Personalized therapeutic strategies for patients with retinitis pigmentosa

Abstract

Introduction: Retinitis pigmentosa (RP) encompasses many different hereditary retinal degenerations that are caused by a vast array of different gene mutations and have highly variable disease presentations and severities. This heterogeneity poses a significant therapeutic challenge, although an answer may eventually be found through two recent innovations: induced pluripotent stem cells (iPSCs) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas genome editing.

Areas covered: This review discusses the wide-ranging applications of iPSCs and CRISPR–including disease modelling, diagnostics and therapeutics – with an ultimate view towards understanding how these two technologies can come together to address disease heterogeneity and orphan genes in a novel personalized medicine platform. An extensive literature search was conducted in PubMed and Google Scholar, with a particular focus on high-impact research published within the last 1 – 2 years and centered broadly on the subjects of retinal gene therapy, iPSC-derived outer retina cells, stem cell transplantation and CRISPR/Cas gene editing.

Expert opinion: For the retinal pigment epithelium, autologous transplantation of gene-corrected grafts derived from iPSCs may well be technically feasible in the near future. Photoreceptor transplantation faces more significant unresolved technical challenges but remains an achievable, if more distant, goal given the rapid pace of advancements in the field.

Keywords:

• clustered regularly interspaced short palindromic repeats
• gene therapy
• induced pluripotent stem cells
• retinal degenerations

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Corrigendum

Declaration of interest

The Bernard & Shirlee Brown Glaucoma Laboratory and Barbara & Donald Jonas Stem Cell Laboratory are supported by NIH core grants 5P30CA013696 and 5P30EY019007 and unrestricted funds from Research to Prevent Blindness (New York, NY, USA). SH Tsang is a member of the RD-CURE consortium and is supported by the Tistou and Charlotte Kerstan Foundation. This work is also supported by NIH R01EY018213, the Research to Prevent Blindness Physician-Scientist Award, the Nancy and Kobi Karp Foundation, the Schneeweiss Stem Cell Fund, New York State (M09G-302), the Foundation Fighting Blindness New York Regional Research Center Grant (C-NY-0705-0312), the Joel Hoffman Fund, Charles Culpeper Scholarship, the Irma T. Hirschl Charitable Trust, the Professor Gertrude Rothschild Stem Cell Foundation and Gebroe Family Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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