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Aptamers and riboswitches: perspectives in biotechnology


Aptamers are short, single stranded nucleic acids which bind a wide range of different ligands with extraordinary high binding affinity and specificity. The steadily increasing number of aptamers is accompanied by an expanding range of applications in biotechnology. We will describe new developments in the field including the use of aptamers for conditional gene regulation and as biosensors. In addition, we will discuss the potential of aptamers as tags to visualize RNA and protein distribution in living cells and as therapeutics. Furthermore, we will consider biotechnological applications of riboswitches for gene regulation and as drug target.

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  1. Adler A, Forster N, Homann M, Goringer HU (2008) Post-SELEX chemical optimization of a trypanosome-specific RNA aptamer. Comb Chem High Throughput Screen 11:16–23

  2. An CI, Trinh VB, Yokobayashi Y (2006) Artificial control of gene expression in mammalian cells by modulating RNA interference through aptamer-small molecule interaction. RNA 12:710–716

  3. Apte RS (2008) Pegaptanib sodium for the treatment of age-related macular degeneration. Expert Opin Pharmacother 9:499–508

  4. Babendure JR, Adams SR, Tsien RY (2003) Aptamers switch on fluorescence of triphenylmethane dyes. J Am Chem Soc 125:14716–14717

  5. Beisel CL, Bayer TS, Hoff KG, Smolke CD (2008) Model-guided design of ligand-regulated RNAi for programmable control of gene expression. Mol Syst Biol 4:224

  6. Bertrand E, Chartrand P, Schaefer M, Shenoy SM, Singer RH, Long RM (1998) Localization of ASH1 mRNA particles in living yeast. Mol Cell 2:437–445

  7. Blount KF, Wang JX, Lim J, Sudarsan N, Breaker RR (2007) Antibacterial lysine analogs that target lysine riboswitches. Nat Chem Biol 3:44–49

  8. Cao X, Li S, Chen L, Ding H, Xu H, Huang Y, Li J, Liu N, Cao W, Zhu Y, Shen B, Shao N (2009) Combining use of a panel of ssDNA aptamers in the detection of Staphylococcus aureus. Nucleic Acids Res 37(14):4621–4628

  9. Cheah MT, Wachter A, Sudarsan N, Breaker RR (2007) Control of alternative RNA splicing and gene expression by eukaryotic riboswitches. Nature 447:497–500

  10. Chen X, Li N, Ellington AD (2007) Ribozyme catalysis of metabolism in the RNA world. Chem Biodivers 4:633–655

  11. Cox JC, Ellington AD (2001) Automated selection of anti-protein aptamers. Bioorg Med Chem 9:2525–2531

  12. de-los Santos-Alvarez N, Lobo-Castanon MJ, Miranda-Ordieres AJ, Tunon-Blanco P (2007) Modified-RNA aptamer-based sensor for competitive impedimetric assay of neomycin B. J Am Chem Soc 129:3808–3809

  13. Desai SK, Gallivan JP (2004) Genetic screens and selections for small molecules based on a synthetic riboswitch that activates protein translation. J Am Chem Soc 126:13247–13254

  14. Ehrentreich-Forster E, Orgel D, Krause-Griep A, Cech B, Erdmann VA, Bier F, Scheller FW, Rimmele M (2008) Biosensor-based on-site explosives detection using aptamers as recognition elements. Anal Bioanal Chem 391:1793–1800

  15. Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822

  16. Eulberg D, Buchner K, Maasch C, Klussmann S (2005) Development of an automated in vitro selection protocol to obtain RNA-based aptamers: identification of a biostable substance P antagonist. Nucleic Acids Res 33:e45

  17. Eydeler K, Magbanua E, Werner A, Ziegelmuller P, Hahn U (2009) Fluorophore binding aptamers as a tool for RNA visualization. Biophys J 96:3703–3707

  18. Fowler CC, Brown ED, Li Y (2008) A FACS-based approach to engineering artificial riboswitches. ChemBioChem 9:1906–1911

  19. Grate D, Wilson C (2001) Inducible regulation of the S. cerevisiae cell cycle mediated by an RNA aptamer-ligand complex. Bioorg Med Chem 9:2565–2570

  20. Gusti V, Kim DS, Gaur RK (2008) Sequestering of the 3′ splice site in a theophylline-responsive riboswitch allows ligand-dependent control of alternative splicing. Oligonucleotides 18:93–99

  21. Hafner M, Vianini E, Albertoni B, Marchetti L, Grune I, Gloeckner C, Famulok M (2008) Displacement of protein-bound aptamers with small molecules screened by fluorescence polarization. Nat Protoc 3:579–587

  22. Hanson S, Berthelot K, Fink B, McCarthy JE, Suess B (2003) Tetracycline-aptamer-mediated translational regulation in yeast. Mol Microbiol 49:1627–1637

