Abstract
The use of DNA as a building material for designing nanoscale objects is one of the exciting fields of nanotechnology. DNA origami, specifically, has only recently emerged as an extension of smaller folded DNA units since the appearance of immobile junctions and the assortment of structures that followed. DNA origami is the folding of a long single strand of DNA with many short complimentary oligonucleotides that act as “staples,” in which hybridization of duplex DNA through Watson–Crick base pairing drives assembly without the use of restriction enzymes or DNA ligase to construct the final two- or three-dimensional form (Rothemund 2006). This technique is valuable primarily due to the multi-nanometer to sub-micrometer scale of the structures produced and their finite nature, which offers greater control over self-assembly within a system in comparison to previously synthesized array structures that had the capacity to extend indefinitely (Mao et al. 1999a). The increasing complexity of structures produced parallels the technological advances in other areas as the availability of computing power and decreasing cost of creating synthetic oligonucleotides gave way to the first true DNA origami structures in 2006 (Rothemund 2006).
Arriving at multidimensional, precise origami assemblies provides a platform for spatial organization of other functional materials. Overhangs of oligonucleotides within the structure can be used as a specific address for heteroelements such as other DNA molecules (Rothemund 2006), RNA (Ke et al. 2008; Zhang et al. 2010; Subramanian et al. 2011; Rinker et al. 2008), proteins (Voigt et al. 2010; Shen et al. 2009), carbon nanotubes (Maune et al. 2010), metallic nanoparticles (Zheng et al. 2012; Ding et al. 2010a, b; Hung et al. 2009; Sharma et al. 2008; Pal et al. 2009), and quantum dots (Stearns et al. 2009; Bui et al. 2010; Tikhomirov et al. 2011) with nanometer precision. The defined and highly stable structure of DNA as a scaffold has great potential for enabling self-assembly of increasingly intricate systems, with applications that can be extended into almost any field of biochemistry, chemistry, or biophysics. In this chapter we will discuss the principles of designing DNA origami structures, the methods by which nanoscale assembly has been developed with increasing complexity, tools for creating and analyzing DNA structures, and examples of the functional applications of DNA origami.
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References
Andersen ES, Dong MD, Nielsen MM, Jahn K, Lind-Thomsen A, Mamdouh W, Gothelf KV, Besenbacher F, Kjems J (2008) DNA origami design of dolphin-shaped structures with flexible tails. ACS Nano 2:1213–1218
Andersen ES, Dong M, Nielsen MM et al (2009) Self-assembly of a nanoscale DNA box with a controllable lid. Nature 459:73–75
Anker JN et al (2008) Biosensing with plasmonic nanosensors. Nat Mater 7:442–453
Batey RT, Rambo RP, Doudna JA (1999) Tertiary motifs in RNA structure and folding. Angew Chem Int Ed Engl 38:2326–2343
Bui H, Onodera C, Kidwell C, Tan Y, Graugnard E, Kuang W, Lee J, Knowlton WB, Yurke B, Hughes WL (2010) Programmable periodicity of quantum dot arrays with DNA origami nanotubes. Nano Lett 10:3367–3372
Castro CE, Kilchherr F, Kim DN, Enrique LS, Wauer T, Wortmann P, Bathe M, Dietz H (2011) A primer to scaffolded DNA origami. Nat Methods 8(3):221–229
Chworos A, Severcan I, Koyfman AY, Weinkam P, Oroudjev E, Hansma HG, Jaeger L (2004) Building programmable jigsaw puzzles with RNA. Science 306:2068–2072
Cohen JD, Sadowski JP, Dervan PB (2007) Programming multiple protein patterns on a single DNA nanostructure. J Am Chem Soc 130:402–403
