Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

DNA as a universal chemical substrate for computing and data storage

Subjects

Abstract

DNA computing and DNA data storage are emerging fields that are unlocking new possibilities in information technology and diagnostics. These approaches use DNA molecules as a computing substrate or a storage medium, offering nanoscale compactness and operation in unconventional media (including aqueous solutions, water-in-oil microemulsions and self-assembled membranized compartments) for applications beyond traditional silicon-based computing systems. To build a functional DNA computer that can process and store molecular information necessitates the continued development of strategies for computing and data storage, as well as bridging the gap between these fields. In this Review, we explore how DNA can be leveraged in the context of DNA computing with a focus on neural networks and compartmentalized DNA circuits. We also discuss emerging approaches to the storage of data in DNA and associated topics such as the writing, reading, retrieval and post-synthesis editing of DNA-encoded data. Finally, we provide insights into how DNA computing can be integrated with DNA data storage and explore the use of DNA for near-memory computing for future information technology and health analysis applications.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: DNA as a substrate for computing and data storage.
Fig. 2: DNA logic gates and neural networks.
Fig. 3: DNA nanostructures for DNA computing.
Fig. 4: Bead-based and compartmentalized DNA computing.
Fig. 5: Writing and reading information in DNA.
Fig. 6: Retrieval and manipulation of DNA-encoded data.

Similar content being viewed by others

References

  1. Rampioni, G. et al. A synthetic biology approach to bio-chem-ICT: first moves towards chemical communication between synthetic and natural cells. Nat. Comput. 13, 333–349 (2014).

    MathSciNet  CAS  Google Scholar 

  2. Amos, M., Dittrich, P., McCaskill, J. & Rasmussen, S. Biological and chemical information technologies. Procedia Comput. Sci. 7, 56–60 (2011).

    Google Scholar 

  3. Watson, J. D. & Crick, F. H. C. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature 171, 737–738 (1953).

    ADS  CAS  PubMed  Google Scholar 

  4. Simmel, F. C., Yurke, B. & Singh, H. R. Principles and applications of nucleic acid strand displacement reactions. Chem. Rev. 119, 6326–6369 (2019).

    CAS  PubMed  Google Scholar 

  5. Zadeh, J. N. et al. NUPACK: analysis and design of nucleic acid systems. J. Comput. Chem. 32, 170–173 (2011).

    CAS  PubMed  Google Scholar 

  6. Fu, T. et al. DNA-based dynamic reaction networks. Trends Biochem. Sci. 43, 547–560 (2018).

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Adleman, L. M. Molecular computation of solutions to combinatorial problems. Science 266, 1021–1024 (1994).

    ADS  CAS  PubMed  Google Scholar 

  8. Davis, J. Microvenus. Art J. 55, 70–74 (1996).

    Google Scholar 

  9. Yurke, B., Turberfield, A. J., Mills, A. P., Simmel, F. C. & Neumann, J. L. A DNA-fuelled molecular machine made of DNA. Nature 406, 605–608 (2000).

    ADS  CAS  PubMed  Google Scholar 

  10. Seelig, G., Soloveichik, D., Zhang, D. Y. & Winfree, E. Enzyme-free nucleic acid logic circuits. Science 314, 1585–1588 (2006).

    ADS  CAS  PubMed  Google Scholar 

  11. Zhang, D. Y., Turberfield, A. J., Yurke, B. & Winfree, E. Engineering entropy-driven reactions and networks catalyzed by DNA. Science 318, 1121–1125 (2007).

    ADS  CAS  PubMed  Google Scholar 

  12. Stojanovic, M. N., Mitchell, T. E. & Stefanovic, D. Deoxyribozyme-based logic gates. J. Am. Chem. Soc. 124, 3555–3561 (2002).

    CAS  PubMed  Google Scholar 

  13. Benenson, Y. et al. Programmable and autonomous computing machine made of biomolecules. Nature 414, 430–434 (2001).

    ADS  CAS  PubMed  Google Scholar 

  14. Kim, J., White, K. S. & Winfree, E. Construction of an in vitro bistable circuit from synthetic transcriptional switches. Mol. Syst. Biol. 2, 68 (2006).

    PubMed Central  PubMed  Google Scholar 

  15. 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).

    PubMed Central  PubMed  Google Scholar 

  16. 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).

    ADS  CAS  PubMed  Google Scholar 

  17. Seeman, N. C. Nucleic acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982).

    ADS  CAS  PubMed  Google Scholar 

  18. Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006).

    ADS  CAS  PubMed  Google Scholar 

  19. Mao, C., LaBean, T. H., Reif, J. H. & Seeman, N. C. Logical computation using algorithmic self-assembly of DNA triple-crossover molecules. Nature 407, 493–496 (2000).

    ADS  CAS  PubMed  Google Scholar 

  20. Chatterjee, G., Dalchau, N., Muscat, R. A., Phillips, A. & Seelig, G. A spatially localized architecture for fast and modular DNA computing. Nat. Nanotechnol. 12, 920–927 (2017).

    ADS  CAS  PubMed  Google Scholar 

  21. Woods, D. et al. Diverse and robust molecular algorithms using reprogrammable DNA self-assembly. Nature 567, 366–372 (2019).

    ADS  CAS  PubMed  Google Scholar 

  22. Seeman, N. C. & Sleiman, H. F. DNA nanotechnology. Nat. Rev. Mater. 3, 17068 (2017).

    ADS  Google Scholar 

  23. Machines smarter than men? Interview with Dr Norbert Wiener. Joshua Lederberg — Profiles in Science. https://profiles.nlm.nih.gov/spotlight/bb/catalog/nlm:nlmuid-101584906X7699-doc (U.S. News and World Report, 1964).

  24. Cox, J. P. L. Long-term data storage in DNA. Trends Biotechnol. 19, 247–250 (2001).

    CAS  PubMed  Google Scholar 

  25. Ceze, L., Nivala, J. & Strauss, K. Molecular digital data storage using DNA. Nat. Rev. Genet. 20, 456–466 (2019).

    CAS  PubMed  Google Scholar 

  26. Zhirnov, V., Zadegan, R. M., Sandhu, G. S., Church, G. M. & Hughes, W. L. Nucleic acid memory. Nat. Mater. 15, 366–370 (2016).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  27. Dickinson, G. D. et al. An alternative approach to nucleic acid memory. Nat. Commun. 12, 2371 (2021).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  28. Chen, K. et al. Digital data storage using DNA nanostructures and solid-state nanopores. Nano Lett. 19, 1210–1215 (2019).

