CRISPR-Cas9 fixes a gene mutation to restore lebercilin protein and its placement in lab-grown human retinal tissue

Mutations in the lebercilin-encoding gene are associated with one of the most severe forms of Leber congenital amaurosis.

• A patient-specific cellular model was generated using CRISPR-Cas9 technology to correct a homozygous nonsense variant in patient-derived induced pluripotent stem cells.
• Whole-genome sequencing demonstrated the absence of off-target editing in the gene-corrected control cells.
• Differentiation of the patient, gene-corrected, and unrelated control iPSCs into three-dimensional retina-like cells revealed opsin and rhodopsin mislocalization in patient-derived organoids.
• Lebercilin expression and localization along the ciliary axoneme were rescued in the gene-corrected organoids.

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