Somatic cells reprogramming and genome editing for stargardt disease modeling for investigation and treatment

Abstract

Degeneration of the retina occurs both in relation to age, and as a consequence of hereditary pathologies. A clinically similar pattern is often associated with different molecular pathways and gene mutations. The arsenal of therapeutic approaches for these patients is very limited. Modern advances in cellular reprogramming and genome editing make it possible to establish a model for the disease investigation and treatment. In this study we established induced pluripotent stem cells (iPSCs) from patients with a clinical diagnosis of Stargardt>s disease. Mutation in the peripherin 2 gene was found and it was shown that the mutation does not affect the efficiency of differentiation in the pigment epithelium of the retina. Using the CRISPR/Cas9 system the mutation was corrected in the patient's iPSCs. As a result, isogeneic iPSC lines with a corrected mutation have been generated for establishing of an in vitro model of the disease and potentially suitable for personalized therapy of Stargardt disease.