Adeno-associated virus serotype 2 capsid protein (AAV2 capsid)

The Adeno-associated virus serotype 2 (AAV2) capsid is a 25-nm icosahedral protein shell composed of 60 subunits of three viral proteins (VP1, VP2, and VP3) in a 1:1:10 ratio (UniProt: P03135). It is the most extensively studied AAV serotype and serves as the foundational scaffold for many gene therapy vectors (PubMed: 12610124). The capsid's primary biological role is to protect the viral genome and facilitate its delivery into host cells by binding to heparan sulfate proteoglycans (HSPG) and the AAV receptor (AAVR) (PubMed: 26751251). In a clinical context, the AAV2 capsid is a therapeutic tool used to treat inherited disorders, most notably in the FDA-approved gene therapy Voretigene neparvovec for Leber congenital amaurosis (FDA: Luxturna). However, its use is limited by pre-existing immunity in the human population, as many individuals have neutralizing antibodies that can block the vector's efficacy (PubMed: 16713361). Furthermore, high doses of AAV2-based vectors can trigger innate and adaptive immune responses, leading to inflammation or loss of transgene expression (PubMed: 21422300).

Other names

AAV2 VP1/VP2/VP3AAV-2 capsidAdeno-associated virus 2 shellAAV2 VP1AAV2 VP2AAV2 VP3

The AAV2 capsid acts as a delivery vehicle that encapsulates a therapeutic gene. It facilitates target cell entry by binding to heparan sulfate proteoglycans (HSPG) and the AAV receptor (AAVR), followed by endocytosis and trafficking to the nucleus for gene expression (PubMed: 26751251, PubMed: 12610124).