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G-Quadruplex Structure Improves the Immunostimulatory Effects of CpG Oligonucleotides

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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.

Alternative title
  • G4 improves immunostimulatory effects of CpG ODNs
DOI
First published at
Creator
  • Name
    Hoshi, Kazuaki
    Organization
    Tokyo University of Agriculture and Technology
    Role
    author
    Name
    Yamazaki, Tomohiko
    ORCID
    http://orcid.org/0000-0003-2136-8042
    Organization
    National Institute for Materials Science
    Role
    author
    Name
    Sugiyama, Yuuki
    Organization
    Tokyo University of Agriculture and Technology
    Role
    author
    Name
    Tsukakoshi, Kaori
    Organization
    Tokyo University of Agriculture and Technology
    Role
    author
    Name
    Tsugawa, Wakako
    Organization
    Tokyo University of Agriculture and Technology
    Role
    author
    Name
    Sode, Koji
    Organization
    University of North Carolina at Chapel Hill and North Carolina State University
    Role
    author
    Name
    Ikebukuro, Kazunori
    Organization
    Tokyo University of Agriculture and Technology
    Role
    author
Keyword
Resource type
Publisher
Date published
  • 06/08/2019
Rights statement
Licensed Date
  • 06/08/2019
Journal
  • Title
    Nucleic Acid Therapeutics
    Alternative title
    Nucleic Acid Ther
    Volume
    29
    Issue
    4
    Start page
    224
    End page
    229
    Total number of pages
    6
Language
Last modified
  • 18/10/2022

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