AAV5-CAG-GCaMP6f

AAV is a small, single-stranded DNA virus belonging to the Parvoviridae family, whose three viral capsid proteins (VP1, VP2, and VP3) form a non-enveloped shell with icosahedral symmetry. Due to wild-type (wt) AAVs possess wide tissue tropism and low pathogenicity (as replication-deficient dependoparvoviruses), recombinantly produced AAV vectors (rAAV) have become an excellent vehicle for therapeutic gene delivery, with clinical payloads replacing the ~4.7 kb native genome. Promiscuous attachment of AAV to cell surface glycans is thought to increase the probability of internalization by increasing contacts with transmembrane receptor proteins that mediate entry. Expression of specific glycan types can affect binding and internalization in a serotype-specific manner and may have an effect on tropism. AAV viruses cross the plasma membrane by receptor-mediated endocytosis. Early studies focused on serotype 2 as an AAV model. Heparan sulfate proteoglycans (HSPGs) have been shown to be required for cell binding and transduction and are considered the first known receptors. Subsequently, different glycans emerged that were specific for other serotypes, for example, the sialic acid (SIA) moiety for AAV5, -1, -6, and -4, and galactose for AAV9. These proteoglycans are referred to as “primary receptors” because they are determinants of cell tropism, but other protein “co-receptors” are also thought to be required for internalization.