Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates.
Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates.
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DOI：
10.1038/nature14442
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发表时间：
2015-05-21
期刊：
影响因子：
64.8
通讯作者：
Geisbert, Thomas W.
中科院分区：
文献类型：
--
作者：
Thi, Emily P.;Mire, Chad E.;Lee, Amy C. H.;Geisbert, Joan B.;Zhou, Joy Z.;Agans, Krystle N.;Snead, Nicholas M.;Deer, Daniel J.;Barnard, Trisha R.;Fenton, Karla A.;MacLachlan, Ian;Geisbert, Thomas W.
目前，西非埃博拉病毒（EBOV）疫情史无前例，造成的病例和死亡人数超过了以往所有疫情的总和，且尚未得到控制。在富有同情心的情况下，已经采用了几种暴露后干预措施来治疗一些被遣返回欧洲和美国的患者。然而，这些干预措施针对新爆发的埃博拉病毒株的体内功效尚不清楚。在这里，我们表明，当在暴露后 3 天开始治疗时，当动物处于病毒血症和临床疾病状态时，脂质纳米颗粒 (LNP) 封装的 siRNA 能够快速适应针对 EBOV Makona 爆发株，能够保护 100% 的恒河猴免受致命攻击。尽管所有受感染的动物均表现出晚期疾病的证据，包括异常血液学、血液化学和凝血病，但siRNA治疗的动物具有较温和的临床特征并完全康复，而未经治疗的对照动物则死亡。这些结果首次成功证明了针对非人灵长类动物 (NHP) 中新爆发病毒株的抗埃博拉病毒治疗功效，并突显了 LNP 递送的 siRNA 作为对抗这种高度致命的人类疾病的对策的快速发展。
The current outbreak of Ebola virus (EBOV) in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled. Several postexposure interventions have been employed under compassionate use to treat a number of patients repatriated to Europe and the United States. However, the in vivo efficacy of these interventions against the new outbreak strain of EBOV is unknown. Here, we show that lipid nanoparticle (LNP)-encapsulated siRNAs rapidly adapted to target the Makona outbreak strain of EBOV are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days postexposure while animals were viremic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal hematology, blood chemistry, and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered while the untreated control animals succumbed. These results represent the first successful demonstration of therapeutic anti-EBOV efficacy against the new outbreak strain in nonhuman primates (NHPs) and highlight the rapid development of LNP-delivered siRNA as a countermeasure against this highly lethal human disease.
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影响因子：
14.9
作者：
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DOI：
10.1126/science.1259657
发表时间：
2014-09-12
期刊：
Science (New York, N.Y.)
影响因子：
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Sabeti PC
DOI：
10.1016/s0140-6736(10)60357-1
发表时间：
2010-05-29
期刊：
Lancet (London, England)
影响因子：
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作者：
Geisbert TW;Lee AC;Robbins M;Geisbert JB;Honko AN;Sood V;Johnson JC;de Jong S;Tavakoli I;Judge A;Hensley LE;Maclachlan I
通讯作者：
Maclachlan I