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Gene therapy for retinal disease

  • Michelle E. McClements
    Affiliations
    Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
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  • Robert E. MacLaren
    Correspondence
    Reprint requests: Robert E. MacLaren, Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, The John Radcliffe Hospital, Headley Way, OX3 9DU, UK
    Affiliations
    Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

    Moorfields Eye Hospital Foundation Trust and UCL Institute of Ophthalmology National Institute for Health Research Biomedical Research Centre, London, United Kingdom

    Oxford Eye Hospital, Oxford University Hospitals NHS Trust and National Institute for Health Biomedical Research Centre, Oxford, United Kingdom
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Published:January 10, 2013DOI:https://doi.org/10.1016/j.trsl.2012.12.007
      Gene therapy strategies for the treatment of inherited retinal diseases have made major advances in recent years. This review focuses on adeno-associated viral (AAV) vector approaches to treat retinal degeneration and, thus, prevent or delay the onset of blindness. Data from human clinical trials of gene therapy for retinal disease show encouraging signs of safety and efficacy from AAV vectors. Recent progress in enhancing cell-specific targeting and transduction efficiency of the various retinal layers plus the use of AAV-delivered growth factors to augment the therapeutic effect and limit cell death suggest even greater success in future human trials is possible.

      Abbreviations:

      661W (murine photoreceptor-derived retinal cell line), AAV (adeno-associated virus), ABCA4 (ATP-binding casette, sub-family A, member 4), AIPL1 (aryl hydrocarbon receptor interacting protein like-1), ARPE19 (retinal pigment epithelia cell line), beta-Pde6 (phosphodiesterase 6 beta subunit), Cabp5 (calcium binding protein 5), CAG (CMV early enhancer element fused with the chicken beta-actin promoter), CAR (cone arrestin), CBA (chicken beta-actin), CD8+ T cells (cytotoxic T cells with CD8 surface protein), Chx10 (homeobox-containing transcription factor), CMV (cytomegalovirus), Cnga3 (cone photoreceptor cGMP-gated cation channel alpha subunit), CNGB3 (cone photoreceptor cGMP-gated cation channel beta subunit), CNTF (ciliary neurotrophic factor), cpfl5 (cone photoreceptor function loss 5), F (phenylalanine), FLT1/VEGF (fms-related tyrosine kinase 1/vascular endothelial growth factor), GC1KO (guanylate cyclase-1 knockout), GCL (ganglion cell layer), GFP (green fluorescent protein), GNAT2 (guanine nucleotide binding protein, alpha transducing polypeptide 2), Grm6 (glutamate receptor), metabotropic 6 (Gucy2d/GC), guanylate cyclase-1 (HEK293), human embryonic kidney 293 cells (hGRK1), human rhodopsin kinase (IGF-1), insulin-like growth factor 1 INL (inner nuclear layer), IRDs (inherited retinal diseases), ITR (inverted terminal repeat), K296E (Lysine296Glutamic Acid), L (long (cone opsin)), LCA (Leber congenital amaurosis), LV (lentiviral), M (medium (cone opsin)), Mertk (c-mer proto-oncogene tyrosine kinase), Mfrp (membrane-type frizzled-related protein), MYO7A (myosin VIIA), ONL (outer nuclear layer), P23H (Proline23Histidine), PR2.1 (L/M cone photoreceptor specific promoter 2.1kb), Prph2/rds (peripherin 2/retinal degeneration slow), rAAV (recombinant AAV), RCS (Royal College of Surgeons), rd (retinal degeneration), REP1 (Rab escort protein 1), RHO (rhodopsin), RP (retinitis pigmentosa), RPE (retinal pigment epithelium), RPE65 (retinal pigment epithelium-specific 65kDa protein), RPGR (retinitis pigmentosa GTPase regulator), RPGRIP1 (retinitis pigmentosa GTPase regulator interacting protein 1), S (short (cone opsin)), scAAV (self-complementary AAV), SV40 (Simian vacuolating virus 40), UTR (untranslated region), VMD2 (bestrophin 1 (vitelliform macular dystrophy)), WT (wild type), Y (tyrosine)
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