Adeno-associated virus capsid protein (AAV Cap protein)

The Adeno-associated virus (AAV) capsid protein is the structural shell of the AAV virion, composed of 60 subunits of three overlapping proteins: VP1, VP2, and VP3, typically in a 1:1:10 molar ratio (1.2.1, 1.3.4). It plays a critical role in the viral life cycle by mediating cell surface receptor binding, endocytosis, and intracellular trafficking, including endosomal escape facilitated by a phospholipase A2 (PLA2) domain located in the N-terminus of the VP1 subunit (1.2.2, 1.5.1). In the field of gene therapy, the AAV capsid serves as the primary delivery vehicle for therapeutic genetic payloads, with different serotypes exhibiting distinct tissue tropisms based on their capsid structure (1.3.3, 1.4.1). However, the capsid is also a major target for the host immune system; pre-existing neutralizing antibodies can prevent successful transduction, and capsid-derived peptides can elicit cytotoxic T-cell responses against transduced cells (1.3.4, 1.3.5). Consequently, the Cap protein is a central focus of bioengineering efforts aimed at enhancing delivery efficiency, expanding tropism, and evading immune detection (1.3.1, 1.5.1). Clinical management of AAV-based therapies often involves the use of corticosteroids or antibody-cleaving enzymes like imlifidase to mitigate these immune-related challenges and ensure therapeutic efficacy (1.2.1, 1.3.5).

Other names

Capsid proteinVP1VP2VP3Cap gene productAAV capsidViral protein 1Viral protein 2Viral protein 3

The AAV Cap protein facilitates the delivery of therapeutic genetic material by binding to host cell receptors and mediating endosomal escape and nuclear entry. Drugs targeting the capsid include neutralizing antibodies that block this process, while therapeutic strategies use immunosuppressants or IgG-cleaving enzymes to prevent immune-mediated clearance of the capsid and enhance transduction efficiency.