Nucleic Acid Nanotechnology: Modified Backbones and Topological Polymer Templates

Part of the RNA Technologies book series (RNATECHN)


DNA-based nanotechnology has revolutionized the construction of nanoscale objects and devices—primarily by using Watson–Crick base-pairing to program the self-assembly (and reaction pathways) of DNA oligomers into branched structures. However, Watson–Crick-controlled self-assembly is not limited to the use of the “natural” d-(deoxy)ribose phosphodiester backbone.

This chapter describes nanoscale objects synthesized from oligomers containing sugars other than d-deoxyribose or linkages other than phosphodiester linkages. This chapter also focuses on using the backbone of DNA as a topological guide for polymer synthesis.

As these chemical modifications profoundly affect the bioavailability, nuclease resistance, protein binding, optoelectronic, and materials properties of nano-objects compared to their “natural” DNA counterparts, they may find great utility in biomedicine.


DNA Polynucleotides Templated syntheses Backbones Nylon Conducting polymers Nanotechnology DNA nanotechnology DNA-based nanotechnology Junctions l-DNA PNA LNA GNA Methylphosphonate 


  1. Barton JK, Olmon ED, Sontz PA (2011) Metal complexes for DNA-mediated charge transport. Coord Chem Rev 255:619–634PubMedCrossRefGoogle Scholar
  2. Beharry AA, Woolley GA (2011) Azobenzene photoswitches for biomolecules. Chem Soc Rev 40:4422–4437PubMedCrossRefGoogle Scholar
  3. Bhatia D, Surana S, Chakraborty S et al (2011) A synthetic icosahedral DNA-based host-cargo complex for functional in vivo imaging. Nat Commun 2:339PubMedCrossRefGoogle Scholar
  4. Brudno Y, Liu DR (2009) Recent progress toward the templated synthesis and directed evolution of sequence-defined synthetic polymers. Chem Biol 16:265–276PubMedCrossRefGoogle Scholar
  5. Caminade AM, Turrin CO, Majoral JP (2008) Dendrimers and DNA: combinations of two special topologies for nanomaterials and biology. Chemistry 14:7422–7432PubMedCrossRefGoogle Scholar
  6. Chen W, Schuster GB (2012) DNA-programmed modular assembly of cyclic and linear nanoarrays for the synthesis of two-dimensional conducting polymers. J Am Chem Soc 134:840–843PubMedCrossRefGoogle Scholar
  7. Chen W, Guler G, Kuruvilla E et al (2010) Development of self-organizing, self-directing molecular nanowires: synthesis and characterization of conjoined DNA-2,5-bis (2-thienyl)pyrrole oligomers. Macromolecules 43:4032–4404CrossRefGoogle Scholar
  8. Ciengshin T, Sha R, Seeman NC (2011) Automatic molecular weaving prototyped by using single-stranded DNA. Angew Chem Int Ed 50:4419–4422CrossRefGoogle Scholar
  9. Clever GH, Shionoya M (2010) Metal-base pairing in DNA. Coord Chem Rev 254:2391–2402CrossRefGoogle Scholar
  10. Corradini R, Sforza S, Tedeschi T et al (2011) Peptide nucleic acids with a structurally biased backbone. Updated review and emerging challenges. Curr Top Med Chem 11:1535–1554PubMedCrossRefGoogle Scholar
  11. Cronican JJ, Thompson DB, Beier KT et al (2010) Potent delivery of functional proteins into mammalian cells in vitro and in vivo using a supercharged protein. ACS Chem Biol 5:747–752PubMedCrossRefGoogle Scholar
  12. Datta B, Schuster GB (2008) DNA-directed synthesis of aniline and 4-aminobiphenyl, oligomers: programmed transfer of sequence information to a conjoined polymer nanowire. J Am Chem Soc 130:2965–2973PubMedCrossRefGoogle Scholar
  13. Datta B, Schuster GB, McCook A et al (2006) DNA-directed assembly of polyanilines: modified cytosine nucleotides transfer sequence programmability to a conjoined polymer. J Am Chem Soc 128:14428–14429PubMedCrossRefGoogle Scholar
  14. Dobrowolski JC (2003) DNA knots and links. Polimery 48:3–15Google Scholar
  15. Duckett DR, Murchie AIH, Diekmann S et al (1988) The structure of the holliday junction, and its resolution. Cell 55:79–89PubMedCrossRefGoogle Scholar
