Stargardt’s disease is an inherited macular neurodegenerative disorder that causes retinal dystrophy and vision loss. Stargardt disease is caused by mutations in the ABCA4 gene, which encodes a protein involved in the visual cycle and the transport of toxic photoproducts out of the retina. Currently, there is no treatment for Stargardt’s disease, and although restoring ABCA4 expression may help prevent or treat the retinal dystrophy of Stargardt’s disease, gene replacement therapy has not yet succeeded in preventing retinal dystrophy or improving vision. In a recent study, a team of researchers used the CRISPR-Cas9 system to modify pathogenic ABCA4 mutations in human-induced pluripotent stem cells (iPSCs) from two patients with Stargardt disease. This approach led to successful correction of both pathogenic ABCA4 variants without causing detectable off-target effects. Siles also noted that the use of single-stranded oligodeoxynucleotides as donor templates for CRISPR-mediated ABCA4 editing ensured permanent restoration of the ABCA4 sequence. However, as this approach is still in its infancy, a further increase in the specificity and precision of gene editing is crucial. The team also plans to validate the feasibility of this method using in vitro 3D retinal cultures.
