Scientists using tiny particles of genetic material to interfere in the replication process of the deadly Ebola virus have successfully prevented monkeys exposed to that virus from dying of hemorrhagic fever. The proof-of-concept study, published in this week's issue of The Lancet, suggests that such protection also should be possible in humans.
"Over the past decade, we have evaluated numerous therapeutic approaches for the treatment of lethal viruses, such as Ebola," said co-author Dr. Lisa E. Hensley of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). "None of them have conferred complete protection to Ebola virus-infected primatesuntil now."
Using particles called small interfering RNAs (siRNAs), the authors targeted a protein (called the L protein) that is essential for Ebola virus replication. RNA inhibitors, as they are commonly called, are based on a natural gene silencing mechanism used by all cells, and RNAi therapeutics rely on a delivery technology to be effective.
Lipid nanoparticles (LNPs) are the most widely used siRNA delivery approaches. In this study, the research team used a proprietary technology called SNALP, or stable nucleic acid-lipid particles, to deliver the therapeutics to disease sites in animal models infected with the Zaire strain of Ebola virus (ZEBOV).
A group of three rhesus macaques was given anti-ZEBOV siRNAs intravenously, 30 minutes after exposure to the virus, and again on days 1, 3, and 5. A second group of four macaques was given the treatment after 30 minutes, and on days 1, 2, 3, 4, 5, and 6, after challenge with ZEBOV.
Two of the three animals in the first group (which received four post-exposure treatments) were protected from lethal ZEBOV infection and survived. All four of the monkeys given seven post-exposure treatments were protected. The treatment regimen in the second study was well tolerated, with minor changes in liver enzymes
|Contact: Caree Vander Linden|
US Army Medical Research Institute of Infectious Diseases