Syn-jGCaMP7f AAV (Serotype 9)

Recombinant adeno-associated virus (rAAV) vector gene transfer systems have emerged as a powerful tool for therapeutic gene delivery, favored over other viral vectors due to their low immunogenicity, ability to transduce both dividing and non-dividing cells, persistent gene expression, lack of pathogenicity, and important clinical safety profile. The most commonly used AAV vectors are based on AAV serotype 2. Several AAV serotypes allow cross-packaging of the AAV2 vector backbone. As AAV transduction is regulated by the presence and distribution of cell surface receptors, different cell tropisms and transduction efficiencies are observed.

Wild-type (WT) AAV consists of a 4.7 kb genome encoding nonstructural (rep), structural (cap), assembly-activating (aap), and membrane-associated accessory (maap) proteins. The AAV cap gene encodes three capsid subunits, VP1–VP3, which are randomly assembled into a T = 1 icosahedral capsid consisting of 60 subunits. Diversity between AAV serotypes is generally defined by amino acid differences within nine variable regions (VRs) found in VP3 (VR-I through VR-IX). These VRs are located on the capsid surface and are associated with specific functional roles in the AAV life cycle, including receptor binding and antigen specificity. AAV vectors have several properties, such as long-term expression in non-dividing cells, ease of manufacturing, and relatively low immunogenicity, making them ideal for clinical gene therapy applications. To date, three capsid serotypes (AAV1, AAV2, and AAV9) have received regulatory approval for commercial use in patients.