HDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing

Molecular Therapy: Nucleic Acids

Shaohua Yao¹  Yun Hu²  Yanhong Wang²  Jingming Liu²  Lifang Zhou²  Shengyong Yang²  Nan Liu²  Yaoge Jiao²  Guifeng Lin² 

[1] Corresponding author Shengyong Yang, Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan university, Renmin Nanlu 17, Chengdu 610041, Sichuan, China.;Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu 610041, Sichuan, China;

关键词: MT: RNA/DNA Editing;    CRISPR-Cas9;    HDAC inhibitors;    prime editing;    base editing;    UNG;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown