Fig. 7

An integrative, multidisciplinary approach for future gene therapy in IRDs. IRD patient’s blood sample can be reprogrammed into induced pluripotent stem cells (iPSCs) followed by the differentiation into retinal organoids. These patient-derived retinal organoids exhibit disease-specific features and can be applied as a reliable platform for assessing disease progression and treatment outcome (e.g. XLRS-patient-derived retinal organoids exhibit severe retinoschisis-like features). Researchers can utilize optimized NPs loaded with plasmid DNA encoding CRISPR-Cas9 machinery to achieve efficient gene delivery and precise gene editing. This results in the rescue of the disease phenotypes associated with the specific IRDs (e.g. the splitting phenotype in XLRS-patient-derived retinal organoids can be rescued as shown above). Integrating patient-derived retinal organoids, CRISPR-Cas9 technologies, and NPs promotes precision gene therapy applications for IRDs