Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Aptamers come of age – at last

Nature Reviews Microbiology volume 4, pages 588–596 (2006)Cite this article

Key Points

  • Nucleic-acid aptamers can be isolated robotically in vitro to provide novel molecular recognition tools for research. They can be developed for use in various applications, including diagnostics and therapeutics.

  • Most molecular targets can be used to isolate tightly binding aptamers, potentially extending aptamer application to most molecular sciences.

  • Analysis of aptamers has yielded insights into the evolution of natural protein/ligand–nucleic-acid complexes.

  • Small-molecule ligand binding to RNA aptamers often induces conformational changes that can be used to develop novel diagnostic reagents.

  • Nature has made use of these properties to evolve riboswitches — sequence elements that directly regulate gene expression at the level of mRNA in response to ligand binding and temperature changes.

  • Clinically effective aptamer drugs are now entering use and many more are in clinical trials.

  • Research has identified a large number of potential anti-viral aptamers, including those targeted against HIV, hepatitis C virus and influenza virus.

Abstract

Nucleic-acid aptamers have the molecular recognition properties of antibodies, and can be isolated robotically for high-throughput applications in diagnostics, research and therapeutics. Unlike antibodies, however, they can be chemically derivatized easily to extend their lifetimes in biological fluids and their bioavailability in animals. The first aptamer-based clinical drugs have recently entered service. Meanwhile, active research programmes have identified a wide range of anti-viral aptamers that could form the basis for future therapeutics.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Basic outline of a single SELEX round.
Figure 2: Structural lessons from RNA aptamer–protein complexes.
Figure 3: Schematic showing the use of aptamers in array formats.

Similar content being viewed by others

References

  1. Kruger, K. et al. Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena. Cell 31, 147–157 (1982).

    CAS  PubMed  Google Scholar 

  2. Stark, B. C., Kole, R., Bowman, E. J. & Altman, S. Ribonuclease P: an enzyme with an essential RNA component. Proc. Natl Acad. Sci. USA 75, 3712–3721 (1978).

    Google Scholar 

  3. Robertson, D. L. & Joyce, G. F. Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature Struct. Biol. 344, 467–468 (1990).

    CAS  Google Scholar 

  4. Tuerk, C. & Gold, L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA-polymerase. Science 249, 505–510 (1990). This paper describes the first use of the term SELEX and explains the basics of the process.

    CAS  PubMed  Google Scholar 

  5. 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 

  6. Wilson, C. & Szostak, J. W. In vitro evolution of a self-alkylatlng ribozyme. Nature 374, 766–767 (1995).

    Google Scholar 

  7. Seelig, B. & Jaschke, A. A small catalytic RNA motif with Diels–Alderase activity. Chem. Biol. 6, 167–176 (1999).

    CAS  PubMed  Google Scholar 

  8. Gilbert, W. The RNA world. Nature 319, 818 (1986).

    Google Scholar 

  9. Cox, J. C. et al. Automated selection of aptamers against protein targets translated in vitro: from gene to aptamer. Nucleic Acids Res. 30, e108 (2002).

    PubMed Central  PubMed  Google Scholar 

  10. Cox, J. C., Rudolph, P. & Ellington, A. D. Automated RNA selection. Biotechnol. Prog. 14, 845–850 (1998).

    CAS  PubMed  Google Scholar 

  11. Ellington, A. D., Cox, J. C., Lee, J. F. & Collett, J. R. in The RNA World 3rd edn (eds Gesteland, R. F., Cech, T. R. & Atkins, J. F.) 683–719 (Cold Spring Harbor Press, New York, 2006). This chapter explains the basic considerations of all aptamer isolation experiments from initial pool diversity and library size to high-throughput techniques. Applications of aptamers are also briefly discussed.

    Google Scholar 

  12. Mandal, M. & Breaker, R. R. Gene regulation by riboswitches. Nature Rev. Mol. Cell Biol. 5, 451–463 (2004).

    CAS  Google Scholar 

  13. Tucker, B. J. & Breaker, R. R. Riboswitches as versatile gene control elements. Curr. Opin. Struct. Biol. 15, 342–348 (2005).

    CAS  PubMed  Google Scholar 

  14. Schachat, A. P. New treatments for age-related macular degeneration. Ophthalmology 112, 531–532 (2005).

    PubMed  Google Scholar 

  15. Lee, J. H. et al. A therapeutic aptamer inhibits angiogenesis by specifically targeting the heparin binding domain of VEGF165. Proc. Natl Acad. Sci. USA 102, 18902–18907 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Ng, E. W. M. et al. Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nature Rev. Drug Discov. 5, 123–132 (2006). This paper describes the various steps in creating the first clinically available therapeutic aptamer, from initial isolation to subsequent development.

