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The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives

Making discrete and precise genetic changes to wild populations has been proposed as a means of addressing some of the world’s most pressing ecological and public health challenges caused by insect pests. Technologies that would allow this, such as synthetic gene drives, have been under development...

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Autores principales: Verkuijl, Sebald A. N., Ang, Joshua X. D., Alphey, Luke, Bonsall, Michael B., Anderson, Michelle A. E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996256/
https://www.ncbi.nlm.nih.gov/pubmed/35419354
http://dx.doi.org/10.3389/fbioe.2022.856981
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author Verkuijl, Sebald A. N.
Ang, Joshua X. D.
Alphey, Luke
Bonsall, Michael B.
Anderson, Michelle A. E.
author_facet Verkuijl, Sebald A. N.
Ang, Joshua X. D.
Alphey, Luke
Bonsall, Michael B.
Anderson, Michelle A. E.
author_sort Verkuijl, Sebald A. N.
collection PubMed
description Making discrete and precise genetic changes to wild populations has been proposed as a means of addressing some of the world’s most pressing ecological and public health challenges caused by insect pests. Technologies that would allow this, such as synthetic gene drives, have been under development for many decades. Recently, a new generation of programmable nucleases has dramatically accelerated technological development. CRISPR-Cas9 has improved the efficiency of genetic engineering and has been used as the principal effector nuclease in different gene drive inheritance biasing mechanisms. Of these nuclease-based gene drives, homing endonuclease gene drives have been the subject of the bulk of research efforts (particularly in insects), with many different iterations having been developed upon similar core designs. We chart the history of homing gene drive development, highlighting the emergence of challenges such as unintended repair outcomes, “leaky” expression, and parental deposition. We conclude by discussing the progress made in developing strategies to increase the efficiency of homing endonuclease gene drives and mitigate or prevent unintended outcomes.
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spelling pubmed-89962562022-04-12 The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives Verkuijl, Sebald A. N. Ang, Joshua X. D. Alphey, Luke Bonsall, Michael B. Anderson, Michelle A. E. Front Bioeng Biotechnol Bioengineering and Biotechnology Making discrete and precise genetic changes to wild populations has been proposed as a means of addressing some of the world’s most pressing ecological and public health challenges caused by insect pests. Technologies that would allow this, such as synthetic gene drives, have been under development for many decades. Recently, a new generation of programmable nucleases has dramatically accelerated technological development. CRISPR-Cas9 has improved the efficiency of genetic engineering and has been used as the principal effector nuclease in different gene drive inheritance biasing mechanisms. Of these nuclease-based gene drives, homing endonuclease gene drives have been the subject of the bulk of research efforts (particularly in insects), with many different iterations having been developed upon similar core designs. We chart the history of homing gene drive development, highlighting the emergence of challenges such as unintended repair outcomes, “leaky” expression, and parental deposition. We conclude by discussing the progress made in developing strategies to increase the efficiency of homing endonuclease gene drives and mitigate or prevent unintended outcomes. Frontiers Media S.A. 2022-03-28 /pmc/articles/PMC8996256/ /pubmed/35419354 http://dx.doi.org/10.3389/fbioe.2022.856981 Text en Copyright © 2022 Verkuijl, Ang, Alphey, Bonsall and Anderson. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Verkuijl, Sebald A. N.
Ang, Joshua X. D.
Alphey, Luke
Bonsall, Michael B.
Anderson, Michelle A. E.
The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives
title The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives
title_full The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives
title_fullStr The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives
title_full_unstemmed The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives
title_short The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives
title_sort challenges in developing efficient and robust synthetic homing endonuclease gene drives
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996256/
https://www.ncbi.nlm.nih.gov/pubmed/35419354
http://dx.doi.org/10.3389/fbioe.2022.856981
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