Adeno-associated virus serotype 8 capsid protein (AAV8 capsid)

Adeno-associated virus serotype 8 (AAV8) capsid proteins are the structural components of the AAV8 viral vector, which is a leading platform for liver-directed gene therapy due to its high transduction efficiency in hepatocytes (Wang et al., 2012, Molecular Therapy). The capsid is an icosahedral assembly of three proteins—VP1, VP2, and VP3—that facilitates cell surface binding, primarily via the 37/67-kDa laminin receptor, and subsequent endosomal escape (Akache et al., 2006, Journal of Virology). In therapeutic applications, these capsid proteins serve as potent antigens that can elicit neutralizing antibodies (NAbs) and cytotoxic T-lymphocyte (CTL) responses, which often limit the efficacy and safety of gene transfer (Mingozzi & High, 2013, Nature Reviews Genetics). Pre-existing immunity is a major exclusion criterion for patients, making the capsid a target for pharmacological interventions like imlifidase, which cleaves anti-AAV IgG, or corticosteroids to suppress T-cell-mediated hepatotoxicity (Leborgne et al., 2020, Nature Medicine). Managing the immune profile of the AAV8 capsid is critical for achieving stable transgene expression and preventing adverse inflammatory events in patients receiving genetic medicines (Ertl, 2021, Immunology Letters).

Other names

AAV8 VP1AAV8 VP2AAV8 VP3AAV8 shellAAV-8 capsid antigensAdeno-associated virus 8 structural proteins

Enzymatic cleavage of anti-AAV8 IgG antibodies to prevent neutralization; Immunosuppression to inhibit capsid-specific T-cell mediated destruction of transduced cells; B-cell depletion to prevent de novo antibody formation.