Assembling OX40 aptamers on a molecular scaffold to create a receptor-activating aptamer.
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-kappaB, cytokine production, and cell proliferation, as well as enhance the potency of dendritic cell-based tumor vaccines when systemically delivered to mice.
Dollins
Claudia M
CM
University Program in Genetics and Genomics, Duke University Medical Center, Durham, NC 27710, USA.
Nair
Smita
S
Boczkowski
David
D
Lee
Jaewoo
J
Layzer
Juliana M
JM
Gilboa
Eli
E
Sullenger
Bruce A
BA
D000818:Animals; D052158:Aptamers, Peptide / Q000737:chemistry*; D019496:Cancer Vaccines / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003713:Dendritic Cells / Q000166:cytology; D015195:Drug Design; D005260:Female; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009368:Neoplasm Transplantation; D053262:Receptors, OX40 / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*
D052158:Aptamers, Peptide; D019496:Cancer Vaccines; D008024:Ligands; D016328:NF-kappa B; D053262:Receptors, OX40