Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem Cells

Abstract

Induced pluripotent stem cells (iPSCs) generated from patient fibroblasts could potentially be used as a source of autologous cells for transplantation in retinal disease. Patient-derived iPSCs, however, would still harbor disease-causing mutations. To generate healthy patient-derived cells, mutations might be repaired with new gene-editing technology based on the bacterial system of clustered regularly interspersed short palindromic repeats (CRISPR)/Cas9, thereby yielding grafts that require no patient immunosuppression. We tested whether CRISPR/Cas9 could be used in patient-specific iPSCs to precisely repair an RPGR point mutation that causes X-linked retinitis pigmentosa (XLRP). Fibroblasts cultured from a skin-punch biopsy of an XLRP patient were transduced to produce iPSCs carrying the patient’s c.3070G > T mutation. The iPSCs were transduced with CRISPR guide RNAs, Cas9 endonuclease, and a donor homology template. Despite the gene’s repetitive and GC-rich sequences, 13% of RPGR gene copies showed mutation correction and conversion to the wild-type allele. This is the first report using CRISPR to correct a pathogenic mutation in iPSCs derived from a patient with photoreceptor degeneration. This important proof-of-concept finding supports the development of personalized iPSC-based transplantation therapies for retinal disease.

Preclinical disease and preventive strategies in IBD: perspectives, challenges and opportunities

“…Thus, the future management of IBD should also consider the paradigm changing opportunities (and challenges) in precision medicine. Looking to the field of oncology, promising advancements are being described whereby individual therapies are constructed and/or screened based specifically on the molecular features of an individual's tumour profile 125 126. The application of such precision medicine methods for IMIDs should also be considered, and in fact, the future of clinical testing of individuals for unique biomarker profiles that direct specific therapies in such conditions is here 127…”

Redesigning Nature:To Be or not to Be?

“…Bassuk et al 8 reported that this system can be used to repair genetic defects in stem cells of patients suffering from retinitis pigmentosa. They showed that 13% of the defective gene copies could be completely replaced by the corrected copy.…”

Reprogrammed Cell?based Therapy for Liver Disease: From Lab to Clinic

“…crRNAs can recognize the exogenous genome if a viral reinfection occurs. through CRISPR/Cas9 approach (19), which opens a promising era in regenerative medicine and genome engineering.…”

“…Utilization of patient's cells in order to avoid ethical concerns and rejection complications is possible by cellular reprogramming, particularly iPSCs technology (19).…”