  16. El-Sagheer AH, Brown T (2010) Click chemistry with DNA. Chem Soc Rev 39:1388–1405PubMedCrossRefGoogle Scholar
  17. Eschenmoser A (2011) Etiology of potentially primordial biomolecular structures: from vitamin B12 to the nucleic acids and an inquiry into the chemistry of life’s origin: a retrospective. Angew Chem Int Ed 50:12412–12472CrossRefGoogle Scholar
  18. Fox KR, Brown T (2005) An extra dimension in nucleic acid sequence recognition. Q Rev Biophys 38:311–320PubMedCrossRefGoogle Scholar
  19. Geerts N, Eiser E (2010) DNA-functionalized colloids: physical properties and applications. Soft Matter 6:4647–4660CrossRefGoogle Scholar
  20. Gu Q, Cheng CD, Gonela R et al (2006) DNA nanowire fabrication. Nanotechnology 17:R14–R25CrossRefGoogle Scholar
  21. Houlton A, Pike AR, Galindo MA et al (2009) DNA-based routes to semiconducting nanomaterials. Chem Commun 14:1797–1806CrossRefGoogle Scholar
  22. Jones MR, Osberg KD, Macfarlane RJ et al (2011) Templated techniques for the synthesis and assembly of plasmonic nanostructures. Chem Rev 111:3736–3827PubMedCrossRefGoogle Scholar
  23. Kallenbach NR, Ma RI, Seeman NC (1983) An immobile nucleic-acid junction constructed from oligonucleotides. Nature 305:829–831CrossRefGoogle Scholar
  24. Ke Y, Bellot G, Voigt NV et al (2012) Two design strategies for enhancement of multilayer-DNA-origami folding: underwinding for specific intercalator rescue and staple-break positioning. Chem Sci 3:2587–2597CrossRefGoogle Scholar
  25. Keum JW, Ahn JH, Bermudez H (2011) Design, assembly, and activity of antisense DNA nanostructures. Small 7:3529–3535PubMedCrossRefGoogle Scholar
  26. Kleiner RE, Dumelin CE, Liu DR (2011) Small-molecule discovery from DNA-encoded chemical libraries. Chem Soc Rev 40:5707–5717PubMedCrossRefGoogle Scholar
  27. Li XJ, Yang XP, Qi J et al (1996) Antiparallel DNA double crossover molecules as components for nanoconstruction. J Am Chem Soc 118:6131–6140CrossRefGoogle Scholar
  28. Lin CX, Ke YG, Li Z et al (2009) Mirror image DNA nanostructures for chiral supramolecular assemblies. Nano Lett 9:433–436PubMedCrossRefGoogle Scholar
  29. Liu J, Declais AC, Lilley DMJ (2004) Electrostatic interactions and the folding of the four-way DNA junction: analysis by selective methyl phosphonate substitution. J Mol Biol 343:851–864PubMedCrossRefGoogle Scholar
  30. Liu J, Declais AC, McKinney SA et al (2005) Stereospecific effects determine the structure of a four-way DNA junction. Chem Biol 12:217–228PubMedCrossRefGoogle Scholar
  31. Liu Y, Wang RS, Ding L et al (2008) Thermodynamic analysis of nylon nucleic acids. Chembiochem 9:1641–1648PubMedCrossRefGoogle Scholar
  32. Liu Y, Wang R, Ding L et al (2012) Templated synthesis of nylon nucleic acids and characterization by nuclease digestion. Chem Sci 3:1930–1937PubMedCrossRefGoogle Scholar
  33. Lubin AA, Plaxco KW (2010) Folding-based electrochemical biosensors: the case for responsive nucleic acid architectures. Acc Chem Res 43:496–505PubMedCrossRefGoogle Scholar
  34. Lukeman PS, Mittal AC, Seeman NC (2004) Two dimensional PNA/DNA arrays: estimating the helicity of unusual nucleic acid polymers. Chem Commun (Camb) 15:1694–1695CrossRefGoogle Scholar
  35. Ma Y, Zhang J, Zhang G et al (2004) Polyaniline nanowires on si surfaces fabricated with DNA templates. J Am Chem Soc 126:7097–7101PubMedCrossRefGoogle Scholar
  36. Mei QA, Wei XX, Su FY et al (2011) Stability of DNA origami nanoarrays in cell lysate. Nano Lett 11:1477–1482PubMedCrossRefGoogle Scholar
  37. Milnes PJ, McKee ML, Bath J et al (2012) Sequence-specific synthesis of macromolecules using DNA-templated chemistry. Chem Commun 48:5614–5616CrossRefGoogle Scholar
  38. Mukherjee A, Vasquez KM (2011) Triplex technology in studies of DNA damage, DNA repair, and mutagenesis. Biochimie 93:1197–1208PubMedCrossRefGoogle Scholar