  23. Harvey I, Garneau P, Pelletier J (2002) Inhibition of translation by RNA-small molecule interactions. RNA 8:452–463

  24. Hermann T, Patel DJ (2000) Adaptive recognition by nucleic acid aptamers. Science 287:820–825

  25. Holeman LA, Robinson SL, Szostak JW, Wilson C (1998) Isolation and characterization of fluorophore-binding RNA aptamers. Fold Des 3:423–431

  26. Homann M, Lorger M, Engstler M, Zacharias M, Goringer HU (2006) Serum-stable RNA aptamers to an invariant surface domain of live African trypanosomes. Comb Chem High Throughput Screen 9:491–499

  27. Huang CC, Chang HT (2008) Aptamer-based fluorescence sensor for rapid detection of potassium ions in urine. Chem Commun (Camb) 12:1461–1463

  28. Jo JJ, Shin JS (2009) Construction of intragenic synthetic riboswitches for detection of a small molecule. Biotechnol Lett. doi:

  29. Kim DS, Gusti V, Pillai SG, Gaur RK (2005) An artificial riboswitch for controlling pre-mRNA splicing. RNA 11:1667–1677

  30. Kim DS, Gusti V, Dery KJ, Gaur RK (2008) Ligand-induced sequestering of branchpoint sequence allows conditional control of splicing. BMC Mol Biol 9:23

  31. Kotter P, Weigand JE, Meyer B, Entian KD, Suess B (2009) A fast and efficient translational control system for conditional expression of yeast genes. Nucleic Acids Res. doi:

  32. Lee ER, Blount KF, Breaker RR (2009a) Roseoflavin is a natural antibacterial compound that binds to FMN riboswitches and regulates gene expression. RNA Biol 6(2)

  33. Lee HJ, Kim BC, Kim KW, Kim YK, Kim J, Oh MK (2009b) A sensitive method to detect Escherichia coli based on immunomagnetic separation and real-time PCR amplification of aptamers. Biosens Bioelectron 24(12):3550–3555

  34. Levy M, Griswold KE, Ellington AD (2005) Direct selection of trans-acting ligase ribozymes by in vitro compartmentalization. RNA 11:1555–1562

  35. Li W, Yang X, Wang K, Tan W, He Y, Guo Q, Tang H, Liu J (2008) Real-time imaging of protein internalization using aptamer conjugates. Anal Chem 80:5002–5008

  36. Liss M, Petersen B, Wolf H, Prohaska E (2002) An aptamer-based quartz crystal protein biosensor. Anal Chem 74:4488–4495

  37. Liu CW, Huang CC, Chang HT (2009) Highly selective DNA-based sensor for lead(II) and mercury(II) ions. Anal Chem 81:2383–2387

  38. Lynch SA, Gallivan JP (2009) A flow cytometry-based screen for synthetic riboswitches. Nucleic Acids Res 37:184–192

  39. Lynch SA, Desai SK, Sajja HK, Gallivan JP (2007) A high-throughput screen for synthetic riboswitches reveals mechanistic insights into their function. Chem Biol 14:173–184

  40. Mayer G (2009) The chemical biology of aptamers. Angew Chem Int Ed Engl 48:2672–2689

  41. Muranaka N, Sharma V, Nomura Y, Yokobayashi Y (2009) An efficient platform for genetic selection and screening of gene switches in Escherichia coli. Nucleic Acids Res 37:e39

  42. Nomura Y, Yokobayashi Y (2007) Reengineering a natural riboswitch by dual genetic selection. J Am Chem Soc 129:13814–13815

  43. Ott E, Stolz J, Lehmann M, Mack M (2009) The RFN riboswitch of Bacillus subtilis is a target for the antibiotic roseoflavin produced by Streptomyces davawensis. RNA Biol 6

  44. Roth A, Breaker RR (2009) The structural and functional diversity of metabolite-binding riboswitches. Annu Rev Biochem 78:305–334

  45. Sando S, Narita A, Aoyama Y (2007) Light-up Hoechst-DNA aptamer pair: generation of an aptamer-selective fluorophore from a conventional DNA-staining dye. ChemBioChem 8:1795–1803

  46. Serganov A, Huang L, Patel DJ (2008) Structural insights into amino acid binding and gene control by a lysine riboswitch. Nature 455:1263–1267

  47. Serganov A, Huang L, Patel DJ (2009) Coenzyme recognition and gene regulation by a flavin mononucleotide riboswitch. Nature 458:233–237

  48. Sharma V, Nomura Y, Yokobayashi Y (2008) Engineering complex riboswitch regulation by dual genetic selection. J Am Chem Soc 130:16310–16315

  49. Sparano BA, Koide K (2007) Fluorescent sensors for specific RNA: a general paradigm using chemistry and combinatorial biology. J Am Chem Soc 129:4785–4794

