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摘要 : 封装在类脂纳米颗粒中以埃博拉病毒为目标的siRNAs (TKM-Ebola) ,以前被发现对非人类灵长类动物能够提供针对致命剂量埃博拉病毒挑战的接触后保护(post-exposure protection)。该疗法从同情角度出发在当前疫情中也曾被用于若干个人类患者,尽管它对人类的疗效尚不知道。在这项研究中,Thomas Geisbert及同事迅速针对当前疫情中的病毒类型对TKM-Ebola鸡尾酒疗法进行了改造,发现在用当前疫情中的西非EBOV分离毒株进行挑战之后3天施用,它完全能够保护非人类灵长类动物。一

 封装在类脂纳米颗粒中以埃博拉病毒为目标的siRNAs (TKM-Ebola) ,以前被发现对非人类灵长类动物能够提供针对致命剂量埃博拉病毒挑战的接触后保护(post-exposure protection)。该疗法从同情角度出发在当前疫情中也曾被用于若干个人类患者,尽管它对人类的疗效尚不知道。在这项研究中,Thomas Geisbert及同事迅速针对当前疫情中的病毒类型对TKM-Ebola鸡尾酒疗法进行了改造,发现在用当前疫情中的西非EBOV分离毒株进行挑战之后3天施用,它完全能够保护非人类灵长类动物。一旦有了病毒序列数据,该药物在只有8星期的时间内就可以针对新病毒被改造和生产。

原文标题:Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates

原文摘要:The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled1. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States2. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown. Here we show that lipid-nanoparticle-encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viraemic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal haematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first, to our knowledge, successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in nonhuman primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease.

对应Nature杂志: 2015年05月21日Nature杂志精选

来源: Nature 浏览次数:15


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