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Biotechnological and Therapeutic Applications of Natural Nucleic Acid Structural Motifs

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Abstract

Genetic information and the blueprint of life are stored in the form of nucleic acids. The primary sequence of DNA, read from the canonical double helix, provides the code for RNA and protein synthesis. Yet these already-information-rich molecules have higher-order structures which play critical roles in transcription and translation. Uncovering the sequences, parameters, and conditions which govern the formation of these structural motifs has allowed researchers to study them and to utilize them in biotechnological and therapeutic applications in vitro and in vivo. This review covers both DNA and RNA structural motifs found naturally in biological systems including catalytic nucleic acids, non-coding RNA, aptamers, G-quadruplexes, i-motifs, and Holliday junctions. For each category, an overview of the structural characteristics, biological prevalence, and function will be discussed. The biotechnological and therapeutic applications of these structural motifs are highlighted. Future perspectives focus on the addition of proteins and unnatural modifications to enhance structural stability for greater applicability.

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References

  1. Watson JD, Crick FHC (1953) Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature 171(4356):737–738. https://doi.org/10.1038/171737a0

    Article  CAS  PubMed  Google Scholar 

  2. Das J, Mukherjee S, Mitra A, Bhattacharyya D (2006) Non-canonical base pairs and higher order structures in nucleic acids: crystal structure database analysis. J Biomol Struct Dyn 24(2):149–161. https://doi.org/10.1080/07391102.2006.10507108

    Article  CAS  PubMed  Google Scholar 

  3. Lipps HJ, Gruissem W, Prescott DM (1982) Higher order DNA structure in macronuclear chromatin of the hypotrichous ciliate Oxytricha nova. Proc Natl Acad Sci 79(8):2495. https://doi.org/10.1073/pnas.79.8.2495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Guéron M, Leroy J-L (2000) The i-motif in nucleic acids. Curr Opin Struct Biol 10(3):326–331. https://doi.org/10.1016/S0959-440X(00)00091-9

    Article  PubMed  Google Scholar 

  5. Watson J, Baker TA, Bell SP, Gann A, Levine M, Losick R (2014) The structures of DNA and RNA. In: Molecular biology of the gene. Pearson, London

  6. Salazar M, Fedoroff OY, Miller JM, Ribeiro NS, Reid BR (1993) The DNA strand in DNA–RNA hybrid duplexes is neither B-form nor A-form in solution. Biochemistry 32(16):4207–4215. https://doi.org/10.1021/bi00067a007

    Article  CAS  PubMed  Google Scholar 

  7. Rich A, Nordheim A, Wang AHJ (1984) The chemistry and biology of left-handed Z-DNA. Annu Rev Biochem 53(1):791–846. https://doi.org/10.1146/annurev.bi.53.070184.004043

    Article  CAS  PubMed  Google Scholar 

  8. Herbert A, Rich A (1998) Left-handed Z-DNA: structure and function. In: Bradbury EM, Pongor S (eds) Structural biology and functional genomics, vol 71. Kluwer, Dordrecht. https://doi.org/10.1007/978-94-011-4631-9_3

    Chapter  Google Scholar 

  9. Conn GL, Draper DE (1998) RNA structure. Curr Opin Struct Biol 8(3):278–285. https://doi.org/10.1016/S0959-440X(98)80059-6

    Article  CAS  PubMed  Google Scholar 

  10. Staple DW, Butcher SE (2005) Pseudoknots: RNA structures with diverse functions. PLoS Biol 3(6):e213–e213. https://doi.org/10.1371/journal.pbio.0030213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Qi X, Zhang F, Su Z, Jiang S, Han D, Ding B, Liu Y, Chiu W, Yin P, Yan H (2018) Programming molecular topologies from single-stranded nucleic acids. Nat Commun 9(1):4579. https://doi.org/10.1038/s41467-018-07039-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Batey RT, Rambo RP, Doudna JA (1999) Tertiary motifs in RNA structure and folding. Angew Chem Int Ed 38(16):2326–2343. https://doi.org/10.1002/(SICI)1521-3773(19990816)38:16%3c2326:AID-ANIE2326%3e3.0.CO;2-3

    Article  CAS  Google Scholar 

  13. Butcher SE, Pyle AM (2011) The molecular interactions that stabilize RNA tertiary structure: RNA motifs, patterns, and networks. Acc Chem Res 44(12):1302–1311. https://doi.org/10.1021/ar200098t

    Article  CAS  PubMed  Google Scholar 

  14. Clark DP, Pazdernik NJ (2016) RNA-based technologies, chapter 5. In: Clark DP, Pazdernik NJ (eds) Biotechnology, 2nd edn. Academic Cell, Boston, pp 131–179. https://doi.org/10.1016/B978-0-12-385015-7.00005-3

    Chapter  Google Scholar 

  15. Mercer TR, Mattick JS (2013) Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol 20:300. https://doi.org/10.1038/nsmb.2480

    Article  CAS  PubMed  Google Scholar 

  16. Jaskiewicz L, Filipowicz W (2008) Role of dicer in posttranscriptional RNA silencing. In: Paddison PJ, Vogt PK (eds) RNA interference. Springer, Berlin, pp 77–97. https://doi.org/10.1007/978-3-540-75157-1_4

    Chapter  Google Scholar 

  17. Houseley J, Tollervey D (2009) The many pathways of RNA degradation. Cell 136(4):763–776. https://doi.org/10.1016/j.cell.2009.01.019

