Letter | Published:

DNA computing circuits using libraries of DNAzyme subunits

Nature Nanotechnology volume 5, pages 417422 (2010) | Download Citation

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  • A Corrigendum to this article was published on 09 February 2011

This article has been updated

Abstract

Biological systems that are capable of performing computational operations1,2,3 could be of use in bioengineering and nanomedicine4,5, and DNA and other biomolecules have already been used as active components in biocomputational circuits6,7,8,9,10,11,12,13. There have also been demonstrations of DNA/RNA-enzyme-based automatons12, logic control of gene expression14, and RNA systems for processing of intracellular information15,16. However, for biocomputational circuits to be useful for applications it will be necessary to develop a library of computing elements, to demonstrate the modular coupling of these elements, and to demonstrate that this approach is scalable. Here, we report the construction of a DNA-based computational platform that uses a library of catalytic nucleic acids (DNAzymes)10, and their substrates, for the input-guided dynamic assembly of a universal set of logic gates and a half-adder/half-subtractor system. We demonstrate multilayered gate cascades, fan-out gates and parallel logic gate operations. In response to input markers, the system can regulate the controlled expression of anti-sense molecules, or aptamers, that act as inhibitors for enzymes.

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Change history

  • 09 February 2011

    In the version of this Letter originally published, components of the systems illustrated in Figs 3a–d, 4a and 4d were incorrectly labelled. In the Supplementary Information, components of the systems illustrated in Figs S7a, S9a–c and S10 were also incorrectly labelled. These errors have now been corrected in the HTML and PDF versions of the text, and in the Supplementary Information.

References

  1. 1.

    Molecular computing with deoxyribozymes. Prog. Nucleic Acid Res. Mol. Biol. 82, 199–217 (2008).

  2. 2.

    & Molecular logic and computing. Nature Nanotech. 2, 399–410 (2007).

  3. 3.

    Biocomputers: from test tubes to live cells. Mol. Biosyst. 5, 675–685 (2009).

  4. 4.

    et al. Nanomedicine—challenge and perspectives. Angew. Chem. Int. Ed. 48, 872–897 (2009).

  5. 5.

    Towards biomedical applications for nucleic acid nanodevices. Nanomedicine 2, 817–839 (2007).

  6. 6.

    , , & Logical computation using algorithmic self-assembly of DNA triple-crossover molecules. Nature 407, 493–496 (2000).

  7. 7.

    , , & Sequence-addressable DNA logic. Small 4, 427–431 (2008).

  8. 8.

    , , & Enzyme-free nucleic acid logic circuits. Science 314, 1585–1589 (2006).

  9. 9.

    , , , & Logic gates and antisense DNA machine operating on translator scaffold. ACS Nano 3, 1831–1843 (2009).

  10. 10.

    & A deoxyribozyme-based molecular automaton. Nature Biotechnol. 21, 1069–1074 (2003).

  11. 11.

    & Computational design and experimental validation of oligonucleotide-sensing allosteric ribozymes. Nature Biotechnol. 23, 1424–1433 (2005).

  12. 12.

    , , , & Programmable and autonomous computing machine made of biomolecules. Nature 414, 430–434 (2001).

  13. 13.

    , , , & Concatenated logic gates using four coupled biocatalysts operating in series. Proc. Natl Acad. Sci. USA 103, 17160–17163 (2006).

  14. 14.

    , , , & An autonomous molecular computer for logical control of gene expression. Nature 429, 423–429 (2004).

  15. 15.

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

  16. 16.

    & Higher-order cellular information processing with synthetic RNA devices. Science 322, 456–460 (2008).

  17. 17.

    DNA enzymes. Nature Biotechnol. 15, 427–431 (1997).

  18. 18.

    & Functional DNA nanotechnology: emerging applications of DNAzymes and aptamers. Curr. Opin. Biotechnol. 17, 580–588 (2006).

  19. 19.

    , , & DNAzymes for sensing, nanobiotechnology and logic gate applications. Chem. Soc. Rev. 37, 1153–1165 (2008).

  20. 20.

    A binary deoxyribozyme for nucleic acid analysis. ChemBioChem 8, 2039–2042 (2007).

  21. 21.

    , , & Cooperative multicomponent self-assembly of nucleic acid structures for the activation of DNAzyme cascades: a paradigm for DNA sensors and aptasensors. Chem. Eur. J. 14, 3411–3418 (2009).

  22. 22.

    Catalytic DNAs as potential therapeutic agents and sequence-specific molecular tools to dissect biological function. J. Clin. Invest. 106, 1189–1195 (2000).

  23. 23.

    , , & Targeted cleavage of HIV-1 coreceptor-CXCR-4 by RNA-cleaving DNA-enzyme: inhibition of coreceptor function. Antivir. Res. 46, 125–134 (2000).

  24. 24.

    & A DNA enzyme with Mg2+-dependent RNA phosphoesterase activity. Chem. Biol. 2, 655–660 (1995).

  25. 25.

    Thrombin in inflammatory brain diseases. Autoimmun. Rev. 5, 528–531 (2006).

  26. 26.

    , , , & Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 355, 564–566 (1992).

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Acknowledgements

Parts of this research are supported by the EC Project MOLOC and by the Office of Naval Research, USA. F.R. is Director of Research at Fonds National de la Recherche Scientifique (FNRS), Belgium. J.E. acknowledges a Converging Technologies Fellowship (Israel Science Foundation).

Author information

Affiliations

  1. The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel

    • Johann Elbaz
    • , Oleg Lioubashevski
    • , Fuan Wang
    • , Raphael D. Levine
    •  & Itamar Willner
  2. Chemistry Department, B6c, University of Liège, 4000 Liège, Belgium

    • Françoise Remacle

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Contributions

J.E. designed the systems, performed the experiments, analysed the results and participated in the formulation of the paper. O.L. participated in designing the system, discussing the research results and the formulation of the paper. F.W. participated in designing the system and performed the experiments. R.D.L and F.R. participated in discussing the research results and the formulation of the paper. I.W. supervised the project, evaluated the research results and participated in the formulation of the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Itamar Willner.

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DOI

https://doi.org/10.1038/nnano.2010.88

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