Spatiotemporal Control of CRISPR/Cas9 Gene Editing

    Chenya Zhuo, Jiabin Zhang, Jung Hwan Lee, Ju Jiao, Du Cheng, Li Liu, Hae-Won Kim, Yu Tao, Mingqiang Li
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    TLDR The document concludes that while there are promising methods to control CRISPR/Cas9 gene editing, more research is needed to overcome challenges related to safety and effectiveness for clinical use.
    The document reviews strategies for precise spatiotemporal control of CRISPR/Cas9 gene editing to minimize off-target effects and enhance clinical applicability. It discusses genetic regulation methods like cell-specific promoters, chemical methods including small molecule activation and inhibition, and physical methods such as light, heat, ultrasound, and magnetic field control. The review highlights the potential of these strategies but also acknowledges their limitations, such as lack of specificity, reversibility, and in vivo applicability. It emphasizes the need for further research to improve these strategies for safe and effective clinical use. Specific examples include the use of multiple sgRNAs for increased transcriptional activation, transcription repression domains for improved inhibition efficiency, anti-CRISPR proteins for rapid Cas9 activity limitation, and SORT nanoparticles for tissue-specific mRNA delivery. Despite advancements, challenges remain in clinical translation, including delivery efficiency, specificity, immune response, and off-target effects.
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