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Aptamers for allosteric regulation

Abstract

Aptamers are useful for allosteric regulation because they are nucleic acid–based structures in which ligand binding induces conformational changes that may alter the function of a connected oligonucleotide at a distant site. Through this approach, a specific input is efficiently converted into an altered output. This property makes these biomolecules ideally suited to function as sensors or switches in biochemical assays or inside living cells. The ability to select oligonucleotide-based recognition elements in vitro in combination with the availability of nucleic acids with enzymatic activity has led to the development of a wide range of engineered allosteric aptasensors and aptazymes. Here, we discuss recent progress in the screening, design and diversity of these conformational switching oligonucleotides. We cover their application in vitro and for regulating gene expression in both prokaryotes and eukaryotes.

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Figure 1: Signal transduction by aptamer-mediated allostery.
Figure 2: Designs of allosteric aptasensors for application in vitro.
Figure 3: Modular logic gate designs based on the HHR.
Figure 4: Allosteric ribozymes for regulation of gene expression in prokaryotes.
Figure 5: Control over eukaryotic gene expression by artificially designed allosteric RNAs.

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References

  1. Golynskiy, M.V., Koay, M.S., Vinkenborg, J.L. & Merkx, M. Engineering protein switches: sensors, regulators, and spare parts for biology and biotechnology. ChemBioChem 12, 353–361 (2011).

    CAS  PubMed  Google Scholar 

  2. Mayer, G. The chemical biology of aptamers. Angew. Chem. Int. Edn Engl. 48, 2672–2689 (2009).

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  4. Ellington, A.D. & Szostak, J.W. In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818–822 (1990).

    CAS  PubMed  Google Scholar 

  5. Famulok, M., Hartig, J.S. & Mayer, G. Functional aptamers and aptazymes in biotechnology, diagnostics, and therapy. Chem. Rev. 107, 3715–3743 (2007).

    CAS  PubMed  Google Scholar 

  6. Famulok, M. & Mayer, G. Aptamers as tools in molecular biology and immunology. Curr. Top. Microbiol. Immunol. 243, 123–136 (1999).

    CAS  PubMed  Google Scholar 

  7. Tang, J. & Breaker, R.R. Rational design of allosteric ribozymes. Chem. Biol. 4, 453–459 (1997).

    CAS  PubMed  Google Scholar 

  8. Stojanovic, M.N. & Kolpashchikov, D.M. Modular aptameric sensors. J. Am. Chem. Soc. 126, 9266–9270 (2004).

    CAS  PubMed  Google Scholar 

  9. Nudler, E. Flipping riboswitches. Cell 126, 19–22 (2006).

    CAS  PubMed  Google Scholar 

  10. Winkler, W.C. & Breaker, R.R. Genetic control by metabolite-binding riboswitches. ChemBioChem 4, 1024–1032 (2003).

    CAS  PubMed  Google Scholar 

  11. Liu, J., Cao, Z. & Lu, Y. Functional nucleic acid sensors. Chem. Rev. 109, 1948–1998 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Tombelli, S., Minunni, M. & Mascini, M. Analytical applications of aptamers. Biosens. Bioelectron. 20, 2424–2434 (2005).

    CAS  PubMed  Google Scholar 

  13. Soukup, G.A. & Breaker, R.R. Nucleic acid molecular switches. Trends Biotechnol. 17, 469–476 (1999).

    CAS  PubMed  Google Scholar 

  14. Famulok, M. Allosteric aptamers and aptazymes as probes for screening approaches. Curr. Opin. Mol. Ther. 7, 137–143 (2005).

    CAS  PubMed  Google Scholar 

  15. Mayer, G., Raddatz, M.S., Grunwald, J.D. & Famulok, M. RNA ligands that distinguish metabolite-induced conformations in the TPP riboswitch. Angew. Chem. Int. Edn Engl. 46, 557–560 (2007).

    CAS  Google Scholar 

  16. Rentmeister, A., Mayer, G., Kuhn, N. & Famulok, M. Conformational changes in the expression domain of the Escherichia coli thiM riboswitch. Nucleic Acids Res. 35, 3713–3722 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Vaish, N.K. et al. Monitoring post-translational modification of proteins with allosteric ribozymes. Nat. Biotechnol. 20, 810–815 (2002).

