CAG-ChIEF-tdTOMATO AAV (Serotype 5)

Adeno-associated virus (AAV) is one of the most actively investigated gene therapy vectors. It was originally discovered as a contaminant of adenoviral preparations, hence the name. In brief, AAV is a protein coat that surrounds and protects a small single-stranded DNA genome of approximately 4.8 kilobases (kb). AAV belongs to the family Parvoviridae and relies on co-infection with other viruses, primarily adenoviruses, for replication. AAV genes were initially differentiated serologically, and molecular cloning has identified hundreds of unique AAV strains in many species.

The AAV genome contains three genes, Rep (replication), Cap (capsid), and aap (assembly). These three genes generate at least nine gene products through the use of three promoters, alternative translation start sites, and differential splicing. These coding sequences are flanked by inverted terminal repeats (ITRs) required for genome replication and packaging. The Rep gene encodes four proteins (Rep78, Rep68, Rep52, and Rep40) that are required for viral genome replication and packaging, while Cap expression produces viral capsid proteins (VP; VP1/VP2/VP3), which form a shell that protects the viral genome and are actively involved in cell binding and internalization. The viral capsid is estimated to be composed of 60 proteins arranged in an icosahedral structure with a capsid protein molar ratio of 1:1:10 (VP1:VP2:VP3).