Adeno‑Associated Virus 4 (AAV4) is a serotype of adeno‑associated virus isolated from rhesus monkeys. Like other AAVs it is non‑enveloped with an icosahedral capsid and a single‑stranded DNA genome of approximately 4.7 kb. AAV4 uses sialic acid residues on host cell surfaces as a primary receptor; its co‑receptors have not been definitively identified. The virus shows natural tropism for the eye, lungs, kidney and central nervous system.
Explanation
AAV4 belongs to the genus Dependoparvovirus and requires co‑infection with adenovirus or a related helper virus for productive replication. Its genome contains rep and cap genes flanked by inverted terminal repeats that regulate replication and packaging. Wild‑type infections in primates are asymptomatic; the virus persists as episomal DNA and does not integrate into host chromosomes at high frequency. AAV4 has lower transduction efficiency in many peripheral tissues compared with other serotypes, but it shows selective uptake in certain cell types. In the central nervous system, AAV4 efficiently transduces ependymal cells and astrocytes when injected directly into the brain, and in ocular tissues it targets cells of the retina and ciliary body. Pre‑existing neutralizing antibodies to AAV4 are relatively uncommon in humans, which may benefit vector use.
Research applications and observations
Recombinant AAV4 vectors are used primarily in preclinical research. Their selective tropism for ependymal cells makes them valuable for delivering genes that modify cerebrospinal fluid composition or influence neurogenesis. AAV4 has been explored for delivering neurotrophic factors to treat neurodegenerative diseases and for modulating retinal pigment epithelium in ocular models. In respiratory research, AAV4 has been used to investigate gene transfer to airway epithelia. Because it transduces certain tissues less efficiently than AAV1 or AAV8, AAV4 has not been widely used in clinical trials. Ongoing studies aim to engineer the AAV4 capsid to improve tropism and to explore its potential in gene therapy with reduced immune cross‑reactivity. AAV4 is a primate‑derived adeno‑associated virus serotype with distinct tissue preferences. Its replication‑defective nature and selective transduction of ependymal, ocular and respiratory cells make it a useful research tool. Further engineering may expand its applications in gene therapy. Related Terms: Adeno‑Associated Virus 5, Adeno‑Associated Virus 2, Adeno‑Associated Virus 6, Adeno‑Associated Virus 8, Adeno‑Associated Virus 9