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Single-strand oligodeoxynucleotides (ODNs) containing unmethylated cytosine-phosphate-guanine (CpG) are recognized by the toll-like receptor 9, a component of the innate immunity. Therefore, they could act as immunotherapeutic agents. Chemically modified CpG ODNs containing a phosphorothioate backbone instead of phosphodiester (PD) were developed as immunotherapeutic agents resistant to nuclease degradation. However, they cause adverse side effects, and so there is a necessity to generate novel CpG ODNs. In the present study, we designed a nuclease-resistant nonmodified CpG ODN that forms G-quadruplex structures. G-quadruplex formation in CpG ODNs increased nuclease resistance and cellular uptake. The CpG ODNs designed in this study induced interleukin-6 production in a human B lymphocyte cell line and human peripheral blood mononuclear cells. These results indicate that G-quadruplex formation can be used to increase the immunostimulatory activity of CpG ODNs having a natural PD backbone.

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Keyword: IL-6, toll-like receptor 9, CpG ODN, G-quadruplex, peripheral blood mononuclear cells

Date published: 2019-03-05

Publisher: Mary Ann Liebert

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Manuscript type: Author's original (Submitted manuscript)

MDR DOI: https://doi.org/10.48505/nims.1443

First published URL: https://doi.org/10.1089/nat.2018.0761

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Updated at: 2024-01-05 22:13:10 +0900

Published on MDR: 2021-08-13 01:20:03 +0900