Delebecque CJ, Linder AB, Silber PA, Aldaye FA (2011) Organization of intracellular reactions with rationally designed RNA assemblies. Science 333:470–474
Dietz H, Douglas SM, Shih WM (2009) Folding DNA into twisted and curved nanoscale shapes. Science 325:725–729
Ding B, Deng Z, Yan H, Cabrini S, Zuckermann RN, Bokor J (2010a) Gold nanoparticle self-similar chain structure organized by DNA origami. J Am Chem Soc 132:3248–3249
Ding B, Wu H, Zhao Z, Liu Y, Yu H, Yan H (2010b) Interconnecting gold islands with DNA origami nanotubes. Nano Lett 10:5065–5069
Douglas SM, Chou JJ, Shih WM (2007) DNA-nanotube-induced alignment of membrane proteins for NMR structure determination. Proc Natl Acad Sci USA 104(16):6644–6648
Douglas SM, Dietz H, Liedl T, Hoegberg B, Graf F, Shih WM (2009a) Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459(7245):414–418
Douglas SM, Marblestone AH, Teerapittayanon S, Vazquez A, Church GM, Shih WM (2009b) Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic Acids Res 37(15):5001–5006
Du SM, Zhang SW, Seeman NC (1992) Dna junctions, antijunctions, and mesojunctions. Biochemistry 31(45):10955–10963
Endo M, Hidaka K, Kato T, Namba K, Sugiyama H (2009) DNA prism structures constructed by folding of multiple rectangular arms. J Am Chem Soc 131(43):15570–15571
Endo M, Sugita T, Katsuda Y, Hidaka K, Sugiyama H (2010) Programmed-assembly system using DNA jigsaw pieces. Chem Eur J 16:5362–5368
Fu T, Seeman NC (1993) DNA double-crossover molecules. Biochemistry 32(13):3211–3220
Fu J, Liu M, Liu Y, Woodbury NM, Yan H (2012a) Interenzyme substrate diffusion for an enzyme cascade organized on spatially addressable DNA nanostructures. J Am Chem Soc 134:5516–5519
Fu J, Liu M, Liu Y, Yan H (2012b) Spatially-interactive biomolecular networks organized by nucleic acid nanostructures. Acc Chem Res 8:1215–1226
Gu H, Chao J, Xiao SJ, Seeman NC (2010) A proximity-based programmable DNA nanoscale assembly line. Nature 465:202–205
Guo P (2010) The emerging field of RNA technology. Nat Nanotechnol 5:833–842
Han DR, Pal S, Liu Y, Yan H (2010) Folding and cutting DNA into reconfigurable topological nanostructures. Nat Nanotechnol 5:712–717
Han D, Pal S, Nangreave J, Deng Z, Liu Y, Yan H (2011) DNA origami with complex curvatures in three-dimensional space. Science 332:342–346
Högberg B, Leidl T, Shih WM (2009) Folding DNA origami from a double-stranded source of scaffold. J Am Chem Soc 131:9154–9155
Hung AM, Micheel CM, Bozano LD, Osterbur LW, Wallraff GM, Cha JN (2009) Large-area spatially ordered arrays of gold nanoparticles directed by lithographically confined DNA origami. Nat Nanotechnol 5:121–126
Jaeger L (2009) Defining the syntax for self-assembling RNA tertiary architecture. Nucleic Acids Symp Ser 53:83–84
Jahn K, Tørring T, Voigt NV, Sørensen RS, Kodal ALB, Andersen ES, Gothelf KV, Kjems J (2011) Functional patterning of DNA origami by parallel enzymatic modification. Bioconjug Chem 22:819–823
Jungmann R, Steinhauer C, Scheible M, Kuzyk A, Tinnefeld P, Simmel FC (2010) Single-molecule kinetics and super-resolution microscopy by fluorescence imaging of transient binding on DNA origami. Nano Lett 10:4756–4761
Ke Y, Lindsay S, Chang Y, Liu Y, Yan H (2008) Self-assembled water-soluble nucleic acid probe tiles for label-free RNA hybridization assays. Science 319:180–183
Ke Y, Sharma J, Liu M, Jahn K, Liu Y, Yan H (2009a) Scaffolded DNA origami of a DNA tetrahedron molecular container. Nano Lett 9(6):2445–2447
Ke Y, Douglas SM, Liu M et al (2009b) Multilayer DNA origami packed on a square lattice. J Am Chem Soc 131(43):15903–15908
