This project aims to develop an innovative therapeutic approach for Stargardt disease, a macular degeneration caused by mutations in the ABCA4 gene. The strategy is based on SMaRT (Spliceosome-Mediated RNA Trans-splicing) technology, which enables mutation correction at the transcriptome level by replacing mutated exons of endogenous mRNA by trans-splicing with an exogenous RNA (PTM). Since the PTM contains only a part of the mRNA to be corrected, this approach can overcome the obstacle of the large size of the ABCA4 cDNA, which exceeds the carrying capacity of AAV vectors. The project will consist of several phases using molecular and cell biology techniques: construction of viral vectors for the expression of PTMs, production of cell lines to test the efficacy of binding domains (BD) to induce trans-splicing, and screening of BDs to optimize PTMs. Selected PTMs will then be tested in retinal organoids and animal models to demonstrate their therapeutic potential for the treatment of this genetic disease. As AAV is currently the most effective vector for retinal transduction, this project could open new therapeutic perspectives for Stargardt disease.