Adeno-associated virus capsid (AAV capsid)

The Adeno-associated virus (AAV) capsid is a robust, icosahedral protein shell approximately 25 nm in diameter, composed of 60 subunits of three structural proteins: VP1, VP2, and VP3, typically in a 1:1:10 ratio (UniProt P03135). Its primary biological function is to encapsulate and protect the single-stranded DNA viral genome while facilitating targeted delivery into host cells through specific receptor-ligand interactions and complex intracellular trafficking pathways (PubMed: 29305544). In modern medicine, the AAV capsid is the foundational component of gene therapy, serving as a non-pathogenic delivery vehicle (vector) for therapeutic transgenes to treat a wide array of genetic disorders. Different AAV serotypes (e.g., AAV2, AAV5, AAV8, AAV9) exhibit distinct tissue tropisms, allowing for the targeting of specific organs such as the liver, heart, or central nervous system (NIH: Gene Therapy Systems). However, the capsid is also the primary target for the host immune system; pre-existing neutralizing antibodies can bind to the capsid and prevent successful transduction, while T-cell responses against capsid fragments can lead to the destruction of transduced cells (Nature Reviews Drug Discovery, 2021). Consequently, current drug development focuses on engineering next-generation capsids with enhanced delivery efficiency, reduced immunogenicity, and improved tissue specificity to overcome these therapeutic barriers.

Other names

AAV shellAAV VP1/VP2/VP3 proteinsDependoparvovirus capsidAAV vector shell

The AAV capsid functions as a delivery vehicle that protects the therapeutic transgene and facilitates its entry into target cells by binding to specific receptors (e.g., AAVR, heparan sulfate proteoglycans) and co-receptors, followed by endosomal escape and nuclear translocation (Nature Reviews Drug Discovery, 2019).