Ke Y, Ong LL, Shih WM, Yin P (2012) Three-dimensional structures self-assembled from DNA bricks. Science 338:1177–1183
Kim D, Kilchherr F, Dietz H, Bathe M (2012) Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures. Nucleic Acids Res 40(7):2862–2868
Ko SH, Su M, Zhang C, Ribbe AE, Jiang W, Mao C (2010) Synergistic self-assembly of RNA and DNA molecules. Nat Chem 2:1050–1055
Kosuri S (2010) Scalable gene synthesis by selective amplification of DNA pools from high-fidelity microchips. Nat Nanotechnol 28:1295–1299
Kuzuya A, Komiyama M (2009) Design and construction of a box-shaped 3D-DNA origami. Chem Commun 28:4182–4184
Kuzuya A, Kimura M, Numajiri K, Koshi N, Ohnishi T, Okada F, Komiyama M (2009) Precisely programmed and robust 2D streptavidin nanoarrays by using periodical nanometer-scale wells embedded in DNA origami assembly. Chembiochem 10:1811–1815
Kuzyk A, Laitinen KT, Torma P (2009) DNA origami as a nanoscale template for protein assembly. Nanotechnology 20:235305
Li Z, Liu M, Wang L, Nangreave J, Yan H, Liu Y (2010) Molecular behavior of DNA origami in higher-order self-assembly. J Am Chem Soc 132(38):13545–13552
Li Z, Wang L, Yan H, Liu Y (2012) Effect of DNA hairpin loops on the twist of planar DNA origami tiles. Langmuir 28(4):1959–1965
Liedl T, Högberg B, Tytell J, Ingber DE, Shih WM (2010) Self-assembly of three-dimensional prestressed tensegrity structures from DNA. Nat Nanotechnol 5:520–524
Lin C, Rinker S, Wang X, Liu Y, Seeman NC, Yan H (2007) Rolling circle enzymatic replication of a complex multi-crossover DNA nanostructure. J Am Chem Soc 129:14475–14481
Lin C, Rinker S, Wang X, Liu Y, Seeman NC, Yan H (2008) In vivo cloning of artificial DNA nanostructures. Proc Natl Acad Sci USA 105:17626–17631
Liu J, Geng Y, Pound E, Gyawali S, Ashton JR, Hickey J, Woolley AT, Harb JH (2001) Metallization of branched DNA origami for nanoelectronic circuit fabrication. ACS Nano 5(3):2240–2247
Liu D, Wang M, Deng Z, Walulu R, Mao C (2004) Tensegrity: construction of rigid DNA triangles with flexible four-arm DNA junctions. J Am Chem Soc 126(8):2324–2325
Liu H, Tørring T, Dong M, Rosen CB, Besenbacher F, Gothelf KV (2010) DNA-templated covalent coupling of G4 PAMAM dendrimers. J Am Chem Soc 132:18054–18056
Liu W, Zhong H, Wang R, Seeman NC (2011) Crystalline two-dimensional DNA-origami arrays. Angew Chem Int Ed Engl 50:264–267
Lund K, Manzo AJ, Dabby N, Michelotti N, Johnson-Buck A, Nangreave J, Taylor S, Pei R, Stojanovic MN, Walter NG, Winfree E, Yan H (2010) Molecular robots guided by prescriptive landscapes. Nature 465:206–210
Maier SA et al (2003) Local detection of electromagnetic energy transport below the diffraction limit in metal nanoparticle plasmon waveguides. Nat Mater 2:229–232
Majumder U, Rangnekar A, Gothelf KV, Reif JH, LaBean TH (2011) Design and construction of a double-decker tile as a route to three-dimensional periodic assembly of DNA. J Am Chem Soc 133:3843–3845
Mao C, Sun W, Seeman NC (1999a) Designed two-dimensional DNA Holliday junction arrays visualized by atomic force microscopy. J Am Chem Soc 121(23):5437–5442
Mao C, Sun W, Shen Z, Seeman NC (1999b) A nanomechanical device based on the B-Z transition of DNA. Nature 397:144–146
Maune HT, Han SP, Barish RD, Bockrath M, Goddard WA, Rothemund PWK, Winfree E (2010) Self-assembly of carbon nanotubes into two-dimensional geometries using DNA origami templates. Nat Nanotechnol 5:61–66
Mei Q, Wei X, Su F, Liu Y, Youngbull C, Johnson R, Lindsay S, Yan H, Meldrum D (2011) Stability of DNA origami nanoarrays in cell lysate. Nano Lett 11:1477–1482