    Article  CAS  PubMed  Google Scholar 

  18. Tuschl T (2001) RNA interference and small interfering RNAs. ChemBioChem 2(4):239–245. https://doi.org/10.1002/1439-7633(20010401)2:4%3c239:AID-CBIC239%3e3.0.CO;2-R

    Article  CAS  PubMed  Google Scholar 

  19. Ozata DM, Gainetdinov I, Zoch A, O’Carroll D, Zamore PD (2019) PIWI-interacting RNAs: small RNAs with big functions. Nat Rev Genet 20(2):89–108. https://doi.org/10.1038/s41576-018-0073-3

    Article  CAS  PubMed  Google Scholar 

  20. Paul CP, Good PD, Winer I, Engelke DR (2002) Effective expression of small interfering RNA in human cells. Nat Biotechnol 20(5):505–508. https://doi.org/10.1038/nbt0502-505

    Article  CAS  PubMed  Google Scholar 

  21. Aftab MN, He H, Skogerbø G, Chen R (2008) Microarray analysis of ncRNA expression patterns in Caenorhabditis elegans after RNAi against snoRNA associated proteins. BMC Genom 9(1):278. https://doi.org/10.1186/1471-2164-9-278

    Article  CAS  Google Scholar 

  22. Kiss T (2002) Small nucleolar RNAs: an abundant group of noncoding RNAs with diverse cellular functions. Cell 109(2):145–148. https://doi.org/10.1016/S0092-8674(02)00718-3

    Article  CAS  PubMed  Google Scholar 

  23. Fang W, Bartel DP (2015) The menu of features that define primary microRNAs and enable de novo design of microRNA genes. Mol Cell 60(1):131–145. https://doi.org/10.1016/j.molcel.2015.08.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hammond SM (2006) RNAi, microRNAs, and human disease. Cancer Chemother Pharmacol 58(1):63–68. https://doi.org/10.1007/s00280-006-0318-2

    Article  CAS  Google Scholar 

  25. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854. https://doi.org/10.1016/0092-8674(93)90529-Y

    Article  CAS  PubMed  Google Scholar 

  26. Ganot P, Bortolin M-L, Kiss T (1997) Site-specific pseudouridine formation in preribosomal RNA is guided by small nucleolar RNAs. Cell 89(5):799–809. https://doi.org/10.1016/S0092-8674(00)80263-9

    Article  CAS  PubMed  Google Scholar 

  27. Kim D, Rossi J (2008) RNAi mechanisms and applications. Biotechniques 44(5):613–616. https://doi.org/10.2144/000112792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Setten RL, Rossi JJ, Han S-p (2019) The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov 18(6):421–446. https://doi.org/10.1038/s41573-019-0017-4

    Article  CAS  PubMed  Google Scholar 

  29. Weng Y, Xiao H, Zhang J, Liang X-J, Huang Y (2019) RNAi therapeutic and its innovative biotechnological evolution. Biotechnol Adv 37(5):801–825. https://doi.org/10.1016/j.biotechadv.2019.04.012

    Article  CAS  PubMed  Google Scholar 

  30. Fernandes JCR, Acuña SM, Aoki JI, Floeter-Winter LM, Muxel SM (2019) Long non-coding RNAs in the regulation of gene expression: physiology and disease. Noncoding RNA 5(1):17. https://doi.org/10.3390/ncrna5010017

    Article  CAS  PubMed Central  Google Scholar 

  31. Hsu Patrick D, Lander Eric S, Zhang F (2014) Development and applications of CRISPR-Cas9 for genome engineering. Cell 157(6):1262–1278. https://doi.org/10.1016/j.cell.2014.05.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096):816. https://doi.org/10.1126/science.1225829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jiang F, Taylor DW, Chen JS, Kornfeld JE, Zhou K, Thompson AJ, Nogales E, Doudna JA (2016) Structures of a CRISPR-Cas9 R-loop complex primed for DNA cleavage. Science 351(6275):867. https://doi.org/10.1126/science.aad8282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nishimasu H, Ran FA, Hsu Patrick D, Konermann S, Shehata Soraya I, Dohmae N, Ishitani R, Zhang F, Nureki O (2014) Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell 156(5):935–949. https://doi.org/10.1016/j.cell.2014.02.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Dominguez AA, Lim WA, Qi LS (2015) Beyond editing: repurposing CRISPR–Cas9 for precision genome regulation and interrogation. Nat Rev Mol Cell Biol 17:5. https://doi.org/10.1038/nrm.2015.2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Donohoue PD, Barrangou R, May AP (2018) Advances in industrial biotechnology using CRISPR-Cas systems. Trends Biotechnol 36(2):134–146. https://doi.org/10.1016/j.tibtech.2017.07.007

    Article  CAS  PubMed  Google Scholar 

  37. Guo P (2010) The emerging field of RNA nanotechnology. Nat Nanotechnol 5:833. https://doi.org/10.1038/nnano.2010.231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li M, Zheng M, Wu S, Tian C, Liu D, Weizmann Y, Jiang W, Wang G, Mao C (2018) In vivo production of RNA nanostructures via programmed folding of single-stranded RNAs. Nat Commun 9(1):2196. https://doi.org/10.1038/s41467-018-04652-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Grabow WW, Jaeger L (2014) RNA self-assembly and RNA nanotechnology. Acc Chem Res 47(6):1871–1880. https://doi.org/10.1021/ar500076k

