Monomeric G-Quadruplex-Based CpG Oligodeoxynucleotides as Potent Toll-Like Receptor 9 Agonists.

Monomeric G-Quadruplex-Based CpG Oligodeoxynucleotides as Potent Toll-Like Receptor 9 Agonists.
Biomacromolecules. 2020 Aug 28;:
Authors: Tu ATT, Hoshi K, Ikebukuro K, Hanagata N, Yamazaki T
Abstract
Synthetic oligodeoxynucleotides (ODNs) containing unmethylated cytosine-phosphate-guanine (CpG) motifs trigger the immune response by stimulating endosomal Toll-like receptor (TLR) 9. Natural linear ODNs are susceptible to nuclease degradation, thereby limiting their clinical applications. Here, we designed monomeric G-quadruplex-based CpG ODNs (G4 CpG ODNs) containing CpG motifs in the central loop region of the G4 structure. The monomeric G4 CpG ODNs were more stable in serum than the linear ODNs. The monomeric G4 CpG ODNs containing two or three CpG motifs induced the production of immunostimulatory cytokines interleukin (IL)-6, IL-12, and interferon (IFN)-β in mouse macrophage-like RAW264 cells. We also showed that the number of CpG motifs and the number of nucleotides between the CpG motif and G-tracts define the efficacy of the G4 CpG ODNs in activating TLR9. Incubating human peripheral blood mononuclear cells with G4 CpG ODNs promoted IL-6 and IFN-γ production, confirming their stimulatory effects on human immune cells. Mice given intraperitoneal injections of G4 CpG ODNs produced higher plasma IL-6 compared with injections of linear ODNs. These findings provide further understanding of the parameters governing the immunostimula...

Source: Biomacromolecules - August 27, 2020 Category: Biochemistry Authors: Tu ATT, Hoshi K, Ikebukuro K, Hanagata N, Yamazaki T Tags: Biomacromolecules Source Type: research