Gene therapy vectors based on adeno-associated virus: characteristics and applications to acquired and inherited diseases (review)

Adeno-associated virus (AAV), a defective parvovirus, was discovered more than 30 years ago. Interest in this virus for human gene therapy applications focuses on its non-pathogenicity, broad tropism and infectivity, site-specific integration and long-term persistence. The field of rAAV research has considerably advanced: titers of 1014 p/ml have been achieved, plasmid systems devised to produce helper-free viruses, chimaeric vectors combining properties of rAAV ITRs and large sequence capacity from Ad/HS vectors in parallel with the revolutionary intron strategy based on heterodimerisation of the forming concatamers have expanded the vector capacity. Muscle cells and neurons (post-mitotic cells) are amongst the most efficient targets of rAAV delivery and AAV receptors and co-receptors have been identified. This review will describe advances in the field of rAAV technology that overcome certain limitations of the vector as a gene delivery system and overview applications involving these recombinant vectors for the treatment of acquired and inherited diseases.