Significant progress has been achieved in mitochondrial gene therapy. Dutch researchers successfully employed mitochondrial base editing tools, notably the DdCBE cytosine base editor, to precisely correct pathogenic mutations in mitochondrial DNA within patient-derived human cells and organoid models. This CRISPR-independent approach circumvents the traditional challenges of mitochondrial genome editing due to membrane impermeability and lack of RNA import mechanisms. These advances promise transformative therapeutic potential for rare mitochondrial diseases, addressing a historically intractable genetic target.