Review Article

DNA nanotechnology

  • Nature Reviews Materials 3, Article number: 17068 (2017)
  • doi:10.1038/natrevmats.2017.68
  • Download Citation
Published online:

Abstract

DNA is the molecule that stores and transmits genetic information in biological systems. The field of DNA nanotechnology takes this molecule out of its biological context and uses its information to assemble structural motifs and then to connect them together. This field has had a remarkable impact on nanoscience and nanotechnology, and has been revolutionary in our ability to control molecular self-assembly. In this Review, we summarize the approaches used to assemble DNA nanostructures and examine their emerging applications in areas such as biophysics, diagnostics, nanoparticle and protein assembly, biomolecule structure determination, drug delivery and synthetic biology. The introduction of orthogonal interactions into DNA nanostructures is discussed, and finally, a perspective on the future directions of this field is presented.

  • Subscribe to Nature Reviews Materials for full access:

    $59

    Subscribe

Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.

References

  1. 1.

    & Emulating biology: building nanostructures from the bottom up. Proc. Natl Acad. Sci. USA 99, 6451–6455 (2002).

  2. 2.

    Nucleic-acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982).

  3. 3.

    , & An immobile nucleic-acid junction constructed from oligonucleotides. Nature 305, 829–831 (1983).

  4. 4.

    & Synthesis from DNA of a molecule with the connectivity of a cube. Nature 350, 631–633 (1991).

  5. 5.

    & DNA double-crossover molecules. Biochemistry 32, 3211–3220 (1993).

  6. 6.

    , , & Antiparallel DNA double crossover molecules as components for nanoconstruction. J. Am. Chem. Soc. 118, 6131–6140 (1996).

  7. 7.

    , , & Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544 (1998).

  8. 8.

    , , & A nanomechanical device based on the B–Z transition of DNA. Nature 397, 144–146 (1999).

  9. 9.

    , , & DNA tile based self-assembly: building complex nanoarchitectures. ChemPhysChem 7, 1641–1647 (2006).

  10. 10.

    & An investigation of several deoxynucleoside phosphoramidites useful for synthesizing deoxyoligonucleotides. Tetrahedron Lett. 24, 245–248 (1983).

  11. 11.

    & Large-scale de novo DNA synthesis: technologies and applications. Nat. Methods 11, 499–507 (2014).

  12. 12.

    & DNA synthesis and assembly: putting the synthetic in synthetic biology. Cold Spring Harb. Perspect. Biol. 9, a023812 (2017).

  13. 13.

    , & Assembling materials with DNA as the guide. Science 321, 1795–1799 (2008).

  14. 14.

    , , , & Self-assembly of hexagonal DNA two-dimensional (2D) arrays J. Am. Chem. Soc. 127, 12202–12203 (2005).

  15. 15.

    , & Highly connected two-dimensional crystals of DNA six-point-stars. J. Am. Chem. Soc. 128, 15978–15979 (2006).

  16. 16.

    An organic semiconductor organized into 3D DNA arrays via ‘bottom-up’ rational design Angew. Chem. Int. Ed. 56, 6445–6448 (2017).

  17. 17.

    , , & Tensegrity: construction of rigid DNA triangles from flexible four-arm DNA junctions. J. Am. Chem. Soc. 126, 2324–2325 (2004).

  18. 18.

    & Substrate-assisted assembly of interconnected single-duplex DNA nanostructures. Angew. Chem. Int. Ed. 48, 6820–6823 (2009).

  19. 19.

    , , & Directed nucleation assembly of DNA tile complexes for barcode-patterned lattices. Proc. Natl Acad. Sci. USA 100, 8103–8108 (2003).

  20. 20.

    , & Sequential growth of long DNA strands with user-defined patterns for nanostructures and scaffolds. Nat. Commun. 6, 7065 (2015).

  21. 21.

    & Minimalist approach to complexity: templating the assembly of DNA tile structures with sequentially grown input strands. ACS Nano 10, 6542–6551 (2016).

  22. 22.

    et al. Sequence symmetry as a tool for designing DNA nanostructures. Angew. Chem. Int. Ed. 44, 6694–6696 (2005).

  23. 23.

    , & Algorithmic self-assembly of DNA Sierpinski triangles. PLoS Biol. 2, e424 (2004).

  24. 24.

    & Physical principles for DNA tile self-assembly. Chem. Soc. Rev. 46, 3808–3829 (2017).

  25. 25.

    Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006).

  26. 26.

    , & A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron. Nature 427, 618–621 (2004).

