Abstract Genetic blindness is prevalent with limited treatment options. Despite tremendous progress in the development of editing technology as potential therapy for blindness, the ability to deliver the editing complex into the retina for efficient editing remains a major challenge. The current prevailing method of delivery of editing machinery is by viral vectors especially AAV. For AAV vectors, issues such as immunogenicity, genome integration and long-term effect remain a safety concern. Further, more complexed editing strategies including base editing (BE) and prime editing (PE), require the packaging of multiple components into different AAVs, which further limits their efficiency. This proposal is to use lipid nanoparticles (LNP) we have developed in the parental SCGE program for the mRNA delivery of a base editor (ABE) to repair the mutation in a Leber Congenital Amaurosis (LCA) mouse model rd12 that harbors a human mutation for the recovery of vision. We have previously demonstrated that the LNP mediates the delivery of Cas9 mRNA-gRNA that targets the retinal pigment epithelium for efficient editing. We have further demonstrated the feasibility of the LNP delivery of base editing complex by mRNA in a mouse model. Combined, we will evaluate the application of new LNP for mRNA delivery of the base editor and mutation correction by local subretinal injection, and correlate with the functional restoration of vision in the rd12 mice. The success of the project will enable LNP-based transient delivery of editing machinery to treat genetic blindness due to RPE mutations efficiently and safely.