AAV and Compacted DNA Nanoparticles for the Treatment of Retinal Disorders: Challenges and Future Prospects

Gene therapy based on delivery of viral and nonviral vectors has shown great promise for the treatment of human ocular diseases; however, limitations have consistently prevented its widespread clinical application. Viral vectors have generally been better in terms of efficiency but have safety concerns. Nonviral vectors, on the other hand, offer safety but have often been disappointing in terms of efficiency of nuclear delivery and gene expression. Extensive animal studies have reported significant progress using both systems, but thus far only a few studies have shown promise in human clinical trials. This article reviews both viral and nonviral work with focus on two candidates for clinical ocular application-AAV and nanoparticles. Of particular interest are various requirements for successful clinical application of these technologies including vector trafficking, delivery, specific gene expression, and treatment safety, and tolerance. (Invest Ophthalmol Vis Sci. 2011;52:3051-3059) DOI:10.1167/iovs.10-6916