    ADS  CAS  PubMed  Google Scholar 

  29. Grass, R. N., Heckel, R., Puddu, M., Paunescu, D. & Stark, W. J. Robust chemical preservation of digital information on DNA in silica with error‐correcting codes. Angew. Chem. Int. Ed. Engl. 54, 2552–2555 (2015).

    CAS  PubMed  Google Scholar 

  30. Goldman, N. et al. Towards practical, high-capacity, low-maintenance information storage in synthesized DNA. Nature 494, 77–80 (2013).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  31. Zhang, D. Y. & Seelig, G. Dynamic DNA nanotechnology using strand-displacement reactions. Nat. Chem. 3, 103–113 (2011).

    CAS  PubMed  Google Scholar 

  32. Zhang, D. Y. & Winfree, E. Control of DNA strand displacement kinetics using toehold exchange. J. Am. Chem. Soc. 131, 17303–17314 (2009).

    CAS  PubMed  Google Scholar 

  33. Qian, L. & Winfree, E. Scaling up digital circuit computation with DNA strand displacement cascades. Science 332, 1196–1201 (2011).

    ADS  CAS  PubMed  Google Scholar 

  34. Genot, A. J., Bath, J. & Turberfield, A. J. Combinatorial displacement of DNA strands: application to matrix multiplication and weighted sums. Angew. Chem. Int. Ed. Engl. 52, 1189–1192 (2013).

    CAS  PubMed  Google Scholar 

  35. Qian, L., Winfree, E. & Bruck, J. Neural network computation with DNA strand displacement cascades. Nature 475, 368–372 (2011).

    CAS  PubMed  Google Scholar 

  36. Wang, B., Thachuk, C., Ellington, A. D., Winfree, E. & Soloveichik, D. Effective design principles for leakless strand displacement systems. Proc. Natl Acad. Sci. USA 115, E12182–E12191 (2018).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  37. Wang, F. et al. Implementing digital computing with DNA-based switching circuits. Nat. Commun. 11, 121 (2020).

    ADS  PubMed Central  PubMed  Google Scholar 

  38. Nikitin, M. P. Non-complementary strand commutation as a fundamental alternative for information processing by DNA and gene regulation. Nat. Chem. 15, 70–82 (2023).

    CAS  PubMed  Google Scholar 

  39. Thubagere, A. J. et al. Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components. Nat. Commun. 8, 14373 (2017).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  40. Mayer, T., Oesinghaus, L. & Simmel, F. C. Toehold-mediated strand displacement in random sequence pools. J. Am. Chem. Soc. 145, 634–644 (2023).

    CAS  PubMed  Google Scholar 

  41. Srinivas, N., Parkin, J., Seelig, G., Winfree, E. & Soloveichik, D. Enzyme-free nucleic acid dynamical systems. Science 358, eaal2052 (2017).

    PubMed  Google Scholar 

  42. Wilhelm, D., Bruck, J. & Qian, L. Probabilistic switching circuits in DNA. Proc. Natl Acad. Sci. USA 115, 903–908 (2018).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  43. Scalise, D., Dutta, N. & Schulman, R. DNA strand buffers. J. Am. Chem. Soc. 140, 12069–12076 (2018).

    CAS  PubMed  Google Scholar 

  44. Lapteva, A. P., Sarraf, N. & Qian, L. DNA strand-displacement temporal logic circuits. J. Am. Chem. Soc. 144, 12443–12449 (2022).

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Lakin, M. R. et al. A design and analysis tool for DNA strand displacement systems. Bioinformatics 27, 3211–3213 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  46. LeCun, Y., Bengio, Y. & Hinton, G. Deep learning. Nature 521, 436–444 (2015).

    ADS  CAS  PubMed  Google Scholar 

  47. Farhat, N.H. & Del Moral Hernandez, E. Logistic networks with DNA-like encoding and interactions. In From Natural to Artificial Neural Computation: International Workshop on Artificial Neural Networks, Malaga-Torremolinos, Spain, June 7–9, 1995 (eds Mira, J. & Sandoval, F.) Vol. 930 (Springer, 1995); https://doi.org/10.1007/3-540-59497-3_178

  48. Rosenblatt, F. The perceptron: a probabilistic model for information storage and organization in the brain. Psychol. Rev. 65, 386–408 (1958).

    CAS  PubMed  Google Scholar 

  49. Cherry, K. M. & Qian, L. Scaling up molecular pattern recognition with DNA-based winner-take-all neural networks. Nature 559, 370–376 (2018).

    ADS  CAS  PubMed  Google Scholar 

  50. Xiong, X. et al. Molecular convolutional neural networks with DNA regulatory circuits. Nat. Mach. Intell. 4, 625–635 (2022).

    Google Scholar 

  51. Lopez, R., Wang, R. & Seelig, G. A molecular multi-gene classifier for disease diagnostics. Nat. Chem. 10, 746–754 (2018).

    CAS  PubMed  Google Scholar 

  52. Zhang, C. et al. Cancer diagnosis with DNA molecular computation. Nat. Nanotechnol. 15, 709–715 (2020).

    ADS  PubMed  Google Scholar 

  53. Ma, Q. et al. An automated DNA computing platform for rapid etiological diagnostics. Sci. Adv. 8, eade0453 (2022).

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Lakin, M. R. & Stefanovic, D. Supervised learning in adaptive DNA strand displacement networks. ACS Synth. Biol. 5, 885–897 (2016).

    CAS  PubMed  Google Scholar 

  55. Nagipogu, R. T., Fu, D. & Reif, J. H. A survey on molecular-scale learning systems with relevance to DNA computing. Nanoscale 15, 7676–7694 (2023).

    CAS  PubMed  Google Scholar 

  56. Kieffer, C., Genot, A. J., Rondelez, Y. & Gines, G. Molecular computation for molecular classification. Adv. Biol. 7, 2200203 (2023).

    Google Scholar 

  57. Stern, M. & Murugan, A. Learning without neurons in physical systems. Annu. Rev. Condens. Matter Phys. 14, 417–441 (2023).

    ADS  Google Scholar 

  58. Stern, M., Dillavou, S., Miskin, M. Z., Durian, D. J. & Liu, A. J. Physical learning beyond the quasistatic limit. Phys. Rev. Res. 4, L022037 (2022).

