A part of the CEP290 protein helps fix mutant CEP290 and prevents vision loss in Rd16 mice

A specific CEP290 fragment reconstituted function and improved photoreceptor survival in mouse models of Leber congenital amaurosis.

• Mutations in the CEP290 gene are linked to ciliogenesis defects and various clinical conditions, particularly Leber congenital amaurosis (LCA).
• Delivering the full 7.4 kb CEP290 coding sequence for gene therapy is challenging in living organisms.
• The C-terminal 989 residues of the CEP290 protein were shown to restore function and preserve cone photoreceptors while delaying rod photoreceptor death.
• This C-terminal domain also enhanced cilia formation in both mouse embryonic fibroblasts and induced pluripotent stem cell-derived retinal organoids with CEP290 mutations.
• The findings support the idea that a specific fragment of CEP290 could compensate for mutations in the gene, opening potential avenues for therapy.

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