A modular approach for the identification of chemically modified aptamers for to date non-targetable molecules

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The project described herein enables the selection, characterization and application of novel aptamers, which are chemically modified at their nucleobase positions. The modifications are introduced through Cu(I)-catalysed Azide-Alkyne Cycloaddition. This approach enables the modular assembly of nucleic acid libraries for in vitro selection purposes. In this way, tailored aptamers will be accessible, which recognize target molecules that are currently not available by traditional selection processes. Within the described project, novel ways will be opened allowing the introduction of a chemical modification into DNA libraries not only via ethinyl-dU but also through adenine-nucleotides. With this, novel structural solutions of presenting introduced modifications by DNA molecules will be accessible and expanded towards purines. With the established methods, we will select modified aptamers recognizing tetrahydrocannabinol and Dectin-1. Both molecules are yet not accessible with traditional selection procedures, using DNA libraries built from canonical nucleotides. Additionally, we will employ the developed selection procedure to generate tumour-specific modified aptamers, enabling access to novel tools for targeted tumour therapies. In regard of its manifold application spectrum, the developed procedures are generically applicable to evolve novel ligands, which are not accessible to date and can be applied to target molecules independent of their properties. These ligands represent valuable tools for basic and applied sciences.