AAV6-hSyn-FLuc

Adeno-associated virus (AAV) is a single-stranded DNA (ssDNA) virus of the Parvoviridae family. Its genome consists of two genes, rep and cap, flanked by 145 bp inverted terminal repeats (ITRs) and packaged into a T = 1 icosahedral capsid composed of 60 protein subunits arranged in precise stoichiometry. The cap gene encodes the VP1, VP2, and VP3 C-terminal overlapping proteins that constitute the viral capsid, while the rep gene encodes four multifunctional proteins involved in essential functions of viral replication, such as DNA binding, site-specific endonuclease activity, and helicase activity. Due to its good toxicity and immunogenicity, ability to mediate stable and long-term expression of therapeutic transgenes, and efficient transduction of dividing and non-dividing cells, AAV has become a powerful gene transfer vector system for gene therapy of inherited and acquired diseases. The capsid is not just an inert protein shell, it also controls the interaction of the virus with cellular receptors and intracellular trafficking. Recent studies suggest that the capsid may be involved in second-strand synthesis and genome transcription. Twelve AAV serotypes have been identified, as well as numerous variants from humans and nonhuman primates, with different serological characteristics, cell surface receptor utilization, and tissue tropism. Serotypes can be broadly divided according to their primary cell surface receptor utilization: AAV2, AAV3, and AAV6 bind to heparan sulfate proteoglycans (HSPGs), AAV1, AAV4, AAV5, and AAV6 bind to sialic acid, and AAV9 binds to galactose. The coreceptors for internalization are also diverse and include laminin receptors, epidermal growth factor receptors, hepatocyte growth factor receptors, platelet-derived growth factor receptors, and several integrins. A recently discovered novel receptor, AAVR, appears to be required for infection by some variants. Most serotypes rely on AAVR for successful cell internalization, but differ in how they bind and interact with it. AAV4 and the chimeric variant AAVrh32.33 are exceptions, which use pathways that are independent of AAVR.