U6-shRNA-GFP AAV (Serotype 8)

Adeno-associated viruses (AAVs) are small viruses that can infect cells without integrating into the host genome, making them a safer alternative for delivering therapeutic genes to target cells. Discovered in non-human primates, AAV8 is characterized by its ability to efficiently transduce various tissues, particularly liver, muscle, and heart tissues, following systemic administration. This makes it an ideal candidate for treating diseases affecting these organs. Multiple studies have demonstrated preferential liver transduction by AAV8 vectors in non-human primate and canine models. Although absolute transgene expression levels in primate and canine livers are lower than in mouse models, promising therapeutic indicators have been achieved in larger animals. For example, intravenous administration of self-complementary AAV8 vectors in non-human primate livers mediates factor IX expression levels sufficient to correct the phenotype of hemophilia patients and sustained correction of disease in a canine hemophilia model. The effects of transient immunosuppression on AAV8 liver transduction in non-human primates and the ability of proteasome inhibitors to enhance AAV8 liver transduction in a canine model have also been evaluated. Furthermore, a recent study evaluating intrauterine gene transfer using AAV8 vectors in rhesus macaques showed liver-specific expression of factor IX for up to 2 years in injected offspring.