Gene therapy for two forms of inherited retinal degeneration have met promising safety and efficacy endpoints in early stage clinical trials. These approaches made use of a replication defective virus or vector based on the adeno-associated virus type 2 (AAV2), a small non enveloped ssDNA virus endemic in human population. AAV2 targets the retinal pigment epithelium (RPE) at high efficiency in small and large animal models, which is the primary target in these studies. Retinal disease however has a range of etiologies and cell types at the basis of its pathogenesis, and a broader set of tools to deliver therapeutic genes to the retina is required. Here, we describe our past and current efforts to develop novel vectors and therapeutic strategies to unlock genetic treatment for retinal blinding disorders.