    Article  CAS  PubMed  Google Scholar 

  40. Cech TR (2002) Ribozymes, the first 20 years. Biochem Soc Trans 30(6):1162. https://doi.org/10.1042/bst0301162

    Article  CAS  PubMed  Google Scholar 

  41. Cech TR (1990) Self-splicing and enzymatic activity of an intervening sequence RNA from Tetrahymena. Biosci Rep 10(3):239. https://doi.org/10.1007/BF01117241

    Article  CAS  PubMed  Google Scholar 

  42. Doudna JA, Lorsch JR (2005) Ribozyme catalysis: not different, just worse. Nat Struct Mol Biol 12(5):395–402. https://doi.org/10.1038/nsmb932

    Article  CAS  PubMed  Google Scholar 

  43. Tanner NK (1999) Ribozymes: the characteristics and properties of catalytic RNAs. FEMS Microbiol Rev 23(3):257–275. https://doi.org/10.1111/j.1574-6976.1999.tb00399.x

    Article  CAS  PubMed  Google Scholar 

  44. Walter NG, Engelke DR (2002) Ribozymes: catalytic RNAs that cut things, make things, and do odd and useful jobs. Biologist (London) 49(5):199–203

    Google Scholar 

  45. Fedoruk-Wyszomirska A, Szymański M, Głodowicz P, Gabryelska M, Wyszko E, Estrin William J, Barciszewski J (2015) Inhibition of HIV-1 gp41 expression with hammerhead ribozymes. Biochem J 471(1):53. https://doi.org/10.1042/BJ20150398

    Article  CAS  PubMed  Google Scholar 

  46. James HA, Gibson I (1998) The therapeutic potential of ribozymes. Blood 91(2):371

    Article  CAS  PubMed  Google Scholar 

  47. Fedor MJ (2000) Structure and function of the hairpin ribozyme. J Mol Biol 297(2):269–291. https://doi.org/10.1006/jmbi.2000.3560

    Article  CAS  PubMed  Google Scholar 

  48. Famulok M, Hartig JS, Mayer G (2007) Functional aptamers and aptazymes in biotechnology, diagnostics, and therapy. Chem Rev 107(9):3715–3743. https://doi.org/10.1021/cr0306743

    Article  CAS  PubMed  Google Scholar 

  49. Suslov NB, DasGupta S, Huang H, Fuller JR, Lilley DMJ, Rice PA, Piccirilli JA (2015) Crystal structure of the Varkud satellite ribozyme. Nat Chem Biol 11:840. https://doi.org/10.1038/nchembio.1929. https://www.nature.com/articles/nchembio.1929#supplementary-information

  50. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249(4968):505. https://doi.org/10.1126/science.2200121

    Article  CAS  PubMed  Google Scholar 

  51. Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346(6287):818–822. https://doi.org/10.1038/346818a0

    Article  CAS  PubMed  Google Scholar 

  52. Breaker RR, Joyce GF (1994) A DNA enzyme that cleaves RNA. Chem Biol 1(4):223–229. https://doi.org/10.1016/1074-5521(94)90014-0

    Article  CAS  PubMed  Google Scholar 

  53. Cuenoud B, Szostak JW (1995) A DNA metalloenzyme with DNA ligase activity. Nature 375(6532):611–614. https://doi.org/10.1038/375611a0

    Article  CAS  PubMed  Google Scholar 

  54. Burge S, Parkinson GN, Hazel P, Todd AK, Neidle S (2006) Quadruplex DNA: sequence, topology and structure. Nucleic Acids Res 34(19):5402–5415. https://doi.org/10.1093/nar/gkl655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kwok CK, Merrick CJ (2017) G-Quadruplexes: prediction, characterization, and biological application. Trends Biotechnol 35(10):997–1013. https://doi.org/10.1016/j.tibtech.2017.06.012

    Article  CAS  PubMed  Google Scholar 

  56. Lam EYN, Beraldi D, Tannahill D, Balasubramanian S (2013) G-quadruplex structures are stable and detectable in human genomic DNA. Nat Commun 4:1796. https://doi.org/10.1038/ncomms2792. https://www.nature.com/articles/ncomms2792#supplementary-information

  57. Asamitsu S, Obata S, Yu Z, Bando T, Sugiyama H (2019) Recent progress of targeted G-quadruplex-preferred ligands toward cancer therapy. Molecules 24(3):429. https://doi.org/10.3390/molecules24030429

    Article  CAS  PubMed Central  Google Scholar 

  58. Asamitsu S, Li Y, Bando T, Sugiyama H (2016) Ligand-mediated G-quadruplex induction in a double-stranded DNA context by cyclic imidazole/lysine polyamide. ChemBioChem 17(14):1317–1322. https://doi.org/10.1002/cbic.201600198

    Article  CAS  PubMed  Google Scholar 

  59. Brown RV, Danford FL, Gokhale V, Hurley LH, Brooks TA (2011) Demonstration that drug-targeted down-regulation of MYC in non-Hodgkins lymphoma is directly mediated through the promoter G-quadruplex. J Biol Chem 286(47):41018–41027. https://doi.org/10.1074/jbc.M111.274720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Dutta D, Debnath M, Müller D, Paul R, Das T, Bessi I, Schwalbe H, Dash J (2018) Cell penetrating thiazole peptides inhibit c-MYC expression via site-specific targeting of c-MYC G-quadruplex. Nucleic Acids Res 46(11):5355–5365. https://doi.org/10.1093/nar/gky385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hu M-H, Wang Y-Q, Yu Z-Y, Hu L-N, Ou T-M, Chen S-B, Huang Z-S, Tan J-H (2018) Discovery of a new four-leaf clover-like ligand as a potent c-MYC transcription inhibitor specifically targeting the promoter G-quadruplex. J Med Chem 61(6):2447–2459. https://doi.org/10.1021/acs.jmedchem.7b01697