    CAS  PubMed  Google Scholar 

  18. Srinivasan, J. et al. ADP-specific sensors enable universal assay of protein kinase activity. Chem. Biol. 11, 499–508 (2004).

    CAS  PubMed  Google Scholar 

  19. Chiuman, W. & Li, Y. Simple fluorescent sensors engineered with catalytic DNA 'MgZ' based on a non-classic allosteric design. PLoS ONE 2, e1224 (2007).

    PubMed  PubMed Central  Google Scholar 

  20. Sekella, P.T., Rueda, D. & Walter, N.G. A biosensor for theophylline based on fluorescence detection of ligand-induced hammerhead ribozyme cleavage. RNA 8, 1242–1252 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Hartig, J.S. et al. Protein-dependent ribozymes report molecular interactions in real time. Nat. Biotechnol. 20, 717–722 (2002).

    CAS  PubMed  Google Scholar 

  22. Najafi-Shoushtari, S.H. & Famulok, M. DNA aptamer-mediated regulation of the hairpin ribozyme by human alpha-thrombin. Blood Cells Mol. Dis. 38, 19–24 (2007).

    CAS  PubMed  Google Scholar 

  23. Najafi-Shoushtari, S.H., Mayer, G. & Famulok, M. Sensing complex regulatory networks by conformationally controlled hairpin ribozymes. Nucleic Acids Res. 32, 3212–3219 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Yin, P., Choi, H.M., Calvert, C.R. & Pierce, N.A. Programming biomolecular self-assembly pathways. Nature 451, 318–322 (2008).

    CAS  PubMed  Google Scholar 

  25. Choi, H.M. et al. Programmable in situ amplification for multiplexed imaging of mRNA expression. Nat. Biotechnol. 28, 1208–1212 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Liu, J. & Lu, Y. Adenosine-dependent assembly of aptazyme-functionalized gold nanoparticles and its application as a colorimetric biosensor. Anal. Chem. 76, 1627–1632 (2004).

    CAS  PubMed  Google Scholar 

  27. Liu, J. & Lu, Y. Smart nanomaterials responsive to multiple chemical stimuli with controllable cooperativity. Adv. Mater. 18, 1667–1671 (2006).

    CAS  Google Scholar 

  28. Liu, J., Mazumdar, D. & Lu, Y. A simple and sensitive 'dipstick' test in serum based on lateral flow separation of aptamer-linked nanostructures. Angew. Chem. Int. Edn Engl. 45, 7955–7959 (2006). This application involves gold nanoparticles functionalized with allosteric aptamers in a 'dipstick' test to detect cocaine levels in serum with the naked eye.

    CAS  Google Scholar 

  29. Mazumdar, D., Liu, J., Lu, G., Zhou, J. & Lu, Y. Easy-to-use dipstick tests for detection of lead in paints using non-cross-linked gold nanoparticle-DNAzyme conjugates. Chem. Commun. (Camb.) 46, 1416–1418 (2010).

    CAS  Google Scholar 

  30. Helm, M., Petermeier, M., Ge, B., Fiammengo, R. & Jaschke, A. Allosterically activated Diels-Alder catalysis by a ribozyme. J. Am. Chem. Soc. 127, 10492–10493 (2005).

    CAS  PubMed  Google Scholar 

  31. Robertson, M.P. & Ellington, A.D. In vitro selection of an allosteric ribozyme that transduces analytes to amplicons. Nat. Biotechnol. 17, 62–66 (1999).

    CAS  PubMed  Google Scholar 

  32. Cho, E.J., Yang, L., Levy, M. & Ellington, A.D. Using a deoxyribozyme ligase and rolling circle amplification to detect a non-nucleic acid analyte, ATP. J. Am. Chem. Soc. 127, 2022–2023 (2005).

