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PLoS Pathog. 2006 Jan;2(1):e1. Epub 2006 Jan 13.

Gene-specific countermeasures against Ebola virus based on antisense phosphorodiamidate morpholino oligomers.

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1
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA.

Abstract

The filoviruses Marburg virus and Ebola virus (EBOV) quickly outpace host immune responses and cause hemorrhagic fever, resulting in case fatality rates as high as 90% in humans and nearly 100% in nonhuman primates. The development of an effective therapeutic for EBOV is a daunting public health challenge and is hampered by a paucity of knowledge regarding filovirus pathogenesis. This report describes a successful strategy for interfering with EBOV infection using antisense phosphorodiamidate morpholino oligomers (PMOs). A combination of EBOV-specific PMOs targeting sequences of viral mRNAs for the viral proteins (VPs) VP24, VP35, and RNA polymerase L protected rodents in both pre- and post-exposure therapeutic regimens. In a prophylactic proof-of-principal trial, the PMOs also protected 75% of rhesus macaques from lethal EBOV infection. The work described here may contribute to development of designer, "druggable" countermeasures for filoviruses and other microbial pathogens.

PMID:
16415982
PMCID:
PMC1326218
DOI:
10.1371/journal.ppat.0020001
[Indexed for MEDLINE]
Free PMC Article
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