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Inherently confinable split-drive systems in Drosophila
CRISPR-based gene-drive systems, which copy themselves via gene conversion mediated by the homology-directed repair (HDR) pathway, have the potential to revolutionize vector control. However, mutant alleles generated by the competing non-homologous end-joining (NHEJ) pathway, resistant to Cas9 cleav...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935863/ https://www.ncbi.nlm.nih.gov/pubmed/33674604 http://dx.doi.org/10.1038/s41467-021-21771-7 |
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author | Terradas, Gerard Buchman, Anna B. Bennett, Jared B. Shriner, Isaiah Marshall, John M. Akbari, Omar S. Bier, Ethan |
author_facet | Terradas, Gerard Buchman, Anna B. Bennett, Jared B. Shriner, Isaiah Marshall, John M. Akbari, Omar S. Bier, Ethan |
author_sort | Terradas, Gerard |
collection | PubMed |
description | CRISPR-based gene-drive systems, which copy themselves via gene conversion mediated by the homology-directed repair (HDR) pathway, have the potential to revolutionize vector control. However, mutant alleles generated by the competing non-homologous end-joining (NHEJ) pathway, resistant to Cas9 cleavage, can interrupt the spread of gene-drive elements. We hypothesized that drives targeting genes essential for viability or reproduction also carrying recoded sequences that restore endogenous gene functionality should benefit from dominantly-acting maternal clearance of NHEJ alleles combined with recessive Mendelian culling processes. Here, we test split gene-drive (sGD) systems in Drosophila melanogaster that are inserted into essential genes required for viability (rab5, rab11, prosalpha2) or fertility (spo11). In single generation crosses, sGDs copy with variable efficiencies and display sex-biased transmission. In multigenerational cage trials, sGDs follow distinct drive trajectories reflecting their differential tendencies to induce target chromosome damage and/or lethal/sterile mosaic Cas9-dependent phenotypes, leading to inherently confinable drive outcomes. |
format | Online Article Text |
id | pubmed-7935863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79358632021-03-21 Inherently confinable split-drive systems in Drosophila Terradas, Gerard Buchman, Anna B. Bennett, Jared B. Shriner, Isaiah Marshall, John M. Akbari, Omar S. Bier, Ethan Nat Commun Article CRISPR-based gene-drive systems, which copy themselves via gene conversion mediated by the homology-directed repair (HDR) pathway, have the potential to revolutionize vector control. However, mutant alleles generated by the competing non-homologous end-joining (NHEJ) pathway, resistant to Cas9 cleavage, can interrupt the spread of gene-drive elements. We hypothesized that drives targeting genes essential for viability or reproduction also carrying recoded sequences that restore endogenous gene functionality should benefit from dominantly-acting maternal clearance of NHEJ alleles combined with recessive Mendelian culling processes. Here, we test split gene-drive (sGD) systems in Drosophila melanogaster that are inserted into essential genes required for viability (rab5, rab11, prosalpha2) or fertility (spo11). In single generation crosses, sGDs copy with variable efficiencies and display sex-biased transmission. In multigenerational cage trials, sGDs follow distinct drive trajectories reflecting their differential tendencies to induce target chromosome damage and/or lethal/sterile mosaic Cas9-dependent phenotypes, leading to inherently confinable drive outcomes. Nature Publishing Group UK 2021-03-05 /pmc/articles/PMC7935863/ /pubmed/33674604 http://dx.doi.org/10.1038/s41467-021-21771-7 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Terradas, Gerard Buchman, Anna B. Bennett, Jared B. Shriner, Isaiah Marshall, John M. Akbari, Omar S. Bier, Ethan Inherently confinable split-drive systems in Drosophila |
title | Inherently confinable split-drive systems in Drosophila |
title_full | Inherently confinable split-drive systems in Drosophila |
title_fullStr | Inherently confinable split-drive systems in Drosophila |
title_full_unstemmed | Inherently confinable split-drive systems in Drosophila |
title_short | Inherently confinable split-drive systems in Drosophila |
title_sort | inherently confinable split-drive systems in drosophila |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935863/ https://www.ncbi.nlm.nih.gov/pubmed/33674604 http://dx.doi.org/10.1038/s41467-021-21771-7 |
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