    Article  CAS  PubMed  Google Scholar 

  62. Taka T, Joonlasak K, Huang L, Randall Lee T, Chang S-WT, Tuntiwechapikul W (2012) Down-regulation of the human VEGF gene expression by perylene monoimide derivatives. Bioorg Med Chem Lett 22(1):518–522. https://doi.org/10.1016/j.bmcl.2011.10.089

    Article  CAS  PubMed  Google Scholar 

  63. Wu Y, Zan L-P, Wang X-D, Lu Y-J, Ou T-M, Lin J, Huang Z-S, Gu L-Q (2014) Stabilization of VEGF G-quadruplex and inhibition of angiogenesis by quindoline derivatives. Biochim Biophys Acta 9:2970–2977. https://doi.org/10.1016/j.bbagen.2014.06.002

    Article  CAS  Google Scholar 

  64. Amato J, Pagano A, Capasso D, Di Gaetano S, Giustiniano M, Novellino E, Randazzo A, Pagano B (2018) Targeting the BCL2 gene promoter G-quadruplex with a new class of furopyridazinone-based molecules. ChemMedChem 13(5):406–410. https://doi.org/10.1002/cmdc.201700749

    Article  CAS  PubMed  Google Scholar 

  65. Gu Y, Lin D, Tang Y, Fei X, Wang C, Zhang B, Zhou J (2018) A light-up probe targeting for Bcl-2 2345 G-quadruplex DNA with carbazole TO. Spectrochim Acta Part A Mol Biomol Spectrosc 191:180–188. https://doi.org/10.1016/j.saa.2017.10.012

    Article  CAS  Google Scholar 

  66. Bejugam M, Sewitz S, Shirude PS, Rodriguez R, Shahid R, Balasubramanian S (2007) Trisubstituted isoalloxazines as a new class of G-quadruplex binding ligands: small molecule regulation of c-kit oncogene expression. J Am Chem Soc 129(43):12926–12927. https://doi.org/10.1021/ja075881p

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gunaratnam M, Collie GW, Reszka AP, Todd AK, Parkinson GN, Neidle S (2018) A naphthalene diimide G-quadruplex ligand inhibits cell growth and down-regulates BCL-2 expression in an imatinib-resistant gastrointestinal cancer cell line. Bioorg Med Chem 26(11):2958–2964. https://doi.org/10.1016/j.bmc.2018.04.050

    Article  CAS  PubMed  Google Scholar 

  68. McLuckie KIE, Waller ZAE, Sanders DA, Alves D, Rodriguez R, Dash J, McKenzie GJ, Venkitaraman AR, Balasubramanian S (2011) G-quadruplex-binding benzo[a]phenoxazines down-regulate c-KIT expression in human gastric carcinoma cells. J Am Chem Soc 133(8):2658–2663. https://doi.org/10.1021/ja109474c

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Głuszyńska A, Juskowiak B, Kuta-Siejkowska M, Hoffmann M, Haider S (2018) Carbazole derivatives’ binding to c-KIT G-quadruplex DNA. Molecules 23(5):1134. https://doi.org/10.3390/molecules23051134

    Article  CAS  PubMed Central  Google Scholar 

  70. Kang H-J, Cui Y, Yin H, Scheid A, Hendricks WPD, Schmidt J, Sekulic A, Kong D, Trent JM, Gokhale V, Mao H, Hurley LH (2016) A pharmacological chaperone molecule induces cancer cell death by restoring tertiary DNA structures in mutant hTERT promoters. J Am Chem Soc 138(41):13673–13692. https://doi.org/10.1021/jacs.6b07598

    Article  CAS  PubMed  Google Scholar 

  71. Lavrado J, Brito H, Borralho PM, Ohnmacht SA, Kim N-S, Leitão C, Pisco S, Gunaratnam M, Rodrigues CMP, Moreira R, Neidle S, Paulo A (2015) KRAS oncogene repression in colon cancer cell lines by G-quadruplex binding indolo[3,2-c]quinolines. Sci Rep 5:9696. https://doi.org/10.1038/srep09696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Cogoi S, Paramasivam M, Filichev V, Géci I, Pedersen EB, Xodo LE (2009) Identification of a new G-quadruplex motif in the KRAS promoter and design of pyrene-modified G4-decoys with antiproliferative activity in pancreatic cancer cells. J Med Chem 52(2):564–568. https://doi.org/10.1021/jm800874t

    Article  CAS  PubMed  Google Scholar 

  73. Li F, Zhou J, Xu M, Yuan G (2018) Exploration of G-quadruplex function in c-Myb gene and its transcriptional regulation by topotecan. Int J Biol Macromol 107:1474–1479. https://doi.org/10.1016/j.ijbiomac.2017.10.010

    Article  CAS  PubMed  Google Scholar 

  74. Schultze P, Macaya RF, Feigon J (1994) Three-dimensional solution structure of the thrombin-binding DNA aptamer d(GGTTGGTGTGGTTGG). J Mol Biol 235(5):1532–1547. https://doi.org/10.1006/jmbi.1994.1105

    Article  CAS  PubMed  Google Scholar 

  75. Travascio P, Li Y, Sen D (1998) DNA-enhanced peroxidase activity of a DNA aptamer–hemin complex. Chem Biol 5(9):505–517. https://doi.org/10.1016/S1074-5521(98)90006-0

