Gene therapy for visual loss: Opportunities and concerns. (January 2019)

• Record Type: Journal Article
• Authors: Lee, Jia Hui; Wang, Jiang-Hui; Chen, Jinying; Li, Fan; Edwards, Thomas L.; Hewitt, Alex W.; Liu, Guei-Sheung
• Is Part Of: Progress in retinal and eye research. Volume 68(2019:Jan.)
• Page Start: 31
• Page End: 53
• Publication Date: 2019-01
• Subjects: Eye -- Gene therapy -- Genome editing; AAV adeno-associated virus -- AAVS1 AAV integration site 1 -- AMD age-related macular degeneration -- Cas CRISPR-associated protein -- CNV choroid neovascularization -- CRISPR clustered regularly interspaced short palindromic repeats -- crRNA CRISPR RNA -- dCas catalytically deactivated Cas -- DME diabetic macular edema -- DSB DNA double-strand break -- EIAV equine infectious anemia virus -- ELSI ethical legal and social implication -- FDA food and drug administration -- GWAS genome-wide association studies -- HDR homology-directed repair -- HITI homology-independent targeted integration -- Indels insertions or deletions -- IOP intraocular pressure -- LCA leber congenital amaurosis -- LHON leber's hereditary optic neuropathy -- NGS next-generation sequencing -- NHEJ nonhomologous end-joining -- OIR oxygen-induced retinopathy -- PAM protospacer adjacent motif -- RPE retinal pigment epithelium -- SCID-X1 X-linked severe combined immunodeficiency disease -- sgRNA single guide RNA -- siRNA small-interfering RNA -- SNP single-nucleotide polymorphism -- TALEN transcription activator-like effector nuclease -- VEGF vascular endothelial growth factor -- ZFN zinc finger nuclease; Retina -- Periodicals; Retina -- Research -- Methodology -- Periodicals; Eye -- Diseases -- Periodicals; Eye -- Periodicals; Eye Diseases -- Periodicals; Retina -- Periodicals; Rétine -- Périodiques; Rétine -- Recherche -- Méthodologie -- Périodiques; 617.7005
• DOI: 10.1016/j.preteyeres.2018.08.003
• Languages: English
• ISSNs: 1350-9462

Abstract

Abstract: Many clinical trials using gene therapy have shown significant therapeutic benefits and exceptional safety records. Increasing evidence is verifying the long sought-after promise that gene therapy will genetically 'cure' some severely disabling diseases. In particular, the first gene therapy bioproduct for RPE65 -associated Leber's congenital amaurosis, which was approved by the US Food and Drug Administration in 2017, has provided tremendous encouragement to the field of gene therapy. Recent developments in genome editing technologies have significantly advanced our capability to precisely engineer genomes in eukaryotic cells. Programmable nucleases, particularly the CRISPR/Cas system, have been widely adopted in studies applying genome engineering therapy to ocular diseases with the hope of managing these diseases. In this review article, we summarize the current approaches that have been developed in the area of gene therapy for ocular disease. We also discuss the challenges and opportunities facing gene therapy for ocular diseases, as well as its prospects.