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  • Title: G-Quadruplex Structure Improves the Immunostimulatory Effects of CpG Oligonucleotides.
    Author: Hoshi K, Yamazaki T, Sugiyama Y, Tsukakoshi K, Tsugawa W, Sode K, Ikebukuro K.
    Journal: Nucleic Acid Ther; 2019 Aug; 29(4):224-229. PubMed ID: 30835633.
    Abstract:
    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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