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*
Department of Life Science, Center for Biofunctional Molecules, Pohang University of Science and Technology, Pohang, Korea; and
Magnetic Resonance Team, Korea Basic Science Institute, Taejon, Korea
CpG oligodeoxynucleotides (ODNs) are promising immunomodulatory
agents for treating human diseases and vaccine development.
Phosphodiester CpG ODNs were demonstrated to have poor
immunostimulatory potentials for cytokine production. However, the
conjugation of consecutive deoxyriboguanosine residues, called a dG
run, at the 3' terminus of phosphodiester CpG ODNs significantly
enhanced TNF-
and IL-12 production from mouse splenic dendritic
cells (DCs). The optimal induction of cytokine production was achieved
by the addition of a hexameric dG (dG6) run. In contrast,
the existence of a dG6 run either at the 5' terminus of
phosphodiester CpG ODNs or at the 3' terminus of phosphorothioate CpG
ODNs diminished CpG-mediated cytokine induction, suggesting that the
effects of a dG run depend on its location and the chemical property of
the ODN backbone, respectively. In addition, we provided the evidence
that the conjugation of a dG6 run caused the structural
transformation of CpG ODNs, which facilitates their targeting into
mouse APCs such as splenic DCs, B cells, and peritoneal macrophages
with a scavenger receptor type A ligand specificity. Among primary
APCs, DCs were the most potent for CpG ODN-mediated IL-12 production.
Furthermore, we demonstrated that the conjugation of a dG6
run into the 3' terminus of phosphodiester CpG ODNs was crucial for
their ability to generate Th1 immunity in vivo. Thus, the conjugation
of a dG6 run into phosphodiester CpG ODNs would be an
alternative way to optimize their immunostimulatory potentials in vitro
and in vivo.
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