    Article  CAS  PubMed  Google Scholar 

  76. Paige JS, Wu KY, Jaffrey SR (2011) RNA mimics of green fluorescent protein. Science 333(6042):642. https://doi.org/10.1126/science.1207339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ebrahimi M, Raoof JB, Ojani R (2017) Design of a novel electrochemical biosensor based on intramolecular G-quadruplex DNA for selective determination of lead(II) ions. Anal Bioanal Chem 409(20):4729–4739. https://doi.org/10.1007/s00216-017-0416-5

    Article  CAS  PubMed  Google Scholar 

  78. Gogichaishvili S, Lomidze L, Kankia B (2014) Quadruplex priming amplification combined with nicking enzyme for diagnostics. Anal Biochem 466:44–48. https://doi.org/10.1016/j.ab.2014.08.025

    Article  CAS  PubMed  Google Scholar 

  79. Taylor A, Joseph A, Okyere R, Gogichaishvili S, Musier-Forsyth K, Kankia B (2013) Isothermal quadruplex priming amplification for DNA-based diagnostics. Biophys Chem 171:1–8. https://doi.org/10.1016/j.bpc.2012.11.001

    Article  CAS  PubMed  Google Scholar 

  80. Gehring K, Leroy JL, Guéron M (1993) A tetrameric DNA structure with protonated cytosine–cytosine base pairs. Nature 363(6429):561–565. https://doi.org/10.1038/363561a0

    Article  CAS  PubMed  Google Scholar 

  81. Wright EP, Huppert JL, Zoë ZAE (2017) Identification of multiple genomic DNA sequences which form i-motif structures at neutral pH. Nucleic Acids Res. https://doi.org/10.1093/nar/gkx090

    Article  PubMed  PubMed Central  Google Scholar 

  82. Abou Assi H, Garavís M, González C, Damha MJ (2018) i-Motif DNA: structural features and significance to cell biology. Nucleic Acids Res 46(16):8038–8056. https://doi.org/10.1093/nar/gky735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Benabou S, Aviñó A, Eritja R, González C, Gargallo R (2014) Fundamental aspects of the nucleic acid i-motif structures. RSC Adv 4(51):26956–26980. https://doi.org/10.1039/c4ra02129k

    Article  CAS  Google Scholar 

  84. Gurung SP, Schwarz C, Hall JP, Cardin CJ, Brazier JA (2015) The importance of loop length on the stability of i-motif structures. Chem Commun 51(26):5630–5632. https://doi.org/10.1039/c4cc07279k

    Article  CAS  Google Scholar 

  85. Day HA, Pavlou P, Waller ZAE (2014) i-Motif DNA: structure, stability and targeting with ligands. Bioorg Med Chem 22(16):4407–4418. https://doi.org/10.1016/j.bmc.2014.05.047

    Article  CAS  PubMed  Google Scholar 

  86. Zeraati M, Langley DB, Schofield P, Moye AL, Rouet R, Hughes WE, Bryan TM, Dinger ME, Christ D (2018) I-motif DNA structures are formed in the nuclei of human cells. Nat Chem 10(6):631–637. https://doi.org/10.1038/s41557-018-0046-3

    Article  CAS  PubMed  Google Scholar 

  87. Snoussi K, Nonin-Lecomte S, Leroy JL (2001) The RNA i-motif. J Mol Biol 309(1):139–153. https://doi.org/10.1006/jmbi.2001.4618

    Article  CAS  PubMed  Google Scholar 

  88. Sedghi Masoud S, Nagasawa K (2018) i-Motif-binding ligands and their effects on the structure and biological functions of i-motif. Chem Pharm Bull 66(12):1091–1103. https://doi.org/10.1248/cpb.c18-00720

    Article  Google Scholar 

  89. Dexheimer TS, Carey SS, Zuohe S, Gokhale VM, Hu X, Murata LB, Maes EM, Weichsel A, Sun D, Meuillet EJ, Montfort WR, Hurley LH (2009) NM23-H2 may play an indirect role in transcriptional activation of c-myc gene expression but does not cleave the nuclease hypersensitive element III(1). Mol Cancer Ther 8(5):1363–1377. https://doi.org/10.1158/1535-7163.MCT-08-1093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zhang XY, Luo HQ, Li NB (2014) Crystal violet as an i-motif structure probe for reversible and label-free pH-driven electrochemical switch. Anal Biochem 455:55–59. https://doi.org/10.1016/j.ab.2014.03.015

    Article  CAS  PubMed  Google Scholar 

  91. Li X, Peng Y, Ren J, Qu X (2006) Carboxyl-modified single-walled carbon nanotubes selectively induce human telomeric i-motif formation. Proc Natl Acad Sci 103(52):19658. https://doi.org/10.1073/pnas.0607245103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Chen X, Zhou X, Han T, Wu J, Zhang J, Guo S (2013) Stabilization and induction of oligonucleotide i-motif structure via graphene quantum dots. ACS Nano 7(1):531–537. https://doi.org/10.1021/nn304673a

    Article  CAS  PubMed  Google Scholar 

  93. Kendrick S, Muranyi A, Gokhale V, Hurley LH, Rimsza LM (2017) Simultaneous drug targeting of the promoter MYC G-quadruplex and BCL2 i-motif in diffuse large B-cell lymphoma delays tumor growth. J Med Chem 60(15):6587–6597. https://doi.org/10.1021/acs.jmedchem.7b00298

