title: Efficient regulation of viral replication by siRNA in a non-human primate surrogate model for hepatitis C.
abstract: RNA interference (RNAi) represents a new technology which could offer potential applications for the therapeutics of human diseases. RNAi-mediated therapy has recently been shown to be effective toward infectious diseases in in vitro and rodent models, however, it remains unclear whether RNAi therapy with systemic application could be effective in primates. In this study, we examined if RNAi therapy could be effective toward infectious diseases by using a non-human primate surrogate model for hepatitis C. Administration into marmosets of cationic liposome-encapsulated siRNA (CL-siRNA) for GB virus B (GBV-B), which is most closely related to hepatitis C virus, repressed GBV-B replication in a dose-dependent manner. Especially, 5 mg/kg of the CL-siRNA completely inhibited the viral replication. Since the serum interferons (IFNs) were induced by CL-siRNA in vivo, inhibition of viral regulation by anti-GBV-B CL-siRNA may include an antiviral effect of IFN. However, contribution of induced IFN may be partial, since the control CL-siRNA which induced a stronger IFN response than GBV-B CL-siRNA could only delay the viral replication. Our results suggest the feasibility of systemic administration of CL-siRNA as an antiviral strategy.
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. tak-yokota.nuro@tmd.ac.jp
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
authors.forename: Sayuki
authors.initials: S
authors.lastname: Iijima
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kubodera
authors.forename: Koji
authors.initials: K
authors.lastname: Ishii
authors.forename: Yuko
authors.initials: Y
authors.lastname: Katakai
authors.forename: Naohide
authors.initials: N
authors.lastname: Ageyama
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Chen
authors.forename: Young-Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Toshinori
authors.initials: T
authors.lastname: Unno
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Nishina
authors.forename: Yuki
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Noboru
authors.initials: N
authors.lastname: Maki
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Akari
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002144:Callithrix; D004195:Disease Models, Animal; D029406:GB virus B / Q000235:genetics / Q000502:physiology*; D017930:Genes, Reporter; D006526:Hepatitis C / Q000821:virology*; D007372:Interferons / Q000097:blood; D008081:Liposomes; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D008992:Monkey Diseases / Q000821:virology*; D009690:Nucleic Acid Conformation; D034741:RNA, Small Interfering / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D014779:Virus Replication / Q000502:physiology*
chemical_list: D020121:5' Untranslated Regions; D008081:Liposomes; D034741:RNA, Small Interfering; D012367:RNA, Viral; D007372:Interferons