A New Therapeutic Approach Using a Schizophyllan-based Drug Delivery System for Inflammatory Bowel Disease

被引：48

作者：

Takedatsu, Hidetoshi ^{[1
]}

Mitsuyama, Keiichi ^{[1
]}

Mochizuki, Shinichi ^{[2
]}

Kobayashi, Teppei ^{[1
]}

Sakurai, Kazuo ^{[2
]}

Takeda, Hiroshi ^{[3
]}

Fujiyama, Yoshihide ^{[4
]}

Koyama, Yoshikazu ^{[5
]}

Nishihira, Jun ^{[6
]}

Sata, Michio ^{[1
]}

机构：

[1] Kurume Univ, Div Gastroenterol, Dept Med, Sch Med, Kurume, Fukuoka 8300011, Japan

[2] Univ Kitakyushu, Dept Chem Proc & Environm, Kitakyushu, Fukuoka, Japan

[3] Hokkaido Univ, Fac Pharmaceut Sci, Dept Pathophysiol & Therapeut, Sapporo, Hokkaido 060, Japan

[4] Shiga Univ Med Sci, Dept Internal Med, Otsu, Shiga 52021, Japan

[5] Hokkai Gakuen Univ, Elect & Informat Engn Dept, Fac Engn, Sapporo, Hokkaido, Japan

[6] Hokkaido Informat Univ, Dept Med Management & Informat, Fac Business Adm & Informat Sci, Ebetsu, Hokkaido, Japan

来源：

MOLECULAR THERAPY | 2012年 / 20卷 / 06期

关键词：

MIGRATION-INHIBITORY FACTOR; MIF TAUTOMERASE ACTIVITY; BETA-GLUCAN RECOGNITION; SODIUM-INDUCED COLITIS; MACROPHAGE; DECTIN-1; MICE; HYPERSENSITIVITY; EXPRESSION; VITRO;

D O I：

10.1038/mt.2012.24

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Antisense technologies for the targeted inhibition of gene expression could provide an effective strategy for the suppression of inflammation. However, the effective use of antisense oligonucleotides (ODN) has been limited because of several problems. Therefore, a delivery system for antisense ODNs that enhances antisense stability, while maintaining the specificity of antisense for its target RNA or DNA is needed. We have developed a delivery system for antisense ODN using schizophyllan (SPG), a polysaccharide that belongs to the beta-(1-3) glucan family. This system has several advantages enabling the effective suppression of targeted RNA or DNA: the SPG complex is stable in vivo and does not dissolve in the presence of deoxyribonuclease, and the SPG complex is effectively taken up into macrophages by phagocytosis through Dectin-1. Macrophage-migration inhibitory factor (MIF), which is mainly produced by macrophages has been shown to have a pathogenetic role in inflammatory bowel disease (IBD). We developed a technique to create an SPG complex that highly conformed to the antisense MIF. The administration of antisense MIF/SPG complex effectively suppressed MIF production and significantly ameliorated intestinal inflammation. Our result demonstrated a possible new therapeutic approach, i.e., the administration of antisense MIF/SPG complex, for the treatment of IBD.

引用

页码：1234 / 1241

页数：8

共 30 条

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