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 language | English |
|---|---|
| Pages (from-to) | 675-682 |
| Number of pages | 8 |
| Journal | Chemistry and Biology |
| Volume | 15 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 21 2008 |
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Keywords
- CHEMBIO
- RNA
ASJC Scopus subject areas
- Organic Chemistry
Cite this
Assembling OX40 Aptamers on a Molecular Scaffold to Create a Receptor-Activating Aptamer. / Dollins, Claudia M.; Nair, Smita; Boczkowski, David; Lee, Jaewoo; Layzer, Juliana M.; Gilboa, Eli; Sullenger, Bruce A.
In: Chemistry and Biology, Vol. 15, No. 7, 21.07.2008, p. 675-682.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Assembling OX40 Aptamers on a Molecular Scaffold to Create a Receptor-Activating Aptamer
AU - Dollins, Claudia M.
AU - Nair, Smita
AU - Boczkowski, David
AU - Lee, Jaewoo
AU - Layzer, Juliana M.
AU - Gilboa, Eli
AU - Sullenger, Bruce A.
PY - 2008/7/21
Y1 - 2008/7/21
N2 - 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.
AB - 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.
KW - CHEMBIO
KW - RNA
UR - http://www.scopus.com/inward/record.url?scp=46849111987&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=46849111987&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2008.05.016
DO - 10.1016/j.chembiol.2008.05.016
M3 - Article
C2 - 18635004
AN - SCOPUS:46849111987
VL - 15
SP - 675
EP - 682
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 7
ER -