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

PLoS Pathog. 2006 Jan;2(1):e1. doi: 10.1371/journal.ppat.0020001. Epub 2006 Jan 13.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antisense Elements (Genetics) / pharmacology*
  • Ebolavirus / drug effects*
  • Ebolavirus / genetics
  • Ebolavirus / physiology
  • Female
  • Hemorrhagic Fever, Ebola / prevention & control*
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morpholines / pharmacology*
  • Morpholinos
  • Protein Biosynthesis / drug effects
  • RNA, Viral / antagonists & inhibitors
  • Viral Proteins / antagonists & inhibitors
  • Viral Regulatory and Accessory Proteins
  • Virus Replication / drug effects


  • Antisense Elements (Genetics)
  • Morpholines
  • Morpholinos
  • RNA, Viral
  • VP24 protein, Ebola virus
  • VP35 protein, filovirus
  • Viral Proteins
  • Viral Regulatory and Accessory Proteins