  27. 27.

    , & Complex shapes self-assembled from single-stranded DNA tiles. Nature 485, 623–626 (2012).

  28. 28.

    et al. Scalable amplification of strand subsets from chip-synthesized oligonucleotide libraries. Nat. Commun. 6, 8634 (2015).

  29. 29.

    , , & One-pot assembly of a hetero-dimeric DNA origami from chip-derived staples and double-stranded scaffold. ACS Nano 7, 903–910 (2013).

  30. 30.

    , , , & Controlled nucleation and growth of DNA tile arrays within prescribed DNA origami frames and their dynamics. J. Am. Chem. Soc. 136, 3724–3727 (2014).

  31. 31.

    , , & Crystalline two-dimensional DNA-origami arrays. Angew. Chem. Int. Ed. 50, 264–267 (2011).

  32. 32.

    , & A single-stranded architecture for cotranscriptional folding of RNA nanostructures. Science 345, 799–804 (2014).

  33. 33.

    et al. Building programmable jigsaw puzzles with RNA. Science 306, 2068–2072 (2004).

  34. 34.

    et al. In vitro assembly of cubic RNA-based scaffolds designed in silico. Nat. Nanotechnol. 5, 676–682 (2010).

  35. 35.

    et al. Construction of RNA nanocages by re-engineering the packaging RNA of Phi29 bacteriophage. Nat. Commun. 5, 3890 (2014).

  36. 36.

    , , & Organization of intracellular reactions with rationally designed RNA assemblies. Science 333, 470–474 (2011).

  37. 37.

    & Construction of a DNA-truncated octahedron. J. Am. Chem. Soc. 116, 1661–1669 (1994).

  38. 38.

    , & The single-step synthesis of a DNA tetrahedron. Chem. Commun. (Camb.)1372–1373 (2004).

  39. 39.

    & Modular access to structurally switchable 3D discrete DNA assemblies. J. Am. Chem. Soc. 129, 13376–13377 (2007).

  40. 40.

    et al. Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra. Nature 452, 198–201 (2008).

  41. 41.

    et al. Directed self-assembly of DNA tiles into complex nanocages. Angew. Chem. Int. Ed. 53, 8041–8044 (2014).

  42. 42.

    et al. Metal-nucleic acid cages. Nat. Chem. 1, 390–396 (2009).

  43. 43.

    & Knitting complex weaves with DNA origami. Curr. Opin. Struct. Biol. 20, 276–282 (2010).

  44. 44.

    et al. Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459, 414–418 (2009).

  45. 45.

    et al. Multilayer DNA origami packed on a square lattice. J. Am. Chem. Soc. 131, 15903–15908 (2009).

  46. 46.

    et al. Folding DNA into twisted and curved nanoscale shapes. Science 325, 725–730 (2009).

  47. 47.

    et al. Self-assembly of a nanoscale DNA box with a controllable lid. Nature 459, 73–75 (2009).

  48. 48.

    et al. Scaffolded DNA origami of a DNA tetrahedron molecular container. Nano Lett. 9, 2445–2447 (2009).

  49. 49.

    et al. DNA origami with complex curvatures in three-dimensional space. Science 332, 342–346 (2011).

  50. 50.

    , , , & DNA prism structures constructed by folding of multiple rectangular arms. J. Am. Chem. Soc. 131, 15570–15571 (2009).

  51. 51.

    et al. DNA rendering of polyhedral meshes at the nanoscale. Nature 523, 441–444 (2015).

  52. 52.

    et al. Complex wireframe DNA origami nanostructures with multi-arm junction vertices. Nat. Nanotechnol. 10, 779–784 (2015).

  53. 53.

    , , & Three-dimensional structures self-assembled from DNA bricks. Science 338, 1177–1183 (2012).

  54. 54.

    , , , & Approaching the limit: can one DNA oligonucleotide assemble into large nanostructures? Angew. Chem. Int. Ed. 45, 1942–1945 (2006).

  55. 55.

    et al. Design and characterization of programmable DNA nanotubes. J. Am. Chem. Soc. 126, 16344–16352 (2004).

  56. 56.

    , , , & Self-assembly of chiral DNA nanotubes. J. Am. Chem. Soc. 126, 16342–16343 (2004).

  57. 57.

    et al. Functional DNA nanotube arrays: bottom-up meets top-down. Angew. Chem. Int. Ed. 46, 6089–6092 (2007).

  58. 58.

    et al. Six-helix bundles designed from DNA. Nano Lett. 5, 661–665 (2005).