    CAS  Google Scholar 

  17. Shtatland, T. et al. Interactions of Escherichia coli RNA with bacteriophage MS2 coat protein: genomic SELEX. Nucleic Acids Res. 28, e93 (2000).

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Hirao, I., Spingola, M., Peabody, D. & Ellington, A. D. The limits of specificity: an experimental analysis with RNA aptamers to MS2 coat protein variants. Mol. Divers. 4, 75–89 (1999).

    CAS  Google Scholar 

  19. Rowsell, S. et al. Crystal structures of a series of RNA aptamers complexed to the same protein target. Nature Struct. Biol. 5, 970–975 (1998).

    CAS  PubMed  Google Scholar 

  20. Convery, M. A. et al. The crystal structure of an RNA aptamer protein complex at 2.8Å resolution. Nature Struct. Biol. 5, 133–139 (1998).

    CAS  PubMed  Google Scholar 

  21. He, Y.-Y., Stockley, P. G. & Gold, L. In vitro evolution of the DNA binding sites of Escherichia coli methionine repressor, MetJ. J. Mol. Biol. 255, 55–66 (1996).

    CAS  PubMed  Google Scholar 

  22. Wang, Y. & Rando, R. R. Specific binding of aminoglycoside antibiotics to RNA. Chem. Biol. 2, 281–290 (1995).

    CAS  PubMed  Google Scholar 

  23. Wallace, S. T. & Schroeder, R. In vitro selection and characterization of RNAs with high affinity to antibiotics. Meth. Enzymol. 318, 214–229 (2000).

    CAS  Google Scholar 

  24. Jiang, L. & Patel, D. J. Solution structure of the tobramycin-RNA aptamer complex. Nature Struct. Biol. 5, 769–774 (1998).

    CAS  PubMed  Google Scholar 

  25. Tereshko, V., Skripkin, E. & Patel, D. J. Encapsulating streptomycin within a small 40-mer RNA. Chem. Biol. 10, 175–187 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Serganov, A. et al. Structural basis for Diels–Alder ribozyme-catalyzed carbon–carbon bond formation. Nature Struct. Mol. Biol. 12, 218–224 (2005).

    CAS  Google Scholar 

  27. Khati, M. et al. Neutralization of infectivity of diverse R5 clinical isolates of human immunodeficiency virus type 1 by gp120-binding 2′ F-RNA aptamers. J. Virol. 77, 12692–12698 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Misono, T. S. & Kumar, P. K. R. Selection of RNA aptamers against human influenza virus hemagglutinin using surface plasmon resonance. Anal. Biochem. 342, 312–317 (2005).

    CAS  PubMed  Google Scholar 

  29. Berezovski, M. et al. Nonequilibrium capillary electrophoresis of equilibrium mixtures: a universal tool for development of aptamers. J. Am. Chem. Soc. 127, 3165–3171 (2005).

    CAS  PubMed  Google Scholar 

  30. Pieken, W. A., Olsen, D. B., Benseler, F., Aurup, H. & Eckstein, F. Kinetic characterisation of ribonuclease-resistant hammerhead ribozymes. Science 253, 314–316 (1991).

    CAS  PubMed  Google Scholar 

  31. Beigelman, L. et al. Chemical modification of hammerhead ribozymes. Catalytic activity and nuclease resistance. J. Biol. Chem. 270, 25702–25708 (1995). This paper shows how incorporation of modified nucleotides can dramatically increase the half-lives of aptamers.

    CAS  PubMed  Google Scholar 

  32. Chelliserrykattil, J. & Ellington, A. D. Evolution of a T7 RNA polymerase variant that transcribes 2′-O-methyl RNA. Nature Biotechnol. 22, 1155–1160 (2004).

    CAS  Google Scholar 

  33. Kato, Y. et al. New NTP analogs: the synthesis of 4′-thioUTP and 4′-thioCTP and their utility for SELEX. Nucleic Acids Res. 33, 2942–2951 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Klussmann, S., Nolte, A., Bald, R., Erdmann, V. A. & Fürste, J. P. Mirror-image RNA that binds D-adenosine. Nature Biotechnol. 14, 1112–1115 (1996). This paper outlines an alternative approach to generate nuclease-resistant aptamers that relies on the use of chemical symmetry to create aptamers based on L -ribose.

