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WIREs Nanomed Nanobiotechnol
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Overview of DNA origami for molecular self‐assembly

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Abstract Judging by the number of atoms and the precision with which they are organized in three‐dimensional space, DNA origami assemblies represent the current acme of human molecular engineering accomplishments. A subset of structural DNA nanotechnology, DNA origami makes use of the programmable molecular recognition of complementary DNA cohesions to assemble designed structures. This review will discuss the development of concepts and methods involved in DNA origami with an eye toward future increases in origami size and sequence complexity, as well as exploring different methods for the production of the DNA molecular components (long biologically synthesized scaffold strands and the complex set of chemically synthesized staple strands). In future applications, the incorporation and organization of other materials (metals and other inorganics, protein enzymes, and other nanomaterials) upon or within DNA origami should result in tools for “bottom‐up” nanofabrication of biomedical, electronic, and photonic devices and materials. WIREs Nanomed Nanobiotechnol 2013, 5:150–162. doi: 10.1002/wnan.1204 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures

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Development of DNA origami. (a) Concept of folding a large scaffold strand (black) with shorter strands (gray) by basepairing (gray crosshatches) and strand exchange crossovers. (Reprinted with permission from Ref 18. Copyright 2003 World Scientific Publishing) (b) Three panels showing the scaffold strand trace and two atomic force microscopy (AFM) images of triangular origami from Rothemund's original paper. (Reprinted with permission from Ref 11. Copyright 2006 Nature Publishing Group). (c) The schematic plan and corresponding AFM image of hairpin decorated origami displaying the depiction of western hemisphere. (Reprinted with permission from Ref 11. Copyright 2006 Nature Publishing Group) (d) Schematic cartoon and TEM images from negative stained sample of 3D origami shapes constructed from honeycomb lattice. (Reprinted with permission from Ref 23. Copyright 2009 Nature Publishing Group) (e) Cartoon and TEM images from twisted 3D origami structures. (Reprinted with permission from Ref 23. Copyright 2009 Nature Publishing Group)

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A conceptual phase‐diagram of DNA Nanotechnology and DNA Origami with blurred boundaries between several phases. The blurred boundaries are between: [1] 2D and 3D origami; [2] super‐origami backbone; [3] large complex 2D and 3D structures; [4] periodic structures; [5] tile and lattice architectures; [6] probe arrays. Several stages are yet to be explored as researchers are limited by scaffold size and staple pool complexity.

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The design‐fabricate‐test cycle for DNA origami via eight steps from conception to microscopy confirmation. (a) Examples of currently available CAD software. (Reprinted with permission from http://cando‐dna‐origami.org/and http://openwetware.org/wiki/User:NUS_Dnamazing. Copyright) (b, c) ssDNA scaffold of different sizes can be made by PCR or biologically derived dsDNA can also be utilized. (d,e) Staples can be manufactured using bulk column synthesizer or off of DNA arrays. (f,g) Thermal or denaturant‐assisted annealing can be used for folding structures. (Reprinted with permission from Ref 27. Copyright 2008 American Chemical Society) (h,i) Origami structures can be gel or enzymatically purified. (j) Hierarchical assembly of designs can lead to multi‐part structures. (Reprinted with permission from Ref. 28. Copyright 2011 American Chemical Society)

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Therapeutic Approaches and Drug Discovery > Emerging Technologies
Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures

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