Syn-NES-jRGECO1b AAV (Serotype 8)

Adeno-associated viruses (AAVs) belong to the genus Dependovirus of the family Parvoviridae and have been used as therapeutic gene delivery vectors. Of the 12 different human and non-human primate AAV serotypes identified to date, AAV8 shows higher liver transduction efficiency compared to the other serotypes and has been used as a liver-directed gene therapy vector. The increased transduction efficiency of AAV8 compared to AAV2 is reported to be due to faster capsid uncoating and, therefore, faster onset of gene expression in the former serotype.

AAV capsids are assembled from 60 (total) copies of overlapping capsid viral proteins (VPs) VP1, VP2, and VP3, encoded by the cap open reading frame, in a suggested ratio of 1:1:10, respectively. VP1 has a unique 137 amino acid N-terminal region in AAV8 and shares only an additional 66 residues with VP2. The overlapping VP1-VP3 region (~530 C-terminal residues) has multiple functions, contributing to receptor attachment, cell transduction, capsid assembly and genome packaging, and is a target for host immune responses to the capsid. A unique N-terminal region of VP1 (VP1u) possesses phospholipase A2 (PLA2) activity, which is required for acidification-associated viral escape from endosomes during trafficking to the nucleus for DNA replication. This VP1u also contains a nuclear localization signal (NLS) and is predicted to change from an internal to an external configuration while the capsid remains intact.