AAV8-CAG-iCre

Adeno-associated viruses (AAVs) are small, ∼260 Å, T = 1, icosahedral non-enveloped viruses belonging to the Dependoparvovirus genus of the Parvoviridae family. Their capsids serve as vectors to deliver the virally packaged genome to the nucleus for replication. Currently, 13 human and non-human primate AAV serotypes and more than 150 genotypes have been identified. The AAV capsid consists of a total of 60 copies of viral protein (VP)1 (approximately 87 kDa), VP2 (approximately 73 kDa), and VP3 (approximately 61 kDa) in a population ratio of 1:1:10, respectively. AAV VPs share a common VP3 C-terminal sequence, with VP1 and VP2 extending at their N-termini. Compared to VP2, VP1 has a further extended N-terminus, with the VP1 unique (VP1u) region containing the phospholipase A2 (PLA2) domain, which is required for infectivity. Differences in amino acid sequence and capsid structure mediate the interaction of AAV serotypes with different host cell receptors, resulting in different cell or tissue tropisms. For example, AAV1 tropism is for skeletal muscle, while AAV8 tropism is for liver. AAV gene therapy has developed into one of the main treatment strategies for various monogenic diseases. These vectors are recombinant AAV (rAAV) that package a transgene expression cassette instead of the wild-type (WT) viral genome. Early development of AAV gene therapy systems focused on AAV2. However, new AAV serotypes have been isolated, and some of them have been found to exhibit higher transduction efficiency than AAV2 in certain cells or tissues. This has led to an increase in the number of capsid libraries that can be used to package different therapeutic genes. As a result, many recent clinical trials have utilized a range of AAV serotypes for therapeutic gene delivery. Notably, the rAAV1 vector for the treatment of lipoprotein lipase deficiency is the first approved human gene therapy biologic and has been certified by European medical authorities.