Binding assay of human Dectin-1 variants to DNA/β-glucan complex for active-targeting delivery of antisense DNA

Nobuaki Fujiwara; Hiroto Izumi; Ryoma Kira; Yasuo Morimoto; Shinichi Mochizuki; Kazuo Sakurai

doi:10.1016/j.carres.2020.108219

Binding assay of human Dectin-1 variants to DNA/β-glucan complex for active-targeting delivery of antisense DNA

Carbohydr Res. 2021 Feb:500:108219. doi: 10.1016/j.carres.2020.108219. Epub 2020 Dec 13.

Authors

Nobuaki Fujiwara¹, Hiroto Izumi², Ryoma Kira¹, Yasuo Morimoto², Shinichi Mochizuki³, Kazuo Sakurai⁴

Affiliations

¹ Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka, 808-0135, Japan.
² University of Occupational and Environmental Health, 1-1 Isegaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
³ 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.
⁴ Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka, 808-0135, Japan. Electronic address: sakurai@kitakyu-u.ac.jp.

PMID: 33339585
DOI: 10.1016/j.carres.2020.108219

Abstract

The lectin Dectin-1 is a good target for β-glucan-mediated drug delivery. Although many murine studies of Dectin-1 have been performed, its human analog has not been studied well in terms of being a drug delivery target. We thus analyzed human Dectin-1 cDNA obtained from chronic myelogenous leukemia-derived cells, CML-1, and confirmed the findings of previous studies that there are many isoforms of human Dectin-1 due to exon skipping, although murine Dectin-1 has only two forms. When we transfected the Dectin-1 gene into a non-Dectin-1-expressing cell line and examined cellular uptake of the antisense DNA/β-glucan complex, we confirmed that expression of the target gene was effectively suppressed through β-glucan/Dectin-1-mediated uptake. The present results suggest that the β-glucan complex would be an effective tool to deliver antisense oligonucleotide (AS-ODN) to Dectin-1-expressing cells not only for mice but also for humans.

Keywords: Active-targeting delivery; Antisense; Dectin-1; Immunocyte; Schizophyllan.

MeSH terms

Binding Sites
Carbohydrate Conformation
DNA / chemistry*
Drug Delivery Systems*
Humans
Lectins, C-Type / chemistry*
Oligonucleotides, Antisense / chemistry*
Tumor Cells, Cultured
beta-Glucans / chemistry*

Substances

CLEC7A protein, human
Lectins, C-Type
Oligonucleotides, Antisense
beta-Glucans
DNA