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Reviews

Gene therapy for inherited retinal diseases: progress and possibilities

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon show all
Pages 444-454 | Received 03 Aug 2020, Accepted 16 Dec 2020, Published online: 02 Mar 2021

References

  • Daiger SP. Summaries of genes and loci causing retinal diseases. Retnet. [cited 2020 Feb 14]. Available from: https://sph.uth.edu/retnet/sum-dis.htm
  • Berger W, Kloeckener-Gruissem B, Neidhardt J. The molecular basis of human retinal and vitreoretinal diseases. Prog Retin Eye Res. 2010;29:335–375.
  • Liew G, Michaelides M, Bunce C. A comparison of the causes of blindness certifications in England and Wales in working age adults (16-64 years), 1999-2000 with 2009-2010. BMJ Open. 2014;4:e004015.
  • Stone EM, Andorf JL, Whitmore SS, et al. Clinically focused molecular investigation of 1000 consecutive families with inherited retinal disease. Ophthalmology. 2017;124:1314–1331.
  • Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368:1795–1809.
  • Edwards TL, Groppe M, Jolly JK, et al. Correlation of retinal structure and function in choroideremia carriers. Ophthalmology. 2015;122:1274–1276.
  • Morgan JI, Han G, Klinman E, et al. High-resolution adaptive optics retinal imaging of cellular structure in choroideremia. Invest Ophthalmol Vis Sci. 2014;55:6381–6397.
  • Chao DL, Burr A, Pennesi M. RPE65-related leber congenital amaurosis/early-onset severe retinal dystrophy. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews((R)). Seattle (WA): University of Washington, Seattle; 1993. Available at https://www.ncbi.nlm.nih.gov/books/NBK549574/]
  • Tanna P, Strauss RW, Fujinami K, et al. Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options. Br J Ophthalmol. 2017;101:25–30.
  • Kohl S, Jagle H, Wissinger B. Achromatopsia. In: Adam MP, Ardinger HH, Pagon RA, et al. editors. GeneReviews((R)). Seattle (WA):  University of Washington, Seattle; 1993-2021. Available at https://www.ncbi.nlm.nih.gov/books/NBK1418/
  • Naldini L. Ex vivo gene transfer and correction for cell-based therapies. Nat Rev Genet. 2011;12:301–315.
  • Conley SM, Cai X, Naash MI. Nonviral ocular gene therapy: assessment and future directions. Curr Opin Mol Ther. 2008;10:456–463.
  • Wirth T, Parker N, Yla-Herttuala S. History of gene therapy. Gene. 2013;525:162–169.
  • Yla-Herttuala S. Endgame: glybera finally recommended for approval as the first gene therapy drug in the European union. Mol Ther. 2012;20:1831–1832.
  • Bach PB, Giralt SA, Saltz LB. FDA approval of tisagenlecleucel: promise and complexities of a $475000 cancer drug. JAMA. 2017;318:1861–1862.
  • Lee JH, Wang JH, Chen J, et al. Gene therapy for visual loss: opportunities and concerns. Prog Retin Eye Res. 2019;68:31–53.
  • Burnight ER, Giacalone JC, Cooke JA, et al. CRISPR-Cas9 genome engineering: treating inherited retinal degeneration. Prog Retin Eye Res. 2018;65:28–49.
  • Farrar GJ, Millington-Ward S, Chadderton N, et al. Gene-based therapies for dominantly inherited retinopathies. Gene Ther. 2012;19:137–144.
  • Deloitte Access Economics. The socioeconomic impact of inherited retinal dystrophies (IRDs) in the United Kingdom. 2019.
  • Chacon-Camacho OF, Garcia-Montano LA, Zenteno JC. The clinical implications of molecular monitoring and analyses of inherited retinal diseases. Expert Rev Mol Diagn. 2017;17:1009–1021.
