AAV DJ-Null

Adeno-associated viruses (AAVs) hold promise as vectors for human gene therapy. Gene therapy involves the delivery of DNA to target cells with the goal of alleviating genetic disease or mitigating genetic susceptibility, for example, by providing a fully functional replacement for a mutated gene. Dozens of clinical trials have safely exploited the properties of AAV vectors, with demonstrated efficacy in treating congenital blindness and Parkinson's disease, as well as promising results in treating factor IX in hemophilia B and other diseases.

AAV-DJ has the desired enhanced hepatocyte targeting, combining the best properties of AAV-2 with AAV-8 and AAV-9. Like AAV-2, it is able to efficiently transduce a wide range of cell types in vitro, but has a specific liver tropism in vivo, and like AAV-8 and AAV-9, it is better able to evade immune neutralization and effectively deliver more therapeutic DNA. Mutation studies have shown that the heparin-binding domain (HBD) of AAV-2 is key to high cell attachment and transduction efficiency in vitro, which is 105-fold higher than that of AAV-8 and AAV-9. In vivo, AAV-DJ produced 20-fold higher levels of human factor IX expression in mouse liver than AAV-2 and comparable to the best native serotypes, AAV-8 and AAV-9. Interestingly, the mutations showed that efficient liver transduction was not dependent on the HBD, as was the case with AAV-2.