Researchers at University Medical Center Utrecht and colleagues have achieved precision mitochondrial base editing to correct pathogenic mitochondrial DNA mutations in patient-derived cells. Utilizing the DddA-derived cytosine base editor, this CRISPR-independent technology enables targeted single-nucleotide substitutions without double-stranded breaks. Demonstrations in liver organoids reveal restored mitochondrial function, marking a critical advance towards gene therapy options for mitochondrial diseases long considered untreatable due to mitochondrial genome inaccessibility.