Site-specific integration by the adeno-associated virus rep protein

Inserting genetic information at precise locations into the human genome has been the goal of gene transfertechnology for almost two decades. The spectacular progress of mammalian genetics in the last two decades has led to thedevelopment of technology for genome editing and homologous recombination in human somatic cells that is finally approachingefficiency compatible with clinical application. Site-specific integration, or the insertion of genes at known locationsby enzymes with target recognition capacity, has progressed slowly but steadily in recent years, and could verywell be the basis of the next generation of gene transfer technology. This review focuses on the use of Rep, the replicase/integrase of the adeno-associated virus (AAV), to insert genes at the natural AAV integration site on human chromosome19. This region (AAVS1) has characteristics that make it an ideal target for somatic transgenesis