    Article  CAS  PubMed  Google Scholar 

  94. Modi S, Swetha MG, Goswami D, Gupta GD, Mayor S, Krishnan Y (2009) A DNA nanomachine that maps spatial and temporal pH changes inside living cells. Nat Nanotechnol 4(5):325–330. https://doi.org/10.1038/nnano.2009.83

    Article  CAS  PubMed  Google Scholar 

  95. Zhao Y, Cao L, Ouyang J, Wang M, Wang K, Xia X-H (2013) Reversible plasmonic probe sensitive for pH in micro/nanospaces based on i-motif-modulated morpholino-gold nanoparticle assembly. Anal Chem 85(2):1053–1057. https://doi.org/10.1021/ac302915a

    Article  CAS  PubMed  Google Scholar 

  96. Dong Y, Yang Z, Liu D (2014) DNA nanotechnology based on i-motif structures. Acc Chem Res 47(6):1853–1860. https://doi.org/10.1021/ar500073a

    Article  CAS  PubMed  Google Scholar 

  97. Chen C, Pu F, Huang Z, Liu Z, Ren J, Qu X (2010) Stimuli-responsive controlled-release system using quadruplex DNA-capped silica nanocontainers. Nucleic Acids Res 39(4):1638–1644. https://doi.org/10.1093/nar/gkq893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Ghodke HB, Krishnan R, Vignesh K, Kumar GVP, Narayana C, Krishnan Y (2007) The I-tetraplex building block: rational design and controlled fabrication of robust 1D DNA scaffolds through non-Watson–Crick interactions. Angew Chem Int Ed 46(15):2646–2649. https://doi.org/10.1002/anie.200604461

    Article  CAS  Google Scholar 

  99. Yang Y, Zhou C, Zhang T, Cheng E, Yang Z, Liu D (2012) DNA pillars constructed from an i-motif stem and duplex branches. Small 8(4):552–556. https://doi.org/10.1002/smll.201102061

    Article  CAS  PubMed  Google Scholar 

  100. Cheng E, Xing Y, Chen P, Yang Y, Sun Y, Zhou D, Xu L, Fan Q, Liu D (2009) A pH-triggered, fast-responding DNA hydrogel. Angew Chem Int Ed 48(41):7660–7663. https://doi.org/10.1002/anie.200902538

    Article  CAS  Google Scholar 

  101. Bruyere A, Wantroba M, Flasinski S, Dzianott A, Bujarski JJ (2000) Frequent homologous recombination events between molecules of one RNA component in a multipartite RNA virus. J Virol 74(9):4214–4219. https://doi.org/10.1128/jvi.74.9.4214-4219.2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Seeman NC (1982) Nucleic acid junctions and lattices. J Theor Biol 99(2):237–247. https://doi.org/10.1016/0022-5193(82)90002-9

    Article  CAS  PubMed  Google Scholar 

  103. Kallenbach NR, Ma R-I, Seeman NC (1983) An immobile nucleic acid junction constructed from oligonucleotides. Nature 305(5937):829–831. https://doi.org/10.1038/305829a0

    Article  CAS  Google Scholar 

  104. Ma R-I, Kallenbach NR, Sheardy RD, Petrillo ML, Seeman NC (1986) Three-arm nucleic acid junctions are flexible. Nucleic Acids Res 14(24):9745–9753. https://doi.org/10.1093/nar/14.24.9745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Wang X, Seeman NC (2007) Assembly and characterization of 8-arm and 12-arm DNA branched junctions. J Am Chem Soc 129(26):8169–8176. https://doi.org/10.1021/ja0693441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Wang Y, Mueller JE, Kemper B, Seeman NC (1991) Assembly and characterization of five-arm and six-arm DNA branched junctions. Biochemistry 30(23):5667–5674. https://doi.org/10.1021/bi00237a005

    Article  CAS  PubMed  Google Scholar 

  107. Lilley DMJ (2000) Structures of helical junctions in nucleic acids. Q Rev Biophys 33(2):109–159. https://doi.org/10.1017/s0033583500003590

    Article  CAS  PubMed  Google Scholar 

  108. Ariyoshi M, Vassylyev DG, Iwasaki H, Nakamura H, Shinagawa H, Morikawa K (1994) Atomic structure of the RuvC resolvase: a Holliday junction-specific endonuclease from E. coli. Cell 78(6):1063–1072. https://doi.org/10.1016/0092-8674(94)90280-1

    Article  CAS  PubMed  Google Scholar 

  109. Gopaul DN, Guo F, Van Duyne GD (1998) Structure of the Holliday junction intermediate in Cre–loxP site-specific recombination. EMBO J 17(14):4175–4187. https://doi.org/10.1093/emboj/17.14.4175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Seeman NC (2010) Nanomaterials based on DNA. Annu Rev Biochem 79:65–87. https://doi.org/10.1146/annurev-biochem-060308-102244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Um SH, Lee JB, Park N, Kwon SY, Umbach CC, Luo D (2006) Enzyme-catalysed assembly of DNA hydrogel. Nat Mater 5(10):797–801. https://doi.org/10.1038/nmat1741

    Article  CAS  PubMed  Google Scholar 

  112. Wang J, Chao J, Liu H, Su S, Wang L, Huang W, Willner I, Fan C (2017) Clamped hybridization chain reactions for the self-assembly of patterned DNA hydrogels. Angew Chem Int Ed 56(8):2171–2175. https://doi.org/10.1002/anie.201610125

