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Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates

The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled1. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the U... Full description

Journal Title: Nature May 21, 2015, Vol.521(7552), p.362
Main Author: Thi, Emily P.
Other Authors: Mire, Chad E. , Lee, Amy C. H. , Geisbert, Joan B. , Zhou, Joy Z. , Agans, Krystle N. , Snead, Nicholas M. , Deer, Daniel J. , Barnard, Trisha R. , Fenton, Karla A. , Maclachlan, Ian , Geisbert, Thomas W.
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0028-0836 ; DOI: 10.1038/nature14442
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recordid: gale_hrca488528447
title: Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates
format: Article
creator:
  • Thi, Emily P.
  • Mire, Chad E.
  • Lee, Amy C. H.
  • Geisbert, Joan B.
  • Zhou, Joy Z.
  • Agans, Krystle N.
  • Snead, Nicholas M.
  • Deer, Daniel J.
  • Barnard, Trisha R.
  • Fenton, Karla A.
  • Maclachlan, Ian
  • Geisbert, Thomas W.
subjects:
  • Ebola Hemorrhagic Fever -- Care And Treatment
  • Ebola Virus
  • Primates
ispartof: Nature, May 21, 2015, Vol.521(7552), p.362
description: The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled1. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States2. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown. Here we show that lipid-nanoparticle encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viraemic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal haematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first, to our knowledge, successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in nonhuman primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease.
language: English
source:
identifier: ISSN: 0028-0836 ; DOI: 10.1038/nature14442
fulltext: fulltext
issn:
  • 0028-0836
  • 00280836
url: Link


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titleLipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates
creatorThi, Emily P. ; Mire, Chad E. ; Lee, Amy C. H. ; Geisbert, Joan B. ; Zhou, Joy Z. ; Agans, Krystle N. ; Snead, Nicholas M. ; Deer, Daniel J. ; Barnard, Trisha R. ; Fenton, Karla A. ; Maclachlan, Ian ; Geisbert, Thomas W.
ispartofNature, May 21, 2015, Vol.521(7552), p.362
identifierISSN: 0028-0836 ; DOI: 10.1038/nature14442
subjectEbola Hemorrhagic Fever -- Care And Treatment ; Ebola Virus ; Primates
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descriptionThe current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled1. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States2. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown. Here we show that lipid-nanoparticle encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viraemic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal haematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first, to our knowledge, successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in nonhuman primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease.
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titleLipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates
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