Nakata E, Liew FF, Uwatoko C, Kiyonaka S, Mori Y, Katsuda Y, Endo M, Sugiyama H, Morii T (2012) Zinc-finger proteins for site-specific protein positioning on DNA-origami structures. Angew Chem Int Ed Engl 51:2421–2424
Numajiri K, Kimura M, Kuzuya A, Komiyama M (2010a) Stepwise and reversible nanopatterning of proteins on a DNA origami scaffold. Chem Commun 46:5127–5129
Numajiri K, Yamazaki T, Kimura M, Kuzuya A, Komiyama M (2010b) Discrete and active enzyme nanoarrays on DNA origami scaffolds purified by affinity tag separation. J Am Chem Soc 132:9937–9939
Ozbay E (2006) Plasmonics: merging photonics and electronics at nanoscale dimensions. Science 311:189–193
Pal S, Sharma J, Yan H, Liu Y (2009) Stable silver nanoparticle-DNA conjugates for directed self-assembly of core-satellite silver-gold nanoclusters. Chem Commun (Camb) (40):6059–6061
Pal S, Varghese R, Deng Z, Zhao Z, Kumar A, Yan H, Liu Y (2011) Site-specific synthesis and in situ immobilization of fluorescent silver nanoclusters on DNA nanoscaffolds by use of the Tollens reaction. Angew Chem Int Ed Engl 50:4176–4179
Pinheiro AV, Han D, Shih WM, Yan H (2011) Challenges and opportunities for structural DNA nanotechnology. Nat Nanotechnol 6(12):763–772
Pound E, Ashton JR, Becerril HA, Woolley AT (2009) Polymerase chain reaction based scaffold preparation for the production of thin, branched DNA origami nanostructures of arbitrary sizes. Nano Lett 9(12):4302–4305
Rinker S, Ke Y, Liu Y, Chhabra Y, Yan H (2008) Self-assembled DNA nanostructures for distance dependent multivalent ligand-protein binding. Nat Nanotechnol 3(7):418–422
Rothemund P (2006) Folding DNA, to create nanoscale shapes and patterns. Nature 440:297–302
Rothemund PWK, Papadakis N, Winfree E (2004) Algorithmic self-assembly of DNA sierpinski triangles. PLoS Biol 2(12):2041–2053
Saaem I, Kuo-Sheng M, Marchi AN, LaBean TH, Tian J (2010) In situ synthesis of DNA microarray on functionalized cyclic olefin copolymer substrate. ACS Appl Mater Interfaces 2:491–497
Sacca B, Meyer R, Erkelenz M, Kiko K, Arndt A, Schroeder H, Rabe KS, Niemeyer CM (2010) Orthogonal protein decoration of DNA origami. Angew Chem Int Ed Engl 49:9378–9383
Schuller JA et al (2010) Plasmonics for extreme light concentration and manipulation. Nat Mater 9:193–204
Severcan I, Geary C, Verzemnieks E, Chworos A, Jaeger L (2009) Square-shaped RNA particles from different RNA folds. Nano Lett 9(3):1270–1277
Sharma J, Chhabra R, Andersen CS, Gothelf KV, Yan H, Liu Y (2008) Toward reliable gold nanoparticle patterning on self-assembled DNA nanoscaffold. J Am Chem Soc 130:7820–7821
Sharonov A, Hochstrasser RM (2006) Wide-field subdiffraction imaging by accumulated binding of diffusing probes. Proc Natl Acad Sci USA 103:18911–18916
Shen W, Zhong H, Neff D, Norton ML (2009) NTA directed protein nanopatterning on DNA origami nanoconstructs. J Am Chem Soc 131:6660–6661
Shih W, Quispe J, Joyce G (2004) A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron. Nature 427(6975):618–621
Shipway AN, Katz E, Willner I (2000) Nanoparticle arrays on surfaces for electronic, optical, and sensor applications. Chemphyschem 1:18–52
Snelson K (1996) Snelson on the tensegrity invention. Int J Space Struct 11:43–48
Stearns LA, Chhabra R, Sharma J, Liu Y, Petuskey WT, Yan H, Chaput JC (2009) Template-directed nucleation and growth of inorganic nanoparticles on DNA scaffolds. Angew Chem Int Ed Engl 48:8494–8496
Stein IH, Schüller V, Böhm P, Tinnefeld P, Liedl T (2011a) Single-molecule FRET ruler based on rigid DNA origami blocks. Chemphyschem 12:689–695
Stein IH, Steinhauer C, Tinnefeld P (2011b) Single-molecule four-color FRET visualizes energy-transfer paths on DNA origami. J Am Chem Soc 133:4193–4195
