zheng, L.; Ye, H. M. Applications of catalytic hairpin assembly reaction in biosensing. Small 2019, 15, 1902989.
Crossref Google Scholar
[24]

Lee, C. Y.; Jang, H.; Park, K. S.; Park, H. G. A label-free and enzyme-free signal amplification strategy for a sensitive RNase H activity assay. Nanoscale 2017, 9, 16149–16153.
Crossref Google Scholar
[25]

Xing, C.; Chen, Z. Y.; Zhang, C.; Wang, J.; Lu, C. H. Target-directed enzyme-free dual-amplification DNA circuit for rapid signal amplification. J. Mater. Chem. B 2020, 8, 10770–10775.
Crossref Google Scholar
[26]

Yang, J.; Wu, R. F.; Li, Y. F.; Wang, Z. Y.; Pan, L. Q.; Zhang, Q.; Lu, Z. H.; Zhang, C. Entropy-driven DNA logic circuits regulated by DNAzyme. Nucleic Acids Res. 2018, 46, 8532–8541.
Crossref Google Scholar
[27]

Zhang, C.; Wang, Z. Y.; Liu, Y.; Yang, J.; Zhang, X. X.; Li, Y. F.; Pan, L. Q.; Ke, Y. G.; Yan, H. Nicking-assisted reactant recycle to implement entropy-driven DNA circuit. J. Am. Chem. Soc. 2019, 141, 17189–17197.
Crossref Google Scholar
[28]

He, L.; Lu, D. Q.; Liang, H.; Xie, S. T.; Zhang, X. B.; Liu, Q. L.; Yuan, Q.; Tan, W. H. mRNA-initiated, three-dimensional DNA amplifier able to function inside living cells. J. Am. Chem. Soc. 2018, 140, 258–263.
Crossref Google Scholar
[29]

Bai, M.; Chen, F.; Cao, X. W.; Zhao, Y.; Xue, J.; Yu, X.; Fan, C. H.; Zhao, Y. X. Intracellular entropy-driven multi-bit DNA computing for tumor progression discrimination. Angew. Chem., Int. Ed. 2020, 59, 13267–13272.
Crossref Google Scholar
[30]

Olson, X.; Kotani, S.; Padilla, J. E.; Hallstrom, N.; Goltry, S.; Lee, J.; Yurke, B.; Hughes, W. L.; Graugnard, E. Availability: A metric for nucleic acid strand displacement systems. ACS Synth. Biol. 2017, 6, 84–93.
Crossref Google Scholar
[31]

Lysne, D.; Jones, K.; Stosius, A.; Hachigian, T.; Lee, J.; Graugnard, E. Availability-driven design of hairpin fuels and small interfering strands for leakage reduction in autocatalytic networks. J. Phys. Chem. B 2020, 124, 3326–3335.
Crossref Google Scholar
[32]

Zhang, D. Y.; Winfree, E. Control of DNA strand displacement kinetics using toehold exchange. J. Am. Chem. Soc. 2009, 131, 17303–17314.
Crossref Google Scholar
[33]

Qian, L. L.; Winfree, E.; Bruck, J. Neural network computation with DNA strand displacement cascades. Nature 2011, 475, 368–372.
Crossref Google Scholar
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

1335

Views

18

Crossref

16

Web of Science

17

Scopus

1

CSCD

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