Treffer: Heat-rechargeable computation in DNA logic circuits and neural networks.
Title:
Heat-rechargeable computation in DNA logic circuits and neural networks.
Authors:
Song T; Bioengineering, California Institute of Technology, Pasadena, CA, USA., Qian L; Bioengineering, California Institute of Technology, Pasadena, CA, USA. luluqian@caltech.edu.; Computer Science, California Institute of Technology, Pasadena, CA, USA. luluqian@caltech.edu.; Computation and Neural Systems, California Institute of Technology, Pasadena, CA, USA. luluqian@caltech.edu.
Source:
Nature [Nature] 2025 Oct; Vol. 646 (8084), pp. 315-322. Date of Electronic Publication: 2025 Oct 01.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
Imprint Name(s):
Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
Original Publication: London, Macmillan Journals ltd.
MeSH Terms:
References:
Yurke, B., Turberfield, A. J., Mills Jr, A. P., Simmel, F. C. & Neumann, J. L. A DNA-fuelled molecular machine made of DNA. Nature 406, 605–608 (2000). (PMID: 1094929610.1038/35020524)
Yan, H., Zhang, X., Shen, Z. & Seeman, N. C. A robust DNA mechanical device controlled by hybridization topology. Nature 415, 62–65 (2002). (PMID: 1178011510.1038/415062a)
Turberfield, A. J. et al. DNA fuel for free-running nanomachines. Phys. Rev. Lett. 90, 118102 (2003). (PMID: 1268896910.1103/PhysRevLett.90.118102)
Simmel, F. C. DNA nanotechnology out of equilibrium. in Visions of DNA Nanotechnology at 40 for the Next 40: A Tribute to Nadrian C. Seeman (eds Jonoska, N. & Winfree, E.) 17–29 (Springer, 2023).
Dirks, R. M. & Pierce, N. A. Triggered amplification by hybridization chain reaction. Proc. Natl Acad. Sci. USA 101, 15275–15278 (2004). (PMID: 1549221052446810.1073/pnas.0407024101)
Bois, J. S. Analysis of Interacting Nucleic Acids in Dilute Solutions (California Institute of Technology, 2006).
Kim, J., White, K. S. & Winfree, E. Construction of an in vitro bistable circuit from synthetic transcriptional switches. Mol. Syst. Biol. 2, 68 (2006). (PMID: 17170763176208610.1038/msb4100099)
Montagne, K., Plasson, R., Sakai, Y., Fujii, T. & Rondelez, Y. Programming an in vitro DNA oscillator using a molecular networking strategy. Mol. Syst. Biol. 7, 466 (2011). (PMID: 21283142306368910.1038/msb.2010.120)
Schaffter, S. W. et al. Standardized excitable elements for scalable engineering of far-from-equilibrium chemical networks. Nat. Chem. 14, 1224–1232 (2022). (PMID: 3592732910.1038/s41557-022-01001-3)
Okumura, S. et al. Nonlinear decision-making with enzymatic neural networks. Nature 610, 496–501 (2022). (PMID: 3626155310.1038/s41586-022-05218-7)
Montagne, K., Gines, G., Fujii, T. & Rondelez, Y. Boosting functionality of synthetic DNA circuits with tailored deactivation. Nat. Commun. 7, 13474 (2016). (PMID: 27845324511607710.1038/ncomms13474)
Simpson, Z. B., Tsai, T. L., Nguyen, N., Chen, X. & Ellington, A. D. Modelling amorphous computations with transcription networks. J. R. Soc. Interface 6, S523–S533 (2009). (PMID: 19474083284395710.1098/rsif.2009.0014.focus)
Zhang, D. Y. & Winfree, E. Robustness and modularity properties of a non-covalent DNA catalytic reaction. Nucleic Acids Res. 38, 4182–4197 (2010). (PMID: 20194118289650910.1093/nar/gkq088)
Qian, L. & Winfree, E. Scaling up digital circuit computation with DNA strand displacement cascades. Science 332, 1196–1201 (2011). (PMID: 2163677310.1126/science.1200520)
Lv, H. et al. DNA-based programmable gate arrays for general-purpose DNA computing. Nature 622, 292–300 (2023). (PMID: 3770473110.1038/s41586-023-06484-9)
Cherry, K. M. & Qian, L. Scaling up molecular pattern recognition with DNA-based winner-take-all neural networks. Nature 559, 370–376 (2018). (PMID: 2997372710.1038/s41586-018-0289-6)
Xiong, X. et al. Molecular convolutional neural networks with DNA regulatory circuits. Nat. Mach. Intell. 4, 625–635 (2022). (PMID: 10.1038/s42256-022-00502-7)
Genot, A. J., Bath, J. & Turberfield, A. J. Reversible logic circuits made of DNA. J. Am. Chem. Soc. 133, 20080–20083 (2011). (PMID: 2211151410.1021/ja208497p)
Wang, B., Chalk, C., Doty, D. & Soloveichik, D. Molecular computation at equilibrium via programmable entropy. Preprint at bioRxiv 10.1101/2024.09.13.612990v1 (2024).