Steinhauer C, Jungmann R, Sobey TL, Simmel FC, Tinnefeld P (2009) DNA origami as a nanoscopic ruler for super-resolution microscopy. Angew Chem Int Ed Engl 48:8870–8873
Stephanopoulos N, Liu MH, Tong GJ, Li Z, Liu Y, Yan H, Francis MB (2010) Immobilization and one-dimensional arrangement of virus capsids with nanoscale precision using DNA origami. Nano Lett 10:2714–2720
Subramani R, Juul S, Rotaru A, Andersen FF, Gothelf KV, Mamdouh W, Besenbacher F, Dong M, Knudsen BR (2010) A novel secondary DNA binding site in human topoisomerase I unravelled by using a 2D DNA origami platform. ACS Nano 4:5969–5977
Subramanian HKK, Chakraborty B, Sha R, Seeman NC (2011) The label-free unambiguous detection and symbolic display of single nucleotide polymorphisms on DNA origami. Nano Lett 11:910–913
Thomas T, Voigt NV, Nangreave J, Yan H, Gothelf KV (2011) DNA origami: a quantum leap for self-assembly of complex structures. Chem Soc Rev 40(12):5636–5646
Tian J, Ma K, Saaem I (2009) Advancing high-throughput assembly of nanoclusters. Mol Biosyst 5:714–722
Tikhomirov G, Hoogland S, Lee PE, Fischer A, Sargent EH, Kelley SO (2011) DNA-based programming of quantum dot valency, self-assembly and luminescence. Nat Nanotechnol 6:485–490
Voigt NV, Tørring T, Rotaru A, Jacobsen MF, Rabnsbæk JB, Subramani R, Mamdouh W, Kjems J, Mokhir A, Besenbacher F, Gothelf KV (2010) Single-molecule chemical reactions on DNA origami. Nat Nanotechnol 5:200–203
Wei B, Dai M, Yin P (2012) Complex shapes self-assembled from single-stranded DNA tiles. Nature 485:623–627
Westhof E, Masquida B, Jaeger L (1996) RNA tectonics: towards RNA design. Fold Des 1:R78–R88
Wickham SF, Endo M, Katsuda Y, Hidaka K, Bath J, Sugiyama H, Turberfield AJ (2011) Direct observation of stepwise movement of a synthetic molecular transporter. Nat Nanotechnol 6:166–169
Williams S, Lund K, Lin C, Wonka P, Lindsay S, Yan H (2009) Tiamat: a three-dimensional editing tool for complex DNA structures. Lect Notes Comp Sci 5347:90–101
Woo S, Rothemund PWK (2011) Programmable molecular recognition based on the geometry of DNA nanostructures. Nat Chem 3:620–627
Yan H, LaBean TH, Feng L, Reif JH (2003) Directed nucleation assembly of DNA tile complexes for barcode-patterned lattices. Proc Natl Acad Sci USA 100(14):1803–1808
Yang Y, Han D, Nangreave J, Liu Y, Yan H (2012) DNA origami with double-stranded DNA as a unified scaffold. ACS Nano 6(9):8209–8215
Yoshidome T, Endo M, Kashiwazaki G, Hidaka K, Bando T, Sugiyama H (2012) Sequence-selective single-molecule alkylation with a pyrrole-imidazole polyamide visualized in a DNA nanoscaffold. J Am Chem Soc 134:4654–4660
Zhang Z, Zeng D, Ma H, Feng G, Hu J, He L, Li C, Fan C (2010) A DNA-origami chip platform for label-free SNP genotyping using toehold-mediated strand displacement. Small 6(17):1854–1858
Zhang H, Chao J, Pan D, Liu H, Huang Q, Fan C (2012) Folding super-sized DNA origami with scaffold strands from long-range PCR. Chem Commun 48:6405–6407
Zhao Z, Yan H, Liu Y (2010) A route to scale up DNA origami using DNA tiles as folding staples. Angew Chem Int Ed Engl 49:1414–1417
Zheng Y, Li Y, Deng Z (2012) Silver nanoparticle-DNA bionanoconjugates bearing a discrete number of DNA ligands. Chem Commun 48:6160–6162
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Edwards, A., Yan, H. (2014). DNA Origami. In: Kjems, J., Ferapontova, E., Gothelf, K. (eds) Nucleic Acid Nanotechnology. Nucleic Acids and Molecular Biology, vol 29. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38815-6_5
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