    CAS  Google Scholar 

  35. Osborne, S. E., Völker, J., Stevens, S. Y., Breslauer, K. J. & Glick, G. D. Design, synthesis and analysis of disulphide cross-linked DNA duplexes. J. Am. Chem. Soc. 118, 11993–12003 (1996).

    CAS  Google Scholar 

  36. Willis, M. C. et al. Liposome anchored vascular endothelial growth factor aptamers. Bioconjug. Chem. 9, 573–582 (1998).

    CAS  PubMed  Google Scholar 

  37. Ruckman, J. et al. 2′-Fluoropyrimidine RNA-based aptamers to the 165-amino-acid form of the vascular endothelial growth factor (VEGF165). J. Biol. Chem. 273, 20556–20567 (1998).

    CAS  PubMed  Google Scholar 

  38. Boomer, R. M. et al. Conjugation to polyethylene glycol polymer promotes aptamer biodistribution to healthy and inflamed tissues. Oligonucleotides 15, 183–195 (2005).

    CAS  PubMed  Google Scholar 

  39. de Smidt, P. C., Doan, T. L., de Falco, S. & van Berkel, T. J. C. Association of antisense oligonucleotides with lipoproteins prolongs the plasma half-life and modifies the tissue distribution. Nucleic Acids Res. 19, 4695–4700 (1991).

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Dougan, H. et al. Extending the lifetime of anticoagulant oligodeoxynucleotide aptamers in blood. Nucl. Med. Bio. 27, 289–297 (2000). This paper shows how further chemical modifications to aptamers can affect their biodistribution and availability.

    CAS  Google Scholar 

  41. White, W. et al. Generation of species cross-reactive aptamers using 'toggle' SELEX. Mol. Ther. 4, 567–573 (2001).

    CAS  PubMed  Google Scholar 

  42. Vater, A., Jarosch, F., Buchner, K. & Klussmann, S. Short bioactive Spiegelmers to migraine-associated calcitonin gene-related peptide rapidly identified by a novel approach: tailored-SELEX. Nucleic Acids Res. 31, el30 (2003).

    Google Scholar 

  43. Golden, M. C., Collins, B. D., Willis, M. C., Koch, T. H. Diagnostic potential of PhotoSELEX-evolved ssDNA aptamers. J. Biotechnol. 81, 167–178 (2000).

    CAS  PubMed  Google Scholar 

  44. Romig, T. S., Bell, C. & Drolet, D. W. Aptamer affinity chromatography: combinatorial chemistry applied to protein purification. J. Chromat. 731, 275–284 (1999).

    CAS  Google Scholar 

  45. Michaud, M. et al. A DNA aptamer as a new target-specific chiral selector for HPLC. J. Am. Chem. Soc. 125, 8672–8679 (2003).

    CAS  PubMed  Google Scholar 

  46. Koita, R. B., Li, L., McGown, L. B. Separation of non-target compounds by DNA aptamers. Anal. Chem. 72, 827–831 (2000).

    Google Scholar 

  47. Hartmuth, K., Vornlocher, H. P. & Luhrmann, R. Tobramycin affinity tag purification of spliceosomes. Meth. Mol. Biol. 257, 47–64 (2004).

    CAS  Google Scholar 

  48. Murphy, M. B., Fuller, S. T., Richardson, P. M. & Doyle, S. A. An improved method for the in vitro evolution of aptamers and applications in protein detection and purification. Nucleic Acids Res. 31, e110 (2003).

    PubMed Central  PubMed  Google Scholar 

  49. Seiwert, S. D., Nahreini, T. S., Aigner, S., Ahn, N. G. & Uhlenbeck, O. C. RNA aptamers as pathway-specific MAP kinase inhibitors. Chem. Biol. 7, 833–843 (2000).

    CAS  PubMed  Google Scholar 

  50. Vuyisich, M. & Beal, P. A. Controlling protein activity with ligand-regulated RNA aptamers. Chem. Biol. 9, 907–913 (2002). This paper demonstrates the use of aptamers to regulate protein activity, showing how aptamers can be activated and de-activated at will, making them more useful than conventional diagnostic and therapeutic agents.

    CAS  PubMed  Google Scholar 

  51. Rusconi, C. P. et al. Aptamers as reversible antagonists of coagulation factor IXa. Nature 419, 90–94 (2002).

    CAS  PubMed  Google Scholar 

  52. Heckel, A. & Mayer, G. Light regulation of aptamer activity: an anti-thrombin aptamer with caged thymidine nucleobases. J. Am. Chem. Soc. 127, 822–823 (2005).