    CAS  Google Scholar 

  59. Su, H., Xu, J., Wang, Q., Wang, F. & Zhou, X. High-efficiency and integrable DNA arithmetic and logic system based on strand displacement synthesis. Nat. Commun. 10, 5390 (2019).

    ADS  PubMed Central  PubMed  Google Scholar 

  60. 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).

    CAS  PubMed  Google Scholar 

  61. Schaffter, S. W. & Strychalski, E. A. Cotranscriptionally encoded RNA strand displacement circuits. Sci. Adv. 8, eabl4354 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  62. Jung, J. K., Archuleta, C. M., Alam, K. K. & Lucks, J. B. Programming cell-free biosensors with DNA strand displacement circuits. Nat. Chem. Biol. 18, 385–393 (2022).

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Sharon, J. A. et al. Trumpet is an operating system for simple and robust cell-free biocomputing. Nat. Commun. 14, 2257 (2023).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  64. Barrangou, R. et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 1709–1712 (2007).

    ADS  CAS  PubMed  Google Scholar 

  65. Oesinghaus, L. & Simmel, F. C. Switching the activity of Cas12a using guide RNA strand displacement circuits. Nat. Commun. 10, 2092 (2019).

    ADS  PubMed Central  PubMed  Google Scholar 

  66. English, M. A. et al. Programmable CRISPR-responsive smart materials. Science 365, 780–785 (2019).

    ADS  CAS  PubMed  Google Scholar 

  67. Shi, K. et al. A CRISPR–Cas autocatalysis-driven feedback amplification network for supersensitive DNA diagnostics. Sci. Adv. 7, eabc7802 (2021).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  68. Shen, J. et al. Sensitive detection of a bacterial pathogen using allosteric probe-initiated catalysis and CRISPR–Cas13a amplification reaction. Nat. Commun. 11, 267 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  69. Montagud-Martínez, R., Heras-Hernández, M., Goiriz, L., Daròs, J.-A. & Rodrigo, G. CRISPR-mediated strand displacement logic circuits with toehold-free DNA. ACS Synth. Biol. 10, 950–956 (2021).

    PubMed Central  PubMed  Google Scholar 

  70. Ma, L. & Liu, J. Catalytic nucleic acids: biochemistry, chemical biology, biosensors, and nanotechnology. iScience 23, 100815 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  71. Elbaz, J. et al. DNA computing circuits using libraries of DNAzyme subunits. Nat. Nanotechnol. 5, 417–422 (2010).

    ADS  CAS  PubMed  Google Scholar 

  72. Wang, F., Lu, C.-H. & Willner, I. From cascaded catalytic nucleic acids to enzyme–DNA nanostructures: controlling reactivity, sensing, logic operations, and assembly of complex structures. Chem. Rev. 114, 2881–2941 (2014).

    CAS  PubMed  Google Scholar 

  73. Wang, J., Li, Z. & Willner, I. Cascaded dissipative DNAzyme-driven layered networks guide transient replication of coded-strands as gene models. Nat. Commun. 13, 4414 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  74. Schaffter, S. W. & Schulman, R. Building in vitro transcriptional regulatory networks by successively integrating multiple functional circuit modules. Nat. Chem. 11, 829–838 (2019).

    CAS  PubMed  Google Scholar 

  75. Schaffter, S. W. et al. Standardized excitable elements for scalable engineering of far-from-equilibrium chemical networks. Nat. Chem. 14, 1224–1232 (2022).

    CAS  PubMed  Google Scholar 

  76. Del Grosso, E., Franco, E., Prins, L. J. & Ricci, F. Dissipative DNA nanotechnology. Nat. Chem. 14, 600–613 (2022).

    PubMed  Google Scholar 

  77. Montagne, K., Gines, G., Fujii, T. & Rondelez, Y. Boosting functionality of synthetic DNA circuits with tailored deactivation. Nat. Commun. 7, 13474 (2016).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  78. Meijer, L. H. H. et al. Hierarchical control of enzymatic actuators using DNA-based switchable memories. Nat. Commun. 8, 1117 (2017).

    ADS  PubMed Central  PubMed  Google Scholar 

  79. Garenne, D. & Noireaux, V. Cell-free transcription–translation: engineering biology from the nanometer to the millimeter scale. Curr. Opin. Biotechnol. 58, 19–27 (2019).

    CAS  PubMed  Google Scholar 

  80. Rinaudo, K. et al. A universal RNAi-based logic evaluator that operates in mammalian cells. Nat. Biotechnol. 25, 795–801 (2007).

    CAS  PubMed  Google Scholar 

  81. Green, A. A., Silver, P. A., Collins, J. J. & Yin, P. Toehold switches: de-novo-designed regulators of gene expression. Cell 159, 925–939 (2014).

    CAS  PubMed Central  PubMed  Google Scholar 

  82. De Vos, D., Bruggeman, F. J., Westerhoff, H. V. & Bakker, B. M. How molecular competition influences fluxes in gene expression networks. PLoS ONE 6, e28494 (2011).

    ADS  PubMed Central  PubMed  Google Scholar 

  83. Del Vecchio, D., Ninfa, A. J. & Sontag, E. D. Modular cell biology: retroactivity and insulation. Mol. Syst. Biol. 4, 161 (2008).

    PubMed Central  PubMed  Google Scholar 

  84. Jayanthi, S., Nilgiriwala, K. S. & Del Vecchio, D. Retroactivity controls the temporal dynamics of gene transcription. ACS Synth. Biol. 2, 431–441 (2013).

    CAS  PubMed  Google Scholar 

  85. Okumura, S. et al. Nonlinear decision-making with enzymatic neural networks. Nature 610, 496–501 (2022).

    ADS  CAS  PubMed  Google Scholar 

  86. Van Der Linden, A. J. et al. DNA input classification by a riboregulator-based cell-free perceptron. ACS Synth. Biol. 11, 1510–1520 (2022).

    PubMed Central  PubMed  Google Scholar 

  87. Tikhomirov, G., Petersen, P. & Qian, L. Fractal assembly of micrometre-scale DNA origami arrays with arbitrary patterns. Nature 552, 67–71 (2017).

