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Making gene drive biodegradable

Gene drive systems have long been sought to modify mosquito populations and thus combat malaria and dengue. Powerful gene drive systems have been developed in laboratory experiments, but may never be used in practice unless they can be shown to be acceptable through rigorous field-based testing. Suc...

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Autores principales: Zapletal, Josef, Najmitabrizi, Neda, Erraguntla, Madhav, Lawley, Mark A., Myles, Kevin M., Adelman, Zach N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776940/
https://www.ncbi.nlm.nih.gov/pubmed/33357058
http://dx.doi.org/10.1098/rstb.2019.0804
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author Zapletal, Josef
Najmitabrizi, Neda
Erraguntla, Madhav
Lawley, Mark A.
Myles, Kevin M.
Adelman, Zach N.
author_facet Zapletal, Josef
Najmitabrizi, Neda
Erraguntla, Madhav
Lawley, Mark A.
Myles, Kevin M.
Adelman, Zach N.
author_sort Zapletal, Josef
collection PubMed
description Gene drive systems have long been sought to modify mosquito populations and thus combat malaria and dengue. Powerful gene drive systems have been developed in laboratory experiments, but may never be used in practice unless they can be shown to be acceptable through rigorous field-based testing. Such testing is complicated by the anticipated difficulty in removing gene drive transgenes from nature. Here, we consider the inclusion of self-elimination mechanisms into the design of homing-based gene drive transgenes. This approach not only caused the excision of the gene drive transgene, but also generates a transgene-free allele resistant to further action by the gene drive. Strikingly, our models suggest that this mechanism, acting at a modest rate (10%) as part of a single-component system, would be sufficient to cause the rapid reversion of even the most robust homing-based gene drive transgenes, without the need for further remediation. Modelling also suggests that unlike gene drive transgenes themselves, self-eliminating transgene approaches are expected to tolerate substantial rates of failure. Thus, self-elimination technology may permit rigorous field-based testing of gene drives by establishing strict time limits on the existence of gene drive transgenes in nature, rendering them essentially biodegradable. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'.
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spelling pubmed-77769402021-01-08 Making gene drive biodegradable Zapletal, Josef Najmitabrizi, Neda Erraguntla, Madhav Lawley, Mark A. Myles, Kevin M. Adelman, Zach N. Philos Trans R Soc Lond B Biol Sci Articles Gene drive systems have long been sought to modify mosquito populations and thus combat malaria and dengue. Powerful gene drive systems have been developed in laboratory experiments, but may never be used in practice unless they can be shown to be acceptable through rigorous field-based testing. Such testing is complicated by the anticipated difficulty in removing gene drive transgenes from nature. Here, we consider the inclusion of self-elimination mechanisms into the design of homing-based gene drive transgenes. This approach not only caused the excision of the gene drive transgene, but also generates a transgene-free allele resistant to further action by the gene drive. Strikingly, our models suggest that this mechanism, acting at a modest rate (10%) as part of a single-component system, would be sufficient to cause the rapid reversion of even the most robust homing-based gene drive transgenes, without the need for further remediation. Modelling also suggests that unlike gene drive transgenes themselves, self-eliminating transgene approaches are expected to tolerate substantial rates of failure. Thus, self-elimination technology may permit rigorous field-based testing of gene drives by establishing strict time limits on the existence of gene drive transgenes in nature, rendering them essentially biodegradable. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'. The Royal Society 2021-02-15 2020-12-28 /pmc/articles/PMC7776940/ /pubmed/33357058 http://dx.doi.org/10.1098/rstb.2019.0804 Text en © 2020 The Authors. http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Articles
Zapletal, Josef
Najmitabrizi, Neda
Erraguntla, Madhav
Lawley, Mark A.
Myles, Kevin M.
Adelman, Zach N.
Making gene drive biodegradable
title Making gene drive biodegradable
title_full Making gene drive biodegradable
title_fullStr Making gene drive biodegradable
title_full_unstemmed Making gene drive biodegradable
title_short Making gene drive biodegradable
title_sort making gene drive biodegradable
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776940/
https://www.ncbi.nlm.nih.gov/pubmed/33357058
http://dx.doi.org/10.1098/rstb.2019.0804
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