    CAS  PubMed  Google Scholar 

  33. Kim, D.E. & Joyce, G.F. Cross-catalytic replication of an RNA ligase ribozyme. Chem. Biol. 11, 1505–1512 (2004).

    CAS  PubMed  Google Scholar 

  34. Lincoln, T.A. & Joyce, G.F. Self-sustained replication of an RNA enzyme. Science 323, 1229–1232 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Lam, B.J. & Joyce, G.F. Autocatalytic aptazymes enable ligand-dependent exponential amplification of RNA. Nat. Biotechnol. 27, 288–292 (2009). Elegant example in which loop replacement yields allosteric regulation of a self-replicating RNA, providing an accumulative output in response to ligand without requiring a polymerase.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Lam, B.J. & Joyce, G.F. An isothermal system that couples ligand-dependent catalysis to ligand-independent exponential amplification. J. Am. Chem. Soc. 133, 3191–3197 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Travascio, P., Li, Y. & Sen, D. DNA-enhanced peroxidase activity of a DNA-aptamer-hemin complex. Chem. Biol. 5, 505–517 (1998).

    CAS  PubMed  Google Scholar 

  38. Pelossof, G., Tel-Vered, R., Elbaz, J. & Willner, I. Amplified biosensing using the horseradish peroxidase-mimicking DNAzyme as an electrocatalyst. Anal. Chem. 82, 4396–4402 (2010).

    CAS  PubMed  Google Scholar 

  39. Teller, C., Shimron, S. & Willner, I. Aptamer-DNAzyme hairpins for amplified biosensing. Anal. Chem. 81, 9114–9119 (2009).

    CAS  PubMed  Google Scholar 

  40. Li, T., Wang, E. & Dong, S. Lead(II)-induced allosteric G-quadruplex DNAzyme as a colorimetric and chemiluminescence sensor for highly sensitive and selective Pb2+ detection. Anal. Chem. 82, 1515–1520 (2010).

    CAS  PubMed  Google Scholar 

  41. Li, T., Wang, E. & Dong, S. G-quadruplex-based DNAzyme for facile colorimetric detection of thrombin. Chem. Commun. (Camb.) 3654–3656 (2008).

  42. Li, T., Dong, S. & Wang, E. Label-free colorimetric detection of aqueous mercury ion (Hg2+) using Hg2+-modulated G-quadruplex-based DNAzymes. Anal. Chem. 81, 2144–2149 (2009).

    CAS  PubMed  Google Scholar 

  43. Lu, N., Shao, C. & Deng, Z. Rational design of an optical adenosine sensor by conjugating a DNA aptamer with split DNAzyme halves. Chem. Commun. (Camb.) 6161–6163 (2008).

  44. Lu, N., Shao, C. & Deng, Z. Colorimetric Hg2+ detection with a label-free and fully DNA-structured sensor assembly incorporating G-quadruplex halves. Analyst (Lond.) 134, 1822–1825 (2009).

    CAS  Google Scholar 

  45. Elbaz, J., Moshe, M., Shlyahovsky, B. & Willner, I. Cooperative multicomponent self-assembly of nucleic acid structures for the activation of DNAzyme cascades: a paradigm for DNA sensors and aptasensors. Chemistry 15, 3411–3418 (2009).

    CAS  PubMed  Google Scholar 

  46. Constantin, T.P. et al. Synthesis of new fluorogenic cyanine dyes and incorporation into RNA fluoromodules. Org. Lett. 10, 1561–1564 (2008).

    CAS  PubMed  Google Scholar 

  47. Furutani, C., Shinomiya, K., Aoyama, Y., Yamada, K. & Sando, S. Modular blue fluorescent RNA sensors for label-free detection of target molecules. Mol. Biosyst. 6, 1569–1571 (2010).

    CAS  PubMed  Google Scholar 

  48. Yoshida, W., Sode, K. & Ikebukuro, K. Aptameric enzyme subunit for biosensing based on enzymatic activity measurement. Anal. Chem. 78, 3296–3303 (2006).

    CAS  PubMed  Google Scholar 

  49. Chelyapov, N. Allosteric aptamers controlling a signal amplification cascade allow visual detection of molecules at picomolar concentrations. Biochemistry 45, 2461–2466 (2006).

