Date Published:2016 Oct 18
Within the next decade, we will see many gene therapy clinical trials for eye diseases progress, which may lead to treatments for thousands of visually impaired people around the world. To target retinal diseases that affect specific cell types, several recombinant adeno-associated virus (AAV) serotypes have been generated and used successfully in pre-clinical mouse studies. Because there are numerous anatomic, and physiologic differences between the eyes of mice and 'men' and because surgical delivery approaches and immunologic responses also differ between these species, we evaluated the transduction characteristics of two promising new serotypes AAV7m8 and AAV8BP2, in retinas of animals that are most similar to those of humans: non-human primates (NHPs). We report that while AAV7m8 efficiently targets a variety of cell types by subretinal injection in NHPs, transduction after intravitreal delivery was mostly restricted to the inner retina at lower doses that did not induce an immune response. AAV8BP2 targets the cone photoreceptors efficiently but bipolar cells inefficiently by subretinal injection. Additionally, we observed transduction of both serotypes in the anterior chamber of the eye and the optic pathway of the brain post intravitreal delivery. Finally, we assessed immunogenicity, keeping in mind that these AAV capsids may be used in future clinical trials. We found that AAV8BP2 had a better safety profile compared to AAV7m8 even at the highest doses administered. Our studies underscore the differences in AAV transduction between mice and primates highlighting the importance of careful evaluation of therapeutic vectors in NHPs prior to moving into clinical trials.