干扰埃博拉病毒繁殖突破性进展

【资料简介】

美国波士顿大学医学院“全国潜在传染病实验室”专家托马斯·盖斯伯特领导一个团队，选取两组恒河猕猴应用这种试验性药物。

美国研究者利用微粒状基因物质干扰埃博拉病毒繁殖的研究取得突破性进展。实验室研究表明，感染埃博拉病毒的恒河猕猴接受一种试验性药物治疗后死亡率降低。

研究人员介绍，这种药物含有的小型干扰核糖核酸会抑制酶的诱生，从而达到干扰病毒繁殖的目的。

研究人员先为*组中3只猕猴注射可致命剂量的埃博拉病毒亚型“埃博拉－扎伊尔”，随后数天连续为这些猕猴注射4剂试验性药物，结果其中一只猕猴死亡。

第二组4只猕猴注射同等剂量这种病毒亚型后，连续接受7剂试验性药物治疗，结果全部存活。

两组实验猴中均有一只猕猴染病后没有接受试验性药物治疗，zui终死亡。

盖斯伯特说，这是研究人员制出一种能令非人类灵长类动物感染埃博拉病毒后存活的药物，具有突破性意义。

“我们认为，研究为将这种试验性处方发展为（批量）制剂、用于埃博拉病例治疗提供了论证，无论是在实验室病毒外泄还是这种疾病暴发的情形下。”

埃博拉病毒可导致埃博拉病毒出血热，患者可出现发热、恶心、呕吐、腹泻、全身酸痛、体内外出血等症状，致死率可达90％。

世界卫生组织数据显示，自1976年发现感染埃博拉病毒病例以来，累计报告大约1850例这类病例，其中约1200例死亡。

上海劲马生物（）推荐原文出处：

The Lancet Doi:10.1016/S0140-6736（10）60357-1

Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study
Prof Thomas W Geisbert PhD a b c , Amy CH Lee MSc e ?, Marjorie Robbins PhD e ?, Joan B Geisbert a, Anna N Honko PhD d, Vandana Sood MSc e, Joshua C Johnson BSc d, Susan de Jong PhD e, Iran Tavakoli BSc e, Adam Judge PhD e, Lisa E Hensley PhD d, Ian MacLachlan PhD e

Background

We previously showed that small interfering RNAs （siRNAs） targeting the Zaire Ebola virus （ZEBOV） RNA polymerase L protein formulated in stable nucleic acid-lipid particles （SNALPs） compley protected guineapigs when administered shortly after a lethal ZEBOV challenge. Although rodent models of ZEBOV infection are useful for screening prospective countermeasures, they are frequently not useful for prediction of efficacy in the more stringent non-human primate models. We therefore assessed the efficacy of modified non-immunostimulatory siRNAs in a uniformly lethal non-human primate model of ZEBOV haemorrhagic fever.

Methods

A combination of modified siRNAs targeting the ZEBOV L polymerase （EK-1 mod）, viral protein （VP） 24 （VP24-1160 mod）, and VP35 （VP35-855 mod） were formulated in SNALPs. A group of macaques （n=3） was given these pooled anti-ZEBOV siRNAs （2 mg/kg per dose, bolus intravenous infusion） after 30 min, and on days 1, 3, and 5 after challenge with ZEBOV. A second group of macaques （n=4） was given the pooled anti-ZEBOV siRNAs after 30 min, and on days 1, 2, 3, 4, 5, and 6 after challenge with ZEBOV.

Findings

Two （66%） of three rhesus monkeys given four postexposure treatments of the pooled anti-ZEBOV siRNAs were protected from lethal ZEBOV infection, whereas all macaques given seven postexposure treatments were protected. The treatment regimen in the second study was well tolerated with minor changes in liver enzymes that might have been related to viral infection.

Interpretation

This complete postexposure protection against ZEBOV in non-human primates provides a model for the treatment of ZEBOV-induced haemorrhagic fever. These data show the potential of RNA interference as an effective postexposure treatment strategy for people infected with Ebola virus, and suggest that this strategy might also be useful for treatment of other emerging viral infections.

Funding
Defense Threat Reduction Agency.