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

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5-13
Number of pages9
JournalPLoS pathogens
Volume2
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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