A mitochondrial disease model is generated and corrected using engineered base editors in rat zygotes

Efficient generation and correction of mutations in mitochondrial DNA (mtDNA) is challenging. Here, through embryonic injection of an mtDNA adenine base editor (eTd-mtABE), Leigh syndrome rat models were generated efficiently (up to 74%) in the F₀ generation, exhibiting severe defects. To correct this mutation, a precise mtDNA C-to-T base editor was engineered and injected into mutated embryos. It achieved restoration of wild-type alleles to an average of 53%, leading to amelioration of disease symptoms.