Topoisomerase Inhibitors and PIM1 Kinase Inhibitors Improve Gene Editing Efficiency Mediated by CRISPR-Cas9 and Homology-Directed Repair
文献类型：期刊论文
| 作者 | Yun, Ying3; Wang, Min2; Guo, Shimeng2; Xie, Xin1,2,3
|
| 刊名 | MOLECULES
 |
| 出版日期 | 2024-06-01 |
| 卷号 | 29期号:12页码:12 |
| 关键词 | CRISPR-CAS9 gene editing homology-directed repair knock-in |
| DOI | 10.3390/molecules29122890 |
| 通讯作者 | Xie, Xin(xxie@simm.ac.cn) |
| 英文摘要 | The CRISPR-Cas9 system has emerged as the most prevalent gene editing technology due to its simplicity, high efficiency, and low cost. However, the homology-directed repair (HDR)-mediated gene knock-in in this system suffers from low efficiency, which limits its application in animal model preparation, gene therapy, and agricultural genetic improvement. Here, we report the design and optimization of a simple and efficient reporter-based assay to visualize and quantify HDR efficiency. Through random screening of a small molecule compound library, two groups of compounds, including the topoisomerase inhibitors and PIM1 kinase inhibitors, have been identified to promote HDR. Two representative compounds, etoposide and quercetagetin, also significantly enhance the efficiency of CRISPR-Cas9 and HDR-mediated gene knock-in in mouse embryos. Our study not only provides an assay to screen compounds that may facilitate HDR but also identifies useful tool compounds to facilitate the construction of genetically modified animal models with the CRISPR-Cas9 system. |
| WOS关键词 | DNA-REPAIR ; TARGET |
| 资助项目 | Ministry of Science and Technology of China[2022ZD0204700] ; Ministry of Science and Technology of China[2022YFA1104700] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[82304579] ; National Natural Science Foundation of China[82330113] ; Taishan Scholars Program |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001255950000001 |
| 出版者 | MDPI |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/312017]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Xie, Xin |
| 作者单位 | 1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China 2.Chinese Acad Sci, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yun, Ying,Wang, Min,Guo, Shimeng,et al. Topoisomerase Inhibitors and PIM1 Kinase Inhibitors Improve Gene Editing Efficiency Mediated by CRISPR-Cas9 and Homology-Directed Repair[J]. MOLECULES,2024,29(12):12. |
| APA | Yun, Ying,Wang, Min,Guo, Shimeng,&Xie, Xin.(2024).Topoisomerase Inhibitors and PIM1 Kinase Inhibitors Improve Gene Editing Efficiency Mediated by CRISPR-Cas9 and Homology-Directed Repair.MOLECULES,29(12),12. |
| MLA | Yun, Ying,et al."Topoisomerase Inhibitors and PIM1 Kinase Inhibitors Improve Gene Editing Efficiency Mediated by CRISPR-Cas9 and Homology-Directed Repair".MOLECULES 29.12(2024):12. |
入库方式： OAI收割
来源：上海药物研究所
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