Key Points
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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.
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Most molecular targets can be used to isolate tightly binding aptamers, potentially extending aptamer application to most molecular sciences.
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Analysis of aptamers has yielded insights into the evolution of natural protein/ligand–nucleic-acid complexes.
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Small-molecule ligand binding to RNA aptamers often induces conformational changes that can be used to develop novel diagnostic reagents.
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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.
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Clinically effective aptamer drugs are now entering use and many more are in clinical trials.
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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.
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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A. Ellington, M. Famulok and W. James for helpful comments during the preparation of this manuscript and for sharing unpublished or recent work from their laboratories.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.
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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
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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
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(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
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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
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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.
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Bunka, D., Stockley, P. Aptamers come of age – at last. Nat Rev Microbiol 4, 588–596 (2006). https://doi.org/10.1038/nrmicro1458
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DOI: https://doi.org/10.1038/nrmicro1458
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