Abstract

Inserting genetic information at precise locations into the human genome has been the goal of gene transfer technology for almost two decades. The spectacular progress of mammalian genetics has led to the development of technology for genome editing and homologous recombination in human somatic cells that is finally approaching efficiency compatible with clinical application. Site-specific integration, or the insertion of genes at known locations by enzymes with target recognition capacity, has progressed slowly but steadily in recent years, and could very well be the basis of the next generation of gene transfer technology. This review focuses on the use of Rep, the replicase/integrase of the adenoassociated virus (AAV), to insert genes at the natural AAV integration site on human chromosome 19. This region (AAVS1) has characteristics that make it an ideal target for somatic transgenesis.

Keywords: AAV, AAVS1, MBS85, hybrid AAV vectors, Rep, Targeted integration, Rep Protein, Adeno-associated Virus, Site-specific Integration, lentiviral vectors, gene regulation, adeno-associated vector, human chromosome, attP sites, Dependovirus, Parvoviridae