Syn-CaMPARI AAV (Serotype 8)

Adeno-associated virus (AAV) belongs to the genus Dependovirus in the family Parvoviridae. Over the past two decades, researchers have focused on using AAV as the backbone of recombinant viral vectors for in vivo gene transfer due to the properties of recombinant AAV vectors. AAV vectors have been used in gene therapy to treat a variety of diseases, such as hemophilia and Parkinson's disease. There are several different serotypes of AAV, each with its own tropism. Therefore, a specific vector serotype can be selected based on the target organ. At least 13 natural AAV serotypes and more than 100 different variants have been isolated. The existing serotypes share 53% to 99% amino acid sequence homology in each structural protein subunit, but have different tissue tropisms and use a variety of receptors and coreceptors to enter cells. Although X-ray crystallography and more recently cryo-electron microscopy (cryo-EM) of the AAV capsid have revealed a high degree of similarity in the capsid surface topology of different serotypes, most of the differences in tissue tropism can be traced back to their capsid structure. Each AAV capsid subunit contains nine surface-exposed hypervariable regions (VRs), which are the regions where the genomic divergence between different serotypes is most concentrated. Each subunit interacts with other neighboring subunits through complex protein-protein interactions that are defined by the two-, three-, and five-fold symmetry axes of the icosahedral AAV particle. Near the two-fold symmetry axis, the most conserved surface features confer structural stability to the capsid. The five-fold axis contains a cylindrical feature surrounded by depressions that participate in encapsidation of the AAV genome. The three-fold axis is characterized by the three largest external protrusions and contains the most exposed VRs (VR-IV, VR-V, and VR-VIII), which are involved in receptor binding and are therefore key determinants of tropism.