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WIREs Nanomed Nanobiotechnol
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Novel DNA materials and their applications

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The last two decades have witnessed the exponential development of DNA as a generic material instead of just a genetic material. The biological function, nanoscale geometry, biocompatibility, biodegradability, and molecular recognition capacity of DNA make it a promising candidate for the construction of novel functional nanomaterials. As a result, DNA has been recognized as one of the most appealing and versatile nanomaterial building blocks. Scientists have used DNA in this way to construct various amazing nanostructures, such as ordered lattices, origami, supramolecular assemblies, and even three‐dimensional objects. In addition, DNA has been utilized as a guide and template to direct the assembly of other nanomaterials including nanowires, free‐standing membranes, and crystals. Furthermore, DNA can also be used as structural components to construct bulk materials such as DNA hydrogels, demonstrating its ability to behave as a unique polymer. Overall, these novel DNA materials have found applications in various areas in the biomedical field in general, and nanomedicine in particular. In this review, we summarize the development of DNA assemblies, describe the innovative progress of multifunctional and bulk DNA materials, and highlight some real‐world nanomedical applications of these DNA materials. We also show our insights throughout this article for the future direction of DNA materials. WIREs Nanomed Nanobiotechnol 2010 2 648–669

This article is categorized under:

  • Diagnostic Tools > Biosensing
  • Nanotechnology Approaches to Biology > Cells at the Nanoscale
  • Implantable Materials and Surgical Technologies > Nanomaterials and Implants
  • Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Figure 1.

Basic principles of DNA self‐assembly.5 (a) Watson–Crick base‐pairing rules: the double helix is assembled from two single‐stranded DNA by following the Watson–Crick base‐paring rules: adenine (A) with thymine (T) and guanine (G) with cytosine (C). (b) Sticky‐end cohesion. Linear double‐stranded DNA (dsDNA) can be designed with sticky‐end overhangs that are complementary to each other. The two dsDNA can be connected by the hybridization of sticky ends. The nick between the two duplexes can be chemically sealed by an enzyme, resulting in a single duplex. (c) A branched DNA motif must have base‐pair asymmetry to be stable enough to function as a component for DNA assembly. (d) Sticky‐end assembly of branched DNA motifs. A branched DNA motif is shown on the left with four sticky ends: X complementary to X and Y complementary to Y. The four motifs assemble to form a quadrilateral, shown on the right, with further sticky ends on the outside, further allowing the structure to form a 2D lattice..

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Figure 2.

One‐dimensional DNA nanostructures. (a) Nanotubes assembled from double‐crossover DNA tiles with the assistance of a four‐way‐branched DNA connector. (Reprinted with permission from Ref 52. Copyright 2005 Wiley‐VCH Verlag GmbH & Co. KGaA). (b) Nanotubes assembled from a single strand containing four palindromic segments. (Reprinted with permission from Ref 53. Copyright 2006 Wiley‐VCH Verlag GmbH & Co. KGaA). (c) Nanotubes assembled from four half‐tubes. The atomic force microscopy image shows four‐helix bundles. (Reprinted with permission from Ref 54. Copyright 2007 American Chemical Society). (d) Monodisperse DNA tubes with programed circumferences: the molecular program (left) and width plot of opened tubes showing the monodispersity of their circumferences (right). (Reprinted with permission from Ref 55. Copyright 2008 AAAS). (e) DNA nanotubes with well‐defined triangular and square geometries based on a modular approach. (Reprinted with permission from Ref 56. Copyright 2009 Nature Publishing Group). (f) Arrays of DNA nanostrands patterned by molecular combing and soft‐lithography micropatterning. (Reprinted with permission from Ref 58. Copyright 2005 PNAS)..

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Figure 3.