  • Zaneveld J, Wang F, Wang X, et al. Dawn of ocular gene therapy: implications for molecular diagnosis in retinal disease. Sci China Life Sci. 2013;56:125–133.
  • Willett K, Bennett J. Immunology of AAV-mediated gene transfer in the eye. Front Immunol. 2013;4:261.
  • Dalkara D, Goureau O, Marazova K, et al. Let there be light: gene and cell therapy for blindness. Hum Gene Ther Clin Dev. 2016;27:134–147.
  • Surace EM, Auricchio A. Versatility of AAV vectors for retinal gene transfer. Vision Res. 2008;48:353–359.
  • Moore NA, Morral N, Ciulla TA, et al. Gene therapy for inherited retinal and optic nerve degenerations. Expert Opin Biol Ther. 2018;18:37–49.
  • Srivastava A. In vivo tissue-tropism of adeno-associated viral vectors. Curr Opin Virol. 2016;21:75–80.
  • Patricio MI, Barnard AR, Xue K, et al. Choroideremia: molecular mechanisms and development of AAV gene therapy. Expert Opin Biol Ther. 2018;18:807–820.
  • Auricchio A, Kobinger G, Anand V, et al. Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model. Hum Mol Genet. 2001;10:3075–3081.
  • Rabinowitz JE, Rolling F, Li C, et al. Cross-packaging of a single adeno-associated virus (AAV) type 2 vector genome into multiple AAV serotypes enables transduction with broad specificity. J Virol. 2002;76:791–801.
  • Yang GS, Schmidt M, Yan Z, et al. Virus-mediated transduction of murine retina with adeno-associated virus: effects of viral capsid and genome size. J Virol. 2002;76:7651–7660.
  • Lebherz C, Maguire A, Tang W, et al. Novel AAV serotypes for improved ocular gene transfer. J Gene Med. 2008;10:375–382.
  • Petrs-Silva H, Dinculescu A, Li Q, et al. Novel properties of tyrosine-mutant AAV2 vectors in the mouse retina. Mol Ther. 2011;19:293–301.
  • Petrs-Silva H, Dinculescu A, Li Q, et al. High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors. Mol Ther. 2009;17:463–471.
  • Mowat FM, Gornik KR, Dinculescu A, et al. Tyrosine capsid-mutant AAV vectors for gene delivery to the canine retina from a subretinal or intravitreal approach. Gene Ther. 2014;21:96–105.
  • Flannery JG, Visel M. Adeno-associated viral vectors for gene therapy of inherited retinal degenerations. Methods Mol Biol. 2013;935:351–369.
  • Trapani I, Colella P, Sommella A, et al. Effective delivery of large genes to the retina by dual AAV vectors. EMBO Mol Med. 2014;6:194–211.
  • Colella P, Trapani I, Cesi G, et al. Efficient gene delivery to the cone-enriched pig retina by dual AAV vectors. Gene Ther. 2014;21:450–456.
  • Lopes VS, Boye SE, Louie CM, et al. Retinal gene therapy with a large MYO7A cDNA using adeno-associated virus. Gene Ther. 2013;20:824–833.
  • Trapani I. Dual AAV vectors for stargardt disease. Methods Mol Biol. 2018;1715:153–175.
  • Trapani I, Puppo A, Auricchio A. Vector platforms for gene therapy of inherited retinopathies. Prog Retin Eye Res. 2014;43:108–128.
  • Yanez-Munoz RJ, Balaggan KS, MacNeil A, et al. Effective gene therapy with nonintegrating lentiviral vectors. Nat Med. 2006;12:348–353.
  • Kalesnykas G, Kokki E, Alasaarela L, et al. Comparative study of adeno-associated virus, adenovirus, bacu lovirus and lentivirus vectors for gene therapy of the eyes. Curr Gene Ther. 2017;17:235–247.