    Article  CAS  Google Scholar 

  113. Gačanin J, Synatschke CV, Weil T (2019) Biomedical applications of DNA-based hydrogels. Adv Funct Mater. https://doi.org/10.1002/adfm.201906253

    Article  Google Scholar 

  114. Wang D, Hu Y, Liu P, Luo D (2017) Bioresponsive DNA hydrogels: beyond the conventional stimuli responsiveness. Acc Chem Res 50(4):733–739. https://doi.org/10.1021/acs.accounts.6b00581

    Article  CAS  PubMed  Google Scholar 

  115. Shen Z, Yan H, Wang T, Seeman NC (2004) Paranemic crossover DNA: a generalized Holliday structure with applications in nanotechnology. J Am Chem Soc 126(6):1666–1674. https://doi.org/10.1021/ja038381e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Wang X, Chandrasekaran AR, Shen Z, Ohayon YP, Wang T, Kizer ME, Sha R, Mao C, Yan H, Zhang X, Liao S, Ding B, Chakraborty B, Jonoska N, Niu D, Gu H, Chao J, Gao X, Li Y, Ciengshin T, Seeman NC (2019) Paranemic crossover DNA: there and back again. Chem Rev 119(10):6273–6289. https://doi.org/10.1021/acs.chemrev.8b00207

    Article  CAS  PubMed  Google Scholar 

  117. Rothemund PWK (2006) Folding DNA to create nanoscale shapes and patterns. Nature 440(7082):297–302. https://doi.org/10.1038/nature04586

    Article  CAS  PubMed  Google Scholar 

  118. Ma Z, Kawai K, Hirai Y, Tsuchiya T, Tabata O (2017) Tuning porosity and radial mechanical properties of DNA origami nanotubes via crossover design. Jpn J Appl Phys 56(6S1):06GJ02. https://doi.org/10.7567/jjap.56.06gj02

    Article  CAS  Google Scholar 

  119. Ke Y, Ong LL, Shih WM, Yin P (2012) Three-dimensional structures self-assembled from DNA bricks. Science 338(6111):1177. https://doi.org/10.1126/science.1227268

    Article  CAS  PubMed  Google Scholar 

  120. Wei B, Dai M, Yin P (2012) Complex shapes self-assembled from single-stranded DNA tiles. Nature 485(7400):623–626. https://doi.org/10.1038/nature11075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Wang P, Meyer TA, Pan V, Dutta PK, Ke Y (2017) The beauty and utility of DNA origami. Chem 2(3):359–382. https://doi.org/10.1016/j.chempr.2017.02.009

    Article  CAS  Google Scholar 

  122. Linko V, Eerikäinen M, Kostiainen MA (2015) A modular DNA origami-based enzyme cascade nanoreactor. Chem Commun 51(25):5351–5354. https://doi.org/10.1039/C4CC08472A

    Article  CAS  Google Scholar 

  123. Rajendran A, Endo M, Sugiyama H (2012) Single-molecule analysis using DNA origami. Angew Chem Int Ed 51(4):874–890. https://doi.org/10.1002/anie.201102113

    Article  CAS  Google Scholar 

  124. Hu Q, Li H, Wang L, Gu H, Fan C (2019) DNA nanotechnology-enabled drug delivery systems. Chem Rev 119(10):6459–6506. https://doi.org/10.1021/acs.chemrev.7b00663

    Article  CAS  PubMed  Google Scholar 

  125. Ohno H, Akamine S, Saito H (2019) RNA nanostructures and scaffolds for biotechnology applications. Curr Opin Biotechnol 58:53–61. https://doi.org/10.1016/j.copbio.2018.11.006

    Article  CAS  PubMed  Google Scholar 

  126. Geary C, Rothemund PWK, Andersen ES (2014) A single-stranded architecture for cotranscriptional folding of RNA nanostructures. Science 345(6198):799. https://doi.org/10.1126/science.1253920

    Article  CAS  PubMed  Google Scholar 

  127. Chandrasekaran AR, Anderson N, Kizer M, Halvorsen K, Wang X (2016) Beyond the fold: emerging biological applications of DNA origami. ChemBioChem 17(12):1081–1089. https://doi.org/10.1002/cbic.201600038

    Article  CAS  PubMed  Google Scholar 

  128. Albinsson B, Hannestad JK, Börjesson K (2012) Functionalized DNA nanostructures for light harvesting and charge separation. Coord Chem Rev 256(21):2399–2413. https://doi.org/10.1016/j.ccr.2012.02.024

    Article  CAS  Google Scholar 

  129. Anderson NT, Dinolfo PH, Wang X (2018) Synthesis and characterization of porphyrin–DNA constructs for the self-assembly of modular energy transfer arrays. J Mater Chem C 6(10):2452–2459. https://doi.org/10.1039/C7TC05272C

    Article  CAS  Google Scholar 

  130. Anderson NT, Ren S, Chao J, Dinolfo PH, Wang X (2019) Exploiting plasmon-mediated energy transfer to enhance end-to-end efficiency in a DNA origami energy transfer array. ACS Appl Nano Mater 2(9):5563–5572. https://doi.org/10.1021/acsanm.9b01137

    Article  CAS  Google Scholar 

  131. Grossi G, Jaekel A, Andersen ES, Saccà B (2017) Enzyme-functionalized DNA nanostructures as tools for organizing and controlling enzymatic reactions. MRS Bull 42(12):920–924. https://doi.org/10.1557/mrs.2017.269

