Precise large-fragment deletions in mammalian cells and mice generated by dCas9-controlled CRISPR/Cas3
Currently, the Cas9 and Cas12a systems are widely used for genome editing, but their ability to precisely generate large chromosome fragment deletions is limited. Type I-E CRISPR mediates broad and unidirectional DNA degradation, but controlling the size of Cas3-mediated DNA deletions has proven elusive thus far. Here, we demonstrate that the endonuclease deactivation of Cas9 (dCas9) can precisely control Cas3-mediated large-fragment deletions in mammalian cells. In addition, we report the elimination of the Y chromosome and precise retention of the Sry gene in mice using CRISPR/Cas3 and dCas9-controlled CRISPR/Cas3, respectively. In conclusion, dCas9-controlled CRISPR/Cas3-mediated precise large-fragment deletion provides an approach for establishing animal models by chromosome elimination. This method also holds promise as a potential therapeutic strategy for treating fragment mutations or human aneuploidy diseases that involve additional chromosomes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Science advances - 10(2024), 11 vom: 15. März, Seite eadk8052 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Jinze [VerfasserIn] |
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| Themen: |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 18.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/sciadv.adk8052 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369790391 |
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| 520 | |a Currently, the Cas9 and Cas12a systems are widely used for genome editing, but their ability to precisely generate large chromosome fragment deletions is limited. Type I-E CRISPR mediates broad and unidirectional DNA degradation, but controlling the size of Cas3-mediated DNA deletions has proven elusive thus far. Here, we demonstrate that the endonuclease deactivation of Cas9 (dCas9) can precisely control Cas3-mediated large-fragment deletions in mammalian cells. In addition, we report the elimination of the Y chromosome and precise retention of the Sry gene in mice using CRISPR/Cas3 and dCas9-controlled CRISPR/Cas3, respectively. In conclusion, dCas9-controlled CRISPR/Cas3-mediated precise large-fragment deletion provides an approach for establishing animal models by chromosome elimination. This method also holds promise as a potential therapeutic strategy for treating fragment mutations or human aneuploidy diseases that involve additional chromosomes | ||
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| 700 | 1 | |a Zhang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Haoyang |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Mingyang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hongmei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Feiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Xiaodi |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Yuqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Di |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Liangxue |e verfasserin |4 aut | |
| 700 | 1 | |a Sui, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhanjun |e verfasserin |4 aut | |
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