Genome editing mediated by CRISPR-Cas9 has shown great promise for the treatment of retinal dystrophies (RD). Currently, adeno-associated viruses are the most widely used vectors for retinal gene therapies but their small packaging capacity and permanent transgene expression makes them suboptimal for CRISPR-Cas delivery. Transient delivery of Cas9 protein and its guide RNA as ribonucleoprotein (RNP) complexes have been reported in the retinal pigment epithelium (RPE) and into the inner ear cells in vivo. Members of our consortium investigated transient delivery of either Cas9 mRNA or Cas9 RNP into the retinal pigment epithelium (RPE) and photoreceptors as these are the target cells for most prevalent inherited retinal degenerations. Cas9 mRNA complexed with different lipid or peptide vectors led to low rates of indels at the target sequence in vivo and mostly in the RPE. Major changes to the delivery system are needed to increase the efficiency of gene editing, and finally, safety and cost of the therapeutic approach need to be taken into account when designing such vector systems. Our objectives are to address some of these challenges in this project by developing a novel polymer based non-viral carrier for in vivo targeted delivery of CRISPR-based RNP complexes; and to assess the efficacy and safety of our novel delivery approach in a mouse model of retinal dystrophy.