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Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers

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 cha...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1326218/
https://www.ncbi.nlm.nih.gov/pubmed/16415982
http://dx.doi.org/10.1371/journal.ppat.0020001
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author 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
author_facet 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
author_sort Warfield, Kelly L
collection PubMed
description 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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spelling pubmed-13262182006-01-13 Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers 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 PLoS Pathog Research Article 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. Public Library of Science 2006-01 2006-01-13 /pmc/articles/PMC1326218/ /pubmed/16415982 http://dx.doi.org/10.1371/journal.ppat.0020001 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
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
Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers
title Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers
title_full Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers
title_fullStr Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers
title_full_unstemmed Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers
title_short Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers
title_sort gene-specific countermeasures against ebola virus based on antisense phosphorodiamidate morpholino oligomers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1326218/
https://www.ncbi.nlm.nih.gov/pubmed/16415982
http://dx.doi.org/10.1371/journal.ppat.0020001
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