  • Harvey AR, Kamphuis W, Eggers R, et al. Intravitreal injection of adeno-associated viral vectors results in the transduction of different types of retinal neurons in neonatal and adult rats: a comparison with lentiviral vectors. Mol Cell Neurosci. 2002;21:141–157.
  • Davis JL, Gregori NZ, MacLaren RE, et al. Surgical technique for subretinal gene therapy in humans with inherited retinal degeneration. Retina. 2019;39 Suppl 1:S2–S8.
  • Russell S, Bennett J, Wellman JA, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017;390:849–860.
  • Ochakovski GA, Bartz-Schmidt KU, Fischer MD. Retinal gene therapy: surgical vector delivery in the translation to clinical trials. Front Neurosci. 2017;11:174.
  • Dalkara D, Kolstad KD, Caporale N, et al. Inner limiting membrane barriers to AAV-mediated retinal transduction from the vitreous. Mol Ther. 2009;17:2096–2102.
  • Kotterman MA, Yin L, Strazzeri JM, et al. Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates. Gene Ther. 2015;22:116–126.
  • Boye SE, Alexander JJ, Witherspoon CD, et al. Highly Efficient Delivery of Adeno-Associated Viral Vectors to the Primate Retina. Hum Gene Ther. 2016;27:580–597.
  • Takahashi K, Igarashi T, Miyake K, et al. Improved intravitreal AAV-mediated inner retinal gene transduction after surgical internal limiting membrane peeling in cynomolgus monkeys. Mol Ther. 2017;25:296–302.
  • Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119:2537–2548.
  • Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014;121:2247–2254.
  • Lam BL, Davis JL, Gregori NZ, et al. Choroideremia gene therapy phase 2 clinical trial: 24-month results. Am J Ophthalmol. 2019;197:65–73.
  • Petersen-Jones SM, Komaromy AM. Dog models for blinding inherited retinal dystrophies. Hum Gene Ther Clin Dev. 2015;26:15–26.
  • Buck TM, Pellissier LP, Vos RM, et al. AAV serotype testing on cultured human donor retinal explants. Methods Mol Biol. 2018;1715:275–288.
  • Orlans HO, Edwards TL, De Silva SR, et al. Human retinal explant culture for ex vivo validation of AAV gene therapy. Methods Mol Biol. 2018;1715:289–303.
  • Cereso N, Pequignot MO, Robert L, et al. Proof of concept for AAV2/5-mediated gene therapy in iPSC-derived retinal pigment epithelium of a choroideremia patient. Mol. 2014;1:14011.
  • U.S. Food & Drug Administration. Voretigene neparvovec-rzyl BL125610/0 approval letter. 2017 [cited 2020 Sept 26]. Available from: https://www.fda.gov/media/109487/download
  • Ameri H. Prospect of retinal gene therapy following commercialization of voretigene neparvovec-rzyl for retinal dystrophy mediated by RPE65 mutation. J Curr Ophthalmol. 2018;30:1–2.
  • Acland GM, Aguirre GD, Bennett J, et al. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol Ther. 2005;12:1072–1082.
  • Narfstrom K, Vaegan, Katz M, et al. Assessment of structure and function over a 3-year period after gene transfer in RPE65-/- dogs. Doc Ophthalmol. 2005;111:39–48.
  • Bainbridge JW, Smith AJ, Barker SS, et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med. 2008;358:2231–2239.
  • Maguire AM, High KA, Auricchio A, et al. Age-dependent effects of RPE65 gene therapy for Leber’s congenital amaurosis: a phase 1 dose-escalation trial. Lancet. 2009;374:1597–1605.
  • Jacobson SG, Cideciyan AV, Ratnakaram R, et al. Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years. Arch Ophthalmol. 2012;130:9–24.
  • Bennett J, Wellman J, Marshall KA, et al. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Lancet. 2016;388:661–672.