    CAS  PubMed  Google Scholar 

  50. Stojanovic, M.N., Mitchell, T.E. & Stefanovic, D. Deoxyribozyme-based logic gates. J. Am. Chem. Soc. 124, 3555–3561 (2002).

    CAS  PubMed  Google Scholar 

  51. Penchovsky, R. & Breaker, R.R. Computational design and experimental validation of oligonucleotide-sensing allosteric ribozymes. Nat. Biotechnol. 23, 1424–1433 (2005).

    CAS  PubMed  Google Scholar 

  52. Stojanovic, M.N. & Stefanovic, D. A deoxyribozyme-based molecular automaton. Nat. Biotechnol. 21, 1069–1074 (2003).

    CAS  PubMed  Google Scholar 

  53. Kolpashchikov, D.M. & Stojanovic, M.N. Boolean control of aptamer binding states. J. Am. Chem. Soc. 127, 11348–11351 (2005).

    CAS  PubMed  Google Scholar 

  54. Elbaz, J. et al. DNA computing circuits using libraries of DNAzyme subunits. Nat. Nanotechnol. 5, 417–422 (2010).A biocomputing platform with modular architecture based on a library of DNAzyme subunits, pre-designed substrates and different inputs is described.

    CAS  PubMed  Google Scholar 

  55. Yoshida, W. & Yokobayashi, Y. Photonic Boolean logic gates based on DNA aptamers. Chem. Commun. 2007, 195–197 (2007).

    Google Scholar 

  56. Win, M.N. & Smolke, C.D. A modular and extensible RNA-based gene-regulatory platform for engineering cellular function. Proc. Natl. Acad. Sci. USA 104, 14283–14288 (2007); erratum 106, 15514 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Win, M.N. & Smolke, C.D. Higher-order cellular information processing with synthetic RNA devices. Science 322, 456–460 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Klug, S.J., Huttenhofer, A., Kromayer, M. & Famulok, M. In vitro and in vivo characterization of novel mRNA motifs that bind special elongation factor SelB. Proc. Natl. Acad. Sci. USA 94, 6676–6681 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Choi, K.H. et al. Intracellular expression of the T-cell factor-1 RNA aptamer as an intramer. Mol. Cancer Ther. 5, 2428–2434 (2006).

    CAS  PubMed  Google Scholar 

  60. Famulok, M., Blind, M. & Mayer, G. Intramers as promising new tools in functional proteomics. Chem. Biol. 8, 931–939 (2001).

    CAS  PubMed  Google Scholar 

  61. Lee, H.K. et al. B-catenin regulates multiple steps of RNA metabolism as revealed by the RNA aptamer in colon cancer cells. Cancer Res. 67, 9315–9321 (2007).

    CAS  PubMed  Google Scholar 

  62. Werstuck, G. & Green, M.R. Controlling gene expression in living cells through small molecule-RNA interactions. Science 282, 296–298 (1998).

    CAS  PubMed  Google Scholar 

  63. Wieland, M. & Hartig, J.S. Artificial riboswitches: synthetic mRNA-based regulators of gene expression. ChemBioChem 9, 1873–1878 (2008).

    CAS  PubMed  Google Scholar 

  64. Suess, B. & Weigand, J.E. Engineered riboswitches: overview, problems and trends. RNA Biol. 5, 24–29 (2008).

    CAS  PubMed  Google Scholar 

  65. Win, M.N., Liang, J.C. & Smolke, C.D. Frameworks for programming biological function through RNA parts and devices. Chem. Biol. 16, 298–310 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Saito, H. & Inoue, T. Synthetic biology with RNA motifs. Int. J. Biochem. Cell Biol. 41, 398–404 (2009).

    CAS  PubMed  Google Scholar 

  67. Topp, S. & Gallivan, J.P. Emerging applications of riboswitches in chemical biology. ACS Chem. Biol. 5, 139–148 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Khvorova, A., Lescoute, A., Westhof, E. & Jayasena, S.D. Sequence elements outside the hammerhead ribozyme catalytic core enable intracellular activity. Nat. Struct. Biol. 10, 708–712 (2003).

