Assembling OX40 Aptamers on a Molecular Scaffold to Create a Receptor-Activating Aptamer

Claudia M. Dollins, Smita Nair, David Boczkowski, Jaewoo Lee, Juliana M. Layzer, Eli Gilboa, Bruce A. Sullenger

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

We show that a molecular scaffold can be utilized to convert a receptor binding aptamer into a receptor agonist. Many receptors (including tumor necrosis receptor family members) are activated when they are multimerized on the cell surface. Molecular scaffolds have been utilized to assemble multiple receptor binding peptide ligands to generate activators of such receptors. We demonstrate that an RNA aptamer that recognizes OX40, a member of the tumor necrosis factor receptor superfamily, can be converted into a receptor-activating aptamer by assembling two copies on an olignucleotide-based scaffold. The OX40 receptor-activating aptamer is able to induce nuclear localization of nuclear factor-κB, cytokine production, and cell proliferation, as well as enhance the potency of dendritic cell-based tumor vaccines when systemically delivered to mice.

Original languageEnglish (US)
Pages (from-to)675-682
Number of pages8
JournalChemistry and Biology
Volume15
Issue number7
DOIs
StatePublished - Jul 21 2008

Keywords

  • CHEMBIO
  • RNA

ASJC Scopus subject areas

  • Organic Chemistry

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    Dollins, C. M., Nair, S., Boczkowski, D., Lee, J., Layzer, J. M., Gilboa, E., & Sullenger, B. A. (2008). Assembling OX40 Aptamers on a Molecular Scaffold to Create a Receptor-Activating Aptamer. Chemistry and Biology, 15(7), 675-682. https://doi.org/10.1016/j.chembiol.2008.05.016