AAV Rh74-CAG-GFP

Gene therapy is recognized as a powerful tool for treating a wide range of diseases. Of all gene therapy approaches, adeno-associated virus (AAV) is considered one of the safest and most effective methods for delivering therapeutic transgenes to a wide range of tissues. The recombinant adeno-associated virus (rAAV) vector is a small, non-enveloped virus whose rep and cap genes have been removed and replaced with the therapeutic transgene. rAAV is an ideal gene delivery system because it does not cause disease, is unable to replicate, has very low immunogenicity, has very low integration, and provides stable, long-term transgene expression. This has led to rAAV vectors being used in 300 clinical trials that are either recruiting, about to recruit, ongoing, or completed. AAV is a diverse family of viruses with more than 10 serotypes and 100 variants identified to date. Each serotype contains a unique capsid sequence that results in different tissue tropisms. The inherent ability of AAV to "target" specific tissues has, at least in part, made AAV technology the preferred gene delivery vector for many clinical applications. Rhesus macaque serotype 74 (rh74) is a member of the E clade and is closely related to another E clade member, AAV8, with up to 93% homology. Rh74 was discovered in rhesus macaques and was initially isolated from the mesenteric lymph nodes and later from the spleen. In mouse and non-human primate models, rh74 serotypes have high muscle transduction efficiency after intravascular administration and low transduction efficiency after systemic administration. Rh74 serotype has one of the lowest seroprevalence rates of all serotypes, with approximately 86% of Duchenne muscular dystrophy (DMD) patients being seronegative for anti-rh74 antibodies.