    ADS  CAS  PubMed  Google Scholar 

  88. Yao, G. et al. Meta-DNA structures. Nat. Chem. 12, 1067–1075 (2020).

    ADS  CAS  PubMed  Google Scholar 

  89. Thubagere, A. J. et al. A cargo-sorting DNA robot. Science 357, eaan6558 (2017).

    PubMed  Google Scholar 

  90. Chao, J. et al. Solving mazes with single-molecule DNA navigators. Nat. Mater. 18, 273–279 (2019).

    CAS  PubMed  Google Scholar 

  91. Liu, L. et al. A localized DNA finite-state machine with temporal resolution. Sci. Adv. 8, eabm9530 (2022).

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Zhang, Y. et al. DNA origami cryptography for secure communication. Nat. Commun. 10, 5469 (2019).

    ADS  PubMed Central  PubMed  Google Scholar 

  93. Lv, H. et al. DNA-based programmable gate arrays for general-purpose DNA computing. Nature 622, 292–300 (2023).

    ADS  CAS  PubMed  Google Scholar 

  94. Ibusuki, R. et al. Programmable molecular transport achieved by engineering protein motors to move on DNA nanotubes. Science 375, 1159–1164 (2022).

    ADS  CAS  PubMed  Google Scholar 

  95. Meng, W. et al. An autonomous molecular assembler for programmable chemical synthesis. Nat. Chem. 8, 542–548 (2016).

    CAS  PubMed  Google Scholar 

  96. Niu, J., Hili, R. & Liu, D. R. Enzyme-free translation of DNA into sequence-defined synthetic polymers structurally unrelated to nucleic acids. Nat. Chem. 5, 282–292 (2013).

    CAS  PubMed Central  PubMed  Google Scholar 

  97. Douglas, S. M., Bachelet, I. & Church, G. M. A logic-gated nanorobot for targeted transport of molecular payloads. Science 335, 831–834 (2012).

    ADS  CAS  PubMed  Google Scholar 

  98. Groves, B. et al. Computing in mammalian cells with nucleic acid strand exchange. Nat. Nanotechnol. 11, 287–294 (2016).

    ADS  CAS  PubMed  Google Scholar 

  99. Chen, Y.-J., Groves, B., Muscat, R. A. & Seelig, G. DNA nanotechnology from the test tube to the cell. Nat. Nanotechnol. 10, 748–760 (2015).

    ADS  CAS  PubMed  Google Scholar 

  100. Amir, Y. et al. Universal computing by DNA origami robots in a living animal. Nat. Nanotechnol. 9, 353–357 (2014).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  101. Li, S. et al. A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo. Nat. Biotechnol. 36, 258–264 (2018).

    CAS  PubMed  Google Scholar 

  102. Li, F. et al. DNA nanotechnology-empowered nanoscopic imaging of biomolecules. Chem. Soc. Rev. 50, 5650–5667 (2021).

    CAS  PubMed  Google Scholar 

  103. Chen, L. et al. Nucleic acid-based molecular computation heads towards cellular applications. Chem. Soc. Rev. 50, 12551–12575 (2021).

    ADS  CAS  PubMed  Google Scholar 

  104. Hu, Q., Li, H., Wang, L., Gu, H. & Fan, C. DNA nanotechnology-enabled drug delivery systems. Chem. Rev. 119, 6459–6506 (2019).

    CAS  PubMed  Google Scholar 

  105. Kang, H. et al. DNA dynamics and computation based on toehold-free strand displacement. Nat. Commun. 12, 4994 (2021).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  106. Petersen, P., Tikhomirov, G. & Qian, L. Information-based autonomous reconfiguration in systems of interacting DNA nanostructures. Nat. Commun. 9, 5362 (2018).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  107. Agarwal, S., Klocke, M. A., Pungchai, P. E. & Franco, E. Dynamic self-assembly of compartmentalized DNA nanotubes. Nat. Commun. 12, 3557 (2021).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  108. Deng, J., Walther, A. & Autonomous, D. N. A. Nanostructures instructed by hierarchically concatenated chemical reaction networks. Nat. Commun. 12, 5132 (2021).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  109. Pumm, A.-K. et al. A DNA origami rotary ratchet motor. Nature 607, 492–498 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  110. Lee, R. H., Mulder, E. A. B. & Hopkins, J. B. Mechanical neural networks: architected materials that learn behaviors. Sci. Robot. 7, eabq7278 (2022).

    PubMed  Google Scholar 

  111. Stern, M., Arinze, C., Perez, L., Palmer, S. E. & Murugan, A. Supervised learning through physical changes in a mechanical system. Proc. Natl Acad. Sci. USA 117, 14843–14850 (2020).

    ADS  MathSciNet  CAS  PubMed Central  PubMed  Google Scholar 

  112. Lee, C., Lee, J. Y. & Kim, D.-N. Polymorphic design of DNA origami structures through mechanical control of modular components. Nat. Commun. 8, 2067 (2017).

    ADS  PubMed Central  PubMed  Google Scholar 

  113. Zhou, L., Marras, A. E., Su, H.-J. & Castro, C. E. DNA origami compliant nanostructures with tunable mechanical properties. ACS Nano 8, 27–34 (2014).

    CAS  PubMed  Google Scholar 

  114. Lee, J. B. et al. A mechanical metamaterial made from a DNA hydrogel. Nat. Nanotechnol. 7, 816–820 (2012).

    ADS  CAS  PubMed  Google Scholar 

  115. Liu, M. et al. A DNA tweezer-actuated enzyme nanoreactor. Nat. Commun. 4, 2127 (2013).

    ADS  PubMed  Google Scholar 

  116. Gines, G. et al. Microscopic agents programmed by DNA circuits. Nat. Nanotechnol. 12, 351–359 (2017).

    ADS  CAS  PubMed  Google Scholar 

  117. Dehne, H., Reitenbach, A. & Bausch, A. R. Reversible and spatiotemporal control of colloidal structure formation. Nat. Commun. 12, 6811 (2021).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  118. Zadorin, A. S. et al. Synthesis and materialization of a reaction–diffusion French flag pattern. Nat. Chem. 9, 990–996 (2017).

    CAS  PubMed  Google Scholar 

  119. Yao, G. et al. Programming nanoparticle valence bonds with single-stranded DNA encoders. Nat. Mater. 19, 781–788 (2020).

