Efficient and durable gene delivery of self complementary adeno-associated virus 6 vector and impact of pre-existing immunity

Recombinant adeno-associated viral (rAAV) vectors are promising vectors for human gene therapy. However, AAV-mediated gene transduction can be hampered because of the pre-existing neutralized natural antibodies (NAbs) in primates. We evaluated transduction efficiency of rAAV6 expressing human alpha-1-anti-trypsin (hAAT) vectors in murine models, and found that these vectors showed stable and high levels of transgene expression. Fluorescence imaging showed that AAV6 expressing enhanced green fluorescent protein (eGFP) by intravenous administration predominantly targeted the liver, but led to self-limited hepatitis. Besides, our study evaluated epidemiology of anti-AAV6 NAb in non-human primates (NHPs) by NAb assay in vitro. The result indicated that 52.17% of NHPs had detectable NAb at 1:5 dilution rate. In vivo passive transfer experiment showed that AAV6 specific neutralizing antibody, even though with low NAb titer, could significantly inhibit rAAV6 transduction.