Hepatocytes via AAV8-mediated transduction (AAV8-Hepatocyte Transduction)

Hepatocytes via AAV8-mediated transduction is a therapeutic delivery strategy rather than a specific molecular target. It involves the use of Adeno-associated virus serotype 8 (AAV8), a non-enveloped viral vector known for its exceptionally high natural tropism for liver tissue (Gao et al., 2002, PNAS). This approach is widely utilized in gene therapy to treat monogenic metabolic and hematologic disorders by transforming hepatocytes into 'bio-factories' that produce and secrete therapeutic proteins into the systemic circulation. The vector enters hepatocytes by binding to the 37/67-kDa laminin receptor, delivering a genetic payload that persists as an episome in the nucleus (Akache et al., 2006, Journal of Virology). While highly effective in clinical trials for diseases like Hemophilia, the strategy faces significant challenges including pre-existing humoral immunity in the human population and late-onset T-cell mediated immune responses that can clear transduced cells and cause liver enzyme elevations (Mingozzi & High, 2013, Nature Reviews Genetics). Consequently, patient selection often requires screening for low AAV8 neutralizing antibody titers to ensure successful transduction.

Other names

AAV8 liver-directed gene therapyAAV8-mediated hepatic gene transferAdeno-associated virus serotype 8 hepatocyte targetingLiver-directed AAV8 gene delivery

The AAV8 vector utilizes its capsid proteins to bind to specific cell surface receptors, primarily the 37/67-kDa laminin receptor (LamR), on the surface of hepatocytes (Akache et al., 2006, Journal of Virology). Following binding, the vector is internalized via clathrin-mediated endocytosis, undergoes endosomal escape, and translocates to the nucleus. Once inside the nucleus, the viral capsid uncoats, and the single-stranded DNA genome is converted into double-stranded episomal DNA, which serves as a template for the long-term expression of the therapeutic transgene without integrating into the host genome (Gao et al., 2002, PNAS).