    CAS  PubMed  Google Scholar 

  53. Mayer, G., Kröck, L., Mikat, V., Engeser, M. & Heckel, A. Light-induced formation of G-quadruplex DNA secondary structures. Chem. Biochem. 6, 1966–1970 (2005).

    CAS  Google Scholar 

  54. Brockstedt, U., Uzaroeska, A., Montpetit, A., Pfau, W. & Labuda, D. In vitro evolution of RNA aptamers recognizing carcinogenic aromatic amines. Biochem. Biophys. Res. Commun. 313, 1004–1008 (2003).

    Google Scholar 

  55. Stojanovic, M. N. & Kolpashchikov, D. M. Modular aptameric sensors. J. Am. Chem. Soc. 126, 9226–9270 (2004).

    Google Scholar 

  56. Brody, E. N. et al. The use of aptamers in large scale arrays for molecular diagnosis. Mol. Diag. 4, 381–387 (1999).

    CAS  Google Scholar 

  57. Collett, J. R., Cho, E. J. & Ellington, A. D. Production and processing of aptamer microarrays. Methods 37, 4–15 (2005).

    CAS  PubMed  Google Scholar 

  58. Yamamoto-Fujita, R. & Kumar, P. K. R. Aptamer-derived nucleic acid oligos: applications to develop nucleic acid chips to analyze proteins and small ligands. Anal. Chem. 77 17, 5460–5466 (2005).

    Google Scholar 

  59. Levy, M., Cater, S. F. & Ellington, A. D. Quantum-dot aptamer beacons for the detection of proteins. Chem. Biochem. 6, 2163–2166 (2005).

    CAS  Google Scholar 

  60. Liu, J. & Lu, Y. Fast colorimetric sensing of adenosine and cocaine based on a general sensor design involving aptamers and nanoparticles. Angew. Chem. Int. Ed. Engl. 45, 90–94 (2006).

    CAS  Google Scholar 

  61. Tu, D., Blaha, G., Moore, P. B. & Steitz, T. A. Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell 121, 257–270 (2005).

    CAS  PubMed  Google Scholar 

  62. Varghese, J. N., Epa, V. C. & Colman, P. M. Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase. Protein Sci. 4, 1081–1087 (1995).

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Sandberg, J. A. et al. Pharmacokinetics and tolerability of an antiangiogenic ribozyme (Angiozyme) in healthy volunteers. J. Clin. Pharmacol. 40, 1462–1469 (2000). This paper outlines the biodistribution, bioavailability and clearance of RNA-based therapeutics.

    CAS  PubMed  Google Scholar 

  64. Dzau, V. J., Mann, M. J., Morishita, R. & Kandea, Y. Fusigenic viral liposome for gene therapy in cardiovascular diseases. Proc. Natl Acad. Sci. USA 93, 11421–11425 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Usman, N. & Blatt, L. M. Nuclease-resistant synthetic ribozymes: developing a new class of therapeutics. J. Clin. Invest. 106, 1197–1202 (2000).

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Chaloin, L., Lehmann, M. J., Sczakiel, G. & Restle, T. Endogenous expression of a high-affinity pseudoknot RNA aptamer suppresses replication of HIV-1. Nucleic Acid Res. 30, 4001–4008 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Good, P. D. et al. Expression of small, therapeutic RNAs in human cell nuclei. Gene Ther. 4, 45–54 (1997).

    CAS  PubMed  Google Scholar 

  68. Sullenger, B. A., Gallardo, H. F., Ungers, G. E. & Gilboa, E. Over-expression of TAR sequences renders cells resistant to human immunodeficiency virus replication. Cell 63, 601–608 (1990).

    CAS  PubMed  Google Scholar 

  69. Jellinek, D., Green, L. S., Bell, C. & Janjic, N. Inhibition of receptor-binding by high-affinity RNA ligands to vascular endothelial growth-factor. Biochem. 33, 10450–10456 (1994).

    CAS  Google Scholar 

  70. Cerchia, L., Hamm, J., Libri, D., Tavitian, B. & Francisics, V. Nucleic acid aptamers in cancer medicine. FEBS lett. 528, 12–16 (2002). This paper is a short review of the use of aptamers in the treatment of cancers.

