Mitochondrial base editing for disease modeling and therapeutic correction

Recent development of mitochondrial DNA (mtDNA) editors has made it possible to generate experimental models carrying patient-relevant mtDNA mutations, characterize disease-associated phenotypes in cells and animals, and directly correct pathogenic variants in vivo. Here, we summarize the current landscape of mtDNA base editors and discuss key considerations for their application to mitochondrial disease model generation, including target selection, cross-species conservation, editing window constraints, strand bias, sequence-context dependence, and the balance between editing efficiency and safety. We further review strategies for validating mtDNA-edited models at functional, molecular, and organismal levels, and highlight recent studies demonstrating therapeutic rescue in animal models.