Combining the power of stem cell technologies with easy-to-use tools for genetic modification presents an attractive path to treat diseases. In a new paper in Scientific Reports, a team of scientists from Columbia University Medical Center (CUMC) and the University of Iowa show how this combination can be used to develop therapies for eye disease. The research is based in the laboratories of Drs. Stephen Tsang, at CUMC, and Vinit Mahajan at U. Iowa. The scientists started out by generating induced pluripotent stem cells (iPSCs) from a skin sample of a patient with a mutation in the retinitis pigmentosa GTPase regulator (RPGR) gene. RPGR mutations lead to a form of retinitis pigmentosa (RP), a condition that results in degradation of the retina followed by blindness. A single common mutation in RPGR accounts for 90% of cases of so-called X-linked variant of RP, XLRP, making the disease a good target for a therapy based on gene correction. Once iPSCs were generated, the team used CRISPR/Cas9, a relatively new and easy-to-use tool, to snip out the mutation and insert a corrected form of the gene, producing patient-specific gene-corrected iPSCs. While this proof-of-concept report demonstrates the possibilities, there are a number of hurdles yet to overcome. Only 13% of the cells were gene-corrected, a yield that needs to be higher for direct gene therapy injections. The ability to convert iPSCs into functional photoreceptors is still in early stages, and transplanting the resulting cells back into the patient remains a distant goal. This work was supported in part by NYSTEM award C029572 to Dr. Tsang.
Bassuk AG, Zheng A, Li Y, Tsang SH, Mahajan VB. Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem Cells. Science Reports. 2016 Jan 27; 6:11969.