Efficient base editing with high precision in rabbits using YFE-BE4max

Cytidine base editors, composed of a cytidine deaminase fused to Cas9 nickase, enable efficient C-to-T conversion in various organisms. However, current base editors suffer from severe trade-off between editing efficiency and precision. Here, based on rationally mutated cytidine deaminase domain, we...

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Autores principales: Liu, Zhiquan, Chen, Siyu, Shan, Huanhuan, Jia, Yingqi, Chen, Mao, Song, Yuning, Lai, Liangxue, Li, Zhanjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971250/
https://www.ncbi.nlm.nih.gov/pubmed/31959743
http://dx.doi.org/10.1038/s41419-020-2244-3
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author Liu, Zhiquan
Chen, Siyu
Shan, Huanhuan
Jia, Yingqi
Chen, Mao
Song, Yuning
Lai, Liangxue
Li, Zhanjun
author_facet Liu, Zhiquan
Chen, Siyu
Shan, Huanhuan
Jia, Yingqi
Chen, Mao
Song, Yuning
Lai, Liangxue
Li, Zhanjun
author_sort Liu, Zhiquan
collection PubMed
description Cytidine base editors, composed of a cytidine deaminase fused to Cas9 nickase, enable efficient C-to-T conversion in various organisms. However, current base editors suffer from severe trade-off between editing efficiency and precision. Here, based on rationally mutated cytidine deaminase domain, we develop a new base editor, YFE-BE4max, effectively narrow the editing width to as little as approximately three nucleotides while maintaining high efficiency in rabbits. Moreover, YFE-BE4max successfully mediated the Tyr p. Q68Stop and Lmna p. G607G mutation in F0 rabbit with high efficiency and precision, which precisely recapitulates the pathological features of human OCA1 and HGPS, respectively. Collectively, YFE-BE4max system provide promising tools to perform efficient base editing with high precision in rabbits and enhances its capacity to precisely model human diseases.
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spelling pubmed-69712502020-01-22 Efficient base editing with high precision in rabbits using YFE-BE4max Liu, Zhiquan Chen, Siyu Shan, Huanhuan Jia, Yingqi Chen, Mao Song, Yuning Lai, Liangxue Li, Zhanjun Cell Death Dis Article Cytidine base editors, composed of a cytidine deaminase fused to Cas9 nickase, enable efficient C-to-T conversion in various organisms. However, current base editors suffer from severe trade-off between editing efficiency and precision. Here, based on rationally mutated cytidine deaminase domain, we develop a new base editor, YFE-BE4max, effectively narrow the editing width to as little as approximately three nucleotides while maintaining high efficiency in rabbits. Moreover, YFE-BE4max successfully mediated the Tyr p. Q68Stop and Lmna p. G607G mutation in F0 rabbit with high efficiency and precision, which precisely recapitulates the pathological features of human OCA1 and HGPS, respectively. Collectively, YFE-BE4max system provide promising tools to perform efficient base editing with high precision in rabbits and enhances its capacity to precisely model human diseases. Nature Publishing Group UK 2020-01-20 /pmc/articles/PMC6971250/ /pubmed/31959743 http://dx.doi.org/10.1038/s41419-020-2244-3 Text en © The Author(s) 2020 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
Liu, Zhiquan
Chen, Siyu
Shan, Huanhuan
Jia, Yingqi
Chen, Mao
Song, Yuning
Lai, Liangxue
Li, Zhanjun
Efficient base editing with high precision in rabbits using YFE-BE4max
title Efficient base editing with high precision in rabbits using YFE-BE4max
title_full Efficient base editing with high precision in rabbits using YFE-BE4max
title_fullStr Efficient base editing with high precision in rabbits using YFE-BE4max
title_full_unstemmed Efficient base editing with high precision in rabbits using YFE-BE4max
title_short Efficient base editing with high precision in rabbits using YFE-BE4max
title_sort efficient base editing with high precision in rabbits using yfe-be4max
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971250/
https://www.ncbi.nlm.nih.gov/pubmed/31959743
http://dx.doi.org/10.1038/s41419-020-2244-3
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