Nonviral Delivery Systems for Gene Therapy for Retina and Posterior Segment Disease

Abstract

Gene therapy is a hopeful strategy for the treatment of retinal disorders with no effective treatment. Gene replacement therapy is the most widely used strategy to modulate the gene expression in clinical research of inherited or acquired ocular diseases. Viral vectors are at the forefront of translational gene therapy mainly due to their high efficacy; nevertheless, concerns regarding safety have fostered the progress of nonviral therapy. Nonviral systems are non-immunogenic and avoid the risk of insertional mutagenesis. Moreover, they can be easily produced at large scale and have the potential to deliver larger genetic payloads. However, vector engineering to attain tissue-selective targeting and/or regulate the extent of gene expression is a challenging issue of nonviral gene therapy. Subretinal or intravitreal injections are the best option for the success of gene delivery to the posterior segment of the eye, regardless of the type of vector used. Preclinical studies with nonviral vectors have shown encouraging results for the treatment of macular degeneration and some inherited retinal disorders such as X-linked retinoschisis, Stargardt disease, retinitis pigmentosa, and Leber congenital amaurosis. These recent advances point to nonviral gene therapy as a feasible therapeutic tool for retinal disorders.