AAV5-CMV-FLPo

Adeno-associated viruses (AAV) are non-pathogenic, single-stranded DNA viruses of the Parvoviridae family used as vectors for gene delivery applications. These viruses consist of a non-enveloped capsid with T=1 icosahedral symmetry and a diameter of approximately 260 Å. Currently, 13 human and non-human primate AAV serotypes have been described, as well as numerous other isolates from different species. The amino acid sequences of different AAV capsids can differ by up to 50%, enabling them to bind to different host cell receptors, resulting in different cell and tissue tropisms. AAV serotype 5 (AAV5) is the most differentiated of the AAVs, utilizing α2,3-linked sialo-containing glycans as the primary host cell receptor. However, the overall composition of the viral capsid is similar for all AAVs. The capsid is assembled from 60 subunits of three overlapping capsid viral proteins (VPs), VP1 (∼87 kDa), VP2 (∼73 kDa), and VP3 (∼61 kDa), in an estimated ratio of 1:1:10. The individual VPs are expressed in the same open reading frame and share a common C-terminus. VP1 and VP2 represent N-terminal extensions of VP3. In addition, VP1 possesses the N-terminal approximately 137 amino acids of VP2, which contain the phospholipase A2 (PLA2) domain, which is required for AAV infectivity. Variable regions (VRs) I to IX (VR-I to VR-IX) are defined for AAV based on sequence and structural differences clustered at or around these capsid features, resulting in phenotypic differences between AAV serotypes, such as receptor attachment and antigenicity.