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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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).
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.
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Molecular programming: http://molecular-programming.org/
- 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.
A long single-stranded DNA serving as the major component of a DNA origami structure, which will be folded into a defined shape.
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.
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.
The molecular binding strength as a result of multiple, non-covalent interactions, for example between an antibody and a complex antigen.
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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