We revealed that the RNA-targeting activity of the Cas13 family of nucleases allows them to directly target endogenous RNA in mammalian cells. Such activity limits the usage of lentiviral Cas13 systems, and suggests a need for caution when applying Cas13-based systems.
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References
Terns, M. P. CRISPR-based technologies: impact of RNA-targeting systems. Mol. Cell 72, 404–412 (2018). A review article that describes different CRISPR-based RNA-targeting systems.
Perculija, V. et al. Functional features and current applications of the RNA-targeting type VI CRISPR-Cas systems. Adv. Sci. 8, 2004685 (2021). A review article that discusses the characteristics and application of the Cas13a, Cas13b and Cas13d systems.
Cheng, X. et al. Modeling CRISPR-Cas13d on-target and off-target effects using machine learning approaches. Nat. Commun. 14, 752 (2023). This paper reports a deep-learning model and web server for predicting crRNA performance in a Cas13d system.
Abudayyeh, O. O. et al. C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Science 353, aaf5573 (2016). This paper reports both the on-target and collateral activities of Cas13a.
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This is a summary of: Li, Z. et al. Intrinsic targeting of host RNA by Cas13 constrains its utility. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-023-01109-y (2023).
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Intrinsic RNA-targeting activity limits the applicability of CRISPR–Cas13. Nat. Biomed. Eng 8, 116–117 (2024). https://doi.org/10.1038/s41551-023-01124-z
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DOI: https://doi.org/10.1038/s41551-023-01124-z