Personalized therapeutic strategies for patients with retinitis pigmentosa

• Published in: Expert opinion on biological therapy Vol. 15; no. 3; p. 391
• Main Authors: Zheng, Andrew, Li, Yao, Tsang, Stephen H
• Format: Journal Article
• Language: English
• Published: England 01.03.2015
• Subjects: Clustered Regularly Interspaced Short Palindromic Repeats - genetics; Genetic Therapy - methods; Genetic Therapy - trends; Humans; Induced Pluripotent Stem Cells - transplantation; Precision Medicine - methods; Precision Medicine - trends; Retinal Pigment Epithelium - pathology; Retinitis Pigmentosa - diagnosis; Retinitis Pigmentosa - genetics; Retinitis Pigmentosa - therapy; Stem Cell Transplantation - methods; Stem Cell Transplantation - trends; clustered regularly interspaced short palindromic repeats; gene therapy; induced pluripotent stem cells; retinal degenerations
• ISSN: 1744-7682
• DOI: 10.1517/14712598.2015.1006192

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. 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. 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.