  59. 59.

    , & DNA-nanotube-induced alignment of membrane proteins for NMR structure determination. Proc. Natl Acad. Sci. USA 104, 6644–6648 (2007).

  60. 60.

    et al. Programming DNA tube circumferences. Science 321, 824–826 (2008).

  61. 61.

    , & Modular construction of DNA nanotubes of tunable geometry, alternating size, and single- or double-stranded character. J. Biomol. Struct. Dyn. 26, 801 (2009).

  62. 62.

    , , & Covalently linked DNA nanotubes. Nano Lett. 10, 1458–1465 (2010).

  63. 63.

    , , & Crystal structure of a continuous three-dimensional DNA lattice. Chem. Biol. 11, 1119–1126 (2004).

  64. 64.

    et al. From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal. Nature 461, 74–77 (2009).

  65. 65.

    et al. Post-assembly stabilization of rationally designed DNA crystals. Angew. Chem. Int. Ed. 54, 9936–9939 (2015).

  66. 66.

    , , , & Impact of heterogeneity and lattice bond strength on DNA triangle crystal growth. ACS Nano 10, 9156–9164 (2016).

  67. 67.

    et al. Construction and structure determination of a three-dimensional DNA crystal. J. Am. Chem. Soc. 138, 10047–10054 (2016).

  68. 68.

    , , & Crystallization of amphiphilic DNA C-stars. Nano Lett. 17, 3276–3281 (2017).

  69. 69.

    , , , & A DNA-fuelled molecular machine made of DNA. Nature 406, 605–608 (2000).

  70. 70.

    , , & A robust DNA mechanical device controlled by hybridization topology. Nature 415, 62–65 (2002).

  71. 71.

    , , & A two-state DNA lattice switched by DNA nanoactuator. Angew. Chem. Int. Ed. 42, 4342–4346 (2003).

  72. 72.

    & Triggered amplification by hybridization chain reaction. Proc. Natl Acad. Sci. USA 101, 15275–15278 (2004).

  73. 73.

    , , & Programming biomolecular self-assembly pathways. Nature 451, 318–322 (2008).

  74. 74.

    & A precisely controlled DNA bipedal walking device. Nano Lett. 4, 1203–1207 (2004).

  75. 75.

    , & A bipedal DNA Brownian motor with coordinated legs. Science 324, 67–71 (2009).

  76. 76.

    & Molecular gears: a pair of DNA circles continuously rolls against each other. J. Am. Chem. Soc. 126, 11410–11411 (2004).

  77. 77.

    et al. Molecular robots guided by prescriptive landscapes. Nature 465, 206–210 (2010).

  78. 78.

    , , & A proximity-based programmable DNA nanoscale assembly line. Nature 465, 202–205 (2010).

  79. 79.

    & Translation of DNA signals into polymer assembly instructions. Science 306, 2072–2074 (2004).

  80. 80.

    & Autonomous multistep organic synthesis in a single isothermal solution mediated by a DNA walker. Nat. Nanotechnol. 5, 778–782 (2010).

  81. 81.

    et al. A signal-passing DNA-strand-exchange mechanism for active self-assembly of DNA nanostructures. Angew. Chem. Int. Ed. 54, 5939–5942 (2015).

  82. 82.

    , , & Dynamic patterning programmed by DNA tiles captured on a DNA origami substrate. Nat. Nanotechnol. 4, 245–248 (2009).

  83. 83.

    , , , & A bipedal DNA motor that travels back and forth between two DNA origami tiles. Small 11, 568–575 (2015).

  84. 84.

    et al. Reconfigurable, braced, three-dimensional DNA nanostructures. Nat. Nanotechnol. 3, 93–96 (2008).

  85. 85.

    , & Templated synthesis of DNA nanotubes with controlled, predetermined lengths. J. Am. Chem. Soc. 132, 10212–10214 (2010).

  86. 86.

    , , , & Structural transformation: assembly of an otherwise inaccessible DNA nanocage. Angew. Chem. Int. Ed. 54, 5990–5993 (2015).

  87. 87.

    , , & Folding and cutting DNA into reconfigurable topological nanostructures. Nat. Nanotechnol. 5, 712–717 (2010).

  88. 88.

    , , & Photo-controllable DNA origami nanostructures assembling into predesigned multiorientational patterns. J. Am. Chem. Soc. 134, 20645–20653 (2012).

  89. 89.

    et al. Synthesis of azobenzene-tethered DNA for reversible photo-regulation of DNA functions: hybridization and transcription. Nat. Protoc. 2, 203–212 (2007).