    ADS  CAS  PubMed  Google Scholar 

  120. Seo, J., Kim, S., Park, H. H., Choi, D. Y. & Nam, J.-M. Nano-bio-computing lipid nanotablet. Sci. Adv. 5, eaau2124 (2019).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  121. Kim, S. et al. Nanoparticle-based computing architecture for nanoparticle neural networks. Sci. Adv. 6, eabb3348 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  122. Piranej, S., Bazrafshan, A. & Salaita, K. Chemical-to-mechanical molecular computation using DNA-based motors with onboard logic. Nat. Nanotechnol. 17, 514–523 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  123. Teichmann, M., Kopperger, E. & Simmel, F. C. Robustness of localized DNA strand displacement cascades. ACS Nano 8, 8487–8496 (2014).

    CAS  PubMed  Google Scholar 

  124. Jahnke, K. et al. DNA origami signaling units transduce chemical and mechanical signals in synthetic cells. Adv. Funct. Mater. 10.1002/adfm.202301176 (2023).

  125. Mashima, T. et al. DNA‐mediated protein shuttling between coacervate‐based artificial cells. Angew. Chem. Int. Ed. Engl. 61, e202115041 (2022).

    CAS  PubMed Central  PubMed  Google Scholar 

  126. Huang, X. et al. Interfacial assembly of protein–polymer nano-conjugates into stimulus-responsive biomimetic protocells. Nat. Commun. 4, 2239 (2013).

    ADS  PubMed  Google Scholar 

  127. Joesaar, A. et al. DNA-based communication in populations of synthetic protocells. Nat. Nanotechnol. 14, 369–378 (2019).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  128. Weitz, M. et al. Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator. Nat. Chem. 6, 295–302 (2014).

    CAS  PubMed  Google Scholar 

  129. Genot, A. J. et al. High-resolution mapping of bifurcations in nonlinear biochemical circuits. Nat. Chem. 8, 760–767 (2016).

    MathSciNet  CAS  PubMed  Google Scholar 

  130. Gines, G. et al. Isothermal digital detection of microRNAs using background-free molecular circuit. Sci. Adv. 6, eaay5952 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  131. Arter, W. E. et al. Digital sensing and molecular computation by an enzyme-free DNA circuit. ACS Nano 14, 5763–5771 (2020).

    CAS  PubMed  Google Scholar 

  132. Booth, M. J., Schild, V. R., Graham, A. D., Olof, S. N. & Bayley, H. Light-activated communication in synthetic tissues. Sci. Adv. 2, e1600056 (2016).

    ADS  PubMed Central  PubMed  Google Scholar 

  133. Dupin, A. & Simmel, F. C. Signalling and differentiation in emulsion-based multi-compartmentalized in vitro gene circuits. Nat. Chem. 11, 32–39 (2019).

    CAS  PubMed  Google Scholar 

  134. Yang, Q. et al. A cascade signaling network between artificial cells switching activity of synthetic transmembrane channels. J. Am. Chem. Soc. 143, 232–240 (2021).

    CAS  PubMed  Google Scholar 

  135. Niederholtmeyer, H., Chaggan, C. & Devaraj, N. K. Communication and quorum sensing in non-living mimics of eukaryotic cells. Nat. Commun. 9, 5027 (2018).

    ADS  PubMed Central  PubMed  Google Scholar 

  136. Peng, R. et al. DNA-based artificial molecular signaling system that mimics basic elements of reception and response. Nat. Commun. 11, 978 (2020).

    ADS  PubMed Central  PubMed  Google Scholar 

  137. Adamala, K. P., Martin-Alarcon, D. A., Guthrie-Honea, K. R. & Boyden, E. S. Engineering genetic circuit interactions within and between synthetic minimal cells. Nat. Chem. 9, 431–439 (2017).

    CAS  PubMed  Google Scholar 

  138. Wang, D., Yang, Y., Chen, F., Lyu, Y. & Tan, W. Network topology-directed design of molecular CPU for cell-like dynamic information processing. Sci. Adv. 8, eabq0917 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  139. Yang, S., Joesaar, A., Bögels, B. W. A., Mann, S. & De Greef, T. F. A. Protocellular CRISPR/Cas‐based diffusive communication using transcriptional RNA signaling. Angew. Chem. Int. Ed. Engl. 61, e202202436 (2022).

    CAS  PubMed Central  PubMed  Google Scholar 

  140. Zambrano, A. et al. Programmable synthetic cell networks regulated by tuneable reaction rates. Nat. Commun. 13, 3885 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  141. Chirieleison, S. M., Allen, P. B., Simpson, Z. B., Ellington, A. D. & Chen, X. Pattern transformation with DNA circuits. Nat. Chem. 5, 1000–1005 (2013).

    CAS  PubMed Central  PubMed  Google Scholar 

  142. Cangialosi, A. et al. DNA sequence-directed shape change of photopatterned hydrogels via high-degree swelling. Science 357, 1126–1130 (2017).

    ADS  CAS  PubMed  Google Scholar 

  143. Samanta, A., Sabatino, V., Ward, T. R. & Walther, A. Functional and morphological adaptation in DNA protocells via signal processing prompted by artificial metalloenzymes. Nat. Nanotechnol. 15, 914–921 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  144. Merindol, R., Loescher, S., Samanta, A. & Walther, A. Pathway-controlled formation of mesostructured all-DNA colloids and superstructures. Nat. Nanotechnol. 13, 730–738 (2018).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  145. Samanta, A., Hörner, M., Liu, W., Weber, W. & Walther, A. Signal-processing and adaptive prototissue formation in metabolic DNA protocells. Nat. Commun. 13, 3968 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  146. Sato, Y., Sakamoto, T. & Takinoue, M. Sequence-based engineering of dynamic functions of micrometer-sized DNA droplets. Sci. Adv. 6, eaba3471 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  147. Gong, J., Tsumura, N., Sato, Y. & Takinoue, M. Computational DNA droplets recognizing miRNA sequence inputs based on liquid–liquid phase separation. Adv. Funct. Mater. 32, 2202322 (2022).

    CAS  Google Scholar 

  148. Do, S., Lee, C., Lee, T., Kim, D.-N. & Shin, Y. Engineering DNA-based synthetic condensates with programmable material properties, compositions, and functionalities. Sci. Adv. 8, eabj1771 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  149. Yewdall, N. A., André, A. A. M., Lu, T. & Spruijt, E. Coacervates as models of membraneless organelles. Curr. Opin. Colloid Interface Sci. 52, 101416 (2021).

    CAS  Google Scholar 

  150. Choi, S., Meyer, M. O., Bevilacqua, P. C. & Keating, C. D. Phase-specific RNA accumulation and duplex thermodynamics in multiphase coacervate models for membraneless organelles. Nat. Chem. 14, 1110–1117 (2022).

