Details

Autor(en) / Beteiligte

• Warfield, Kelly L
• Swenson, Dana L
• Olinger, Gene G
• Nichols, Donald K
• Pratt, William D
• Blouch, Robert
• Stein, David A
• Aman, M Javad
• Iversen, Patrick L
• Bavari, Sina
• Ross, Susan

Titel

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

Ist Teil von

• PLoS computational biology, 2006-01, Vol.2 (1), p.e1-e1

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.