  90. 90.

    , , , & Switching binary states of nanoparticle superlattices and dimer clusters by DNA strands. Nat. Nanotechnol. 5, 116–120 (2010).

  91. 91.

    & Assembly of novel DNA cycles with rigid tetrahedral linkers. Angew. Chem. Int. Ed.Engl. 36, 111–113 (1997).

  92. 92.

    & Sequential self-assembly of a DNA hexagon as a template for the organization of gold nanoparticles. Angew. Chem. Int. Ed. 118, 2262–2267 (2006).

  93. 93.

    , , & Enhancing the melting properties of small molecule-DNA hybrids through designed hydrophobic interactions: an experimental-computational study. J. Am. Chem. Soc. 134, 7450–7458 (2012).

  94. 94.

    , & The role of organic linkers in directing DNA self-assembly and significantly stabilizing DNA duplexes. J. Am. Chem. Soc. 134, 14382–14389 (2012).

  95. 95.

    , , , & Facile one-step solid-phase synthesis of multitopic organic–DNA hybrids via “click” chemistry. Chem. Sci. 5, 1091–1096 (2014).

  96. 96.

    & A DNA pentaplex incorporating nucleobase quintets. Proc. Natl Acad. Sci. USA 96, 10614–10619 (1999).

  97. 97.

    et al. Reprogramming the assembly of unmodified DNA with a small molecule. Nat. Chem. 8, 368–376 (2016).

  98. 98.

    et al. Transcription, reverse transcription, and analysis of RNA containing artificial genetic components. ACS Synth. Biol. 4, 407–413(2015).

  99. 99.

    & Artificial genetic sets composed of size-expanded base pairs. Angew. Chem. Int. Ed. 52, 12498–12508 (2013).

  100. 100.

    & The expanded genetic alphabet. Angew. Chem. Int. Ed. 54, 11930–11944 (2015).

  101. 101.

    et al. A semi-synthetic organism with an expanded genetic alphabet. Nature 509, 385–388 (2014).

  102. 102.

    et al. A semisynthetic organism engineered for the stable expansion of the genetic alphabet. Proc. Natl Acad. Sci. USA 114, 1317–1322 (2017).

  103. 103.

    , , & Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 254, 1497–1500 (1991).

  104. 104.

    Synthesis of 3′-C- and 4′-C-branched oligodeoxynucleotides and the development of locked nucleic acid (LNA). Acc. Chem. Res. 32, 301–310 (1999).

  105. 105.

    , , , & Synthesis and properties of mirror-image DNA. Nucleic Acids Res. 20, 3325–3332 (1992).

  106. 106.

    et al. Hybrids of RNA and arabinonucleic acids (ANA and 2′F-ANA) are substrates of ribonuclease H. J. Am. Chem. Soc. 120, 12976–12977 (1998).

  107. 107.

    & Designing chemically modified oligonucleotides for targeted gene silencing. Chem. Biol. 19, 937–954 (2012).

  108. 108.

    , , , & Solid-phase synthesis of transition metal linked, branched oligonucleotides. Angew. Chem. Int. Ed. 40, 4629–4632 (2001).

  109. 109.

    , & Self-assembly of cyclic metal-DNA nanostuctures using ruthenium tris(bipyridine)-branched oligonucleotides. Angew. Chem. Int. Ed. 43, 5804–5808 (2004).

  110. 110.

    , & Supramolecular DNA assembly. Chem. Soc. Rev. 40, 5647–5656 (2011).

  111. 111.

    , , & Templated ligand environments for the selective incorporation of different metals into DNA. Angew. Chem. Int. Ed. 48, 9919–9923 (2009).

  112. 112.

    & Templated synthesis of highly stable, electroactive, and dynamic metal–DNA branched junctions. Angew. Chem. Int. Ed. 47, 2443–2446 (2008).

  113. 113.

    et al. Chiral metal–DNA four-arm junctions and metalated nanotubular structures. Angew. Chem. Int. Ed. 50, 4620–4623 (2011).

  114. 114.

    , , , & Reversible bond formation enables the replication and amplification of a crosslinking salen complex as an orthogonal base pair. Nat. Chem. 3, 794–800 (2011).

  115. 115.

    , , , & Modular DNA-programmed assembly of linear and branched conjugated nanostructures. J. Am. Chem. Soc. 126, 1044–1046 (2004).

  116. 116.

    , , , & A discrete self-assembled metal array in artificial DNA. Science 299, 1212–1213 (2003).

