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

Emily P. Thi, Chad Mire, Amy C H Lee, Joan B. Geisbert, Joy Z. Zhou, Krystle N. Agans, Nicholas M. Snead, Daniel J. Deer, Trisha R. Barnard, Karla A. Fenton, Ian Maclachlan, Thomas Geisbert

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

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 controlled. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States. 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.

Original languageEnglish (US)
Pages (from-to)362-365
Number of pages4
JournalNature
Volume521
Issue number7552
DOIs
StatePublished - May 21 2015

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Ebolavirus
Nanoparticles
Primates
Small Interfering RNA
Disease Outbreaks
Lipids
Compassionate Use Trials
Therapeutics
Western Africa
Hematology
Macaca mulatta

ASJC Scopus subject areas

  • General

Cite this

Thi, E. P., Mire, C., Lee, A. C. H., Geisbert, J. B., Zhou, J. Z., Agans, K. N., ... Geisbert, T. (2015). Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates. Nature, 521(7552), 362-365. https://doi.org/10.1038/nature14442

Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates. / Thi, Emily P.; Mire, Chad; 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.

In: Nature, Vol. 521, No. 7552, 21.05.2015, p. 362-365.

Research output: Contribution to journalArticle

Thi, EP, Mire, C, Lee, ACH, Geisbert, JB, Zhou, JZ, Agans, KN, Snead, NM, Deer, DJ, Barnard, TR, Fenton, KA, Maclachlan, I & Geisbert, T 2015, 'Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates', Nature, vol. 521, no. 7552, pp. 362-365. https://doi.org/10.1038/nature14442
Thi EP, Mire C, Lee ACH, Geisbert JB, Zhou JZ, Agans KN et al. Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates. Nature. 2015 May 21;521(7552):362-365. https://doi.org/10.1038/nature14442
Thi, Emily P. ; Mire, Chad ; 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. / Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates. In: Nature. 2015 ; Vol. 521, No. 7552. pp. 362-365.
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