2. Academic Validation
  3. Oligonucleotide delivery to antigen presenting cells by using schizophyllan

Oligonucleotide delivery to antigen presenting cells by using schizophyllan

  • Drug Metab Pharmacokinet. 2022 Feb:42:100434. doi: 10.1016/j.dmpk.2021.100434.
Shinichi Mochizuki 1,  Noriko Miyamoto 2,  Kazuo Sakurai 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka, 808-0135, Japan. Electronic address: mochizuki@kitakyu-u.ac.jp.
  • 2 Department of Applied Chemistry, Aichi Institute of Technology, 1247, Yachigusa, Yakusacho, Toyota, Aichi, 470-0392, Japan.
  • 3 Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka, 808-0135, Japan.
PMID: 34896749 DOI: 10.1016/j.dmpk.2021.100434
Abstract

Schizophyllan (SPG), a member of the β-glucan family, can form novel complexes with homo-polynucleotides such as poly(dA) through hydrogen bonding between two main chain glucoses and the one nucleotide base. Dectin-1, one of the major receptors for β-glucans, is known to be expressed on antigen presenting cells (APCs) such as macrophages and dendritic cells. This suggests that the above-mentioned complexes could deliver bound functional Oligonucleotides (ODNs) including antisense (AS)-ODNs, small interfering RNA, and CpG-ODNs to the APCs. Analysis using a quartz crystal microbalance revealed that a complex consisting of SPG and dA60 with a phosphorothioate backbone was recognized by recombinant Dectin-1 protein. Treatment with this complex containing an AS-ODN for tumor necrosis factor alpha protected mice against lipopolysaccharide-induced hepatitis at a very low AS-ODN dose. Moreover, immunization with CpG-ODN/SPG complex and antigenic proteins induced potent antigen specific immune responses. The present review also represents peptide delivery by conjugation with dA60 and the preparation of a nanogel using DNA-DNA hybridization. These findings indicate that the delivery of a specific ODN using β-glucans could be used for treating various diseases caused by APCs and for activating antigen specific immune responses.

Keywords

Antisense DNA; CpG-DNA; Dectin-1; Delivery; Shizophyllan.

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