In silico design and validation of high-affinity RNA aptamers targeting epithelial cellular adhesion molecule dimers

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Abstract
Significance: Epithelial cellular activating molecule (EpCAM) is vastly overexpressed in tumor cell membranes of certain carcinomas, and thus represents an auspicious clinical target for cancer therapies. To date, therapeutic targeting of EpCAM has principally involved antibodies; smaller, nucleic-acid based aptamers have shown great promise, but have not yet reached clinical application. Here, using experimentally validated in silico techniques, we have designed two RNA aptamers that bind EpCAM with improved affinity over existing aptamers. We confirm that these aptamers bind the EpCAM dimer, a complex distinct from and more physiologically relevant than the oft-targeted EpCAM monomer. This successful structure-based in silico approach advocates for the broad use of such methods in RNA aptamer design.
Funding Information
  • IBM Bluegene Science Program (W125859, W1464125)
  • W.M. Keck Foundation (2019-2022)

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