Vasić, M., Soloveichik, D. & Khurshid, S. CRN++: molecular programming language. Nat. Comput. 19, 391–407 (2020). (PMID: 10.1007/s11047-019-09775-1)
Lakin, M. R. & Stefanovic, D. Supervised learning in adaptive DNA strand displacement networks. ACS Synth. Biol. 5, 885–897 (2016). (PMID: 2711103710.1021/acssynbio.6b00009)
DelRosso, N. V., Hews, S., Spector, L. & Derr, N. D. A molecular circuit regenerator to implement iterative strand displacement operations. Angew. Chem. Int. Ed. Engl. 56, 4443–4446 (2017). (PMID: 2832248610.1002/anie.201610890)
Scalise, D., Dutta, N. & Schulman, R. DNA strand buffers. J. Am. Chem. Soc. 140, 12069–12076 (2018). (PMID: 3020443310.1021/jacs.8b05373)
Garg, S. et al. Renewable time-responsive DNA circuits. Small 14, 1801470 (2018). (PMID: 10.1002/smll.201801470)
Eshra, A., Shah, S., Song, T. & Reif, J. Renewable DNA hairpin-based logic circuits. IEEE Trans. Nanotechnol. 18, 252–259 (2019). (PMID: 10.1109/TNANO.2019.2896189)
Hahn, J. & Shih, W. M. Thermal cycling of DNA devices via associative strand displacement. Nucleic Acids Res. 47, 10968–10975 (2019). (PMID: 31584082684725910.1093/nar/gkz844)
Lakin, M. R., Youssef, S., Cardelli, L. & Phillips, A. Abstractions for DNA circuit design. J. R. Soc. Interface 9, 470–486 (2012). (PMID: 2177532110.1098/rsif.2011.0343)
Lauback, S. et al. Real-time magnetic actuation of DNA nanodevices via modular integration with stiff micro-levers. Nat. Commun. 9, 1446 (2018). (PMID: 29654315589909510.1038/s41467-018-03601-5)
Kopperger, E. et al. A self-assembled nanoscale robotic arm controlled by electric fields. Science 359, 296–301 (2018). (PMID: 2934823210.1126/science.aao4284)
Liang, X., Nishioka, H., Takenaka, N. & Asanuma, H. A DNA nanomachine powered by light irradiation. ChemBioChem 9, 702–705 (2008). (PMID: 1825394010.1002/cbic.200700649)
Song, X., Eshra, A., Dwyer, C. & Reif, J. Renewable DNA seesaw logic circuits enabled by photoregulation of toehold-mediated strand displacement. RSC Adv. 7, 28130–28144 (2017). (PMID: 10.1039/C7RA02607B)
Doty, D., Rogers, T. A., Soloveichik, D., Thachuk, C. & Woods, D. Thermodynamic binding networks. In Proc. DNA Computing and Molecular Programming: 23rd International Conference (eds Brijder, R., Qian, L.) 249–266 (Springer, 2017).
Zhang, D. Y. & Winfree, E. Control of DNA strand displacement kinetics using toehold exchange. J. Am. Chem. Soc. 131, 17303–17314 (2009). (PMID: 1989472210.1021/ja906987s)
Takinoue, M. & Suyama, A. Hairpin-DNA memory using molecular addressing. Small 2, 1244–1247 (2006). (PMID: 1719296710.1002/smll.200600237)
Viasnoff, V., Meller, A. & Isambert, H. DNA nanomechanical switches under folding kinetics control. Nano Lett. 6, 101–104 (2006). (PMID: 1640279510.1021/nl052161c)
Machinek, R. R., Ouldridge, T. E., Haley, N. E., Bath, J. & Turberfield, A. J. Programmable energy landscapes for kinetic control of DNA strand displacement. Nat. Commun. 5, 5324 (2014). (PMID: 2538221410.1038/ncomms6324)
Haley, N. E. et al. Design of hidden thermodynamic driving for non-equilibrium systems via mismatch elimination during DNA strand displacement. Nat. Commun. 11, 2562 (2020). (PMID: 32444600724450310.1038/s41467-020-16353-y)
Chen, H.-L., Doty, D., Reeves, W. & Soloveichik, D. Rate-independent computation in continuous chemical reaction networks. J. ACM 70, 1–61 (2023).
