Gene therapy: recombinant adeno-associated virus vectors

Gene transfer using recombinant adeno-associated virus (rAAV) vectors shows great promise for human gene therapy. The broad host range, low level of immune response, and longevity of gene expression observed with these vectors in numerous disease paradigms has enabled the initiation of a number of clinical trials using this gene delivery system. This review presents an overview of the current developments in the field of AAV-mediated gene delivery. Such developments include the establishment of new production methods allowing the generation of high titer preparations, improved purification methods, the use of alternative AAV serotypes, and the generation of trans-splicing rAAV genomes. Together, these developments have improved results interpretation, host range, and the coding capacity of rAAV vectors. Furthermore, the recent identification of regions within the viral capsid that are amenable to modification has begun to address the issue of direct rAAV vector targeting, which could potentially allow targeted gene delivery to specific cell populations. The versatility shown by this vector has enabled new diseases to be realistically considered for therapeutic intervention and considerably broadened the scope of gene therapy.