Adeno‑Associated Virus 2 (AAV2) is a human serotype of adeno‑associated virus discovered in 1965 as a contaminant of adenovirus preparations. It is a non‑enveloped parvovirus with a 25 nm icosahedral capsid containing a ~4.7 kb single‑stranded DNA genome. The virus binds to heparan sulfate proteoglycans on host cells and uses co‑receptors such as the AAV receptor (AAVR), integrins, laminin receptor, fibroblast growth factor receptor and hepatocyte growth factor receptor, giving it broad natural tropism for liver, central nervous system and muscle tissues.
Explanation
AAV2 belongs to the genus Dependoparvovirus and is replication‑defective, requiring adenovirus or herpesvirus co‑infection for productive replication. Its genome contains rep and cap genes flanked by 145‑base inverted terminal repeats (ITRs) that regulate replication and packaging. Wild‑type AAV2 establishes persistent episomal DNA in the nucleus and is not known to cause human disease. In the presence of Rep proteins, AAV2 can integrate into a specific locus on chromosome 19 (AAVS1), but recombinant vectors lack this ability and persist as episomes. AAV2 has been extensively studied and serves as the prototypical AAV serotype. Neutralizing antibodies are common in humans, reflecting widespread natural exposure.
Therapeutic applications and notable facts
AAV2 has played a central role in the development of gene therapy. Luxturna, the first FDA‑approved gene therapy for a genetic eye disease, uses an rAAV2 vector to deliver the RPE65 gene to retinal cells in patients with Leber congenital amaurosis, restoring functional vision. rAAV2 vectors are also being tested to deliver clotting factor IX for haemophilia, aromatic L‑amino acid decarboxylase for aromatic L‑amino acid decarboxylase deficiency and therapeutic genes for Parkinson’s disease, epilepsy and spinal cord injury. The ability of AAV2 to integrate into AAVS1 has been exploited in research to achieve stable gene insertion, but integration is not necessary for therapeutic efficacy in most applications. Immune responses remain a challenge because many individuals harbour pre‑existing antibodies; various strategies, including immune suppression and capsid engineering, are being developed to improve clinical outcomes.
AAV2 is a widely used and well‑characterized AAV serotype. Its reliance on helper viruses for replication and its ability to persist as episomal DNA make it a safe and effective gene transfer vehicle. Ongoing research aims to refine AAV2‑based therapies and address immune barriers to extend its clinical utility.
Related Terms: Adeno‑Associated Virus 1, Adeno‑Associated Virus 3, Adeno‑Associated Virus 5, Adeno‑Associated Virus 8, Adeno‑Associated Virus 9