CAG-FLEX-jGCaMP7b AAV (Serotype 9)

Adeno-associated virus (AAV) provides the most powerful in vivo gene delivery vector for gene therapy, enabling safe, effective, and sustainable therapeutic gene expression. AAV is a small, non-enveloped virus of the family Parvoviridae that packages a linear single-stranded DNA (ssDNA) genome of approximately 4.7 kb. To date, three AAV-based gene therapy biologics have been approved for commercialization.

The AAV capsid consists of 60 copies of viral protein (VP) subunits, with VP1, VP2, and VP3 in a 1:1:10 ratio. The capsid structures of a few wild-type (WT) AAV serotypes have been determined by cryo-electron microscopy (cryo-EM) and three-dimensional image reconstruction and/or X-ray crystallography. The VP3 monomers of all examined serotypes have a conserved β-barrel core composed of eight antiparallel β-sheets. The macroloop connecting the β-strands contains nine variable regions (VR-I to -IX) that are accessible from the solvent side and interact with cellular receptors and antibodies. The VRs of different serotypes are highly differentiated and may determine capsid characteristics such as tropism and immunogenicity. A striking feature of all known AAV capsid structures is the protrusions surrounding the icosahedral three-fold symmetry axis, where most VRs are located. Therefore, the three-fold protrusions play an important role in shaping the unique properties of each variant capsid.