AAV-DJ/8 Virus-Like Particles (Empty Capsids)

Adeno-associated virus (AAV) is a non-enveloped parvovirus that is non-pathogenic to humans. AAV vectors offer significant advantages for the delivery of therapeutic genes. AAV-based gene therapies have been approved for the treatment of spinal muscular atrophy, familial lipoprotein lipase deficiency, RPE65 mutation-associated retinal degeneration, and hemophilia. More than a thousand human participants have received AAV-based gene therapies in clinical trials. Most early AAV gene therapy studies were conducted with serotype 2 (AAV2) vectors because they exhibit broad tissue tropism and produce long-term transgene expression. But recently, vector systems based on other AAV serotypes are being investigated that have more efficient gene transduction and different cell and tissue specificities. One of the AAV serotypes, AAV serotype DJ/8 (AAV-DJ/8), has been reported to transduce hepatocytes and other cells and was found to be superior to AAV2 in this function. AAV-DJ/8 was developed by rigorous screening of AAV variants on human hepatocytes using human anti-AAV antiserum. AAV-DJ/8 is a heparin-binding domain (HBD) mutant of AAV-DJ that not only outperforms all HBD-negative wild-type viruses (e.g., AAV8 and AAV9) but also significantly outperforms AAV2 in gene transduction into hepatocytes and other cells. The HBD has been implicated in negative transduction in vivo (i.e., HBD deletion alleviates liver restriction and expands transduction into all non-liver tissues, including the brain, which transduce in the same manner as AAV8 and AAV9).