Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka, 808-0135, Japan.
University of Occupational and Environmental Health, 1-1 Isegaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
Carbohydr Res. 2021 Feb;500:108219. doi: 10.1016/j.carres.2020.108219. Epub 2020 Dec 13.
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.
凝集素 Dectin-1 是一种用于β-葡聚糖介导的药物递送的良好靶点。尽管已经进行了许多关于 Dectin-1 的鼠类研究，但作为药物递送靶点，其人类类似物尚未得到很好的研究。因此，我们分析了从慢性髓性白血病衍生细胞 CML-1 获得的人 Dectin-1 cDNA，并证实了之前的研究结果，即由于外显子跳跃，人 Dectin-1 有许多异构体，尽管鼠 Dectin-1 只有两种形式。当我们将 Dectin-1 基因转染到不表达 Dectin-1 的细胞系中，并检测反义 DNA/β-葡聚糖复合物的细胞摄取时，我们证实通过β-葡聚糖/Dectin-1 介导的摄取可以有效地抑制靶基因的表达。这些结果表明，β-葡聚糖复合物不仅对小鼠，而且对人类的 Dectin-1 表达细胞来说，都是一种将反义寡核苷酸（AS-ODN）递送到细胞内的有效工具。
