Yokota Takanori, Iijima Sayuki, Kubodera Takayuki, Ishii Koji, Katakai Yuko, Ageyama Naohide, Chen Yingwei, Lee Young-Jung, Unno Toshinori, Nishina Kazutaka, Iwasaki Yuki, Maki Noboru, Mizusawa Hidehiro, Akari Hirofumi
Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Biochem Biophys Res Commun. 2007 Sep 21;361(2):294-300. doi: 10.1016/j.bbrc.2007.06.182. Epub 2007 Jul 16.
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.
RNA干扰（RNAi）是一项新技术，可为人类疾病的治疗提供潜在应用。最近在体外和啮齿动物模型中已证明RNAi介导的疗法对传染病有效，然而，全身性应用的RNAi疗法在灵长类动物中是否有效仍不清楚。在本研究中，我们通过使用丙型肝炎的非人类灵长类动物替代模型，研究RNAi疗法对传染病是否有效。将与丙型肝炎病毒关系最为密切的GB病毒B（GBV-B）的阳离子脂质体包裹的小干扰RNA（CL-siRNA）给予狨猴，可剂量依赖性地抑制GBV-B复制。特别是，5mg/kg的CL-siRNA可完全抑制病毒复制。由于CL-siRNA在体内可诱导血清干扰素（IFN），抗GBV-B的CL-siRNA对病毒复制的抑制作用可能包括IFN的抗病毒作用。然而，诱导的IFN的作用可能只是部分的，因为诱导出比GBV-B CL-siRNA更强的IFN反应的对照CL-siRNA只能延迟病毒复制。我们的结果表明全身性给予CL-siRNA作为抗病毒策略具有可行性。
