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Unnatural Nucleic Acids for Aptamer Selection

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Aptamers Selected by Cell-SELEX for Theranostics

Abstract

Aptamer and SELEX technology have been proposed over 20 years. Despite the huge success in developing aptamers against all kinds of targets, the effort to cover the natural shortages of nucleic acids, including lack of binding functional diversity and low information densities, has never been stopped. Strategies proposed to improve the aptamer properties include post-selective modifications and introducing unnatural nucleic acids in SELEX process. As a perfect binding ligand can hardly be designed and modified on purpose due to the poor understanding of the intricate biological system, the best way to generate improved aptamers would be through modified SELEX experiment, in which unnatural nucleotides are incorporated into library and perform the in vitro evolution. Those unnatural nucleotides include the modifications on almost every components of nucleic acids, (deoxy) ribose, phosphate linkage, and nucleobases. To increase the chemical diversity and the information density of nucleic acids, researchers developed methods to append functional groups as well as to create replicable expanded genetic systems. Some of these unnatural nucleic acids have now been utilized in SELEX, and a panel of improved aptamers has been delivered. In this book chapter, we mainly discuss the emerged unnatural bases which have been used in SELEX or at least have the potential to be used in SELEX, and how these unnatural nucleic acid help generate improved aptamers.

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Correspondence to Liqin Zhang .

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Zhang, L. (2015). Unnatural Nucleic Acids for Aptamer Selection. In: Tan, W., Fang, X. (eds) Aptamers Selected by Cell-SELEX for Theranostics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46226-3_3

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