    CAS  PubMed  Google Scholar 

  69. Wieland, M. & Hartig, J.S. Improved aptazyme design and in vivo screening enable riboswitching in bacteria. Angew. Chem. Int. Edn Engl. 47, 2604–2607 (2008).

    CAS  Google Scholar 

  70. Ogawa, A. & Maeda, M. An artificial aptazyme-based riboswitch and its cascading system in E. coli. ChemBioChem 9, 206–209 (2008).

    CAS  PubMed  Google Scholar 

  71. Wieland, M., Benz, A., Klauser, B. & Hartig, J.S. Artificial ribozyme switches containing natural riboswitch aptamer domains. Angew. Chem. Int. Edn Engl. 48, 2715–2718 (2009).

    CAS  Google Scholar 

  72. Wieland, M., Berschneider, B., Erlacher, M.D. & Hartig, J.S. Aptazyme-mediated regulation of 16S ribosomal RNA. Chem. Biol. 17, 236–242 (2010).

    CAS  PubMed  Google Scholar 

  73. Ogawa, A. & Maeda, M. A novel label-free biosensor using an aptazyme-suppressor-tRNA conjugate and an amber mutated reporter gene. ChemBioChem 9, 2204–2208 (2008).

    CAS  PubMed  Google Scholar 

  74. Berschneider, B., Wieland, M., Rubini, M. & Hartig, J.S. Small-molecule-dependent regulation of transfer RNA in bacteria. Angew. Chem. Int. Edn Engl. 48, 7564–7567 (2009). Demonstration that aminoacylation of a suppressor tRNA can be used to regulate the expression of an amber-mutated gene.

    CAS  Google Scholar 

  75. Dixon, N. et al. Reengineering orthogonally selective riboswitches. Proc. Natl. Acad. Sci. USA 107, 2830–2835 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Topp, S. & Gallivan, J.P. Guiding bacteria with small molecules and RNA. J. Am. Chem. Soc. 129, 6807–6811 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Sinha, J., Reyes, S.J. & Gallivan, J.P. Reprogramming bacteria to seek and destroy an herbicide. Nat. Chem. Biol. 6, 464–470 (2010). An application-driven approach in which bacteria are reprogrammed to move into the direction of a toxin and then to take up and metabolize this toxin.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Buskirk, A.R., Landrigan, A. & Liu, D.R. Engineering a ligand-dependent RNA transcriptional activator. Chem. Biol. 11, 1157–1163 (2004).

    CAS  PubMed  Google Scholar 

  79. Ausländer, S., Ketzer, P. & Hartig, J.S. A ligand-dependent hammerhead ribozyme switch for controlling mammalian gene expression. Mol. Biosyst. 6, 807–814 (2010). The first example of use of the full-length hammerhead ribozyme to control gene expression in mammalian cells.

    PubMed  Google Scholar 

  80. Chen, Y.Y., Jensen, M.C. & Smolke, C.D. Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems. Proc. Natl. Acad. Sci. USA 107, 8531–8536 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Ogawa, A. Rational design of artificial riboswitches based on ligand-dependent modulation of internal ribosome entry in wheat germ extract and their applications as label-free biosensors. RNA 17, 478–488 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Buratti, E. & Baralle, F.E. Influence of RNA secondary structure on the pre-mRNA splicing process. Mol. Cell. Biol. 24, 10505–10514 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Kim, D.S., Gusti, V., Pillai, S.G. & Gaur, R.K. An artificial riboswitch for controlling pre-mRNA splicing. RNA 11, 1667–1677 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Kim, D.S., Gusti, V., Dery, K.J. & Gaur, R.K. Ligand-induced sequestering of branchpoint sequence allows conditional control of splicing. BMC Mol. Biol. 9, 23 (2008).

