CRISPR-derived base editors can induce guide RNA (gRNA)-independent DNA and RNA off-target edits in eukaryotic cells due to “spurious deamination” by enclosed deaminases. Splitting base editors at a site in a Cas9 nickase-embedded deaminase allows gRNA-mediated base editor reassembly and activation at the target site to suppress unguided off-target edits.
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References
Zhang, H., Li, T., Sun, Y. & Yang, H. Perfecting targeting in CRISPR. Annu. Rev. Genet. 55, 453–477 (2021). A review article that provides an overview of CRISPR-based technologies and solutions to alleviate off-target effects.
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This is a summary of: Xiong, X. et al. Split complementation of base editors to minimize off-target edits. Nat. Plants https://doi.org/10.1038/s41477-023-01540-8 (2023).
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Split complementation of base editors reduces off-target edits. Nat. Plants 9, 1787–1788 (2023). https://doi.org/10.1038/s41477-023-01548-0
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DOI: https://doi.org/10.1038/s41477-023-01548-0