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

Adeno-associated virus serotype 8 (AAV8) capsid proteins are the structural components of a viral vector widely utilized in gene therapy for their potent liver tropism (Gao et al., PNAS, 2002). The capsid is composed of three proteins—VP1, VP2, and VP3—which assemble into an icosahedral shell that protects the therapeutic transgene during delivery. A significant challenge in AAV8-mediated therapy is the host's adaptive immune response, which can recognize these capsid antigens as foreign. This response includes the production of neutralizing antibodies (NAbs) that can block vector entry and the activation of CD8+ T-cells that target and destroy transduced hepatocytes (Mingozzi & High, Nature Reviews Genetics, 2011). Clinical management often involves the use of prophylactic corticosteroids to mitigate T-cell-mediated inflammation and liver enzyme elevation (Nathwani et al., NEJM, 2011). Emerging strategies to address pre-existing immunity include the use of IgG-cleaving enzymes like Imlifidase to temporarily deplete neutralizing antibodies (Leborgne et al., Nature Medicine, 2020).

Other names

AAV8 VP1/VP2/VP3AAV-8 capsidAdeno-associated virus serotype 8 capsidAAV8 capsid antigens

Pharmacological immunosuppression of T-cell and B-cell responses; enzymatic cleavage of neutralizing antibodies.