Syn-FLEX-jGCaMP7f AAV (Serotype 9)

AAV is a non-enveloped, single-stranded DNA virus that was initially defined as a contaminant of adenoviral preparations. The virus belongs to the family Parvoviridae, specifically the genus Dependovirus, as it requires co-infection with a helper virus to replicate and complete its life cycle. Its 4700 bp genome contains two open reading frames (ORFs), rep and cap, flanked by inverted terminal repeats (ITRs) at the 5’ and 3’ ends. The rep ORF encodes four proteins: Rep 40, 52, 68, and 78, corresponding to spliced and unspliced products expressed using different promoters (P5 and P19). These Rep proteins, named according to their molecular weight, are required for AAV replication, transcription, integration, and encapsidation. On the other hand, the cap ORF leads to the production of three structural proteins (VP1, VP2, and VP3), which assemble in a 1:1:10 ratio to produce an icosahedral capsid of approximately 25 nm in diameter.

Over the past few years, twelve natural serotypes and more than a hundred AAV variants have been detected and isolated from humans and other primates. The different serotypes are defined by capsid protein motifs that are recognized by different neutralizing antibodies. In addition to antigenicity, AAV serotypes also display features regarding capsid-receptor interactions. Indeed, certain exposed capsid regions determine the interaction with the main AAV receptors, which are usually cell surface glycans. For example, AAV2 binds heparin sulfate proteoglycans, while AAV9 requires N-terminal galactose residues. These differences in receptor affinity patterns are important in determining the preferential tissue tropism of AAV serotypes. For example, AAV 8 and 9 are considered the best serotypes for targeting the liver, while AAV 5 and 9 are best suited for lung transduction.