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http://mbio.asm.org/content/6/1/e02227-14
Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics
FOOTNOTES
This Article
Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics
- Jeffrey R. Kugelman[SUP]a[/SUP],
- Mariano Sanchez-Lockhart[SUP]a[/SUP],
- Kristian G. Andersen[SUP]b[/SUP],
- Stephen Gire[SUP]b[/SUP],
- Daniel J. Park[SUP]b[/SUP],
- Rachel Sealfon[SUP]c[/SUP],
- Aaron E. Lin[SUP]b[/SUP],
- Shirlee Wohl[SUP]b[/SUP],
- Pardis C. Sabeti[SUP]b[/SUP],
- Jens H. Kuhn[SUP]d[/SUP],
- Gustavo F. Palacios[SUP]a[/SUP]
- aCenter for Genome Sciences Division of the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
- bCenter for Systems Biology, Harvard University, Cambridge, Massachusetts, USA
- cComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
- dIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
- Address correspondence to Gustavo F. Palacios,gustavo.f.palacios.ctr@us.army.mil.
- Editor Jack R. Bennink, National Institute of Allergy and Infectious Diseases
Until recently, Ebola virus (EBOV) was a rarely encountered human pathogen that caused disease among small populations with extraordinarily high lethality. At the end of 2013, EBOV initiated an unprecedented disease outbreak in West Africa that is still ongoing and has already caused thousands of deaths. Recent studies revealed the genomic changes this particular EBOV variant undergoes over time during human-to-human transmission. Here we highlight the genomic changes that might negatively impact the efficacy of currently available EBOV sequence-based candidate therapeutics, such as small interfering RNAs (siRNAs), phosphorodiamidate morpholino oligomers (PMOs), and antibodies. Ten of the observed mutations modify the sequence of the binding sites of monoclonal antibody (MAb) 13F6, MAb 1H3, MAb 6D8, MAb 13C6, and siRNA EK-1, VP24, and VP35 targets and might influence the binding efficacy of the sequence-based therapeutics, suggesting that their efficacy should be reevaluated against the currently circulating strain.
FOOTNOTES
- Citation Kugelman JR, Sanchez-Lockhart M, Andersen KG, Gire S, Park DJ, Sealfon R, Lin AE, Wohl S, Sabeti PC, Kuhn JH, Palacios GF. 2015. Evaluation of the potential impact of Ebola virus genomic drift on the efficacy of sequence-based candidate therapeutics. mBio 6(1):e02227-14. doi:10.1128/mBio.02227-14.
- Received 31 October 2014
- Accepted 14 December 2014
- Published 20 January 2015
- Copyright ? 2015 Kugelman, et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
This Article
- doi: 10.1128/mBio.02227-1420 January 2015 mBio vol. 6no. 1 e02227-14