Open AccessGene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers
Author(s) -
Kelly L. Warfield,
Dana L. Swenson,
Gene G. Olinger,
Donald K. Nichols,
William D. Pratt,
Robert Blouch,
David A. Stein,
M. Javad Aman,
Patrick L. Iversen,
Sina Bavari
Publication year - 2006
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.0020001
Subject(s) - ebola virus , virology , ebolavirus , morpholino , biology , druggability , favipiravir , virus , medicine , gene , genetics , covid-19 , disease , infectious disease (medical specialty) , gene knockdown , pathology
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
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