    PubMed  PubMed Central  Google Scholar 

  85. Weigand, J.E. & Suess, B. Tetracycline aptamer-controlled regulation of pre-mRNA splicing in yeast. Nucleic Acids Res. 35, 4179–4185 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Culler, S.J., Hoff, K.G. & Smolke, C.D. Reprogramming cellular behavior with RNA controllers responsive to endogenous proteins. Science 330, 1251–1255 (2010). This paper describes ligand-induced control over gene expression through regulation of splicing activity using proteins as inputs, resulting in the ability to rewire cellular networks.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Kötter, P., Weigand, J.E., Meyer, B., Entian, K.D. & Suess, B. A fast and efficient translational control system for conditional expression of yeast genes. Nucleic Acids Res. 37, e120 (2009).

    PubMed  PubMed Central  Google Scholar 

  88. Kumar, D., An, C.I. & Yokobayashi, Y. Conditional RNA interference mediated by allosteric ribozyme. J. Am. Chem. Soc. 131, 13906–13907 (2009).

    CAS  PubMed  Google Scholar 

  89. An, C.I., Trinh, V.B. & Yokobayashi, Y. Artificial control of gene expression in mammalian cells by modulating RNA interference through aptamer-small molecule interaction. RNA 12, 710–716 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Beisel, C.L., Bayer, T.S., Hoff, K.G. & Smolke, C.D. Model-guided design of ligand-regulated RNAi for programmable control of gene expression. Mol. Syst. Biol. 4, 224 (2008).

    PubMed  PubMed Central  Google Scholar 

  91. Suess, B. et al. Conditional gene expression by controlling translation with tetracycline-binding aptamers. Nucleic Acids Res. 31, 1853–1858 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Koizumi, M., Soukup, G.A., Kerr, J.N. & Breaker, R.R. Allosteric selection of ribozymes that respond to the second messengers cGMP and cAMP. Nat. Struct. Biol. 6, 1062–1071 (1999).

    CAS  PubMed  Google Scholar 

  93. Piganeau, N., Thuillier, V. & Famulok, M. In vitro selection of allosteric ribozymes: theory and experimental validation. J. Mol. Biol. 312, 1177–1190 (2001).

    CAS  PubMed  Google Scholar 

  94. Muranaka, N., Abe, K. & Yokobayashi, Y. Mechanism-guided library design and dual genetic selection of synthetic OFF riboswitches. ChemBioChem 10, 2375–2381 (2009).

    CAS  PubMed  Google Scholar 

  95. Topp, S. & Gallivan, J.P. Random walks to synthetic riboswitches—a high-throughput selection based on cell motility. ChemBioChem 9, 210–213 (2008).

    CAS  PubMed  Google Scholar 

  96. Lynch, S.A. & Gallivan, J.P. A flow cytometry-based screen for synthetic riboswitches. Nucleic Acids Res. 37, 184–192 (2009). A fast intracellular screening approach involving fluorescence-assisted cell sorting, yielding one of the strongest selected switches for gene regulation so far.

    CAS  PubMed  Google Scholar 

  97. Fowler, C.C., Brown, E.D. & Li, Y.A. FACS-based approach to engineering artificial riboswitches. ChemBioChem 9, 1906–1911 (2008).

    CAS  PubMed  Google Scholar 

  98. Weigand, J.E. et al. Screening for engineered neomycin riboswitches that control translation initiation. RNA 14, 89–97 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Wallis, M.G., von Ahsen, U., Schroeder, R. & Famulok, M. A novel RNA motif for neomycin recognition. Chem. Biol. 2, 543–552 (1995).

    CAS  PubMed  Google Scholar 

  100. Chen, X., Denison, L., Levy, M. & Ellington, A.D. Direct selection for ribozyme cleavage activity in cells. RNA 15, 2035–2045 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Vuyisich, M. & Beal, P.A. Controlling protein activity with ligand-regulated RNA aptamers. Chem. Biol. 9, 907–913 (2002).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We apologize to authors whose work we could not cite owing to space limitations. We are grateful for funding from the Alexander von Humboldt Foundation, the North Rhine–Westphalia research school 'LIMES Chemical Biology', the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, the European Science Foundation and the European Research Council. We also thank B. Weiche for reading the manuscript.

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Vinkenborg, J., Karnowski, N. & Famulok, M. Aptamers for allosteric regulation. Nat Chem Biol 7, 519–527 (2011). https://doi.org/10.1038/nchembio.609

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