Adeno-associated virus serotype 8 capsid (AAV8)

Adeno-associated virus serotype 8 (AAV8) is a non-enveloped viral capsid widely utilized as a delivery vehicle in liver-directed gene therapy. It is characterized by its exceptional tropism for hepatocytes, where it facilitates the efficient transfer of genetic material to treat various inherited metabolic and hematologic disorders (Gao et al., 2002, PMID: 12202744). The transduction process involves the capsid binding to specific cell surface receptors, most notably the 37/67-kDa laminin receptor, followed by endosomal internalization and nuclear translocation (Akache et al., 2006, PMID: 16775011). Once in the nucleus, the therapeutic transgene is expressed episomally, providing a long-term source of the missing or functional protein, as demonstrated in clinical trials for Hemophilia B (Nathwani et al., 2011, PMID: 22149871). Despite its high efficiency, the clinical application of AAV8 is complicated by host immune responses. Pre-existing neutralizing antibodies can prevent successful transduction, while delayed T-cell responses against the capsid can lead to liver inflammation and the loss of transduced cells (Wang et al., 2010, PMID: 20103781). Consequently, patients are often screened for antibody titers and monitored for liver enzyme elevations following administration.

Other names

AAV8AAV-8Adeno-associated virus 8Hepatocyte-tropic AAV vectorAAV8-mediated delivery

The AAV8 capsid mediates hepatocyte-specific transduction by binding to the 37/67-kDa laminin receptor (LamR), facilitating clathrin-mediated endocytosis, endosomal escape, and nuclear import of the viral genome for episomal transgene expression (Akache et al., 2006, PMID: 16775011).