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DNA origami

Nature Reviews Methods Primers volume 1, Article number: 13 (2021) Cite this article

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Abstract

Biological materials are self-assembled with near-atomic precision in living cells, whereas synthetic 3D structures generally lack such precision and controllability. Recently, DNA nanotechnology, especially DNA origami technology, has been useful in the bottom-up fabrication of well-defined nanostructures ranging from tens of nanometres to sub-micrometres. In this Primer, we summarize the methodologies of DNA origami technology, including origami design, synthesis, functionalization and characterization. We highlight applications of origami structures in nanofabrication, nanophotonics and nanoelectronics, catalysis, computation, molecular machines, bioimaging, drug delivery and biophysics. We identify challenges for the field, including size limits, stability issues and the scale of production, and discuss their possible solutions. We further provide an outlook on next-generation DNA origami techniques that will allow in vivo synthesis and multiscale manufacturing.

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Fig. 1: DNA origami technology.
Fig. 2: General principle of DNA origami design and assembly.
Fig. 3: Representative examples of ensemble and single-molecule characterizations of DNA origami structures.
Fig. 4: Typical approaches of DNA origami-based nanofabrication.
Fig. 5: Application examples in nanophotonics and nanoelectronics, catalysis, computation and molecular machines.
Fig. 6: Application examples in drug delivery, bioimaging and biophysics.
Fig. 7: Outlook for DNA origami technology.

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Acknowledgements

C.F. and J.L. were supported by the National Natural Science Foundation of China (21991134, 21834007) and the Shanghai Municipal Science and Technology Commission (19JC1410300). K.V.G. and M.A.D.N. were supported by DNA-Based Modular Nanorobotics (DNA-Robotics) and the Marie Curie Innovative Training Network (MRC ITN) under EU H2020 (Project ID: 765703). P.Z. and N.L. were supported by a European Research Council (ERC Dynamic Nano) grant. B.S. was supported by the Deutsche Forschungsgemeinschaft (CRC-1093).

Author information

Authors and Affiliations

  1. Center for Molecular Design and Biomimetics, The Biodesign Institute, School of Molecular Sciences, Arizona State University, Tempe, AZ, USA

    Swarup Dey & Hao Yan

  2. School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, China

    Chunhai Fan & Jiang Li

  3. 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

  4. Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark

    Kurt V. Gothelf & Minke A. D. Nijenhuis

  5. Department of Chemistry, Aarhus University, Aarhus, Denmark

    Kurt V. Gothelf & Minke A. D. Nijenhuis

  6. Bioimaging Center, Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China

    Jiang Li

  7. Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA

    Chenxiang Lin & Longfei Liu

  8. Nanobiology Institute, Yale University, West Haven, CT, USA

    Chenxiang Lin & Longfei Liu

  9. 2nd Physics Institute, University of Stuttgart, Stuttgart, Germany

    Na Liu & Pengfei Zhan

  10. Max Planck Institute for Solid State Research, Stuttgart, Germany

    Na Liu & Pengfei Zhan

  11. Centre for Medical Biotechnology (ZMB), University of Duisburg–Essen, Essen, Germany

    Barbara Saccà

  12. Physics Department, Technische Universität München, Garching, Germany

    Friedrich C. Simmel

Authors
  1. Swarup Dey
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  2. Chunhai Fan
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  3. Kurt V. Gothelf
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  4. Jiang Li
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  6. Longfei Liu
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  7. Na Liu
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  11. Hao Yan
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  12. Pengfei Zhan
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Contributions

Introduction (C.F. and J.L.); Experimentation (S.D., N.L., H.Y. and P.Z.); Results (B.S.); Applications (C.F., J.L., C.L., L.L., K.V.G. and M.A.D.N.); Reproducibility and data deposition (C.F., N.L. and P.Z.); Limitations and optimizations (C.L. and L.L.); Outlook (F.C.S.); Overview of the Primer (C.F.).

Corresponding authors

Correspondence to Chunhai Fan, Kurt V. Gothelf, Jiang Li, Chenxiang Lin, Na Liu, Barbara Saccà, Friedrich C. Simmel or Hao Yan.

Ethics declarations

Competing interests

C.F. declares an issued Chinese patent (patent number 2018112787266) and a Chinese patent application (2016111794282) based on technologies described in this Primer. F.C.S. has patent applications on DNA origami membrane channels (EP2695949B1) and the electrically driven DNA robotic arm (EP3607646A1). All other authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Methods Primers thanks A. R. Chandrasekaran, S. Lee, S. Pecic, R. Shetty and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

Adenita: https://www.samson-connect.net/element/dda2a078-1ab6-96ba-0d14-ee1717632d7a.html

CaDNAno: https://cadnano.org/

CanDo: http://cando-DNA-origami.org/

COSM: http://vsb.fbb.msu.ru/cosm

DAEDALUS: http://daedalus-DNA-origami.org/

EMAN2: https://blake.bcm.edu/emanwiki/EMAN2

GenBank: https://www.ncbi.nlm.nih.gov/genbank

METIS: http://metis-DNA-origami.org/

Molecular programming: http://molecular-programming.org/

oxDNA: https://oxdna.org/

oxView: https://sulcgroup.github.io/oxdna-viewer/

PERDIX: http://perdix-DNA-origami.org/

TALOS: http://talos-DNA-origami.org/

Tiamat: http://yanlab.asu.edu/Resources.html

vHelix: http://vhelix.net/

Glossary

Holliday junction

A four-stranded cross-shaped DNA structure (named after British geneticist Robin Holliday) that forms during the process of genetic recombination.

DNA nanotechnology

A branch of nanotechnology concerned with the design, study and application of DNA-based synthetic structures to take advantage of the physical and chemical properties of DNA.

DNA tiles

DNA structures that as building blocks can be tiled into higher order (usually periodic) structures.

DNA origami

A class of technologies for building DNA nanostructures by folding a long single-stranded DNA (scaffold) into desired shapes via base pairing.

Scaffold

A long single-stranded DNA serving as the major component of a DNA origami structure, which will be folded into a defined shape.

Staples

Short single-stranded DNAs that help fold the scaffold DNA via crossover base pairing.

Addressable points

The locations of staple DNAs, including their extensions or modifications, on a DNA origami structure. These points can be prescribed as each staple has a globally unique base sequence (a unique address).

Base stacking

A stacking arrangement of the planes of nucleobases or base pairs in the structure of nucleic acids, leading to a strong π–π interaction vertical to the planes, which is a major force that stabilizes DNA duplex structures.

Enzyme cascades

Groups of enzymes in which the reaction product of one enzyme is the substrate for the next.

Abstraction

The translation of concrete DNA reactions into abstracted algorithms and instructions. By this method, the complex details are hidden from the persons operating the computing systems.

In vivo computation

Molecular computation implemented in living organisms, whose inputs/outputs are often interfaced with biological pathways/functions.

DNA origami robot

A molecular machine made by DNA origami that can autonomously perform specified task(s) with precise motions at the nanoscale.

Avidity

The molecular binding strength as a result of multiple, non-covalent interactions, for example between an antibody and a complex antigen.

Tectons

Structural motifs that serve as units for assembly of higher order structures.

Xeno-nucleic acids

(XNAs). Artificially synthesized nucleic acids that do not exist in nature (for example, nucleic acids carrying unnatural backbones, bases or chemical modifications).

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Dey, S., Fan, C., Gothelf, K.V. et al. DNA origami. Nat Rev Methods Primers 1, 13 (2021). https://doi.org/10.1038/s43586-020-00009-8

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