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Genome editing using CRISPR/Cas9 to treat hereditary hematological disorders

Subjects

Abstract

The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system is a versatile and convenient genome-editing tool with prospects in gene therapy. This technique is based on customized site-specific nucleases with programmable guiding RNAs that cleave and introduce double-strand breaks (DSBs) at the target locus and achieve precise genome modification by triggering DNA repair mechanisms. Human hematopoietic stem/progenitor cells (HSPCs) are conventional cell targets for gene therapy in hematological diseases and have been widely used in most studies. Induced pluripotent stem cells (iPSCs) can be generated from a variety of somatic cells and hold great promise for personalized cell-based therapies. CRISPR/Cas9-mediated genome editing in autologous HSPCs and iPSCs is an ideal therapeutic solution for treating hereditary hematological disorders. Here, we review and summarize the latest studies about CRISPR/Cas9-mediated genome editing in patient-derived HSPCs and iPSCs to treat hereditary hematological disorders. Current challenges and prospects are also discussed.

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Fig. 1: Overview of CRISPR/Cas9-mediated therapeutic genome editing in hereditary hematological disorders.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant number 81971886), the Zhujiang Talent Program (grant number 2019QN01Y279) and the Basic and Applied Basic Research Fund of Guangdong Province (grant number 2020A1515010468).

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Chen, Y., Wen, R., Yang, Z. et al. Genome editing using CRISPR/Cas9 to treat hereditary hematological disorders. Gene Ther (2021). https://doi.org/10.1038/s41434-021-00247-9

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