AAV8

AAV8, or adeno-associated virus serotype 8, is a serotype of the adeno-associated virus used extensively as a vector in gene therapy research and development. It is a non-enveloped, single-stranded DNA virus belonging to the Parvoviridae family and dependoparvovirus genus. AAV8 is one of several serotypes exploited for its distinct tissue tropism and transduction efficiency, particularly in liver tissue after systemic delivery.

The genome of AAV8 vectors is derived from the natural AAV genome, which contains the rep and cap genes and inverted terminal repeats (ITRs) necessary for replication and packaging. In recombinant vectors used for therapy, the rep and cap genes are supplied in trans, and the therapeutic gene, driven by a suitable regulatory element, is packaged between the ITRs. The typical packaging capacity of an AAV vector is about 4.7 kilobases, though a self-complementary design reduces usable cargo to roughly 2.3 kilobases to enable faster expression. AAV8 capsids, encoded by the cap gene, determine the vector’s biodistribution and transduction efficiency.

Tropism and delivery characteristics make AAV8 particularly suitable for liver-directed gene therapy. Intravenous delivery often results in robust hepatic transduction in animal models and, in some cases, in humans. AAV8 generally shows lower prevalence of pre-existing neutralizing antibodies compared with AAV2, though such antibodies can still limit efficacy in some patients. In addition to the liver, AAV8 can transduce muscle and other tissues under certain conditions.

Applications in research and clinical contexts include preclinical studies and clinical trials for metabolic and hepatic diseases, such as hemophilia B, where liver-directed expression of therapeutic genes is pursued. Safety considerations include potential immunogenicity to the capsid, dose-related hepatotoxicity risks, and the low but present possibility of integration, warranting careful monitoring during development and use.