Adeno-associated virus

Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genusDependoparvovirus, which in turn belongs to the familyParvoviridae. They are small (approximately 26 nmTooltip nanometers in diameter) replication-defective, non-enveloped viruses and have linear single-stranded DNA (ssDNA) genomes of approximately 4.8 kilobases (kb).

Several features make AAV an attractive candidate for creating viral vectors in the field of molecular biology including animal modeling and the creation of isogenic human disease models. Vectors using AAV can infect both dividing and quiescent cells and persist in an non-integrated extrachromosomal state into the genome of the host cell. Low level integration into the host genome occurs, particularly in the wild type virus setting.

Recombinant or replication-defective AAV has emerged an important technology in the field of gene therapy. This has now led to multiple approved drugs leveraging its gene delivery often for genetic disorders such as Spinal Muscular Atrophy, forms of blindness, and hemophilia. The use of AAV has its limitations including the limited genetic cargo capacity and adverse events, particularly at very high dose levels have been recorded.

In March 2023, a series of Nature papers detected high titres of adeno-associated virus 2 (AAV2), alongside adenovirus and herpesvirus, in samples from a wave of childhood hepatitis. One paper suggested that AAV2 co-infection may contribute to more serious liver disease than infection with only adeno- or herpesviruses and that the causal link remains to be established.