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Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation

Nature Chemistry volume 9, pages 1056–1067 (2017)Cite this article

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Abstract

Nucleic acids have attracted widespread attention due to the simplicity with which they can be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of DNA/RNA nanotechnology offer numerous opportunities for in-cell and in-vivo applications, and the technology holds great promise to advance the growing field of synthetic biology. Many elegant examples have revealed the potential in integrating nucleic acid nanostructures in cells and in vivo where they can perform important physiological functions. In this Review, we summarize the current abilities of DNA/RNA nanotechnology to realize applications in live cells and then discuss the key problems that must be solved to fully exploit the useful properties of nanostructures. Finally, we provide viewpoints on how to integrate the tools provided by DNA/RNA nanotechnology and related new technologies to construct nucleic acid nanostructure-based molecular circuitry for synthetic biology.

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Figure 1: Representative examples of promising DNA nanostructures for synthetic biology.
Figure 2: DNA/RNA nanotechnology-enabled toolbox for synthetic circuits.
Figure 3: Typical AND gate circuits.
Figure 4: I/O interface scheme for synthetic circuits.
Figure 5: Nucleic acid nanostructures as information storage media.
Figure 6: The scheme of an integrated live-cell circuit enabled by DNA/RNA nanotechnology.

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Acknowledgements

Financial support from the Ministry of Science and Technology of China (2013CB932803, 2013CB933802, 2016YFA0201200, 2016YFA0400900), the National Science Foundation of China (21390414, 21227804, 21329501, U1532119) and the Chinese Academy of Sciences (QYZDJ-SSW-SLH031, KJCX2-EW-N03) are acknowledged. Hao Yan also acknowledges financial support from the US National Science Foundation, the National Institutes of Health, the Army Research Office, the Office of Naval Research and funds from Arizona State University. A.A.G. acknowledges financial support from the US National Science Foundation, the Gates Foundation, the Arizona Biomedical Research Commission, an Alfred P. Sloan Research Fellowship (FG-2017-9108) and Arizona State University.

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Authors and Affiliations

  1. Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China

    Jiang Li & Chunhai Fan

  2. Biodesign Center for Molecular Design and Biomimetics at the Biodesign Institute & School of Molecular Sciences, Arizona State University, Tempe, 85287, Arizona, USA

    Alexander A. Green & Hao Yan

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  1. Jiang Li
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Correspondence to Alexander A. Green, Hao Yan or Chunhai Fan.

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Li, J., Green, A., Yan, H. et al. Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation. Nature Chem 9, 1056–1067 (2017). https://doi.org/10.1038/nchem.2852

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