Efficient regulation of viral replication by siRNA in a non-human primate surrogate model for hepatitis C.
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.
Yokota
Takanori
T
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
Iijima
Sayuki
S
Kubodera
Takayuki
T
Ishii
Koji
K
Katakai
Yuko
Y
Ageyama
Naohide
N
Chen
Yingwei
Y
Lee
Young-Jung
YJ
Unno
Toshinori
T
Nishina
Kazutaka
K
Iwasaki
Yuki
Y
Maki
Noboru
N
Mizusawa
Hidehiro
H
Akari
Hirofumi
H
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*
D020121:5' Untranslated Regions; D008081:Liposomes; D034741:RNA, Small Interfering; D012367:RNA, Viral; D007372:Interferons