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CRISPR-CasRx knock-in mice for RNA degradation

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Abstract

The RNA editing tool CRISPR-CasRx has provided a platform for a range of transcriptome analysis tools and therapeutic approaches with its broad efficacy and high specificity. To enable the application of CasRx in vivo, we established a Credependent CasRx knock-in mouse. Using these mice, we specifically knocked down the expression of Meis1 and Hoxb13 in cardiomyocytes, which induced cardiac regeneration after myocardial infarction. We also knocked down the lncRNA Mhrt in cardiomyocytes with the CasRx knock-in mice, causing hypertrophic cardiomyopathy. In summary, we generated a Credependent CasRx knock-in mouse that can efficiently knock down coding gene and lncRNA expression in specific somatic cells. This in vivo CRISPR-CasRx system is promising for gene function research and disease modeling.

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Acknowledgements

This work was supported by the National Key Research and Development Project of China (2019YFA0801500), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS, 2021-I2M-1-008), and the National Natural Science Foundation of China (81770308, 81900343).

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Correspondence to Shengshou Hu or Yu Nie.

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Compliance and ethics The author(s) declare that they have no conflict of interest. All experiments involving animals were performed and approved by the Institutional Animal Care and Use Committee (IACUC), Fuwai Hospital, Chinese Academy of Medical Sciences.

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Li, J., Zhu, D., Hu, S. et al. CRISPR-CasRx knock-in mice for RNA degradation. Sci. China Life Sci. 65, 2248–2256 (2022). https://doi.org/10.1007/s11427-021-2059-5

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