    CAS  PubMed  Google Scholar 

  71. Ylera, F., Lurz, R., Erdmann, V. A. & Fürste, J. P. Selection of RNA aptamers to the Alzheimer's disease amyloid peptide. Biochem. Biophys. Res. Commun. 290, 1583–1588 (2002).

    CAS  PubMed  Google Scholar 

  72. Sayer, N. M. et al. Structural determinants of conformationally selective, prion-binding aptamers. J. Biol. Chem. 279, 13102–13109 (2004).

    CAS  PubMed  Google Scholar 

  73. Rhie, A. et al. Characterization of 2′-fluoro-RNA aptamers that bind preferentially to disease-associated conformations of prion protein and inhibit conversion. J. Biol. Chem. 278, 39697–39705 (2003).

    CAS  PubMed  Google Scholar 

  74. Charlton, J., Sennello, J. & Smith, D. In vivo imaging of inflammation using an aptamer inhibitor of human neutrophil elastase. Chem. Biol. 4, 809–816 (1997).

    CAS  PubMed  Google Scholar 

  75. Held, D. M., Kissel, J. D., Patterson, J. T., Nickens, D. G. & Burke, D. H. HIV-1 inactivation by nucleic acid aptamers. Front. Biosci. 11, 89–112 (2006). This paper provides a comprehensive review of aptamers targeting various crucial proteins in HIV.

    CAS  PubMed  Google Scholar 

  76. Tuerk, C., MacDougal, S. & Gold, L. RNA pseudoknots that inhibit human immunodeficiency virus type 1 reverse transcriptase. Proc. Natl Acad. Sci. USA 89, 6988–6992 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Nickens, D. G., Patterson, J. T. & Burke, D. H. Inhibition of HIV-1 reverse transcriptase by RNA aptamers in Escherichia coli. RNA 9, 1029–1033 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Allen, P., Worland, S. & Gold, L. Isolation of high affinity RNA ligands to HIV-1 integrase from a random pool. Virol. 209, 327–336 (1995).

    CAS  Google Scholar 

  79. Dey, A. K., Griffiths, C., Lea, S. M. & James, W. Structural characterization of an anti-gp120 RNA aptamer that neutralizes R5 strains of HIV-1. RNA 11, 873–884 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Dey, A. K. et al. An aptamer that neutralizes R5 strains of human immunodeficiency virus type 1 blocks gp120-CCR5 interaction. J. Virol. 79, 13806–13810 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Hwang, B. et al. Isolation of specific and high-affinity RNA aptamers against NS3 helicase domain of hepatitis C virus. RNA 10, 1277–1290 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Nishikawa, F., Funaji, K., Fukuda, K. & Nishikawa, S. In vitro selection of RNA aptamers against the HCVNS3 helicase domain. Oligonucleotides 14, 114–129 (2004).

    CAS  PubMed  Google Scholar 

  83. Fukuda, K. et al. An RNA ligand inhibits hepatitis C virus NS3 protease and helicase activities. Biochem. Biophys. Res. Commun. 325, 670–675 (2004).

    CAS  PubMed  Google Scholar 

  84. Zhan, L. S., Zhuo, H. L., Wang, H. Z., Peng, J. C. & Wang, Q. L. Screening and characterization of aptamers of hepatitis C virus NS3 helicase. Prog. Biochem. Biophys. 32, 245–250 (2005).

    CAS  Google Scholar 

  85. Hwang, B. & Lee, S. W. Analysis of in vivo interaction of HCVNS3 protein and specific RNA aptamer with yeast three-hybrid system. J. Micro. Biotechnol. 15, 660–664 (2005).

    CAS  Google Scholar 

  86. Bellecave, P. et al. Selection of DNA aptamers that bind the RNA-dependent RNA polymerase of hepatitis C virus and inhibit viral RNA synthesis in vitro. Oligonucleotides 13, 455–463 (2003).

    CAS  PubMed  Google Scholar 

  87. Romero-Lopez, C., Barroso- del Jesus, A., Puerta-Fernandez, E. & Berzal-Herranz, A. Interfering with hepatitis C virus IRES activity using RNA molecules identified by a novel in vitro selection method. Biol. Chem. 386, 183–190 (2005).

    CAS  PubMed  Google Scholar 

  88. Kikuchi, K. et al. A hepatitis C virus (HCV) internal ribosome entry site (IRES) domain III-IV-targeted aptamer inhibits translation by binding to an apical loop of domain IIId. Nucleic Acids Res. 33, 683–692 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Wang, J., Jiang, H. & Liu, F. In vitro selection of novel RNA ligands that bind human cytomegalovirus and block viral infection. RNA 6, 571–583 (2000).