  • Maguire AM, Russell S, Wellman JA, et al. Efficacy, safety, and durability of voretigene neparvovec-rzyl in RPE65 mutation-associated inherited retinal dystrophy: results of phase 1 and 3 trials. Ophthalmology. 2019;126:1273–1285.
  • Cideciyan AV, Jacobson SG, Beltran WA, et al. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc Natl Acad Sci U S A. 2013;110:E517–525.
  • Gardiner KL, Cideciyan AV, Swider M, et al. Long-term structural outcomes of late-stage RPE65 gene therapy. Mol Ther. 2020;28:266–278.
  • Drack AV, Bennett J, Russell S, et al. Year 3 results and age-stratified analyses for a phase 3 trial of voretigene neparvovec in RPE65 mutation-associated inherited retinal disease. J Am Assoc Pediatr Ophthalmol Strabismus. 2018;22:e13.
  • Michalakis S, Muhlfriedel R, Tanimoto N, et al. Restoration of cone vision in the CNGA3-/- mouse model of congenital complete lack of cone photoreceptor function. Mol Ther. 2010;18:2057–2063.
  • Ofri R, Averbukh E, Ezra-Elia R, et al. Six years and counting: restoration of photopic retinal function and visual behavior following gene augmentation therapy in a sheep model of CNGA3 achromatopsia. Hum Gene Ther. 2018;29:1376–1386.
  • Komaromy AM, Alexander JJ, Rowlan JS, et al. Gene therapy rescues cone function in congenital achromatopsia. Hum Mol Genet. 2010;19:2581–2593.
  • Fischer MD, Michalakis S, Wilhelm B, et al. Safety and vision outcomes of subretinal gene therapy targeting cone photoreceptors in achromatopsia: a nonrandomized controlled trial. JAMA Ophthalmol. 2020;138:643.
  • MacLaren RE, Groppe M, Barnard AR, et al. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet. 2014;383:1129–1137.
  • Edwards TL, Jolly JK, Groppe M, et al. Visual acuity after retinal gene therapy for choroideremia. N Engl J Med. 2016;374:1996–1998.
  • Dimopoulos IS, Hoang SC, Radziwon A, et al. Two-year results after AAV2-mediated gene therapy for choroideremia: the alberta experience. Am J Ophthalmol. 2018;193:130–142.
  • Ghazi NG, Abboud EB, Nowilaty SR, et al. Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial. Hum Genet. 2016;135:327–343.
  • Shu X, Black GC, Rice JM, et al. RPGR mutation analysis and disease: an update. Hum Mutat. 2007;28:322–328.
  • Cehajic-Kapetanovic J, Xue K. Martinez-Fernandez de la Camara C et al. Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nat Med. 2020;26:354–359.
  • Mao H, Gorbatyuk MS, Hauswirth WW, et al. Gene delivery of wild-type rhodopsin rescues retinal function in an autosomal dominant retinitis pigmentosa mouse model. Adv Exp Med Biol. 2012;723:199–205.
  • Mitra RN, Zheng M, Weiss ER, et al. Genomic form of rhodopsin DNA nanoparticles rescued autosomal dominant Retinitis pigmentosa in the P23H knock-in mouse model. Biomaterials. 2018;157:26–39.
  • Bush RA, Zeng Y, Colosi P, et al. Preclinical dose-escalation study of intravitreal AAV-RS1 gene therapy in a mouse model of X-linked retinoschisis: dose-dependent expression and improved retinal structure and function. Hum Gene Ther Clin Dev. 2016;27:376–389.
  • Ye GJ, Budzynski E, Sonnentag P, et al. Safety and biodistribution evaluation in cynomolgus macaques of rAAV2tYF-CB-hRS1, a recombinant adeno-associated virus vector expressing retinoschisin. Hum Gene Ther Clin Dev. 2015;26:165–176.
  • Cukras C, Wiley HE, Jeffrey BG, et al. Retinal AAV8-RS1 gene therapy for X-linked retinoschisis: initial findings from a phase I/IIa trial by intravitreal delivery. Mol Ther. 2018;26:2282–2294.