  39. Nielsen PE (2010) Peptide nucleic acids (PNA) in chemical biology and drug discovery. Chem Biodivers 7:786–804PubMedCrossRefGoogle Scholar
  40. Pinheiro AV, Han DR, Shih WM et al (2011) Challenges and opportunities for structural DNA nanotechnology. Nat Nanotechnol 6:763–772PubMedCrossRefGoogle Scholar
  41. Rajendran A, Endo M, Katsuda Y et al (2011) Photo-cross-linking-assisted thermal stability of DNA origami structures and its application for higher-temperature self-assembly. J Am Chem Soc 133:14488–14491PubMedCrossRefGoogle Scholar
  42. Rinker S, Liu Y, Yan H (2006) Two-dimensional LNA/DNA arrays: estimating the helicity of LNA/DNA hybrid duplex. Chem Commun 25:2675–2677CrossRefGoogle Scholar
  43. Rothemund PWK (2006) Folding DNA to create nanoscale shapes and patterns. Nature 440:297–302PubMedCrossRefGoogle Scholar
  44. Ruiz-Carretero A, Janssen PGA, Kaeser A et al (2011) DNA-templated assembly of dyes and extended pi-conjugated systems. Chem Commun 47:4340–4347CrossRefGoogle Scholar
  45. Sacca B, Niemeyer CM (2011) Functionalization of DNA nanostructures with proteins. Chem Soc Rev 40:5910–5921PubMedCrossRefGoogle Scholar
  46. Sacca B, Niemeyer CM (2012) DNA origami: the art of folding DNA. Angew Chem Int Ed 51:58–66CrossRefGoogle Scholar
  47. Seeman NC (1982) Nucleic acid junctions and lattices. J Theor Biol 99:237–247PubMedCrossRefGoogle Scholar
  48. Seeman NC (2000) In the nick of space: generalized nucleic acid complementarity and DNA nanotechnology. Synlett 11:1536–1548Google Scholar
  49. Seeman NC (2010) Nanomaterials based on DNA. Annu Rev Biochem 79:65–87PubMedCrossRefGoogle Scholar
  50. Srinivasan S, Schuster GB (2008) A conjoined thienopyrrole oligomer formed by using DNA as a molecular guide. Org Lett 10:3657–3660PubMedCrossRefGoogle Scholar
  51. Surana S, Bhat JM, Koushika SP et al (2011) An autonomous DNA nanomachine maps spatiotemporal pH changes in a multicellular living organism. Nat Commun 2:340PubMedCrossRefGoogle Scholar
  52. Tagawa M, Shohda K, Fujimoto K et al (2011) Stabilization of DNA nanostructures by photo-cross-linking. Soft Matter 7:10931–10934CrossRefGoogle Scholar
  53. Totsingan F, Jain V, Bracken WC et al (2010) Conformational heterogeneity in PNA: PNA duplexes. Macromolecules 43:2692–2703CrossRefGoogle Scholar
  54. Walsh AS, Yin HF, Erben CM et al (2011) DNA cage delivery to mammalian cells. ACS Nano 5:5427–5432PubMedCrossRefGoogle Scholar
  55. Wei B, Dai M, Yin P (2012) Complex shapes self-assembled from single-stranded DNA tiles. Nature 485:623–626PubMedCrossRefGoogle Scholar
  56. Winfree E, Liu F, Wenzler LA et al (1998) Design and self-assembly of two-dimensional DNA crystals. Nature 394:539–544PubMedCrossRefGoogle Scholar
  57. Wojciechowski F, Leumann CJ (2011) Alternative DNA base-pairs: from efforts to expand the genetic code to potential material applications. Chem Soc Rev 40:5669–5679PubMedCrossRefGoogle Scholar
  58. Yamamoto T, Nakatani M, Narukawa K et al (2011) Antisense drug discovery and development. Future Med Chem 3:339–365PubMedCrossRefGoogle Scholar
  59. Yang H, Metera KL, Sleiman HF (2010) DNA modified with metal complexes: applications in the construction of higher order metal-DNA nanostructures. Coord Chem Rev 254:2403–2415CrossRefGoogle Scholar
  60. Zhang DY, Seelig G (2011) Dynamic DNA nanotechnology using strand-displacement reactions. Nat Chem 3:103–113PubMedCrossRefGoogle Scholar
  61. Zhang RS, McCullum EO, Chaput JC (2008) Synthesis of two mirror image 4-helix junctions derived from glycerol nucleic acid. J Am Chem Soc 130:5846–5847PubMedCrossRefGoogle Scholar
  62. Zhu L, Lukeman PS, Canary JW et al (2003) Nylon/DNA: single-stranded DNA with a covalently stitched nylon lining. J Am Chem Soc 125:10178–10179PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Chemistry DepartmentSt. John’s UniversityQueensUSA

Personalised recommendations