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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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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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