Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics
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 de...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Society for Microbiology
2015
|
| Online Access: | http://hdl.handle.net/1721.1/94325 |
| _version_ | 1826214741687664640 |
|---|---|
| author | Kugelman, Jeffrey R. Sanchez-Lockhart, Mariano Andersen, Kristian G. Gire, Stephen Park, Daniel J. Lin, Aaron E. Wohl, Shirlee Sabeti, Pardis C. Kuhn, Jens H. Palacios, Gustavo F. Sealfon, Rachel Sima |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Kugelman, Jeffrey R. Sanchez-Lockhart, Mariano Andersen, Kristian G. Gire, Stephen Park, Daniel J. Lin, Aaron E. Wohl, Shirlee Sabeti, Pardis C. Kuhn, Jens H. Palacios, Gustavo F. Sealfon, Rachel Sima |
| author_sort | Kugelman, Jeffrey R. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:10:25Z |
| format | Article |
| id | mit-1721.1/94325 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:10:25Z |
| publishDate | 2015 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | mit-1721.1/943252022-10-02T06:50:18Z Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics Kugelman, Jeffrey R. Sanchez-Lockhart, Mariano Andersen, Kristian G. Gire, Stephen Park, Daniel J. Lin, Aaron E. Wohl, Shirlee Sabeti, Pardis C. Kuhn, Jens H. Palacios, Gustavo F. Sealfon, Rachel Sima Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Sealfon, Rachel Sima 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. United States. Defense Threat Reduction Agency National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant DGE 1144152) 2015-02-11T16:09:18Z 2015-02-11T16:09:18Z 2015-01 2014-10 Article http://purl.org/eprint/type/JournalArticle 2150-7511 http://hdl.handle.net/1721.1/94325 Kugelman, Jeffrey R., Mariano Sanchez-Lockhart, Kristian G. Andersen, Stephen Gire, Daniel J. Park, Rachel Sealfon, Aaron E. Lin, et al. “Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics.” mBio 6, no. 1 (January 20, 2015): e02227–14. en_US http://dx.doi.org/10.1128/mBio.02227-14 mBio Creative Commons Attribution http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf American Society for Microbiology American Society for Microbiology |
| spellingShingle | Kugelman, Jeffrey R. Sanchez-Lockhart, Mariano Andersen, Kristian G. Gire, Stephen Park, Daniel J. Lin, Aaron E. Wohl, Shirlee Sabeti, Pardis C. Kuhn, Jens H. Palacios, Gustavo F. Sealfon, Rachel Sima Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics |
| title | Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics |
| title_full | Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics |
| title_fullStr | Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics |
| title_full_unstemmed | Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics |
| title_short | Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics |
| title_sort | evaluation of the potential impact of ebola virus genomic drift on the efficacy of sequence based candidate therapeutics |
| url | http://hdl.handle.net/1721.1/94325 |
| work_keys_str_mv | AT kugelmanjeffreyr evaluationofthepotentialimpactofebolavirusgenomicdriftontheefficacyofsequencebasedcandidatetherapeutics AT sanchezlockhartmariano evaluationofthepotentialimpactofebolavirusgenomicdriftontheefficacyofsequencebasedcandidatetherapeutics AT andersenkristiang evaluationofthepotentialimpactofebolavirusgenomicdriftontheefficacyofsequencebasedcandidatetherapeutics AT girestephen evaluationofthepotentialimpactofebolavirusgenomicdriftontheefficacyofsequencebasedcandidatetherapeutics AT parkdanielj evaluationofthepotentialimpactofebolavirusgenomicdriftontheefficacyofsequencebasedcandidatetherapeutics AT linaarone evaluationofthepotentialimpactofebolavirusgenomicdriftontheefficacyofsequencebasedcandidatetherapeutics AT wohlshirlee evaluationofthepotentialimpactofebolavirusgenomicdriftontheefficacyofsequencebasedcandidatetherapeutics AT sabetipardisc evaluationofthepotentialimpactofebolavirusgenomicdriftontheefficacyofsequencebasedcandidatetherapeutics AT kuhnjensh evaluationofthepotentialimpactofebolavirusgenomicdriftontheefficacyofsequencebasedcandidatetherapeutics AT palaciosgustavof evaluationofthepotentialimpactofebolavirusgenomicdriftontheefficacyofsequencebasedcandidatetherapeutics AT sealfonrachelsima evaluationofthepotentialimpactofebolavirusgenomicdriftontheefficacyofsequencebasedcandidatetherapeutics |