CAG-GCaMP3 AAV (Serotype 8)

AAV is a single-stranded DNA virus. Its overall structure consists of two parts: an icosahedral protein capsid with a diameter of about 26nm and a 4.7kb single-stranded DNA genome. The capsid contains three viral proteins (VP), VP1, VP2, and VP3. The AAV genome carries two "T"-shaped inverted terminal repeats (ITRs) at both ends. The viral coding region is between the ITR sequences, and the coding region contains two genes, Rep and Cap. The ordered region structure of the AAV8 VP monomer consists of a core eight-stranded β barrel structure and long interchain loops. The long loops include the HI loop (the loop between βH and βI), αA, and a loop region that forms a protrusion around the icosahedral triplet (pL1 to pL3). The complex loops between the β barrel chains constitute the capsid surface.

AAV8 was isolated from rhesus monkey tissues and is highly homologous to other AAVs. The structural similarity between AAV8 and AAV2 capsids is the highest, at 83%. Crystal structure analysis shows that AAV8 and AAV2 viruses have different capsid surface topologies. These differences lie in residues that control transduction efficiency and antibody recognition. In addition, the bulges around the three-fold symmetry axis and the bulge regions between the two- and five-fold symmetry axes result in different receptor recognition regions. The primary receptors for some AAV serotypes are specific glycan motifs. The primary receptor for AAV2 is heparan sulfate proteoglycan, which AAV2 uses for cell recognition with heparin sulfate affinity. On the other hand, AAV8 has no affinity for heparin sulfate, and the 37/67-kDa laminin receptor (LamR) is considered to be the host cell receptor for AAV8. The variation in the sequence and spatial conformation of the AAV8 capsid protein means that there are also differences in the cellular receptors that AAV8 binds to and in the nuclear transport process of the virus particles after entering the cell. These variations together lead to significant differences in vector infectivity and cell transfection efficiency.