Nature research paper: Mitochondrial base editor induces substantial nuclear off-target mutations
We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.DddA-derived cytosine base editors , which are fusions of the split-DddA halves and transcription activator-like effector array proteins, enable targeted C·G-to- T·A conversions in mitochondrial DNA.
Genome-wide, unbiased analysis of its editome reveals hundreds of off-target sites that are TALE array sequence -dependent or -independent. TAS-dependent off-target sites in the nuclear DNA are often specified by only one of the two TALE repeats, challenging the principle that DdCBEs are guided by a paired TALE proteins positioned in close proximity. TAS-independent nDNA off-target sites are frequently shared among DdCBEs with distinct TALE arrays.
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