Mitochondrial adenine base editing of mouse somatic tissues via adeno-associated viral delivery

The development of adenine base editing in mitochondria, alongside cytidine base editing, has significantly expanded the genome engineering capabilities of the mitochondrial DNA. We tested the recent advancements in adenine base editing technology using optimised TALEs targeting genesMt-Cytb, Mt-CoIIandMt-Atp6in mouse cells, and observed successful A:T to G:C conversions within the target windows of each gene. Then, we used the best performing pairs targeting theMt-Atp6gene to inject mice using adeno-associated viral delivery to post-mitotic tissue. We observed limited efficiency of adenine edits in mouse somatic tissue after 4 weeks, suggesting the necessity of further optimisation of this technology.