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HDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing
Recent advances in CRISPR-Cas9 techniques, especially the discovery of base and prime editing, have significantly improved our ability to make precise changes in the genome. We hypothesized that modulating certain endogenous pathway cells could improve the action of those editing tools in mammalian...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207553/ https://www.ncbi.nlm.nih.gov/pubmed/35784015 http://dx.doi.org/10.1016/j.omtn.2022.05.036 |
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author | Liu, Nan Zhou, Lifang Lin, Guifeng Hu, Yun Jiao, Yaoge Wang, Yanhong Liu, Jingming Yang, Shengyong Yao, Shaohua |
author_facet | Liu, Nan Zhou, Lifang Lin, Guifeng Hu, Yun Jiao, Yaoge Wang, Yanhong Liu, Jingming Yang, Shengyong Yao, Shaohua |
author_sort | Liu, Nan |
collection | PubMed |
description | Recent advances in CRISPR-Cas9 techniques, especially the discovery of base and prime editing, have significantly improved our ability to make precise changes in the genome. We hypothesized that modulating certain endogenous pathway cells could improve the action of those editing tools in mammalian cells. We established a reporter system in which a small fragment was integrated into the genome by prime editing (PE). With this system, we screened an in-house small-molecule library and identified a group of histone deacetylase inhibitors (HDACi) increasing prime editing. We also found that HDACi increased the efficiency of both cytosine base editing (CBE) and adenine base editing (ABE). Moreover, HDACi increased the purity of cytosine base editor products, which was accompanied by an upregulation of the acetylation of uracil DNA glycosylase (UNG) and UNG inhibitor (UGI) and an enhancement of their interaction. In summary, our work demonstrated that HDACi improves Cas9-mediated prime editing and base editing. |
format | Online Article Text |
id | pubmed-9207553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-92075532022-06-30 HDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing Liu, Nan Zhou, Lifang Lin, Guifeng Hu, Yun Jiao, Yaoge Wang, Yanhong Liu, Jingming Yang, Shengyong Yao, Shaohua Mol Ther Nucleic Acids Original Article Recent advances in CRISPR-Cas9 techniques, especially the discovery of base and prime editing, have significantly improved our ability to make precise changes in the genome. We hypothesized that modulating certain endogenous pathway cells could improve the action of those editing tools in mammalian cells. We established a reporter system in which a small fragment was integrated into the genome by prime editing (PE). With this system, we screened an in-house small-molecule library and identified a group of histone deacetylase inhibitors (HDACi) increasing prime editing. We also found that HDACi increased the efficiency of both cytosine base editing (CBE) and adenine base editing (ABE). Moreover, HDACi increased the purity of cytosine base editor products, which was accompanied by an upregulation of the acetylation of uracil DNA glycosylase (UNG) and UNG inhibitor (UGI) and an enhancement of their interaction. In summary, our work demonstrated that HDACi improves Cas9-mediated prime editing and base editing. American Society of Gene & Cell Therapy 2022-06-02 /pmc/articles/PMC9207553/ /pubmed/35784015 http://dx.doi.org/10.1016/j.omtn.2022.05.036 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Liu, Nan Zhou, Lifang Lin, Guifeng Hu, Yun Jiao, Yaoge Wang, Yanhong Liu, Jingming Yang, Shengyong Yao, Shaohua HDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing |
title | HDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing |
title_full | HDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing |
title_fullStr | HDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing |
title_full_unstemmed | HDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing |
title_short | HDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing |
title_sort | hdac inhibitors improve crispr-cas9 mediated prime editing and base editing |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207553/ https://www.ncbi.nlm.nih.gov/pubmed/35784015 http://dx.doi.org/10.1016/j.omtn.2022.05.036 |
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