AdenoAssociated

Adeno-associated virus (AAV) is a small, non-enveloped DNA virus from the Parvoviridae family. In nature it is replication-defective unless a helper virus is present (adenovirus or herpesvirus). Because of its low pathogenicity in humans and capacity to deliver genetic cargo, AAV is widely used as a gene therapy vector.

The AAV genome is about 4.7 kilobases and contains inverted terminal repeats that flank a transgene cassette. In recombinant AAV (rAAV) applications, the rep and cap genes are supplied in trans and the therapeutic genome is packaged into capsids. AAV typically forms episomes with long-term expression in non-dividing cells.

There are multiple AAV serotypes (AAV1–AAV12) with differing tissue tropisms. Some serotypes target muscle or liver; others cross the blood–brain barrier (e.g., AAV9), enabling systemic delivery to the CNS and retina. The choice of serotype, dose, and route affects efficacy and safety.

Clinical use includes licensed therapies such as Luxturna (AAV2) for RPE65-related retinal dystrophy and Zolgensma (AAV9) for spinal muscular atrophy. Additional approvals include other organ targets, illustrating AAV’s versatility and the regulatory pathway for gene therapies.

Limitations and challenges include pre-existing immunity to capsids, limited packaging capacity (~4.7 kb), manufacturing complexity, and potential long-term safety concerns. Ongoing research seeks broader tropism, reduced immunogenicity, and scalable production to extend applications.