  117. 117.

    , , , & A novel copper-mediated DNA base pair. J. Am. Chem. Soc. 122, 10714–10715 (2000).

  118. 118.

    , & DNA–metal base pairs. Angew. Chem. Int. Ed. 46, 6226–6236 (2007).

  119. 119.

    et al. Direct conductance measurement of individual metallo-DNA duplexes within single-molecule break junctions. Angew. Chem. Int. Ed. 50, 8886–8890 (2011).

  120. 120.

    et al. Programmable self-assembly of metal ions inside artificial DNA duplexes. Nat. Nanotechnol. 1, 190–194 (2006).

  121. 121.

    , & DNA tube structures controlled by a four-way-branched DNA connector. Angew. Chem. Int. Ed. 44, 6074–6077 (2005).

  122. 122.

    , , & Four-way-branched DNA-porphyrin conjugates for construction of four double-helix-DNA assembled structures. J. Org. Chem. 70, 7468–7472 (2005).

  123. 123.

    & Self-assembly of block copolymers. Chem. Soc. Rev. 41, 5969–5985 (2012).

  124. 124.

    , , & Programmable shape-shifting micelles. Angew. Chem. Int. Ed. 49, 5076–5080 (2010).

  125. 125.

    , , , & Engineering the structural properties of DNA block copolymer micelles by molecular recognition. Angew. Chem. Int. Ed. 46, 1172–1175 (2007).

  126. 126.

    , , & An efficient and modular route to sequence-defined polymers appended to DNA. Angew. Chem. Int. Ed. 53, 4567–4571 (2014).

  127. 127.

    , , , & Precision polymers and 3D DNA nanostructures: emergent assemblies from new parameter space. J. Am. Chem. Soc. 136, 15767–15774 (2014).

  128. 128.

    , , & Synergy of two assembly languages in DNA nanostructures: self-assembly of sequence-defined polymers on DNA cages. J. Am. Chem. Soc. 138, 4416–4425 (2016).

  129. 129.

    , , , & Site-specific positioning of dendritic alkyl chains on DNA cages enables their geometry-dependent self-assembly. Nat. Chem. 5, 868–875 (2013).

  130. 130.

    , & Hydrophobic actuation of a DNA origami bilayer structure. Angew. Chem. Int. Ed. 53, 4236–4239 (2014).

  131. 131.

    et al. Dynamic behavior of DNA cages anchored on spherically supported lipid bilayers. J. Am. Chem. Soc. 136, 12987–12997 (2014).

  132. 132.

    , & Lipid-bilayer-assisted two-dimensional self-assembly of DNA origami nanostructures. Nat. Commun. 6, 8052 (2015).

  133. 133.

    , , & Dynamic assembly/disassembly processes of photoresponsive DNA origami nanostructures directly visualized on a lipid membrane surface. J. Am. Chem. Soc. 136, 1714–1717 (2014).

  134. 134.

    et al. Synthetic lipid membrane channels formed by designed DNA nanostructures. Science 338, 932–936 (2012).

  135. 135.

    & Nanopores formed by DNA origami: a review. FEBS Lett. 588, 3564–3570 (2014).

  136. 136.

    , , & Membrane-spanning DNA nanopores with cytotoxic effect. Angew. Chem. Int. Ed. 53, 12466–12470 (2014).

  137. 137.

    et al. Self-assembly of size-controlled liposomes on DNA nanotemplates. Nat. Chem. 8, 476–483 (2016).

  138. 138.

    et al. Routing of individual polymers in designed patterns. Nat. Nanotechnol. 10, 892–898 (2015).

  139. 139.

    & Applications of colloidal inorganic nanoparticles: from medicine to energy. J. Am. Chem. Soc. 134, 15607–15620 (2012).

  140. 140.

    , & Self-assembled plasmonic nanostructures. Chem. Soc. Rev. 43, 3976–3991 (2014).

  141. 141.

    et al. Organization of ‘nanocrystal molecules’ using DNA. Nature 382, 609–611 (1996).

  142. 142.

    , , & A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382, 607–609 (1996).

  143. 143.

    et al. Two-dimensional nanoparticle arrays show the organizational power of robust DNA motifs. Nano Lett. 6, 1502–1504 (2006).

  144. 144.

    & Dynamic DNA templates for discrete gold nanoparticle assemblies: control of geometry, modularity, write/erase and structural switching. J. Am. Chem. Soc. 129, 4130–4131 (2007).

  145. 145.

