Development of a Monomeric Inhibitory RNA Aptamer Specific for FGFR3 that Acts as an Activator When Dimerized

Nachiket Kamatkar, Matthew Levy, Jean M. Hébert

Research output: Contribution to journalArticle


There have been limited options for people who suffer from fibroblast growth factor receptor (FGFR) signaling disorders. In this study, we developed RNA aptamers specific for FGFR3 as potential therapeutic agents. Using a structured aptamer library, we performed ten rounds of SELEX (systematic evolution of ligands by exponential enrichment) against mouse FGFR3c protein. Using an engineered BaF3 cell line, one aptamer clone from round 6 of the selection inhibited FGF-dependent cell growth with a concentration at which 50% of growth is observed (IC50) of ∼260 nM and bound both mouse and human FGFR3 but not FGFR1 or FGFR2. This inhibitor of FGFR3 signaling (iR3), when dimerized using a template-driven approach, resulted in a functional activator of FGFR3 (aR3). We validated the activity and specificity of iR3 and aR3 on engineered BaF3 cell lines, mouse and human FGFR protein, and primary cultures of neuroepithelial precursor cells.

Original languageEnglish (US)
Pages (from-to)530-539
Number of pages10
JournalMolecular Therapy - Nucleic Acids
Publication statusPublished - Sep 6 2019



  • FGFR3
  • aptamer
  • drug

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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