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Broad dengue neutralization in mosquitoes expressing an engineered antibody

With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with...

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Autores principales: Buchman, Anna, Gamez, Stephanie, Li, Ming, Antoshechkin, Igor, Li, Hsing-Han, Wang, Hsin-Wei, Chen, Chun-Hong, Klein, Melissa J., Duchemin, Jean-Bernard, Crowe, James E., Paradkar, Prasad N., Akbari, Omar S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964813/
https://www.ncbi.nlm.nih.gov/pubmed/31945137
http://dx.doi.org/10.1371/journal.ppat.1008103
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author Buchman, Anna
Gamez, Stephanie
Li, Ming
Antoshechkin, Igor
Li, Hsing-Han
Wang, Hsin-Wei
Chen, Chun-Hong
Klein, Melissa J.
Duchemin, Jean-Bernard
Crowe, James E.
Paradkar, Prasad N.
Akbari, Omar S.
author_facet Buchman, Anna
Gamez, Stephanie
Li, Ming
Antoshechkin, Igor
Li, Hsing-Han
Wang, Hsin-Wei
Chen, Chun-Hong
Klein, Melissa J.
Duchemin, Jean-Bernard
Crowe, James E.
Paradkar, Prasad N.
Akbari, Omar S.
author_sort Buchman, Anna
collection PubMed
description With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Importantly, this is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression. These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses.
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spelling pubmed-69648132020-01-26 Broad dengue neutralization in mosquitoes expressing an engineered antibody Buchman, Anna Gamez, Stephanie Li, Ming Antoshechkin, Igor Li, Hsing-Han Wang, Hsin-Wei Chen, Chun-Hong Klein, Melissa J. Duchemin, Jean-Bernard Crowe, James E. Paradkar, Prasad N. Akbari, Omar S. PLoS Pathog Research Article With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Importantly, this is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression. These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses. Public Library of Science 2020-01-16 /pmc/articles/PMC6964813/ /pubmed/31945137 http://dx.doi.org/10.1371/journal.ppat.1008103 Text en © 2020 Buchman et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Buchman, Anna
Gamez, Stephanie
Li, Ming
Antoshechkin, Igor
Li, Hsing-Han
Wang, Hsin-Wei
Chen, Chun-Hong
Klein, Melissa J.
Duchemin, Jean-Bernard
Crowe, James E.
Paradkar, Prasad N.
Akbari, Omar S.
Broad dengue neutralization in mosquitoes expressing an engineered antibody
title Broad dengue neutralization in mosquitoes expressing an engineered antibody
title_full Broad dengue neutralization in mosquitoes expressing an engineered antibody
title_fullStr Broad dengue neutralization in mosquitoes expressing an engineered antibody
title_full_unstemmed Broad dengue neutralization in mosquitoes expressing an engineered antibody
title_short Broad dengue neutralization in mosquitoes expressing an engineered antibody
title_sort broad dengue neutralization in mosquitoes expressing an engineered antibody
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964813/
https://www.ncbi.nlm.nih.gov/pubmed/31945137
http://dx.doi.org/10.1371/journal.ppat.1008103
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