    , & Pyramidal and chiral groupings of gold nanocrystals assembled using DNA scaffolds. J. Am. Chem. Soc. 131, 8455–8459 (2009).

  146. 146.

    et al. Control of self-assembly of DNA tubules through integration of gold nanoparticles. Science 323, 112–116 (2009).

  147. 147.

    et al. DNA-based self-assembly of chiral plasmonic nanostructures with tailored optical response. Nature 483, 311–314 (2012).

  148. 148.

    et al. Chiral inorganic nanostructures. Chem. Rev. 117, 8041–8093 (2017).

  149. 149.

    et al. Fluorescence enhancement at docking sites of DNA-directed self-assembled nanoantennas. Science 338, 506–510 (2012).

  150. 150.

    et al. Hierarchical assembly of plasmonic nanostructures using virus capsid scaffolds on DNA origami templates. ACS Nano 8, 7896–7904 (2014).

  151. 151.

    , , , & Transfer of molecular recognition information from DNA nanostructures to gold nanoparticles. Nat. Chem. 8, 162–170 (2016).

  152. 152.

    , , & Shape-controlled synthesis of gold nanostructures using DNA origami molds. Nano Lett. 14, 6693–6698 (2014).

  153. 153.

    et al. Casting inorganic structures with DNA molds. Science 346, 1258361 (2014).

  154. 154.

    , , & DNA-guided crystallization of colloidal nanoparticles. Nature 451, 549–552 (2008).

  155. 155.

    et al. DNA-programmable nanoparticle crystallization. Nature 451, 553–556 (2008).

  156. 156.

    et al. Diamond family of nanoparticle superlattices. Science 351, 582–586 (2016).

  157. 157.

    et al. Amyloid fibrils nucleated and organized by DNA origami constructions. Nat. Nanotechnol. 9, 537–541 (2014).

  158. 158.

    et al. DNA-templated protein arrays for single-molecule imaging. Nano Lett. 11, 657–660 (2011).

  159. 159.

    , & Single-molecule protein encapsulation in a rigid DNA cage. Angew. Chem. Int. Ed. 45, 7414–7417 (2006).

  160. 160.

    , , , & Controlled co-reconstitution of multiple membrane proteins in lipid bilayer nanodiscs using DNA as a scaffold. ACS Chem. Biol. 10, 2448–2454 (2015).

  161. 161.

    , , & Oligonucleotide-directed self-assembly of proteins: semisynthetic DNA–streptavidin hybrid molecules as connectors for the generation of macroscopic arrays and the construction of supramolecular bioconjugates. Nucleic Acids Res. 22, 5530–5539 (1994).

  162. 162.

    et al. Enzyme cascades activated on topologically programmed DNA scaffolds. Nat. Nanotechnol. 4, 249–254 (2009).

  163. 163.

    et al. Assembly of multienzyme complexes on DNA nanostructures. Nat. Protoc. 11, 2243–2273 (2016).

  164. 164.

    et al. Multi-enzyme complexes on DNA scaffolds capable of substrate channelling with an artificial swinging arm. Nat. Nanotechnol. 9, 531–536 (2014).

  165. 165.

    et al. Tug-of-war in motor protein ensembles revealed with a programmable DNA origami scaffold. Science 338, 662–665 (2012).

  166. 166.

    et al. A DNA-directed light-harvesting/reaction center system. J. Am. Chem. Soc. 136, 16618–16625 (2014).

  167. 167.

    et al. Multivalent protein binding and precipitation by self-assembling molecules on a DNA pentaplex scaffold. J. Am. Chem. Soc. 131, 5020–5021 (2009).

  168. 168.

    , , , & Self-assembled DNA nanostructures for distance-dependent multivalent ligand–protein binding. Nat. Nanotechnol. 3, 418–422 (2008).

  169. 169.

    & Self-assembly of genetically encoded DNA-protein hybrid nanoscale shapes. Science 355, eaam5488 (2017).

  170. 170.

    et al. Multiplexed 3D cellular super-resolution imaging with DNA-PAINT and Exchange-PAINT. Nat. Methods 11, 313–318 (2014).

  171. 171.

    et al. Submicrometre geometrically encoded fluorescent barcodes self-assembled from DNA. Nat. Chem. 4, 832–839 (2012).

  172. 172.

    et al. DNA origami based visualization system for studying site-specific recombination events. J. Am. Chem. Soc. 136, 211–218 (2014).

  173. 173.

    et al. Single-molecule manipulation of the duplex formation and dissociation at the G-quadruplex/i-motif site in the DNA nanostructure. ACS Nano 9, 9922–9929 (2015).