Kim, J., Hopfield, J. & Winfree, E. Neural network computation by in vitro transcriptional circuits. In Advances in Neural Information Processing Systems 17 (NIPS 2004) (eds Saul, L. K., et al.) 681–688 (MIT Press, 2004).
Genot, A. J., Fujii, T. & Rondelez, Y. Scaling down DNA circuits with competitive neural networks. J. R. Soc. Interface 10, 20130212 (2013). (PMID: 23760296404315410.1098/rsif.2013.0212)
Zhang, D. Y. Cooperative hybridization of oligonucleotides. J. Am. Chem. Soc. 133, 1077–1086 (2011). (PMID: 2116641010.1021/ja109089q)
Zadeh, J. N. et al. NUPACK: analysis and design of nucleic acid systems. J. Comput. Chem. 32, 170–173 (2011). (PMID: 2064530310.1002/jcc.21596)
Lothaire, M. Algebraic Combinatorics on Words, Vol. 90 (Cambridge Univ. Press, 2002). (PMID: 10.1017/CBO9781107326019)
Yin, P., Choi, H. M., Calvert, C. R. & Pierce, N. A. Programming biomolecular self-assembly pathways. Nature 451, 318–322 (2008). (PMID: 1820265410.1038/nature06451)
Chen, X., Briggs, N., McLain, J. R. & Ellington, A. D. Stacking nonenzymatic circuits for high signal gain. Proc. Natl Acad. Sci. USA 110, 5386–5391 (2013). (PMID: 23509255361931710.1073/pnas.1222807110)
Simmel, F. C., Yurke, B. & Singh, H. R. Principles and applications of nucleic acid strand displacement reactions. Chem. Rev. 119, 6326–6369 (2019). (PMID: 3071437510.1021/acs.chemrev.8b00580)
Martin, W., Baross, J., Kelley, D. & Russell, M. J. Hydrothermal vents and the origin of life. Nat. Rev. Microbiol. 6, 805–814 (2008). (PMID: 1882070010.1038/nrmicro1991)
Kishi, J. Y., Schaus, T. E., Gopalkrishnan, N., Xuan, F. & Yin, P. Programmable autonomous synthesis of single-stranded DNA. Nat. Chem. 10, 155–164 (2018). (PMID: 2935975510.1038/nchem.2872)
Song, T. et al. Fast and compact DNA logic circuits based on single-stranded gates using strand-displacing polymerase. Nat. Nanotechnol. 14, 1075–1081 (2019). (PMID: 3154868810.1038/s41565-019-0544-5)
Thubagere, A. J. et al. Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components. Nat. Commun. 8, 14373 (2017). (PMID: 28230154533121810.1038/ncomms14373)
Ouldridge, T. E., Šulc, P., Romano, F., Doye, J. P. & Louis, A. A. DNA hybridization kinetics: zippering, internal displacement and sequence dependence. Nucleic Acids Res. 41, 8886–8895 (2013). (PMID: 23935069379944610.1093/nar/gkt687)
Srinivas, N. et al. On the biophysics and kinetics of toehold-mediated DNA strand displacement. Nucleic Acids Res. 41, 10641–10658 (2013). (PMID: 24019238390587110.1093/nar/gkt801)
SantaLucia Jr, J., & Hicks, D. The thermodynamics of DNA structural motifs. Annu. Rev. Biophys. Biomol. Struct. 33, 415–440 (2004). (PMID: 1513982010.1146/annurev.biophys.32.110601.141800)
Yan, H., Zhang, X., Shen, Z. & Seeman, N. C. A robust DNA mechanical device controlled by hybridization topology. Nature 415, 62–65 (2002). (PMID: 1178011510.1038/415062a)
Turberfield, A. J. et al. DNA fuel for free-running nanomachines. Phys. Rev. Lett. 90, 118102 (2003). (PMID: 1268896910.1103/PhysRevLett.90.118102)
Simmel, F. C. DNA nanotechnology out of equilibrium. in Visions of DNA Nanotechnology at 40 for the Next 40: A Tribute to Nadrian C. Seeman (eds Jonoska, N. & Winfree, E.) 17–29 (Springer, 2023).
