Gene-Specific Countermeasures Against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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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.
- Medicine and Medical Research