  174. 174.

    , , , & Two DNA nanomachines map pH changes along intersecting endocytic pathways inside the same cell. Nat. Nanotechnol. 8, 459–467 (2013).

  175. 175.

    , & Emerging frontiers in drug delivery. J. Am. Chem. Soc. 138, 704–717 (2016).

  176. 176.

    , , & Shape control in engineering of polymeric nanoparticles for therapeutic delivery. Biomater. Sci. 3, 894–907 (2015).

  177. 177.

    , , , & DNA cage delivery to mammalian cells. ACS Nano 5, 5427–5432 (2011).

  178. 178.

    , , , & Rolling circle amplification-templated DNA nanotubes show increased stability and cell penetration ability. J. Am. Chem. Soc. 134, 2888–2891 (2012).

  179. 179.

    et al. Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Sci. Transl Med. 5, 209ra152 (2013).

  180. 180.

    et al. Single-particle tracking and modulation of cell entry pathways of a tetrahedral DNA nanostructure in live cells. Angew. Chem. Int. Ed. 53, 7745–7750 (2014).

  181. 181.

    et al. Receptor-mediated entry of pristine octahedral DNA nanocages in mammalian cells. ACS Nano 10, 5971–5979 (2016).

  182. 182.

    , , , & Development and characterization of gene silencing DNA cages. Biomacromolecules 15, 276–282 (2014).

  183. 183.

    et al. Antisense precision polymer micelles require less poly(ethylenimine) for efficient gene knockdown. Nanoscale 7, 20625–20634 (2015).

  184. 184.

    , , & DNA nanostructure serum stability: greater than the sum of its parts. Chem. Commun. (Camb) 49, 1172–1174 (2013).

  185. 185.

    et al. Stability of DNA origami nanoarrays in cell lysate. Nano Lett. 11, 1477–1482 (2011).

  186. 186.

    , , & Addressing the instability of DNA nanostructures in tissue culture. ACS Nano 8, 8765–8775 (2014).

  187. 187.

    & Magnesium-free self-assembly of multi-layer DNA objects. Nat. Commun. 3, 1103 (2012).

  188. 188.

    et al. Oligolysine-based coating protects DNA nanostructures from low-salt denaturation and nuclease degradation. Nat. Commun. 8, 15654 (2017).

  189. 189.

    et al. DNA origami as a carrier for circumvention of drug resistance. J. Am. Chem. Soc. 134, 13396–13403 (2012).

  190. 190.

    et al. DNA origami delivery system for cancer therapy with tunable release properties. ACS Nano 6, 8684–8691 (2012).

  191. 191.

    , & Delivering cargoes into cancer cells using DNA aptamers targeting internalized surface portals. Biochim. Biophys. Acta 1798, 2190–2200 (2010).

  192. 192.

    et al. Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat. Nanotechnol. 7, 389–393 (2012).

  193. 193.

    , & A logic-gated nanorobot for targeted transport of molecular payloads. Science 335, 831–834 (2012).

  194. 194.

    et al. Sequence-responsive unzipping DNA cubes with tunable cellular uptake profiles. Chem. Sci. 5, 2449–2455 (2014).

  195. 195.

    , & Optimized DNA “nanosuitcases” for encapsulation and conditional release of siRNA. J. Am. Chem. Soc. 138, 14030–14038 (2016).

  196. 196.

    , , , & Development of DNA nanostructures for high-affinity binding to human serum albumin. J. Am. Chem. Soc. 139, 7355–7362 (2017).

  197. 197.

    Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J. Control. Release 132, 171–183 (2008).

  198. 198.

    & 25th Anniversary article: supramolecular materials for regenerative medicine. Adv. Mater. 26, 1642–1659 (2014).

  199. 199.

    , , & A structurally tunable DNA-based extracellular matrix. J. Am. Chem. Soc. 132, 14727–14729 (2010).

  200. 200.

    et al. Bioactive DNA-peptide nanotubes enhance the differentiation of neural stem cells into neurons. Nano Lett. 15, 603–609 (2014).

  201. 201.

    , , , & Design and characterization of 1D nanotubes and 2D periodic arrays self-assembled from DNA multi-helix bundles. J. Am. Chem. Soc. 134, 1606–1616 (2012).

  202. 202.

    , & Plasmonic nanomaterials for biodiagnostics. Chem. Soc. Rev, 43, 3835–3853 (2014).

  203. 203.