Two‐dimensional (2D) DNA nanostructures. (a) 2D crystals formed from double‐crossover motifs. (Reprinted with permission from Refs 4, 12. Copyright 1998, 2003 Nature Publishing Group). (b) Square lattices formed from four‐way junctions. (Reprinted with permission from Ref 49. Copyright 2003 AAAS). (c) Hexagonal lattices formed from three‐point‐star motifs. (Reprinted with permission from Ref 65. Copyright 2005 American Chemical Society). (d) Complex lattices assembled from five‐point‐star motifs. (Reprinted with permission from Ref 66. Copyright 2008 PNAS). (e) 2D periodic arrays assembled from symmetric six‐point‐star motifs. (Reprinted with permission from Ref 67. Copyright 2006 American Chemical Society). (f) 2D periodic arrays assembled from T‐junctions. (Reprinted with permission from Ref 71. Copyright 2009 Wiley‐VCH Verlag GmbH & Co. KGaA). (g) 2D patterns made by DNA origami, in which a long single strand is folded with the help of smaller ‘staple strands’. (Reprinted with permission from Ref 23. Copyright 2006 Nature Publishing Group)..

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Figure 4.

Three‐dimensional (3D) DNA nanostructures. (a) Octahedrons, (Reprinted with permission from Ref 78. Copyright 2004 Nature Publishing Group). (b) tetrahedrons, (Reprinted with permission from Ref 79. Copyright 2005 AAAS). (c) a variety of polyhedrons, (Reprinted with permission from Ref 85. Copyright 2007 American Chemical Society). and (d, e) 3D DNA origami. (Reprinted with permission from Refs 82, 83. Copyright 2009 Nature Publishing Group and AAAS). (f) Hollow polyhedrons have been assembled by engineering flexibility into three‐point‐star motifs, where the curvature dictates the resulting shape. (Reprinted with permission from Ref 81. Copyright 2008 Nature Publishing Group). (g) A DNA box based on DNA origami. The box can be opened by the introduction of two ‘key’ oligonucleotides, which is indicated by a fluorescence signal. (Reprinted with permission from Ref 24. Copyright 2009 Nature Publishing Group)..

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Figure 5.

(a) Dendrimer‐like DNA (DL‐DNA): Y‐shaped DNA with carefully designed overhangs can be enzymatically assembled into DL‐DNA structures one generation at a time.90 (b) DNA hydrogel: palindromic overhangs, on the other hand, will result in a bulk hydrogel on the addition of DNA ligase. (Reprinted with permission from Ref 30. Copyright 2006 Nature Publishing Group). (c, d) DNA nanobarcodes and ABC monomers: monomeric subunits with various modifications, such as molecular probes, fluorescent dyes, and photocrosslinkable moieties, can be rationally assembled into anisotropic dendrimers.33, 34.

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Figure 6.

DNA nanostructures serve as template for assembling nanoscale components. (a) Two‐dimensional tile arrays of gold nanoparticles. (Reprinted with permission from Ref 100. Copyright 2006 American Chemical Society). (b) Programmable subunits enable the arrangement of different‐sized nanoparticles. (Reprinted with permission from Ref 102. Copyright 2006 American Chemical Society). (c) Streptavidin arrays. (Reprinted with permission from Ref 106. Copyright 2005 American Chemical Society). (d) Antibody arrays. (Reprinted with permission from Ref 108. Copyright 2006 American Chemical Society)..

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Figure 7.

DNA nanostructures serve as guide for assembling nanoscale components. (a, b) DNA programmable nanoparticles have been shown to form nanoparticle networks. (Reprinted with permission from Refs 112 and 116. Copyright 1996 and 1998 Nature Publishing Group and American Chemical Society). (c) Molecule‐like nanoparticle arrangements. (Reprinted with permission from Ref 115. Copyright 2009 American Chemical Society). (d) The formation of amorphous or crystalline systems can be controlled by adjusting the DNA spacers.118 (e) Two‐dimensional nanoparticle superlattices have been achieved based on solvent evaporation. (Reprinted with permission from Ref 118. Copyright 2008 Nature Publishing Group)..

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Figure 8.

(a) Nanobarcodes and (b) a target‐driven polymerization of ABC monomers used in a multiplexed detection strategy.33, 34.

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Figure 9.

Protein‐producing DNA hydrogel (‘P‐gel’). The plasmid is ligated into a DNA hydrogel matrix, resulting in gene‐encapsulated P‐gel pads. The pads are then added to a cell lysate to express proteins. A comparison of P‐gel to a solution phase system shows greater expression of two fluorescent proteins by P‐gel.31.

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Nanotechnology Approaches to Biology > Cells at the Nanoscale
Diagnostic Tools > Biosensing
Implantable Materials and Surgical Technologies > Nanomaterials and Implants

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