  • Cideciyan AV, Jacobson SG, Drack AV, et al. Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect. Nat Med. 2019;25:225–228.
  • Wan X, Pei H, Zhao MJ, et al. Efficacy and safety of rAAV2-ND4 treatment for leber’s hereditary optic neuropathy. Sci Rep. 2016;6:21587.
  • Guy J, Feuer WJ, Davis JL, et al. Gene therapy for leber hereditary optic neuropathy: low- and medium-dose visual results. Ophthalmology. 2017;124:1621–1634.
  • Vignal C, Uretsky S, Fitoussi S, et al. Safety of rAAV2/2-ND4 gene therapy for leber hereditary optic neuropathy. Ophthalmology. 2018;125:945–947.
  • Bouquet C, Vignal Clermont C, Galy A, et al. Immune response and intraocular inflammation in patients with leber hereditary optic neuropathy treated with intravitreal injection of recombinant adeno-associated virus 2 carrying the ND4 gene: a secondary analysis of a phase 1/2 clinical trial. JAMA Ophthalmol. 2019;137:399–406.
  • GenSight Biologics. GenSight Biologics reports positive follow-up results at week 72 of the RESCUE phase III clinical trial of GS010 in Leber hereditary optic neuropathy (LHON). 2019 [cited 2020 Oct 3]. Available from: https://www.gensight-biologics.com/2019/04/17/gensight-biologics-reports-positive-follow-up-results-at-week-72-of-the-rescue-phase-iii-clinical-trial-of-gs010-in-leber-hereditary-optic-neuropathy-lhon/
  • GenSight Biologics. GenSight Biologics reports positive 96-week data from REVERSE phase III clinical trial of GS010 for the treatment of Leber hereditary optic neuropathy (LHON). 2019 [cited 2020 Oct 3]. Available from: https://www.gensight-biologics.com/2019/05/15/gensight-biologics-reports-positive-96-week-data-from-reverse-phase-iii-clinical-trial-of-gs010-for-the-treatment-of-leber-hereditary-optic-neuropathy-lhon/
  • Busskamp V, Picaud S, Sahel JA, et al. Optogenetic therapy for retinitis pigmentosa. Gene Ther. 2012;19:169–175.
  • Mace E, Caplette R, Marre O, et al. Targeting channelrhodopsin-2 to ON-bipolar cells with vitreally administered AAV Restores ON and OFF visual responses in blind mice. Mol Ther. 2015;23:7–16.
  • Fernandez-Sanchez L, Lax P, Isiegas C, et al. Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa. Hum Gene Ther Clin Dev. 2012;23:1290–1300.
  • Roddy GW, Yasumura D, Matthes MT, et al. Long-term photoreceptor rescue in two rodent models of retinitis pigmentosa by adeno-associated virus delivery of Stanniocalcin-1. Exp Eye Res. 2017;165:175–181.
  • Dalkara D, Sahel JA. Gene therapy for inherited retinal degenerations. C R Biol. 2014;337:185–192.
  • Darrow JJ. Luxturna: FDA documents reveal the value of a costly gene therapy. Drug Discov Today. 2019;24:949–954.
  • Viriato D, Bennett N, Sidhu R, et al. An economic evaluation of voretigene neparvovec for the treatment of biallelic rpe65-mediated inherited retinal dystrophies in the UK. Adv Ther. 2020;37:1233–1247.
  • Johnson S, Buessing M, O’Connell T, et al. Cost-effectiveness of voretigene neparvovec-rzyl vs standard care for RPE65-mediated inherited retinal disease. JAMA Ophthalmol. 2019;137(10):1115–1123.
  • Zimmermann M, Lubinga SJ, Banken R, et al. Cost utility of voretigene neparvovec for biallelic RPE65-mediated inherited retinal disease. Value Health. 2019;22:161–167.

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