    , & Probing molecular cell event dynamics at the single-cell level with targeted plasmonic gold nanoparticles: a review. Nano Today 10, 542–558 (2015).

  204. 204.

    et al. Sub-100 nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large and highly aggressive triple negative breast tumors. J. Control. Release 191, 90–97 (2014).

  205. 205.

    et al. Template-directed covalent conjugation of DNA to native antibodies, transferrin and other metal-binding proteins. Nat. Chem. 6, 804–809 (2014).

  206. 206.

    et al. Low temperature assembly of functional 3D DNA-PNA-protein complexes. J. Am. Chem. Soc. 136, 8283–8295 (2014).

  207. 207.

    , & Site-selective conjugation of native proteins with DNA. Acc. Chem. Res. 50, 1367–1374 (2017).

  208. 208.

    Structural DNA Nanotechnology (Cambridge Univ. Press, 2016).

  209. 209.

    , , , & Enzymatic production of ‘monoclonal stoichiometric’ single-stranded DNA oligonucleotides. Nat. Methods 10, 647–652 (2013).

  210. 210.

    & Nonenzymatic template-directed RNA synthesis inside model protocells. Science 342, 1098–1100 (2013).

  211. 211.

    Molecular computation of solutions to combinatorial problems. Science 266, 1021–1024 (1994).

  212. 212.

    , & Assembly of Borromean rings from DNA. Nature 386, 137–138 (1997).

  213. 213.

    , , & Logical computation using algorithmic self-assembly of DNA triple crossover molecules. Nature 407, 493–496 (2000).

  214. 214.

    et al. Self-replication of information-bearing nanoscale patterns. Nature 478, 225–228 (2011).

  215. 215.

    Three-helix bundle DNA tiles self-assemble into 2D lattice or 1D templates for silver nanowires. Nano Lett. 5, 693–696 (2005).

  216. 216.

    et al. A device that operates within a self-assembled 3D DNA crystal. Nat. Chem. 9, 824–827 (2017).

  217. 217.

    Biochemistry and structural DNA nanotechnology: an evolving symbiotic relationship. Biochemistry 42, 7259–7269 (2003).

  218. 218.

    Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 310, 1661–1665 (2005).

  219. 219.

    et al. A DNA crystal designed to contain two molecules per asymmetric unit. J. Am. Chem. Soc. 132, 15471–15473 (2010).

  220. 220.

    & Dynamic DNA nanotechnology using strand-displacement reactions Nat. Chem. 3, 103–113 (2011).

  221. 221.

    et al. Loading and selective release of cargo in DNA nanotubes with longitudinal variation. Nat. Chem. 2, 319–328 (2010).

  222. 222.

    & DNA modified with metal complexes: applications in the construction of higher-order metal–DNA nanostructures. Coord. Chem. Rev. 254, 2403–2415 (2010).

  223. 223.

    & The design and synthesis of a knot from single-stranded DNA. J. Am. Chem. Soc. 113, 6306–6308 (1991).

  224. 224.

    , & Stimuli-responsive DNA-based hydrogels: from basic principles to applications. Acc. Chem. Res. 50, 680–690 (2017).

Download references

Acknowledgements

This research has been supported by the following grants to H.F.S.: Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Research Chairs Program, the Canadian Institutes of Health Research (CIHR), Fonds de recherche du Québec — Nature et technologies (FRQNT) and Prostate Cancer Canada. The following grants were provided to N.C.S.: EFRI-1332411 and CCF-1526650 from the National Science Foundation (NSF), MURI W911NF-11-1-0024 from the US Army Research Office (ARO), N000141110729 from the US Office of Naval Research (ONR), DE-SC0007991 from the US Department of Energy (DOE) for DNA synthesis, and partial salary support and grant GBMF3849 from the Gordon and Betty Moore Foundation. The authors thank P. Chidchob, A. Lacroix, N. Avakyan, J. Hsu, D. Bousmail, T. Trinh, D. de Rochambeau, H. Fakih, E. Vengut Climent and M. Dore for help proofreading the manuscript.

Author information

Affiliations

  1. Department of Chemistry, New York University, 100 Washington Square East, New York 10003, USA

    • Nadrian C. Seeman
  2. Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montréal, Québec H3A0B8, Canada.

    • Hanadi F. Sleiman

Authors

  1. Search for Nadrian C. Seeman in:

  2. Search for Hanadi F. Sleiman in:

Contributions

H.F.S. researched the data for the article. H.F.S. and N.C.S. wrote the article and edited it before submission.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Nadrian C. Seeman or Hanadi F. Sleiman.