    CAS  PubMed  Google Scholar 

  151. Lee, W., Yu, M., Lim, D., Kang, T. & Song, Y. Programmable DNA-based Boolean logic microfluidic processing unit. ACS Nano 15, 11644–11654 (2021).

    CAS  PubMed  Google Scholar 

  152. Karzbrun, E., Tayar, A. M., Noireaux, V. & Bar-Ziv, R. H. Programmable on-chip DNA compartments as artificial cells. Science 345, 829–832 (2014).

    ADS  CAS  PubMed  Google Scholar 

  153. Greiss, F., Daube, S. S., Noireaux, V. & Bar-Ziv, R. From deterministic to fuzzy decision-making in artificial cells. Nat. Commun. 11, 5648 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  154. Parrilla-Gutierrez, J. M. et al. A programmable chemical computer with memory and pattern recognition. Nat. Commun. 11, 1442 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  155. Carlson, R. The pace and proliferation of biological technologies. Biosecur. Bioterror. 1, 203–214 (2003).

    PubMed  Google Scholar 

  156. Van Der Valk, T. et al. Million-year-old DNA sheds light on the genomic history of mammoths. Nature 591, 265–269 (2021).

    ADS  PubMed Central  PubMed  Google Scholar 

  157. Pinciroli, R., Yang, L., Alter, J. & Smirni, E. Lifespan and failures of SSDs and HDDs: similarities, differences, and prediction models. IEEE Trans. Dependable Secur. Comput. 20, 256–272 (2023).

    Google Scholar 

  158. Organick, L. et al. An empirical comparison of preservation methods for synthetic DNA data storage. Small Methods 5, 2001094 (2021).

    CAS  Google Scholar 

  159. Antkowiak, P. L. et al. Anhydrous calcium phosphate crystals stabilize DNA for dry storage. Chem. Commun. 58, 3174–3177 (2022).

    CAS  Google Scholar 

  160. Liu, Y. et al. DNA preservation in silk. Biomater. Sci. 5, 1279–1292 (2017).

    CAS  PubMed Central  PubMed  Google Scholar 

  161. Kohll, A. X. et al. Stabilizing synthetic DNA for long-term data storage with earth alkaline salts. Chem. Commun. 56, 3613–3616 (2020).

    CAS  Google Scholar 

  162. Mao, C. et al. Metal–organic frameworks in microfluidics enable fast encapsulation/extraction of DNA for automated and integrated data storage. ACS Nano 17, 2840–2850 (2023).

    CAS  PubMed  Google Scholar 

  163. Organick, L. et al. Probing the physical limits of reliable DNA data retrieval. Nat. Commun. 11, 616 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  164. Katsanis, S. H. & Katsanis, N. Molecular genetic testing and the future of clinical genomics. Nat. Rev. Genet. 14, 415–426 (2013).

    CAS  PubMed Central  PubMed  Google Scholar 

  165. Organick, L. et al. Random access in large-scale DNA data storage. Nat. Biotechnol. 36, 242–248 (2018).

    CAS  PubMed  Google Scholar 

  166. Gao, Y., Chen, X., Qiao, H., Ke, Y. & Qi, H. Low-bias manipulation of DNA oligo pool for robust data storage. ACS Synth. Biol. 9, 3344–3352 (2020).

    CAS  PubMed  Google Scholar 

  167. Ross, M. G. et al. Characterizing and measuring bias in sequence data. Genome Biol. 14, R51 (2013).

    PubMed Central  PubMed  Google Scholar 

  168. Bornholt, J. et al. A DNA-based archival storage system. In Proceedings of the Twenty-First International Conference on Architectural Support for Programming Languages and Operating SystemsASPLOS ’16, 637–649 (ACM Press, 2016).

  169. Koch, J. et al. A DNA-of-things storage architecture to create materials with embedded memory. Nat. Biotechnol. 38, 39–43 (2020).

    CAS  PubMed  Google Scholar 

  170. Paunescu, D., Puddu, M., Soellner, J. O. B., Stoessel, P. R. & Grass, R. N. Reversible DNA encapsulation in silica to produce ROS-resistant and heat-resistant synthetic DNA ‘fossils’. Nat. Protoc. 8, 2440–2448 (2013).

    CAS  PubMed  Google Scholar 

  171. Erlich, Y. & Zielinski, D. DNA fountain enables a robust and efficient storage architecture. Science 355, 950–954 (2017).

    ADS  CAS  PubMed  Google Scholar 

  172. Welzel, M. et al. DNA-Aeon provides flexible arithmetic coding for constraint adherence and error correction in DNA storage. Nat. Commun. 14, 628 (2023).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  173. Hoshika, S. et al. Hachimoji DNA and RNA: a genetic system with eight building blocks. Science 363, 884–887 (2019).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  174. Tabatabaei, S. K. et al. Expanding the molecular alphabet of DNA-based data storage systems with neural network nanopore readout processing. Nano Lett. 22, 1905–1914 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  175. Choi, Y. et al. High information capacity DNA-based data storage with augmented encoding characters using degenerate bases. Sci. Rep. 9, 6582 (2019).

    ADS  PubMed Central  PubMed  Google Scholar 

  176. Tabatabaei, S. K. et al. DNA punch cards for storing data on native DNA sequences via enzymatic nicking. Nat. Commun. 11, 1742 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  177. Bošković, F., Ohmann, A., Keyser, U. F. & Chen, K. DNA structural barcode copying and random access. Small Struct. 2, 2000144 (2021).

    Google Scholar 

  178. Goodwin, S., McPherson, J. D. & McCombie, W. R. Coming of age: ten years of next-generation sequencing technologies. Nat. Rev. Genet. 17, 333–351 (2016).

    CAS  PubMed Central  PubMed  Google Scholar 

  179. Wang, Y., Zhao, Y., Bollas, A., Wang, Y. & Au, K. F. Nanopore sequencing technology, bioinformatics and applications. Nat. Biotechnol. 39, 1348–1365 (2021).

    CAS  PubMed Central  PubMed  Google Scholar 

  180. Takahashi, C. N., Nguyen, B. H., Strauss, K. & Ceze, L. Demonstration of end-to-end automation of DNA data storage. Sci. Rep. 9, 4998 (2019).

