Adeno-associated virus capsid (AAV capsid) (AAV capsid)

Adeno-associated virus (AAV) capsids are the protein shells of small, non-pathogenic viruses used extensively as vectors in gene therapy to deliver genetic material into target cells. When engineered for skeletal muscle transduction, specific serotypes like AAV1, AAV6, AAV8, or AAV9 are selected for their high affinity for myogenic cell surface receptors, such as heparan sulfate proteoglycans or laminin receptors (Wang et al., 2019). Once the capsid binds and enters the skeletal muscle fiber, it undergoes endosomal escape and nuclear trafficking to release its DNA payload, enabling the long-term expression of therapeutic proteins like dystrophin or acid alpha-glucosidase (Zincarelli et al., 2008). Despite their utility, AAV capsids present significant clinical challenges, primarily due to pre-existing immunity and the induction of de novo immune responses. Neutralizing antibodies can block the capsid from reaching the muscle, while capsid-specific CD8+ T-cells can eliminate the transduced muscle fibers, potentially leading to loss of efficacy and inflammatory side effects (Mingozzi & High, 2013). Consequently, managing the immune response to the AAV capsid is a critical component of gene therapy protocols for neuromuscular diseases (Mendell et al., 2017).

Other names

Adeno-associated virus vectorrAAVViral capsidMuscle-tropic AAVAAV serotype

Viral-mediated gene delivery and transduction of myocytes.