AAV5-U6-miRNA-GFP

Recombinant adeno-associated virus (AAV) is a non-pathogenic gene therapy approach that has been used previously in clinical trials. AAV is a good candidate for clinical application because it provides long-term transgene expression in animal models, has minimal toxicity, and has a good overall safety profile in both preclinical animal studies and clinical trials. As with other non-enveloped viruses, the first critical step in recombinant AAV transduction involves recognition of glycans for cell surface attachment. Following binding, cellular uptake of different AAV serotypes appears to involve specific coreceptors on the cell surface. For example, AAV2 utilizes the FGF receptor, while both AAV2 and AAV3 appear to utilize the hepatocyte growth factor receptor/C-Met. In addition, platelet-derived growth factor and epidermal growth factor receptor have been implicated in the cellular uptake of AAV5 and AAV6, respectively. In addition to the potential contribution of these coreceptors to the differential transduction profiles of recombinant AAV serotypes, early reports implicate integrins as playing an important role in cellular uptake of AAV2 capsids. Importantly, the identification of a highly conserved integrin-binding motif (NGR) in the major capsid protein (VP3) subunit of the vast majority of AAV serotypes may indicate that integrins play a nonspecific role in recombinant AAV transduction.