Adeno-Associated Virus (AAV)

The Adeno-associated virus (AAV) is a small, single-stranded DNA virus that belongs to the family of Parvoviridae.

AAV infects humans and other primates; however, it is not known to cause any disease. The lack of pathogenicity makes AAV attractive for its application as a viral vector for gene therapy.

AAV structure and genome

AAV is characterized by an icosahedral capsid and a genome size of 4.7 kb. The genome contains two open reading frames, encoding for rep and cap. Rep is composed of four genes encoding for viral proteins required for replication. Cap contains VP1, VP2, and VP3, which together build the virus capsid.

AAV in gene therapy

The desired therapeutic gene cDNA is inserted between two inverted terminal repeats (ITRs) that aid the packaging of the viral genome into the virus capsid.

Once infected with a recombinant AAV, the introduced therapeutic gene will not integrate into the host genome but remain as episomal concatemers in the cell nucleus. Consequently, AAV DNA is lost upon cell division as the episomal DNA is not replicated.

Compared to other viral vectors, AAV has a rather small cloning capacity and requires the complete replacement of the 4.7 kb genome. This allows for the incorporation of only small therapeutic genes.

The application of AAV as a viral vector for gene therapy is limited by the fact that some patients were unnoticedly infected with AAV and therefore produced neutralizing antibodies against the virus, which impairs the efficiency of the treatment.

Figure 1: Electron micrograph of AAV particles.