  50. Stadtherr K, Wolf H, Lindner P (2005) An aptamer-based protein biochip. Anal Chem 77:3437–3443

  51. Strehlitz B, Nikolaus N, Stoltenburg R (2008) Protein detection with aptamer biosensors. Sensors 8:4296–4307

  52. Sudarsan N, Cohen-Chalamish S, Nakamura S, Emilsson GM, Breaker RR (2005) Thiamine pyrophosphate riboswitches are targets for the antimicrobial compound pyrithiamine. Chem Biol 12:1325–1335

  53. Suess B, Hanson S, Berens C, Fink B, Schroeder R, Hillen W (2003) Conditional gene expression by controlling translation with tetracycline-binding aptamers. Nucleic Acids Res 31:1853–1858

  54. Suess B, Fink B, Berens C, Stentz R, Hillen W (2004) A theophylline responsive riboswitch based on helix slipping controls gene expression in vivo. Nucleic Acids Res 32:1610–1614

  55. Swensen JS, Xiao Y, Ferguson BS, Lubin AA, Lai RY, Heeger AJ, Plaxco KW, Soh HT (2009) Continuous, real-time monitoring of cocaine in undiluted blood serum via a microfluidic, electrochemical aptamer-based sensor. J Am Chem Soc 131:4262–4266

  56. Thore S, Frick C, Ban N (2008) Structural basis of thiamine pyrophosphate analogues binding to the eukaryotic riboswitch. J Am Chem Soc 130:8116–8117

  57. Topp S, Gallivan JP (2008) Riboswitches in unexpected places–a synthetic riboswitch in a protein coding region. RNA 14:2498–2503

  58. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–510

  59. Tuleuova N, An CI, Ramanculov E, Revzin A, Yokobayashi Y (2008) Modulating endogenous gene expression of mammalian cells via RNA-small molecule interaction. Biochem Biophys Res Commun 376:169–173

  60. Tyagi S (2009) Imaging intracellular RNA distribution and dynamics in living cells. Nat Methods 6:331–338

  61. Valencia-Burton M, McCullough RM, Cantor CR, Broude NE (2007) RNA visualization in live bacterial cells using fluorescent protein complementation. Nat Methods 4:421–427

  62. Wachter A, Tunc-Ozdemir M, Grove BC, Green PJ, Shintani DK, Breaker RR (2007) Riboswitch control of gene expression in plants by splicing and alternative 3′ end processing of mRNAs. Plant Cell 19:3437–3450

  63. Weigand JE, Suess B (2007) Tetracycline aptamer-controlled regulation of pre-mRNA splicing in yeast. Nucleic Acids Res 35:4179–4185

  64. Weigand JE, Sanchez M, Gunnesch EB, Zeiher S, Schroeder R, Suess B (2008) Screening for engineered neomycin riboswitches that control translation initiation. RNA 14:89–97

  65. Werstuck G, Green MR (1998) Controlling gene expression in living cells through small molecule-RNA interactions. Science 282:296–298

  66. Wieland M, Hartig JS (2008) Improved aptazyme design and in vivo screening enable riboswitching in bacteria. Angew Chem Int Ed Engl 47:2604–2607

  67. Wieland M, Benz A, Klauser B, Hartig JS (2009a) Artificial ribozyme switches containing natural riboswitch aptamer domains. Angew Chem Int Ed Engl 48:2715–2718

  68. Wieland M, Gfell M, Hartig JS (2009b) Expanded hammerhead ribozymes containing addressable three-way junctions. RNA 15:968–976

  69. Win MN, Smolke CD (2007) A modular and extensible RNA-based gene-regulatory platform for engineering cellular function. Proc Natl Acad Sci U S A 104:14283–14288

  70. Win MN, Smolke CD (2008) Higher-order cellular information processing with synthetic RNA devices. Science 322:456–460

  71. Wochner A, Cech B, Menger M, Erdmann VA, Glokler J (2007) Semi-automated selection of DNA aptamers using magnetic particle handling. Biotechniques 43:344–344, 346, 348 passim

  72. Yamazaki S, Tan L, Mayer G, Hartig JS, Song JN, Reuter S, Restle T, Laufer SD, Grohmann D, Krausslich HG, Bajorath J, Famulok M (2007) Aptamer displacement identifies alternative small-molecule target sites that escape viral resistance. Chem Biol 14:804–812

  73. Zaher HS, Unrau PJ (2007) Selection of an improved RNA polymerase ribozyme with superior extension and fidelity. RNA 13:1017–1026

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We thank Jens Wöhnert for the critical reading of the manuscript. We are grateful to the Aventis Foundation and the Deutsche Forschungsgemeinschaft for their financial support.

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Correspondence to Beatrix Suess.

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Weigand, J.E., Suess, B. Aptamers and riboswitches: perspectives in biotechnology. Appl Microbiol Biotechnol 85, 229–236 (2009).

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  • RNA
  • Aptamer
  • Riboswitch
  • Conditional gene expression
  • Biosensor