Dirks, R. M. & Pierce, N. A. Triggered amplification by hybridization chain reaction. Proc. Natl Acad. Sci. USA 101, 15275–15278 (2004). (PMID: 1549221052446810.1073/pnas.0407024101)
Bois, J. S. Analysis of Interacting Nucleic Acids in Dilute Solutions (California Institute of Technology, 2006).
Kim, J., White, K. S. & Winfree, E. Construction of an in vitro bistable circuit from synthetic transcriptional switches. Mol. Syst. Biol. 2, 68 (2006). (PMID: 17170763176208610.1038/msb4100099)
Montagne, K., Plasson, R., Sakai, Y., Fujii, T. & Rondelez, Y. Programming an in vitro DNA oscillator using a molecular networking strategy. Mol. Syst. Biol. 7, 466 (2011). (PMID: 21283142306368910.1038/msb.2010.120)
Schaffter, S. W. et al. Standardized excitable elements for scalable engineering of far-from-equilibrium chemical networks. Nat. Chem. 14, 1224–1232 (2022). (PMID: 3592732910.1038/s41557-022-01001-3)
Okumura, S. et al. Nonlinear decision-making with enzymatic neural networks. Nature 610, 496–501 (2022). (PMID: 3626155310.1038/s41586-022-05218-7)
Montagne, K., Gines, G., Fujii, T. & Rondelez, Y. Boosting functionality of synthetic DNA circuits with tailored deactivation. Nat. Commun. 7, 13474 (2016). (PMID: 27845324511607710.1038/ncomms13474)
Simpson, Z. B., Tsai, T. L., Nguyen, N., Chen, X. & Ellington, A. D. Modelling amorphous computations with transcription networks. J. R. Soc. Interface 6, S523–S533 (2009). (PMID: 19474083284395710.1098/rsif.2009.0014.focus)
Zhang, D. Y. & Winfree, E. Robustness and modularity properties of a non-covalent DNA catalytic reaction. Nucleic Acids Res. 38, 4182–4197 (2010). (PMID: 20194118289650910.1093/nar/gkq088)
Qian, L. & Winfree, E. Scaling up digital circuit computation with DNA strand displacement cascades. Science 332, 1196–1201 (2011). (PMID: 2163677310.1126/science.1200520)
Lv, H. et al. DNA-based programmable gate arrays for general-purpose DNA computing. Nature 622, 292–300 (2023). (PMID: 3770473110.1038/s41586-023-06484-9)
Cherry, K. M. & Qian, L. Scaling up molecular pattern recognition with DNA-based winner-take-all neural networks. Nature 559, 370–376 (2018). (PMID: 2997372710.1038/s41586-018-0289-6)
Xiong, X. et al. Molecular convolutional neural networks with DNA regulatory circuits. Nat. Mach. Intell. 4, 625–635 (2022). (PMID: 10.1038/s42256-022-00502-7)
Genot, A. J., Bath, J. & Turberfield, A. J. Reversible logic circuits made of DNA. J. Am. Chem. Soc. 133, 20080–20083 (2011). (PMID: 2211151410.1021/ja208497p)
Wang, B., Chalk, C., Doty, D. & Soloveichik, D. Molecular computation at equilibrium via programmable entropy. Preprint at bioRxiv 10.1101/2024.09.13.612990v1 (2024).
