Gene therapy using adeno-associated viral (AAV) vectors is a promising approach for the treatment of monogenic disorders. Long-term multi-year transgene expression has been demonstrated in animal models and clinical studies. Nevertheless, uncertainties remain concerning the nature of AAV vector persistence and whether there is a potential for genotoxicity. Here, we describe the mechanisms of AAV vector persistence in the liver of a severe hemophilia A dog model (male = 4, hemizygous, and …