    ADS  PubMed Central  PubMed  Google Scholar 

  181. Chen, K., Zhu, J., Bošković, F., Keyser, U. F. & Nanopore-Based, D. N. A. Hard drives for rewritable and secure data storage. Nano Lett. 20, 3754–3760 (2020).

    ADS  CAS  PubMed  Google Scholar 

  182. Zhu, J., Ermann, N., Chen, K., Keyser, U. F., Image Encoding Using Multi‐Level DNA. Barcodes with nanopore readout. Small 17, 2100711 (2021).

    CAS  Google Scholar 

  183. Newman, S. et al. High density DNA data storage library via dehydration with digital microfluidic retrieval. Nat. Commun. 10, 1706 (2019).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  184. Yim, S. S. et al. Robust direct digital-to-biological data storage in living cells. Nat. Chem. Biol. 17, 246–253 (2021).

    CAS  PubMed Central  PubMed  Google Scholar 

  185. Shipman, S. L., Nivala, J., Macklis, J. D. & Church, G. M. Molecular recordings by directed CRISPR spacer acquisition. Science 353, aaf1175 (2016).

    PubMed Central  PubMed  Google Scholar 

  186. Bonnet, J., Subsoontorn, P. & Endy, D. Rewritable digital data storage in live cells via engineered control of recombination directionality. Proc. Natl Acad. Sci. USA 109, 8884–8889 (2012).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  187. Colotte, M., Coudy, D., Tuffet, S. & Bonnet, J. Adverse effect of air exposure on the stability of DNA stored at room temperature. Biopreserv. Biobank. 9, 47–50 (2011).

    PubMed  Google Scholar 

  188. Bögels, B. W. A. et al. DNA storage in thermoresponsive microcapsules for repeated random multiplexed data access. Nat. Nanotechnol. 18, 912–921 (2023).

    ADS  PubMed Central  PubMed  Google Scholar 

  189. Choi, Y. et al. DNA micro‐disks for the management of DNA‐based data storage with index and write‐once–read‐many (WORM) memory features. Adv. Mater. 32, 2001249 (2020).

    CAS  Google Scholar 

  190. Banal, J. L. et al. Random access DNA memory using Boolean search in an archival file storage system. Nat. Mater. 20, 1272–1280 (2021).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  191. Lin, K. N., Volkel, K., Tuck, J. M. & Keung, A. J. Dynamic and scalable DNA-based information storage. Nat. Commun. 11, 2981 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  192. Bee, C. et al. Molecular-level similarity search brings computing to DNA data storage. Nat. Commun. 12, 4764 (2021).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  193. Yamamoto, M., Kashiwamura, S., Ohuchi, A., Furukawa, M. & Large-scale, D. N. A. Memory based on the nested PCR. Nat. Comput. 7, 335–346 (2008).

    MathSciNet  CAS  Google Scholar 

  194. Tomek, K. J. et al. Driving the scalability of DNA-based information storage systems. ACS Synth. Biol. 8, 1241–1248 (2019).

    CAS  PubMed  Google Scholar 

  195. Tomek, K. J., Volkel, K., Indermaur, E. W., Tuck, J. M. & Keung, A. J. Promiscuous molecules for smarter file operations in DNA-based data storage. Nat. Commun. 12, 3518 (2021).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  196. Winston, C. et al. Combinatorial PCR method for efficient, selective oligo retrieval from complex oligo pools. ACS Synth. Biol. 11, 1727–1734 (2022).

    CAS  PubMed  Google Scholar 

  197. Meyerhans, A., Vartanian, J.-P. & Wain-Hobson, S. DNA recombination during PCR. Nucleic Acids Res. 18, 1687–1691 (1990).

    CAS  PubMed Central  PubMed  Google Scholar 

  198. Williams, R. et al. Amplification of complex gene libraries by emulsion PCR. Nat. Methods 3, 545–550 (2006).

    CAS  PubMed  Google Scholar 

  199. Terekhov, S. S. et al. Liquid drop of DNA libraries reveals total genome information. Proc. Natl Acad. Sci. USA 117, 27300–27306 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  200. Tabatabaei Yazdi, S. M. H., Yuan, Y., Ma, J., Zhao, H. & Milenkovic, O. A rewritable, random-access DNA-based storage system. Sci. Rep. 5, 14138 (2015).

    ADS  CAS  PubMed Central  Google Scholar 

  201. Liu, Y. et al. In vivo processing of digital information molecularly with targeted specificity and robust reliability. Sci. Adv. 8, eabo7415 (2022).

    CAS  PubMed Central  PubMed  Google Scholar 

  202. Sadremomtaz, A. et al. Digital data storage on DNA tape using CRISPR base editors. Nat. Commun. 14, 6472 (2023).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  203. Wang, B., Wang, S. S., Chalk, C., Ellington, A. D. & Soloveichik, D. Parallel molecular computation on digital data stored in DNA. Proc. Natl Acad. Sci. USA 120, e2217330120 (2023).

    MathSciNet  CAS  PubMed Central  PubMed  Google Scholar 

  204. Pan, C. et al. Rewritable two-dimensional DNA-based data storage with machine learning reconstruction. Nat. Commun. 13, 2984 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  205. Antkowiak, P. L. et al. Integrating DNA encapsulates and digital microfluidics for automated data storage in DNA. Small 18, 2107381 (2022).

    CAS  Google Scholar 

  206. Luo, Y. et al. The emerging landscape of microfluidic applications in DNA data storage. Lab. Chip 23, 1981–2004 (2023).

    CAS  PubMed  Google Scholar 

  207. Zhang, K. et al. A nanopore interface for higher bandwidth DNA computing. Nat. Commun. 13, 4904 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  208. Sadat Mousavi, P. et al. A multiplexed, electrochemical interface for gene-circuit-based sensors. Nat. Chem. 12, 48–55 (2020).

    CAS  PubMed  Google Scholar 

  209. Yin, F. et al. DNA-framework-based multidimensional molecular classifiers for cancer diagnosis. Nat. Nanotechnol. 18, 677–686 (2023).

    ADS  CAS  PubMed  Google Scholar 

  210. Zhang, C. et al. Nicking-assisted reactant recycle to implement entropy-driven DNA circuit. J. Am. Chem. Soc. 141, 17189–17197 (2019).

    CAS  PubMed  Google Scholar 

  211. 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).