Vasić, M., Soloveichik, D. & Khurshid, S. CRN++: molecular programming language. Nat. Comput. 19, 391–407 (2020). (PMID: 10.1007/s11047-019-09775-1)
Lakin, M. R. & Stefanovic, D. Supervised learning in adaptive DNA strand displacement networks. ACS Synth. Biol. 5, 885–897 (2016). (PMID: 2711103710.1021/acssynbio.6b00009)
DelRosso, N. V., Hews, S., Spector, L. & Derr, N. D. A molecular circuit regenerator to implement iterative strand displacement operations. Angew. Chem. Int. Ed. Engl. 56, 4443–4446 (2017). (PMID: 2832248610.1002/anie.201610890)
Scalise, D., Dutta, N. & Schulman, R. DNA strand buffers. J. Am. Chem. Soc. 140, 12069–12076 (2018). (PMID: 3020443310.1021/jacs.8b05373)
Garg, S. et al. Renewable time-responsive DNA circuits. Small 14, 1801470 (2018). (PMID: 10.1002/smll.201801470)
Eshra, A., Shah, S., Song, T. & Reif, J. Renewable DNA hairpin-based logic circuits. IEEE Trans. Nanotechnol. 18, 252–259 (2019). (PMID: 10.1109/TNANO.2019.2896189)
Hahn, J. & Shih, W. M. Thermal cycling of DNA devices via associative strand displacement. Nucleic Acids Res. 47, 10968–10975 (2019). (PMID: 31584082684725910.1093/nar/gkz844)
Lakin, M. R., Youssef, S., Cardelli, L. & Phillips, A. Abstractions for DNA circuit design. J. R. Soc. Interface 9, 470–486 (2012). (PMID: 2177532110.1098/rsif.2011.0343)
Lauback, S. et al. Real-time magnetic actuation of DNA nanodevices via modular integration with stiff micro-levers. Nat. Commun. 9, 1446 (2018). (PMID: 29654315589909510.1038/s41467-018-03601-5)
Kopperger, E. et al. A self-assembled nanoscale robotic arm controlled by electric fields. Science 359, 296–301 (2018). (PMID: 2934823210.1126/science.aao4284)
Liang, X., Nishioka, H., Takenaka, N. & Asanuma, H. A DNA nanomachine powered by light irradiation. ChemBioChem 9, 702–705 (2008). (PMID: 1825394010.1002/cbic.200700649)
Song, X., Eshra, A., Dwyer, C. & Reif, J. Renewable DNA seesaw logic circuits enabled by photoregulation of toehold-mediated strand displacement. RSC Adv. 7, 28130–28144 (2017). (PMID: 10.1039/C7RA02607B)
Doty, D., Rogers, T. A., Soloveichik, D., Thachuk, C. & Woods, D. Thermodynamic binding networks. In Proc. DNA Computing and Molecular Programming: 23rd International Conference (eds Brijder, R., Qian, L.) 249–266 (Springer, 2017).
Zhang, D. Y. & Winfree, E. Control of DNA strand displacement kinetics using toehold exchange. J. Am. Chem. Soc. 131, 17303–17314 (2009). (PMID: 1989472210.1021/ja906987s)
Takinoue, M. & Suyama, A. Hairpin-DNA memory using molecular addressing. Small 2, 1244–1247 (2006). (PMID: 1719296710.1002/smll.200600237)
Viasnoff, V., Meller, A. & Isambert, H. DNA nanomechanical switches under folding kinetics control. Nano Lett. 6, 101–104 (2006). (PMID: 1640279510.1021/nl052161c)
Machinek, R. R., Ouldridge, T. E., Haley, N. E., Bath, J. & Turberfield, A. J. Programmable energy landscapes for kinetic control of DNA strand displacement. Nat. Commun. 5, 5324 (2014). (PMID: 2538221410.1038/ncomms6324)
Haley, N. E. et al. Design of hidden thermodynamic driving for non-equilibrium systems via mismatch elimination during DNA strand displacement. Nat. Commun. 11, 2562 (2020). (PMID: 32444600724450310.1038/s41467-020-16353-y)
Chen, H.-L., Doty, D., Reeves, W. & Soloveichik, D. Rate-independent computation in continuous chemical reaction networks. J. ACM 70, 1–61 (2023).
Kim, J., Hopfield, J. & Winfree, E. Neural network computation by in vitro transcriptional circuits. In Advances in Neural Information Processing Systems 17 (NIPS 2004) (eds Saul, L. K., et al.) 681–688 (MIT Press, 2004).
