Adeno‑associated virus 8 (AAV8) is a naturally occurring adeno‑associated virus serotype first isolated from rhesus macaque tissues. It is a small non‑enveloped parvovirus with a single‑stranded DNA genome of about 4.7 kb enclosed in a 25 nm icosahedral capsid. AAV8 uses the 37/67‑kDa laminin receptor as its primary attachment receptor and requires co‑infection with helper viruses for replication.
Explanation
AAV8 was identified in 2002 in samples from rhesus macaques and characterized as a new serotype distinct from human isolates. Its genome consists of inverted terminal repeats flanking genes for four replication proteins and three structural capsid proteins, arranged similarly to other dependoparvoviruses. Unlike AAV2 and AAV3, AAV8 binds the laminin receptor rather than heparan sulfate; this receptor interaction mediates efficient uptake into cells. Capsid proteins of AAV8 undergo multiple post‑translational modifications, including phosphorylation, glycosylation and acetylation. Purification methods such as dual ion‑exchange chromatography and iodixanol gradient centrifugation exploit differences in capsid charge. A hallmark of AAV8 is its strong tropism to hepatocytes: compared with other serotypes it delivers transgenes to liver cells much more rapidly and with higher efficiency in murine, canine and non‑human primate models. Following systemic delivery in mice, AAV8 also transduces skeletal and cardiac muscles because it can traverse endothelial barriers, a feature lacking in AAV1 and AAV6. Beyond liver and muscle, local administration of AAV8 vectors leads to robust transgene expression in pancreatic islets, kidney tubular epithelium and several retinal cell types.
Applications in gene therapy
The pronounced hepatotropism of AAV8 has made it a leading vector for gene therapy aimed at treating metabolic and coagulation disorders. In preclinical studies, AAV8‑mediated delivery of a codon‑optimized human factor IX gene achieved long‑term expression and correction of hemophilia B phenotypes in dogs and non‑human primates; similar approaches using AAV8 to deliver factor VIII or other liver‑secreted proteins are under clinical evaluation. AAV8 vectors have also been used experimentally to correct metabolic diseases such as glycosylation disorders and lysosomal storage diseases through systemic administration. Localized AAV8 delivery has been applied to transduce pancreatic beta cells for diabetes research and renal or retinal tissues for models of kidney and eye diseases. These examples highlight the versatility of AAV8 as a gene transfer platform. AAV8 stands out among adeno‑associated viruses for its potent liver tropism and ability to transduce multiple tissues after systemic administration. Its unique receptor usage and high efficiency have made it a backbone for many current gene therapy strategies, although careful dose selection is necessary to minimize hepatic inflammation and immune responses. Related Terms: Adeno Associated Virus 6, Adeno Associated Virus 7, Adeno Associated Virus 9, Adeno Associated Virus 2, Parvovirus 4