干擾埃博拉病毒繁殖突破性進展

【資料簡介】

美國波士頓大學醫學院“全國潛在傳染病實驗室”專家托馬斯·蓋斯伯特領導一個團隊，選取兩組恒河獼猴應用這種試驗性藥物。

美國研究者利用微粒狀基因物質干擾埃博拉病毒繁殖的研究取得突破性進展。實驗室研究表明，感染埃博拉病毒的恒河獼猴接受一種試驗性藥物治療后死亡率降低。

研究人員介紹，這種藥物含有的小型干擾核糖核酸會抑制酶的誘生，從而達到干擾病毒繁殖的目的。

研究人員先為*組中3只獼猴注射可致命劑量的埃博拉病毒亞型“埃博拉－扎伊爾”，隨后數天連續為這些獼猴注射4劑試驗性藥物，結果其中一只獼猴死亡。

第二組4只獼猴注射同等劑量這種病毒亞型后，連續接受7劑試驗性藥物治療，結果全部存活。

兩組實驗猴中均有一只獼猴染病后沒有接受試驗性藥物治療，zui終死亡。

蓋斯伯特說，這是研究人員制出一種能令非人類靈長類動物感染埃博拉病毒后存活的藥物，具有突破性意義。

“我們認為，研究為將這種試驗性處方發展為（批量）制劑、用于埃博拉病例治療提供了論證，無論是在實驗室病毒外泄還是這種疾病暴發的情形下。”

埃博拉病毒可導致埃博拉病毒出血熱，患者可出現發熱、惡心、嘔吐、腹瀉、全身酸痛、體內外出血等癥狀，致死率可達90％。

世界衛生組織數據顯示，自1976年發現感染埃博拉病毒病例以來，累計報告大約1850例這類病例，其中約1200例死亡。

上海勁馬生物（）推薦原文出處：

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.