Adeno‑Associated Virus 3 (AAV3) is a human serotype of adeno‑associated virus closely related to AAV2. It is a non‑enveloped virus with an icosahedral capsid and a single‑stranded DNA genome of about 4.7 kb. AAV3 binds to heparan sulfate proteoglycans on host cells and uses co‑receptors such as the AAV receptor (AAVR), laminin receptor, fibroblast growth factor receptor and hepatocyte growth factor receptor. This receptor profile gives the virus a strong natural tropism for the liver.
Explanation
AAV3 is classified within the genus Dependoparvovirus and cannot replicate without a helper virus. Its genome contains rep and cap genes flanked by inverted terminal repeats (ITRs) that regulate replication and packaging. Two variants, AAV3A and AAV3B, differ by a few amino acids in their capsids; AAV3B exhibits greater stability and is often used in recombinant vector development. Wild‑type AAV3 infections are asymptomatic, and the virus persists as episomal DNA when co‑infecting cells with adenovirus or herpesvirus. Compared with other serotypes, AAV3 shows high transduction efficiency in primary human hepatocytes, making it attractive for liver‑directed gene transfer. Pre‑existing neutralizing antibodies are relatively common, and cross‑reactivity with AAV2 can influence vector performance.
Applications and notable facts
Recombinant AAV3 vectors have been developed for liver‑targeted gene therapy. AAV3B vectors efficiently deliver coagulation factor IX in animal models and are under investigation for haemophilia B. The strong hepatocyte tropism is also being explored to treat metabolic diseases and to deliver therapeutic antibodies. Modifications of the AAV3 capsid, including peptides or mutations, further enhance liver transduction or reduce neutralization. Despite promising preclinical data, fewer clinical trials have used AAV3 than AAV2 or AAV8 because of existing immunity and the availability of other serotypes with favorable immunological profiles. AAV3 is a naturally occurring adeno‑associated virus that primarily targets the liver. Its variants, especially AAV3B, are valued for their ability to transduce human hepatocytes, offering potential for liver‑directed gene therapies. Ongoing research focuses on optimizing AAV3 vectors and managing immune responses to improve their clinical utility. Related Terms: Adeno‑Associated Virus 1, Adeno‑Associated Virus 2, Adeno‑Associated Virus 5, Adeno‑Associated Virus 8, Adeno‑Associated Virus 9