Assembling OX40 aptamers on a molecular scaffold to create a receptor-activating aptamer

Area of Science:

• Immunology
• Molecular Biology
• Biotechnology

Background:

• Receptor activation often depends on multimerization on the cell surface.
• Molecular scaffolds can assemble peptide ligands to activate receptors.
• The OX40 receptor is a member of the tumor necrosis factor receptor superfamily.

Purpose of the Study:

• To convert an RNA aptamer that binds the OX40 receptor into a receptor agonist.
• To investigate the potential of aptamer-based receptor activation for immunotherapy.

Main Methods:

• An oligonucleotide-based scaffold was used to assemble two copies of an RNA aptamer targeting OX40.
• The functional activity of the engineered aptamer was assessed in vitro and in vivo.
• The aptamer's ability to activate the OX40 receptor and its effects on immune cells and tumor vaccines were evaluated.

Main Results:

• An RNA aptamer targeting OX40 was successfully converted into a receptor-activating aptamer by scaffold-mediated dimerization.
• The engineered aptamer induced OX40 receptor signaling, including nuclear factor-kappaB (NF-κB) translocation and cytokine production.
• Systemic delivery of the OX40 receptor-activating aptamer enhanced the potency of dendritic cell-based tumor vaccines in mice.

Conclusions:

• Molecular scaffolds can transform aptamers into functional receptor agonists.
• Aptamer-based OX40 activation holds promise for immunotherapy and enhancing vaccine efficacy.
• This strategy offers a novel approach for developing targeted therapeutics for cancer and other diseases.