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Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system

Precise genetic modifications in model animals are essential for biomedical research. Here, we report a programmable “base editing” system to induce precise base conversion with high efficiency in zebrafish. Using cytidine deaminase fused to Cas9 nickase, up to 28% of site-specific single-base mutat...

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Detalles Bibliográficos
Autores principales: Zhang, Yihan, Qin, Wei, Lu, Xiaochan, Xu, Jason, Huang, Haigen, Bai, Haipeng, Li, Song, Lin, Shuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524635/
https://www.ncbi.nlm.nih.gov/pubmed/28740134
http://dx.doi.org/10.1038/s41467-017-00175-6
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author Zhang, Yihan
Qin, Wei
Lu, Xiaochan
Xu, Jason
Huang, Haigen
Bai, Haipeng
Li, Song
Lin, Shuo
author_facet Zhang, Yihan
Qin, Wei
Lu, Xiaochan
Xu, Jason
Huang, Haigen
Bai, Haipeng
Li, Song
Lin, Shuo
author_sort Zhang, Yihan
collection PubMed
description Precise genetic modifications in model animals are essential for biomedical research. Here, we report a programmable “base editing” system to induce precise base conversion with high efficiency in zebrafish. Using cytidine deaminase fused to Cas9 nickase, up to 28% of site-specific single-base mutations are achieved in multiple gene loci. In addition, an engineered Cas9-VQR variant with 5′-NGA PAM specificities is used to induce base conversion in zebrafish. This shows that Cas9 variants can be used to expand the utility of this technology. Collectively, the targeted base editing system represents a strategy for precise and effective genome editing in zebrafish.
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spelling pubmed-55246352017-07-28 Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system Zhang, Yihan Qin, Wei Lu, Xiaochan Xu, Jason Huang, Haigen Bai, Haipeng Li, Song Lin, Shuo Nat Commun Article Precise genetic modifications in model animals are essential for biomedical research. Here, we report a programmable “base editing” system to induce precise base conversion with high efficiency in zebrafish. Using cytidine deaminase fused to Cas9 nickase, up to 28% of site-specific single-base mutations are achieved in multiple gene loci. In addition, an engineered Cas9-VQR variant with 5′-NGA PAM specificities is used to induce base conversion in zebrafish. This shows that Cas9 variants can be used to expand the utility of this technology. Collectively, the targeted base editing system represents a strategy for precise and effective genome editing in zebrafish. Nature Publishing Group UK 2017-07-25 /pmc/articles/PMC5524635/ /pubmed/28740134 http://dx.doi.org/10.1038/s41467-017-00175-6 Text en © The Author(s) 2017 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
Zhang, Yihan
Qin, Wei
Lu, Xiaochan
Xu, Jason
Huang, Haigen
Bai, Haipeng
Li, Song
Lin, Shuo
Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system
title Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system
title_full Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system
title_fullStr Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system
title_full_unstemmed Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system
title_short Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system
title_sort programmable base editing of zebrafish genome using a modified crispr-cas9 system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524635/
https://www.ncbi.nlm.nih.gov/pubmed/28740134
http://dx.doi.org/10.1038/s41467-017-00175-6
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