mtDNA diversity in human populations highlights the merit of haplotype matching in gene therapies

Modern gene therapies aim to prevent the inheritance of mutant mitochondrial DNA (mtDNA) from mother to offspring by using a third-party mtDNA background. Technological limitations mean that these therapies may result in a small amount of maternal mtDNA admixed with a majority of third-party mtDNA. This situation is unstable if the mothers mtDNA experiences a proliferative advantage over the third-party mtDNA, in which case the efficacy of the therapy may be undermined. Animal models suggest that the likelihood of such a proliferative advantage increases with increasing genetic distance between mother and third-party mtDNA, but in real therapeutic contexts the genetic distance, and so the im