PLoS Pathogens (Jan 2006)

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

  • 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

DOI
https://doi.org/10.1371/journal.ppat.0020001
Journal volume & issue
Vol. 2, no. 1
p. e1

Abstract

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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.