AAV9-CMV-RLuc

Among viral vectors, adeno-associated virus (AAV) serotypes have been identified as a promising mode of gene delivery because they have important advantages over other vectors: they are non-pathogenic to humans and provide prolonged transgene expression. Multiple AAV serotypes with variable tropism have been identified; however, they all share some common properties, including genome size and organization, and, apart from minor differences, inverted terminal repeats with identical structure and function. All serotypes are non-enveloped, single-stranded DNA parvoviruses, 25 nanometers in diameter, belonging to the genus Dependovirus. The upstream open reading frame encodes four replication (rep) proteins that enable the AAV2 rep proteins to package AAV2 inverted terminal repeat-flanked transgenes into virions of nearly all serotypes. Recombinant (r) forms of wild-type AAV serotypes retain the ability to enter the nucleus, uncoat, and transduce cells, and their genomes become episomal or integrated proviruses. Twelve serotypes (AAV1-12) have been thoroughly tested for their ability to transduce specific cell types and tissues and are distinguished by capsid protein motifs that bind specific cell surface receptors for cell attachment. For example, AAV1, AAV4, AAV5, AAV7 (sialylated glycoproteins), AAV2/AAV3 (heparin sulfate proteoglycans), AAV9 (galactose), and AAV8 have no known primary receptors, although laminin is a potential coreceptor for these viruses. Recently, a universal receptor, KIAA0319 or AAVR, has been identified that mediates rapid endocytosis after cell binding and attachment for all AAV serotypes. Through viral engineering, hybrid AAV serotypes or pseudo-serotypes have been created that consist of integrated genomes containing the (cis) inverted terminal repeats (ITRs) of AAV2 and capsid genes from other serotypes to improve viral specificity and transduction capacity. Several studies have demonstrated that AAV serotypes differ in transduction in vitro and in vivo; this is dependent on cell type specificity, cytotoxicity, viral delivery method, timing of viral delivery, and stability of AAV transgene expression over time.