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GENOME EDITING

Cytosine base editors go off-target

Nature Reviews Genetics volume 20, pages 254–255 (2019)Cite this article

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Tools that can edit a single base pair in the genome hold promise for the treatment of human disease and crop improvement; however, little is known about their off-target effects. Jin et al. and Zuo et al. show that cytosine base editors (CBEs) (but not adenine base editors (ABEs)) induce notable off-target single-nucleotide variants (SNVs) in rice and in mouse embryos, respectively.

Jin et al. investigated the off-target mutations of the CBEs BE3 and HF1-BE3 (the fidelity of Cas9 is enhanced in HF1-BE3) and an ABE by transforming 17 base editor constructs (14 with sgRNA and 3 without sgRNA) targeting 11 genomic sites into rice. Analysing transgenic plants using whole-genome sequencing (WGS) confirmed on-target base editing and revealed the presence of SNVs and small insertions or deletions (indels) in each plant. A program for predicting off-target effects (Cas-OFFinder) did not predict most of the SNVs identified by WGS, highlighting the limitations of such software.

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Original article

Further reading

  • Rees, H. A. & Liu, D. R. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat. Rev. Genet. 19, 770–788 (2018)

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  1. Nature Reviews Genetics http://www.nature.com/nrg/

    Katharine H. Wrighton

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  1. Katharine H. Wrighton
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Correspondence to Katharine H. Wrighton.

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Wrighton, K.H. Cytosine base editors go off-target. Nat Rev Genet 20, 254–255 (2019). https://doi.org/10.1038/s41576-019-0110-x

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