During the replication of wild-type adeno-associated virus (AAV), viral capsids are assembled in the nucleolus,1 and the capsid proteins interact with the nucleolar proteins nucleolin (NCL) and nucleophosmin (NPM1), possibly promoting their transport from the cytoplasm into the nucleolus.2,3 In the case of replication-incompetent AAV vectors, the nucleolus is also important because vector virions can be found inside the nucleolus soon after entering the cell, and both NCL and NPM1 are involved in this trafficking.4 The nucleolar localization of vector virions is probably responsible for the unusual preference of AAV vectors for integration within the ribosomal DNA (rDNA) repeats, which accounts for 3–8% of all nonhomologous integration events,5,6 or 10- to 30-fold more than expected based on the amount of rDNA per cell. In this issue of Molecular Therapy, two reports from the labs of Markus Grompe and Mark Kay exploit this tendency of AAV virions to localize to the nucleolus by incorporating rDNA sequences into the vector genome and transducing mouse hepatocytes with these “rDNA vectors.”7,8 This simple trick produced dramatic effects, resulting in a 30-fold increase in chromosomal integration, about one third of which occurred within the rDNA repeats.8