The Development of Adeno-Associated Virus as a Vector for In Vivo Gene Therapy

Significant developments in recombinant DNA technology and the increase in our understanding of the molecular basis of infectious agents such as viruses, have given rise to new opportunities for the development of novel delivery system for the correction of genetic diseases. The development of viral vector using the human parvovirus, adeno-associated virus (AAV), has provided a novel delivery system for genes transfer into mammalian cells. In fact, in vivo experiments have shown that recombinant AAV vectors are able to transduce cell populations that are thought to be largely quiescent at remarkably high efficiencies. In addition to demonstrating the potential for gene therapy approaches into neuronal cells using AAV, this finding represents the most conclusive demonstration that recombinant AAV vectors can transduce non-dividing cells. It should be noted that AAV transduction measured by gene expression, as described by the majority of the experiments, does not reflect viral integration, since gene expression can take place from episomal or integrated templates.