title: A new therapeutic approach using a schizophyllan-based drug delivery system for inflammatory bowel disease.
abstract: 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 β-(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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. takedatsu_hidetoshi@kurume-u.ac.jp
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takedatsu
authors.forename: Keiichi
authors.initials: K
authors.lastname: Mitsuyama
authors.forename: Shinichi
authors.initials: S
authors.lastname: Mochizuki
authors.forename: Teppei
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakurai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Koyama
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D007413:Intestinal Mucosa; D037181:Lectins, C-Type / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000737:chemistry; D012566:Sizofiran / Q000008:administration & dosage / Q000737:chemistry*; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D016264:Dextran Sulfate; D037181:Lectins, C-Type; D008263:Macrophage Migration-Inhibitory Factors; D016376:Oligonucleotides, Antisense; D012566:Sizofiran; D000099181:Dectin-1