    Article  CAS  Google Scholar 

  132. Fu J, Li T (2017) Spatial organization of enzyme cascade on a DNA origami nanostructure. In: Ke Y, Wang P (eds) 3D DNA nanostructure: methods and protocols. Springer, New York, pp 153–164. https://doi.org/10.1007/978-1-4939-6454-3_11

    Chapter  Google Scholar 

  133. Xin L, Zhou C, Yang Z, Liu D (2013) Regulation of an enzyme cascade reaction by a DNA machine. Small 9(18):3088–3091. https://doi.org/10.1002/smll.201300019

    Article  CAS  PubMed  Google Scholar 

  134. Krishnan S, Ziegler D, Arnaut V, Martin TG, Kapsner K, Henneberg K, Bausch AR, Dietz H, Simmel FC (2016) Molecular transport through large-diameter DNA nanopores. Nat Commun 7(1):12787. https://doi.org/10.1038/ncomms12787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Wang D, Zhang Y, Wang M, Dong Y, Zhou C, Isbell MA, Yang Z, Liu H, Liu D (2016) A switchable DNA origami nanochannel for regulating molecular transport at the nanometer scale. Nanoscale 8(7):3944–3948. https://doi.org/10.1039/C5NR08206D

    Article  CAS  PubMed  Google Scholar 

  136. Zhang Y, Chao J, Liu H, Wang F, Su S, Liu B, Zhang L, Shi J, Wang L, Huang W, Wang L, Fan C (2016) Transfer of two-dimensional oligonucleotide patterns onto stereocontrolled plasmonic nanostructures through DNA-origami-based nanoimprinting lithography. Angew Chem Int Ed 55(28):8036–8040. https://doi.org/10.1002/anie.201512022

    Article  CAS  Google Scholar 

  137. Selnihhin D, Sparvath SM, Preus S, Birkedal V, Andersen ES (2018) Multifluorophore DNA origami beacon as a biosensing platform. ACS Nano 12(6):5699–5708. https://doi.org/10.1021/acsnano.8b01510

    Article  CAS  PubMed  Google Scholar 

  138. Tinnefeld P, Acuna GP, Wei Q, Ozcan A, Vietz C, Lalkens B, Trofymchuk K, Close CM, Inan H, Ochmann S, Grabenhorst L, Glembockyte V (2019) DNA origami nanotools for single-molecule biosensing and superresolution microscopy. In: Biophotonics congress: optics in the life sciences congress 2019 (BODA,BRAIN,NTM,OMA,OMP), Tucson, 2019/04/15. OSA Technical Digest. Optical Society of America, p AW5E.5. https://doi.org/10.1364/oma.2019.aw5e.5

  139. Kwon PS, Ren S, Kwon S-J, Kizer ME, Kuo L, Xie M, Zhu D, Zhou F, Zhang F, Kim D, Fraser K, Kramer LD, Seeman NC, Dordick JS, Linhardt RJ, Chao J, Wang X (2020) Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition. Nat Chem 12(1):26–35. https://doi.org/10.1038/s41557-019-0369-8

    Article  CAS  PubMed  Google Scholar 

  140. Fang W, Jia S, Chao J, Wang L, Duan X, Liu H, Li Q, Zuo X, Wang L, Wang L, Liu N, Fan C (2019) Quantizing single-molecule surface-enhanced Raman scattering with DNA origami metamolecules. Sci Adv 5(9):eaau4506. https://doi.org/10.1126/sciadv.aau4506

    Article  PubMed  PubMed Central  Google Scholar 

  141. Jasinski D, Haque F, Binzel DW, Guo P (2017) Advancement of the emerging field of RNA nanotechnology. ACS Nano 11(2):1142–1164. https://doi.org/10.1021/acsnano.6b05737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Leontis NB, Westhof E (2014) Self-assembled RNA nanostructures. Science 345(6198):732. https://doi.org/10.1126/science.1257989

    Article  CAS  PubMed  Google Scholar 

  143. Han D, Qi X, Myhrvold C, Wang B, Dai M, Jiang S, Bates M, Liu Y, An B, Zhang F, Yan H, Yin P (2017) Single-stranded DNA and RNA origami. Science 358(6369):eaao2648. https://doi.org/10.1126/science.aao2648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Praetorius F, Dietz H (2017) Self-assembly of genetically encoded DNA–protein hybrid nanoscale shapes. Science 355(6331):eaam5488. https://doi.org/10.1126/science.aam5488

    Article  CAS  PubMed  Google Scholar 

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Funding

Xing Wang was funded by HT Materials Corporation. Jinwei Duan was funded by Natural Science Foundation of Shaanxi Province (Nos. 2017JQ2035, 2018JQ2023) and Fundamental Research Funds for the Central Universities (No. 300102129101).

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Authors and Affiliations

  1. Department of Chemistry and Materials Science, College of Sciences, Chang’an University, Xi’an, 710064, Shaanxi, People’s Republic of China

    Jinwei Duan

  2. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Jinwei Duan & Xing Wang

  3. Holonyak Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Jinwei Duan & Xing Wang

  4. Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Xing Wang

  5. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Megan E. Kizer

  6. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Megan E. Kizer

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  1. Jinwei Duan
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  2. Xing Wang
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This article is part of the Topical Collection “DNA Nanotechnology: From Structure to Functionality”, edited by Chunhai Fan and Yonggang Ke.

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Duan, J., Wang, X. & Kizer, M.E. Biotechnological and Therapeutic Applications of Natural Nucleic Acid Structural Motifs. Top Curr Chem (Z) 378, 26 (2020). https://doi.org/10.1007/s41061-020-0290-z

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