Genot, A. J., Fujii, T. & Rondelez, Y. Scaling down DNA circuits with competitive neural networks. J. R. Soc. Interface 10, 20130212 (2013). (PMID: 23760296404315410.1098/rsif.2013.0212)
Zhang, D. Y. Cooperative hybridization of oligonucleotides. J. Am. Chem. Soc. 133, 1077–1086 (2011). (PMID: 2116641010.1021/ja109089q)
Zadeh, J. N. et al. NUPACK: analysis and design of nucleic acid systems. J. Comput. Chem. 32, 170–173 (2011). (PMID: 2064530310.1002/jcc.21596)
Lothaire, M. Algebraic Combinatorics on Words, Vol. 90 (Cambridge Univ. Press, 2002). (PMID: 10.1017/CBO9781107326019)
Yin, P., Choi, H. M., Calvert, C. R. & Pierce, N. A. Programming biomolecular self-assembly pathways. Nature 451, 318–322 (2008). (PMID: 1820265410.1038/nature06451)
Chen, X., Briggs, N., McLain, J. R. & Ellington, A. D. Stacking nonenzymatic circuits for high signal gain. Proc. Natl Acad. Sci. USA 110, 5386–5391 (2013). (PMID: 23509255361931710.1073/pnas.1222807110)
Simmel, F. C., Yurke, B. & Singh, H. R. Principles and applications of nucleic acid strand displacement reactions. Chem. Rev. 119, 6326–6369 (2019). (PMID: 3071437510.1021/acs.chemrev.8b00580)
Martin, W., Baross, J., Kelley, D. & Russell, M. J. Hydrothermal vents and the origin of life. Nat. Rev. Microbiol. 6, 805–814 (2008). (PMID: 1882070010.1038/nrmicro1991)
Kishi, J. Y., Schaus, T. E., Gopalkrishnan, N., Xuan, F. & Yin, P. Programmable autonomous synthesis of single-stranded DNA. Nat. Chem. 10, 155–164 (2018). (PMID: 2935975510.1038/nchem.2872)
Song, T. et al. Fast and compact DNA logic circuits based on single-stranded gates using strand-displacing polymerase. Nat. Nanotechnol. 14, 1075–1081 (2019). (PMID: 3154868810.1038/s41565-019-0544-5)
Thubagere, A. J. et al. Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components. Nat. Commun. 8, 14373 (2017). (PMID: 28230154533121810.1038/ncomms14373)
Ouldridge, T. E., Šulc, P., Romano, F., Doye, J. P. & Louis, A. A. DNA hybridization kinetics: zippering, internal displacement and sequence dependence. Nucleic Acids Res. 41, 8886–8895 (2013). (PMID: 23935069379944610.1093/nar/gkt687)
Srinivas, N. et al. On the biophysics and kinetics of toehold-mediated DNA strand displacement. Nucleic Acids Res. 41, 10641–10658 (2013). (PMID: 24019238390587110.1093/nar/gkt801)
SantaLucia Jr, J., & Hicks, D. The thermodynamics of DNA structural motifs. Annu. Rev. Biophys. Biomol. Struct. 33, 415–440 (2004). (PMID: 1513982010.1146/annurev.biophys.32.110601.141800)
Substance Nomenclature:
9007-49-2 (DNA)
Entry Date(s):
Date Created: 20251001 Date Completed: 20251009 Latest Revision: 20251113
Update Code:
20251114
PubMed Central ID:
PMC12507696
DOI:
10.1038/s41586-025-09570-2
PMID:
41034583
Database:
MEDLINE
Weitere Informationen
Metabolism enables life to sustain dynamics and to repeatedly interact with the environment by storing and consuming chemical energy. A major challenge for artificial molecular machines is to find a universal energy source akin to ATP for biological organisms and electricity for electromechanical machines. More than 20 years ago, DNA was first used as fuel to drive nanomechanical devices <sup>1,2</sup> and catalytic reactions <sup>3</sup> . However, each system requires distinct fuel sequences, preventing DNA alone from becoming a universal energy source. Despite extensive efforts <sup>4</sup> , we still lack an ATP-like or electricity-like power supply to sustain diverse molecular machines. Here we show that heat can restore enzyme-free DNA circuits from equilibrium to out-of-equilibrium states. During heating and cooling, nucleic acids with strong secondary structures reach kinetically trapped states <sup>5,6</sup> , providing energy for subsequent computation. We demonstrate that complex logic circuits and neural networks, involving more than 200 distinct molecular species, can respond to a temperature ramp and recharge within minutes, allowing at least 16 rounds of computation with varying sequential inputs. Our strategy enables diverse systems to be powered by the same energy source without problematic waste build-up, thereby ensuring consistent performance over time. This scalable approach supports the sustained operation of enzyme-free molecular circuits and opens opportunities for advanced autonomous behaviours, such as iterative computation and unsupervised learning in artificial chemical systems.
(© 2025. The Author(s).)
Competing interests: The authors declare no competing interests.