Adeno-associated virus serotype 9 (AAV9)

Adeno-associated virus serotype 9 (AAV9) is a small, non-enveloped, single-stranded DNA virus belonging to the Parvoviridae family, widely utilized as a premier vector for in vivo gene therapy. It is distinguished by its unique ability to cross the blood-brain barrier (BBB) and its broad tissue tropism, particularly for the central nervous system (CNS), heart, and skeletal muscle. AAV9 enters cells by binding to terminal N-linked galactose residues and the universal adeno-associated virus receptor (AAVR), followed by receptor-mediated endocytosis and nuclear trafficking. Once in the nucleus, the viral genome persists primarily as episomal concatemers, providing long-term expression of the therapeutic transgene without significant integration into the host genome. Clinically, AAV9 is the delivery vehicle for the FDA-approved gene therapy onasemnogene abeparvovec (Zolgensma) for spinal muscular atrophy. Despite its therapeutic success, challenges include pre-existing neutralizing antibodies in the human population and potential high-dose toxicities such as hepatotoxicity and dorsal root ganglion (DRG) inflammation.

Other names

AAV-9AAV9Adeno-associated virus 9Dependoparvovirus primate 1 (serotype 9)

Viral vector-mediated gene delivery via receptor-mediated endocytosis and episomal transgene expression