Adeno-associated virus 9 capsid (AAV9 capsid)

The Adeno-associated virus 9 capsid is the protein shell that encapsulates the viral genome of AAV serotype 9, a member of the Dependoparvovirus genus. Its structure is composed principally of VP1, VP2, and VP3 proteins, assembled in an icosahedral symmetry from 60 monomers (usually at a ratio of 1:1:10 for VP1:VP2:VP3). The capsid determines the cellular tropism of the virus, which in the case of AAV9 includes a unique ability among AAV serotypes to efficiently cross the blood-brain barrier and preferentially target cardiac muscle. These properties result from specific surface features and variable regions (VRs) of the capsid proteins. The VP1 protein contains a unique N-terminal extension with phospholipase A2 activity essential for endosomal escape, nuclear localization, and infection. The AAV9 capsid is widely used in gene therapy to deliver therapeutic genes to a variety of tissues, especially in the central nervous system and heart. Its use is limited by immune responses against the capsid and pre-existing neutralizing antibodies in patients, as well as constraints related to vector size. Engineering of capsid variable regions is used to alter tropism, enhance tissue specificity, and evade host immunity. The capsid itself is not the direct target of drugs, but is a pivotal component in therapeutic vector design and clinical efficacy of gene therapies.

Other names

AAV9 capsidCapsid protein VP1 (specific to the AAV9 serotype)Viral structural proteins VP1, VP2, VP3 (collectively are the AAV9 capsid)

Tissue targeting via capsid tropism (preferential infection of heart, CNS, etc.) and transgene delivery, where the capsid packaging allows efficient cellular uptake and nuclear transport of therapeutic genes.