Dna-based biocomputing circuits and their biomedical applications

ABSTRACT DNA-based biocomputing circuits are chemical reaction networks with information-processing capability that take advantage of DNA molecular interactions. The high parallelism and

intrinsic biocompatibility of DNA circuits allows liquid-phase computing for various biomedical applications. In this Review, we examine the design rules and implementation strategies of DNA

circuits, outlining the engineering and function of DNA computing units, including switches, logic gates, amplifiers and neurons. We further discuss the integration of these computing units

into DNA circuits by 3D free diffusion, surface-confined diffusion, localized diffusion using DNA nanostructures, and algorithmic assembly. Furthermore, we investigate how the temporal

dynamics of DNA circuits can be regulated and highlight their application in cellular imaging, biosensing and diagnostics, in conditional therapeutics, and for the rewiring of endogenous

gene networks. Finally, we discuss the challenges that remain to be addressed for the clinical translation DNA-based biocomputing, outlining key future research directions. KEY POINTS *

DNA-based computing circuits provide an efficient approach for sensing, processing and responding to biomolecular information. * DNA circuits exhibit a variety of computing functions that

allow the selection of design strategies based on application requirements. * DNA-based computing circuits have found wide applications in bioengineering. * Multiple translational challenges

remain to be addressed for the clinical translation of DNA-based computing. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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* Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS PROSPECTS AND CHALLENGES OF DYNAMIC DNA NANOSTRUCTURES IN

BIOMEDICAL APPLICATIONS Article Open access 23 May 2022 DNA-BASED PROGRAMMABLE GATE ARRAYS FOR GENERAL-PURPOSE DNA COMPUTING Article 13 September 2023 DYNAMIC REGULATION OF DNA

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references ACKNOWLEDGEMENTS This work was supported by the National Natural Science Foundation of China (T2188102, 22322704, 21991134, 22122406), the National Key R&D Program of China

(2021YFF1200300), the Science Foundation of Shanghai Municipal Science and Technology Commission (23QA1404800), and the New Cornerstone Science Foundation. AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Zhangjiang Laboratory, Shanghai, China Sisi Jia  (贾思思) * School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, New Cornerstone

Science Laboratory, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, China Sisi Jia  (贾思思), Hui Lv  (吕慧), Qian Li  (李茜), Chunhai Fan  (樊春海) & Fei Wang

  (王飞) * Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acids Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai,

China Chunhai Fan  (樊春海) Authors * Sisi Jia  (贾思思) View author publications You can also search for this author inPubMed Google Scholar * Hui Lv  (吕慧) View author publications You can also

search for this author inPubMed Google Scholar * Qian Li  (李茜) View author publications You can also search for this author inPubMed Google Scholar * Chunhai Fan  (樊春海) View author

publications You can also search for this author inPubMed Google Scholar * Fei Wang  (王飞) View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS

S.J., F.W. and C.F. wrote the manuscript draft. All authors reviewed and edited the manuscript before submission. CORRESPONDING AUTHORS Correspondence to Chunhai Fan  (樊春海) or Fei Wang 

(王飞). ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. PEER REVIEW PEER REVIEW INFORMATION _Nature Reviews Bioengineering_ thanks Thomas Ouldridge and the

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publishing agreement and applicable law. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Jia, S., Lv, H., Li, Q. _et al._ DNA-based biocomputing circuits and their biomedical

applications. _Nat Rev Bioeng_ (2025). https://doi.org/10.1038/s44222-025-00303-8 Download citation * Accepted: 10 March 2025 * Published: 11 April 2025 * DOI:

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