Syn-FLEX-GCaMP6m AAV (Serotype 9)

Adeno-associated virus (AAV) vectors provide sustained, long-term gene expression in a variety of tissues and cause minimal immunological complications compared to other viral vectors used for gene therapy. In recent years, multiple new AAV serotypes have been isolated that exhibit broad tissue tropism, provide efficient transduction and long-term gene expression. In particular, serotypes AAV6, AAV8, and AAV9 preferentially transduce cardiomyocytes after systemic administration and provide uniform gene delivery throughout the myocardium. For AAV9, the primary receptor is a cell surface glycan with a terminal β-galactose. The galactose-binding domain on the AAV9 capsid has been localized to a pocket at the base of a triple protrusion formed by N470, D271, N272, Y446, and W503. The adjacent 512NGR514 tripeptide motif has been implicated in entry into cells in vivo via interaction with integrins. Furthermore, 37/67 kilodalton laminin receptor (LamR) expression levels play a role in AAV9-based vector transduction in vitro, and residues 489–545 and 591–621 of the AAV9 VP correspond to AAV8 VP residues that interact with LamR in a yeast two-hybrid binding assay. A notable feature of AAV9 compared to other serotypes such as AAV1 is its delayed blood clearance, which has been attributed to residues 456–568 and is thought to contribute to the robust cardiac transduction of AAV9 in mice. When mapped to the AAV9 capsid structure, most of the residues involved in receptor binding and blood clearance are located at or near the tripartite protrusions, highlighting their important roles in mediating cellular interactions and determining capsid properties.