AAV8-CMV-iCre

Recombinant adeno-associated virus (AAV) is one of the most widely used gene therapy systems in research and clinical trials. AAV is preferred over other viral vectors because it is non-pathogenic and can establish expression in dividing cells of multiple lineages and in mature non-dividing cells. In addition, AAV vectors can achieve high levels of transduction within weeks and maintain these levels throughout the life of the organism. AAV vectors can effectively transduce many different biological tissues, including muscle, liver, brain, lung, and retina. AAV gene therapy has been successful in multiple human clinical trials, including the treatment of hemophilia B using AAV8 vectors expressing therapeutic levels of factor IX protein and the treatment of Pompe disease using AAV1 vectors. The T = 1 icosahedral capsid is composed of 60 viral proteins (VPs) assembled from VP1 (~80 kDa), VP2 (~65 kDa), and VP3 (~60 kDa) in a ratio of approximately 1:1:10. The VP consists of a conserved α-helix (αA), βA strands, and an eight-stranded antiparallel β barrel (βB-βI) core motif connected by large loops named after the β strands they connect. For example, the HI loop connects the βH and βI strands. These loops constitute the surface morphology of the AAV capsid, including a cylindrical channel at the 5-fold axis, three protrusions around the 3-fold axis, a depression at the 2-fold axis and a depression around the channel at the 5-fold axis, and a raised region between the 2-fold and 5-fold axes, called the 2/5-fold wall. The surface loops exhibit a high degree of sequence and structural variability between AAV serotypes. Nine VRs are defined for AAV, VR-I to VR-IX. These VRs contribute to structural differences between serotypes and contribute to functional phenotypes, including receptor attachment, tissue tropism, transduction efficiency, and antigenic reactivity.