    CAS  PubMed Central  PubMed  Google Scholar 

  90. 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 

  91. Davidson, E. A. & Ellington, A. D. Engineering regulatory RNAs. Trends Biotechnol. 23, 109–112 (2005).

    CAS  PubMed  Google Scholar 

  92. Johansson, J. et al. An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell 110, 551–561 (2002).

    PubMed  Google Scholar 

  93. Winkler, W. C., Nahvi, A., Roth, A., Collins, J. A. & Breaker, R. R. Control of gene expression by a natural metabolite-responsive ribozyme. Nature 428, 281–286 (2004).

    CAS  PubMed  Google Scholar 

  94. Yen, L. et al. Exogenous control of mammalian gene expression through modulation of RNA self-cleavage. Nature 431, 471–476 (2004).

    CAS  PubMed  Google Scholar 

  95. Thompson, K. M., Syrett, H. A., Knudsen, S. M. & Ellington, A. D. Group I aptazymes as genetic regulatory switches. BMC Biotechnol. 2, 21 (2002).

    PubMed Central  PubMed  Google Scholar 

  96. Isaacs, F. J. et al. Engineered riboregulators enable post-transcriptional control of gene expression. Nature Biotechnol. 22, 841–847 (2004).

    CAS  Google Scholar 

  97. Laserson, U., Gan, H. H. & Schlick, T. Predicting candidate genomic sequences that correspond to synthetic functional RNA motifs. Nucleic Acids Res. 33, 6057–6069 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Desai, S. K. & Gallivan, J. P. Genetic screens and selections for small molecules based on a synthetic riboswitch that activates protein translation. J. Am. Chem. Soc. 126, 13247–13254 (2004).

    CAS  PubMed  Google Scholar 

  100. Serganov, A. et al. Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs. Chem. Biol. 11, 1729–1741 (2004). This paper reports the first crystal structures for purine responsive riboswitches with bound effector bases. The molecular basis of base discrimination and ligand-sensor domain folding are revealed.

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank D. Burke, A. Ellington, M. Famulok and W. James for helpful comments during the preparation of this manuscript and for sharing unpublished or recent work from their laboratories. We thank W. Horn for providing figure 2. Aptamer research in the P.G.S. laboratory is supported by the UK Medical Research Council and the Biotechnology and Biological Sciences Research Council, and by The Wellcome Trust and The Leverhulme Trust.

Author information

Authors and Affiliations

  1. Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK

    David H. J. Bunka & Peter G. Stockley

Authors
  1. David H. J. Bunka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter G. Stockley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter G. Stockley.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

Entrez Genome Project

FMDV

FURTHER INFORMATION

Peter Stockley's homepage

The Ellington Laboratory Aptamer Database

Glossary

Macular degeneration

A condition in which the light-sensing cells of the macula, which is in the centre of the retina, malfunction and cease to work, leading to reduction or loss of central vision. The disease can be caused by the leakage of newly forming blood vessels into the retina and it is this process that is susceptible to treatment by Macugen.

Sequence space

All the possible sequence combinations in a nucleic-acid library used for SELEX. As there are many such sequences, it is unlikely that all possible combinations of sequence and function have been 'tried' during evolution.

Surface plasmon resonance

(SPR). A technique for monitoring the affinity between molecules in solution (analytes) as they pass across an immobilized target on the SPR sensorchip. In aptamer research, this technique is used to collect slowly dissociating aptamer species that have higher affinity than those that elute early.

Spiegelmers

A term derived from the German word for mirror. These are RNA aptamers synthesized chemically with L-ribose instead of the natural D-ribose and are therefore resistant to nuclease action.

Enantiomer

Two molecular structures that have identical chemical compositions but are non-superimposable in three dimensions — they are mirror images of each other. For amino acids and ribose sugars these are known as the D- and L-forms.

Capillary electrochromatography

A collection of separation techniques, which involve the application of high voltages across buffer-filled capillaries to achieve separations based on a range of different physical properties.

Pseudoknot

A common three-dimensional feature of RNA, in which bases in a single-stranded loop base pair with complementary bases outside that loop. Pseudoknots are commonly used recognition and control elements in vivo but often stabilize selected aptamers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bunka, D., Stockley, P. Aptamers come of age – at last. Nat Rev Microbiol 4, 588–596 (2006). https://doi.org/10.1038/nrmicro1458

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro1458

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing