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Split complementation of base editors reduces off-target edits

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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Fig. 1: Schematic rationale of the split complementation of a base editor.

References

  1. 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.

    Article  CAS  PubMed  Google Scholar 

  2. Zuo, E. et al. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science 364, 289–292 (2019). This paper reports substantial genome-wide off-target edits by a CBE in mouse embryos.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Jin, S. et al. Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice. Science 364, 292–295 (2019). This paper reports substantial genome-wide off-target edits by a CBE in transgenic rice.

    Article  CAS  PubMed  Google Scholar 

  4. Grünewald et al. Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors. Nature 569, 433–437 (2019). This paper reports that both CBE and ABE can induce substantial transcriptome-wide off-target edits in human cells.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wang, Y., Zhou, L., Liu, N. & Yao, S. BE-PIGS: a base-editing tool with deaminases inlaid into Cas9 PI domain significantly expanded the editing scope. Signal Transduct. Target. Ther. 4, 36 (2019). This paper reports a CBE with a nCas9-inlaid cytidine deaminase.

    Article  PubMed  PubMed Central  Google Scholar 

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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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