    ADS  CAS  Google Scholar 

  212. Pei, Y. et al. Single-molecule resettable DNA computing via magnetic tweezers. Nano Lett. 22, 3003–3010 (2022).

    ADS  CAS  PubMed  Google Scholar 

  213. Deng, J. & Walther, A. Fuel-driven transient DNA strand displacement circuitry with self-resetting function. J. Am. Chem. Soc. 142, 21102–21109 (2020).

    CAS  PubMed Central  PubMed  Google Scholar 

  214. Shu, J.-J., Tan, Z. H., Wang, Q.-W. & Yong, K.-Y. Programmable biomolecule-mediated processors. J. Am. Chem. Soc. 145, 25033–25042 (2023).

    CAS  PubMed Central  PubMed  Google Scholar 

  215. Meiser, L. C. et al. Synthetic DNA applications in information technology. Nat. Commun. 13, 352 (2022).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  216. Li, J., Green, A. A., Yan, H. & Fan, C. Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation. Nat. Chem. 9, 1056–1067 (2017).

    CAS  PubMed  Google Scholar 

  217. Chandrasekaran, A. R. Nuclease resistance of DNA nanostructures. Nat. Rev. Chem. 5, 225–239 (2021).

    CAS  PubMed Central  PubMed  Google Scholar 

  218. Saminathan, A., Zajac, M., Anees, P. & Krishnan, Y. Organelle-level precision with next-generation targeting technologies. Nat. Rev. Mater. 7, 355–371 (2021).

    ADS  Google Scholar 

  219. Boneh, D., Dunworth, C. & Lipton, R. J. Breaking DES using a molecular computer. DIMACS Series in Discrete Mathematics and Theoretical Computer Science 37–65 https://doi.org/10.1090/dimacs/027/04 (1996).

  220. Hoose, A., Vellacott, R., Storch, M., Freemont, P. S. & Ryadnov, M. G. DNA synthesis technologies to close the gene writing gap. Nat. Rev. Chem. 7, 144–161 (2023).

    CAS  PubMed Central  PubMed  Google Scholar 

  221. Chen, Y.-J. et al. Quantifying molecular bias in DNA data storage. Nat. Commun. 11, 3264 (2020).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

  222. Regot, S. et al. Distributed biological computation with multicellular engineered networks. Nature 469, 207–211 (2011).

    ADS  CAS  PubMed  Google Scholar 

  223. Krishnan, J., Lu, L. & Alam, N. A. The interplay of spatial organization and biochemistry in building blocks of cellular signalling pathways. J. R. Soc. Interface 17, 20200251 (2020).

    CAS  PubMed Central  PubMed  Google Scholar 

  224. Wang, B., Chalk, C. & Soloveichik, D. SIMD||DNA: single instruction, multiple data computation with DNA strand displacement cascades. in DNA Computing and Molecular Programming (eds Thachuk, C. & Liu, Y.) 219–235 (Springer International Publishing, 2019).

  225. Rees, H. A. & Liu, D. R. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat. Rev. Genet. 19, 770–788 (2018).

    CAS  PubMed Central  PubMed  Google Scholar 

  226. Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149–157 (2019).

    ADS  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge funding from the National Facility for Translational Medicine (Shanghai), the National Natural Science Foundation of China (grant no. 21991134), the National Key R&D Program of China (grant no. 2022YFE0100600), Microsoft Research PhD Scholarship Programme, the European Research Council (ERC project nos 101000199 AMIGA and EC-2016-674 ADG 740235, PCELLS) and the Eindhoven–Wageningen–Utrecht Alliance (https://ewuu.nl/nl/) that supports the Center for Living Technologies.

Author information

Authors and Affiliations

Authors

Contributions

S.Y., B.W.A.B., C.F. and T.F.A.d.G. researched data for the article. All authors contributed substantially to discussion of the content. S.Y., B.W.A.B., F.W., S.M., C.F. and T.F.A.d.G. wrote the article. All authors reviewed and/or edited the manuscript before submission.

Corresponding authors

Correspondence to Stephen Mann, Chunhai Fan or Tom F. A. de Greef.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Chemistry thanks Maxim Ryadnov, Arun Richard Chandrasekaran and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Anti-factor

A protein that binds sigma factor and thereby inhibits transcription.

Base editors

A gene-editing approach that uses CRISPR–Cas systems to directly introduce point mutations into DNA or RNA.

Boolean logic

Type of algebra that performs logical operations using truth values (TRUE or FALSE) as signals.

Convolutional neural network

A neural network featuring a sparse topology, and thus low connectivity and complexity, to reduce the number of network connections and weight parameters.

DNA circuits

DNA reaction networks that use the concentrations of DNA as signals to perform computational functions, mimicking electronic circuits.

DNA classifiers

Molecular classifiers that use DNA as an input to distinguish different states of a DNA-encoded system.

Feedforward loops

A motif of DNA circuits in which the input has two pathways (direct and indirect) to control the final output.

Fountain codes

Transformation of a data file into an effectively unlimited number of encoded blocks; the original file can be reassembled by any subset of blocks.

Hopfield neural network

Single-layer neural network in which all neurons are both input and output, and they are connected with equal weights.

In vitro transcription and translation (TXTL)

Reactions that harness the cellular transcription and translation machinery to enable protein synthesis in vitro from natural or synthetic DNA templates.

Near-memory computing

An approach in which computing units are located close to the data memory, thereby reducing data movement.

Neural networks

Interconnected artificial neurons in a layered structure that resembles the biological neural network in the human brain.

Perceptron

A basic building block in neural networks that computes a weighted sum of the inputs and their weights and returns a single output value corresponding to the classification of the inputs provided.

Prime editors

A gene-editing approach that uses CRISPR–Cas systems to introduce changes encoded on DNA templates.

Reed Solomon codes

A block coding algorithm in which a message is split into multiple message words, and the encoding algorithm is performed on each message word without any dependency on previously received message words.

Seesaw gate

A gate complex with toehold domains on both sides, enabling reversible exchange of single-stranded DNA.

Sigma factor

A protein required for the initiation of transcription in bacteria.

Threshold gates

A gate that activates when the signal exceeds a set level.

Winner-take-all neural network

Neural network in which neurons compete for activation; the output of a neuron is ON only if the weighted sum of all binary inputs is the largest among all neurons.

XOR encoding

Encoding of data based on XOR logic operations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, S., Bögels, B.W.A., Wang, F. et al. DNA as a universal chemical substrate for computing and data storage. Nat Rev Chem 8, 179–194 (2024). https://doi.org/10.1038/s41570-024-00576-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41570-024-00576-4

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing