Emerging gene therapy products for RPGR-associated X-linked retinitis pigmentosa

References

• Shahryari A, Saghaeian Jazi M, Mohammadi S, et al. Development and clinical translation of approved gene therapy products for genetic disorders. Front Genet. 2019;10:868.
   PubMed Web of Science ®Google Scholar
• Ciulla TA, Hussain RM, Berrocal AM, et al. Voretigene neparvovec-rzyl for treatment of RPE65 -mediated inherited retinal diseases: a model for ocular gene therapy development. Expert Opin Biol Ther. 2020;20(6):565–578.
   PubMed Web of Science ®Google Scholar
• Voretigene neparvovec-rzyl (Luxturna) for inherited retinal dystrophy. Med Lett Drugs Ther. 2018;60(1543):53–55.
   PubMed Web of Science ®Google Scholar
• Darrow JJ. Luxturna: FDA documents reveal the value of a costly gene therapy. Drug Discov Today. 2019;24(4):949–954.
   PubMed Web of Science ®Google Scholar
• Economics DA. The socioeconomic impact of inherited retinal dystrophies (IRDs) in the United Kingdom. 2019.
   Google Scholar
• Ferrari S, S. Sorrentino F, Ponzin D, et al. Retinitis pigmentosa: genes and disease mechanisms. Curr Genomics. 2011;12(4):238–249.
   PubMed Web of Science ®Google Scholar
• Daiger SP. Retinal Information Network. 1996-2020. [cited 13 Jan 2021]; Available from: https://sph.uth.edu/retnet/home.htm.
   Google Scholar
• Daiger SP, Sullivan LS, Bowne SJ. Genes and mutations causing retinitis pigmentosa. Clin Genet. 2013;84(2):132–141.
   PubMed Web of Science ®Google Scholar
• Mathur P, Yang J. Usher syndrome: hearing loss, retinal degeneration and associated abnormalities. Biochim Biophys Acta. 2015;1852(3):406–420.
   PubMed Web of Science ®Google Scholar
• Suspitsin EN, Imyanitov EN. Bardet-biedl syndrome. Mol Syndromol. 2016;7(2):62–71.
   PubMedGoogle Scholar
• Dias MF, Joo K, Kemp JA, et al. Molecular genetics and emerging therapies for retinitis pigmentosa: basic research and clinical perspectives. Prog Retin Eye Res. 2018;63:107–131.
   PubMed Web of Science ®Google Scholar
• Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368(9549):1795–1809.
   PubMed Web of Science ®Google Scholar
• Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol. 1993;111(6):761–772.
   PubMedGoogle Scholar
• Berson EL, Rosner B, Sandberg MA, et al. Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses. Arch Ophthalmol. 2004;122(9):1306–1314.
   PubMedGoogle Scholar
• Hughbanks-Wheaton DK, Birch DG, Fish GE, et al. Safety assessment of docosahexaenoic acid in X-linked retinitis pigmentosa: the 4-year DHAX trial. Invest Ophthalmol Vis Sci. 2014;55(8):4958–4966.
   PubMed Web of Science ®Google Scholar
• Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2010;128(4):403–411.
   PubMed Web of Science ®Google Scholar
• Schwartz SG, Wang X, Chavis P, et al. Vitamin A and fish oils for preventing the progression of retinitis pigmentosa. Cochrane Database Syst Rev. 2020;6(6):CD008428.
   PubMedGoogle Scholar
• Zhao Y, Feng K, Liu R, et al. Vitamins and mineral supplements for Retinitis pigmentosa. J Ophthalmol. 2019;2019:8524607.
   PubMed Web of Science ®Google Scholar
• Vazquez-Dominguez I, Garanto A, Collin RWJ. Molecular therapies for inherited retinal diseases-current standing. Opportunities and Challenges. Genes (Basel). 2019. 10(9)
   Google Scholar
• MacLaren RE, Bennett J, Schwartz SD. Gene therapy and stem cell transplantation in retinal disease: the new frontier. Ophthalmology. 2016;123(10S):S98–S106.
   PubMedGoogle Scholar
• Stern JH, Tian Y, Funderburgh J, et al. Regenerating eye tissues to preserve and restore vision. Cell Stem Cell. 2018;23(3):453.
   PubMed Web of Science ®Google Scholar
• Gagliardi G, Ben M’Barek K, Goureau O. Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa: a pluripotent stem cell-based approach. Prog Retin Eye Res. 2019;71:1–25.
   PubMed Web of Science ®Google Scholar
• Fry LE, Peddle CF, Barnard AR, et al. RNA editing as a therapeutic approach for retinal gene therapy requiring long coding sequences. Int J Mol Sci. 2020;21(3):777.
   PubMed Web of Science ®Google Scholar
• Kantor A, McClements ME, MacLaren RE. CRISPR-cas9 DNA base-editing and prime-editing. Int J Mol Sci. 2020;21(17):6240.
   PubMed Web of Science ®Google Scholar
• Raghupathy RK, Gautier P, Soares DC, et al. Evolutionary characterization of the Retinitis pigmentosa GTPASE regulator gene. Invest Ophthalmol Vis Sci. 2015;56(11):6255–6264.
   PubMed Web of Science ®Google Scholar
• Sandberg MA, Rosner B, Weigel-DiFranco C, et al. Disease course of patients with X-linked retinitis pigmentosa due to RPGR gene mutations. Invest Ophthalmol Vis Sci. 2007;48(3):1298–1304.
   PubMed Web of Science ®Google Scholar
• Talib M, van Schooneveld MJ, Thiadens AA, et al. Clinical and genetic characteristics of male patients with RPGR-associated Retinal dystrophies: a long-term follow-up study. Retina. 2019;39(6):1186–1199.
   PubMed Web of Science ®Google Scholar
• Campochiaro PA, Mir TA. The mechanism of cone cell death in retinitis pigmentosa. Prog Retin Eye Res. 2017;62:24–37 .
   PubMed Web of Science ®Google Scholar
• Demirci FY, Rigatti BW, Wen G, et al. X-linked cone-rod dystrophy (locus COD1): identification of mutations in RPGR exon ORF15. Am J Hum Genet. 2002;70(4):1049–1053.
   PubMed Web of Science ®Google Scholar
• 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(3): 354–359.
   PubMed Web of Science ®Google Scholar
• Menghini M, Jolly JK, Nanda A, et al. Early cone photoreceptor outer segment length shortening in RPGR X-linked retinitis pigmentosa. Ophthalmologica. 2020.
   PubMedGoogle Scholar
• Nanda A, Salvetti AP, Clouston P, et al. Exploring the variable phenotypes of RPGR carrier females in assessing their potential for retinal gene therapy. Genes (Basel). 2018;9(12):643.
   PubMed Web of Science ®Google Scholar
• Salvetti AP, Nanda A, MacLaren RE. RPGR-related X-linked Retinitis pigmentosa carriers with a severe “male pattern.” Ophthalmologica. 2020;1:1–8.
   Google Scholar
• Fahim AT, Sullivan LS, Bowne SJ, et al. X-chromosome inactivation is a biomarker of clinical severity in female carriers of RPGR-associated x-linked retinitis pigmentosa. Ophthalmol Retina. 2020;4(5):510–520.
   PubMedGoogle Scholar
• MacLaren RE. Gene therapy for Retinal disease: what lies ahead. Ophthalmologica. 2015;234(1):1–5.
   PubMed Web of Science ®Google Scholar
• DiCarlo JE, Mahajan VB, Tsang SH. Gene therapy and genome surgery in the retina. J Clin Invest. 2018;128(6):2177–2188.
   PubMed Web of Science ®Google Scholar
• Surace EM, Auricchio A. Versatility of AAV vectors for retinal gene transfer. Vision Res. 2008;48(3):353–359.
   PubMed Web of Science ®Google Scholar
• Hickey DG, Edwards TL, Barnard AR, et al. Tropism of engineered and evolved recombinant AAV serotypes in the rd1 mouse and ex vivo primate retina. Gene Ther. 2017;24(12):787–800.
   PubMed Web of Science ®Google Scholar
• Naso MF, Tomkowicz B, Perry WL, et al. Adeno-Associated Virus (AAV) as a vector for gene therapy. BioDrugs. 2017;31(4):317–334.
   PubMed Web of Science ®Google Scholar
• Bigot K, Gondouin P, Benard R, et al. Transferrin Non-Viral Gene Therapy for Treatment of Retinal Degeneration. Pharmaceutics. 2020;12(9).
   PubMed Web of Science ®Google Scholar
• Bordet T, Behar-Cohen F. Ocular gene therapies in clinical practice: viral vectors and nonviral alternatives. Drug Discov Today. 2019;24(8):1685–1693.
   PubMed Web of Science ®Google Scholar
• Buck TM, Wijnholds J. Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector elements in ocular gene therapy clinical trials and transgene expression and bioactivity assays. Int J Mol Sci. 2020;21(12):4197.
   PubMed Web of Science ®Google Scholar
• Hulliger EC, Hostettler SM, Kleinlogel S. Empowering retinal gene therapy with a specific promoter for human rod and cone ON-Bipolar cells. Mol Ther Methods Clin Dev. 2020;17:505–519.
   PubMed Web of Science ®Google Scholar
• Vervoort R, Lennon A, Bird AC, et al. Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa. Nat Genet. 2000;25(4):462–466.
   PubMed Web of Science ®Google Scholar
• Howe KL, Achuthan P, Allen J, et al. Ensembl 2021. Nucleic Acids Res. 2021;49(D1):D884–D891.
   PubMed Web of Science ®Google Scholar
• Murga-Zamalloa CA, Atkins SJ, Peranen J, et al. Interaction of retinitis pigmentosa GTPase regulator (RPGR) with RAB8A GTPase: implications for cilia dysfunction and photoreceptor degeneration. Hum Mol Genet. 2010;19(18):3591–3598.
   PubMed Web of Science ®Google Scholar
• UniProt C, Martin M-J, Orchard S. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res. 2021;49(D1):D480–D489.
   PubMed Web of Science ®Google Scholar
• Wright RN, Hong DH, Perkins B. RpgrORF15 connects to the usher protein network through direct interactions with multiple whirlin isoforms. Invest Ophthalmol Vis Sci. 2012;53(3):1519–1529.
   PubMed Web of Science ®Google Scholar
• Sergouniotis Panagiotis I, Chakarova C, Murphy C, et al. Biallelic variants in TTLL5, encoding a Tubulin glutamylase, cause retinal dystrophy. Am J Hum Genet. 2014;94(5):760–769.
   PubMed Web of Science ®Google Scholar
• Yang J, Zhou L, Ouyang J, et al. Genotype–phenotype analysis of RPGR variations: reporting of 62 Chinese families and a literature review. Front Genet. 2021;12(827):600210.
   PubMedGoogle Scholar
• Cehajic Kapetanovic J, McClements ME, Martinez-Fernandez de la Camara C, et al. Molecular strategies for RPGR gene therapy. Genes (Basel). 2019;10(9):674.
   PubMed Web of Science ®Google Scholar
• Cehajic-Kapetanovic J, Martinez-Fernandez de la Camara C, Birtel J, et al. Impaired glutamylation of RPGR ORF15 underlies the cone-dominated phenotype associated with truncating distal ORF15 variants. Proc. Natl. Acad. Sci. U.S.A. 2022;119(49). DOI: 10.1073/pnas.2208707119.
   PubMedGoogle Scholar
• Hadalin V, Sustar M, Volk M, et al. Cone dystrophy associated with a novel variant in the terminal codon of the RPGR-ORF15. Genes (Basel). 2021;12(4):499.
   PubMed Web of Science ®Google Scholar
• Mawatari G, Fujinami K, Liu X, et al. Clinical and genetic characteristics of 14 patients from 13 Japanese families with RPGR-associated retinal disorder: report of eight novel variants. Hum Genome Var. 2019;6:34.
   PubMed Web of Science ®Google Scholar
• Nguyen XT, Talib M, van Schooneveld MJ, et al. RPGR-Associated dystrophies: clinical, genetic, and histopathological features. Int J Mol Sci. 2020;21(3):835.
   PubMed Web of Science ®Google Scholar
• Yang L, Yin X, Feng L, et al. Novel mutations of RPGR in Chinese retinitis pigmentosa patients and the genotype-phenotype correlation. PLoS One. 2014;9(1):e85752.
   PubMed Web of Science ®Google Scholar
• Cehajic-Kapetanovic J, McClements ME, Whitfield J, et al. Association of a novel intronic variant in RPGR with hypomorphic phenotype of X-Linked Retinitis Pigmentosa. JAMA Ophthalmol. 2020;138(11): 1151–1158.
   PubMed Web of Science ®Google Scholar
• Deng WT, Dyka FM, Dinculescu A, et al. Stability and safety of an AAV vector for treating RPGR-ORF15 X-linked retinitis pigmentosa. Hum Gene Ther. 2015;26(9):593–602.
   PubMed Web of Science ®Google Scholar
• Beltran WA, Cideciyan AV, Boye SE, et al. Optimization of retinal gene therapy for X-linked retinitis pigmentosa due to RPGR Mutations. Mol Ther. 2017;25(8):1866–1880.
   PubMed Web of Science ®Google Scholar
• Fischer MD, McClements ME, Martinez-Fernandez de la Camara C, et al., Codon-optimized RPGR improves stability and efficacy of AAV8 gene therapy in two mouse models of x-linked retinitis pigmentosa. Mol Ther. 2017;25(8):1854–1865.
   PubMed Web of Science ®Google Scholar
• Martinez-Fernandez De La Camara C, Cehajic-Kapetanovic J, MacLaren RE. RPGR gene therapy presents challenges in cloning the coding sequence. Expert Opin Biol Ther. 2019;20(1):1–9.
   PubMed Web of Science ®Google Scholar
• Wright RN, Hong DH, Perkins B. Misexpression of the constitutive Rpgr(ex1-19) variant leads to severe photoreceptor degeneration. Invest Ophthalmol Vis Sci. 2011;52(8):5189–5201.
   PubMed Web of Science ®Google Scholar
• Shu X, Fry AM, Tulloch B, et al. RPGR ORF15 isoform co-localizes with RPGRIP1 at centrioles and basal bodies and interacts with nucleophosmin. Hum Mol Genet. 2005;14(9):1183–1197.
   PubMed Web of Science ®Google Scholar
• Khanna H, Hurd TW, Lillo C, et al. RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1, SMC3, and microtubule transport proteins. J Biol Chem. 2005;280(39):33580–33587.
   PubMed Web of Science ®Google Scholar
• Adamian M, Pawlyk BS, Hong D-H, et al. Rod and cone opsin mislocalization in an autopsy eye from a carrier of X-linked retinitis pigmentosa with a Gly436Asp mutation in the RPGR gene. Am J Ophthalmol. 2006;142(3):515–518.
   PubMed Web of Science ®Google Scholar
• Hong DH, Pawlyk BS, Shang J, et al. A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3). Proc Natl Acad Sci U S A. 2000;97(7):3649–3654.
   PubMed Web of Science ®Google Scholar
• Wright AF, Shu X. Focus on molecules: RPGR. Exp Eye Res. 2007;85(1):1–2.
   PubMed Web of Science ®Google Scholar
• Patnaik SR, Raghupathy RK, Zhang X, et al. The role of RPGR and its interacting proteins in ciliopathies. J Ophthalmol. 2015;2015:414781.
   PubMed Web of Science ®Google Scholar
• Sun X, Park JH, Gumerson J, et al. Loss of RPGR glutamylation underlies the pathogenic mechanism of retinal dystrophy caused by TTLL5 mutations. Proc Natl Acad Sci U S A. 2016;113(21):E2925–34.
   PubMed Web of Science ®Google Scholar
• Natarajan K, Gadadhar S, Souphron J, et al. Molecular interactions between tubulin tails and glutamylases reveal determinants of glutamylation patterns. EMBO Rep. 2017;18(6):1013–1026.
   PubMed Web of Science ®Google Scholar
• Frederick JM, Hanke-Gogokhia C, Ying G, et al. Diffuse or hitch a ride: how photoreceptor lipidated proteins get from here to there. Biol Chem. 2020;401(5):573–584.
   PubMed Web of Science ®Google Scholar
• Megaw RD, Soares DC, Wright AF. RPGR: its role in photoreceptor physiology, human disease, and future therapies. Exp Eye Res. 2015;138:32–41.
   PubMed Web of Science ®Google Scholar
• Linari M, Ueffing M, Manson F, et al. The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase. Proc Natl Acad Sci U S A. 1999;96(4):1315–1320.
   PubMed Web of Science ®Google Scholar
• Won J, Gifford E, Smith RS, et al. RPGRIP1 is essential for normal rod photoreceptor outer segment elaboration and morphogenesis. Hum Mol Genet. 2009;18(22):4329–4339.
   PubMed Web of Science ®Google Scholar
• Hosch J, Lorenz B, Stieger K. RPGR: role in the photoreceptor cilium, human retinal disease, and gene therapy. Ophthalmic Genet. 2011;32(1):1–11.
   PubMed Web of Science ®Google Scholar
• Anand M, Khanna H. Ciliary transition zone (TZ) proteins RPGR and CEP290: role in photoreceptor cilia and degenerative diseases. Expert Opin Ther Targets. 2012;16(6):541–551.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Giacalone JC, Searby C, et al. Disruption of RPGR protein interaction network is the common feature of RPGR missense variations that cause XLRP. Proc Natl Acad Sci U S A. 2019;116(4):1353–1360.
   PubMed Web of Science ®Google Scholar
• Kai He KL, Jinghua H. The emerging role of tubulin posttranslational modifications in cilia and ciliopathies. Biophysics Reports. 2020;6(4):89–104.
   Google Scholar
• Garnham CP, Vemu A, Wilson-Kubalek E, et al. Multivalent microtubule recognition by tubulin tyrosine ligase-like family glutamylases. Cell. 2015;161(5):1112–1123.
   PubMed Web of Science ®Google Scholar
• Rao KN, Anand M, Khanna H. The carboxyl terminal mutational hotspot of the ciliary disease protein RPGRORF15 (retinitis pigmentosa GTPase regulator) is glutamylated in vivo. Biol Open. 2016;5(4):424–428.
   PubMed Web of Science ®Google Scholar
• Gasteiger E, Gattiker A, Hoogland C, et al. ExPASy: the proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res. 2003;31(13):3784–3788.
   PubMed Web of Science ®Google Scholar
• Latysheva NS, Flock T, Weatheritt RJ, et al. How do disordered regions achieve comparable functions to structured domains? Protein Sci. 2015;24(6):909–922.
   PubMed Web of Science ®Google Scholar
• Mitchell DR. Polyglutamylation: the GLU that makes microtubules sticky. Curr Biol. 2010;20(5):R234–6.
   PubMed Web of Science ®Google Scholar
• Pawlyk BS, Bulgakov OV, Sun X, et al. Photoreceptor rescue by an abbreviated human RPGR gene in a murine model of X-linked retinitis pigmentosa. Gene Ther. 2015;23(2):196–204.
   PubMed Web of Science ®Google Scholar
• Hong DH, Pawlyk BS, Adamian M, et al. Dominant, gain-of-function mutant produced by truncation of RPGR. Invest Ophthalmol Vis Sci. 2004;45(1):36–41.
   PubMed Web of Science ®Google Scholar
• Song C, Conlon TJ, Deng W-T, et al. Toxicology and pharmacology of an AAV vector expressing codon-optimized RPGR in RPGR-deficient rd9 mice. Hum Gene Ther Clin Dev. 2018;29(4):188–197.
   PubMed Web of Science ®Google Scholar
• Dufour VL, Cideciyan AV, Ye G-J, et al. Toxicity and efficacy evaluation of an adeno-associated virus vector expressing codon-optimized RPGR delivered by subretinal injection in a canine model of X-linked retinitis pigmentosa. Hum Gene Ther. 2020;31(3–4):253–267.
   PubMed Web of Science ®Google Scholar
• Natkunarajah M, Trittibach P, McIntosh J, et al. Assessment of ocular transduction using single-stranded and self-complementary recombinant adeno-associated virus serotype 2/8. Gene Ther. 2008;15(6):463–467.
   PubMed Web of Science ®Google Scholar
• Vandenberghe LH, Bell P, Maguire AM, et al. Dosage thresholds for AAV2 and AAV8 photoreceptor gene therapy in monkey. Sci Transl Med. 2011;3(88):88ra54.
   PubMed Web of Science ®Google Scholar
• Ye GJ, Budzynski E, Sonnentag P, et al. Safety and biodistribution evaluation in CNGB3-deficient mice of rAAV2tYF-PR1.7-hCNGB3, a recombinant AAV vector for treatment of achromatopsia. Hum Gene Ther Clin Dev. 2016;27(1):27–36.
   PubMed Web of Science ®Google Scholar
• Ye GJ, Budzynski E, Sonnentag P, et al. Safety and biodistribution evaluation in cynomolgus macaques of rAAV2tYF-PR1.7-hCNGB3, a recombinant AAV vector for treatment of achromatopsia. Hum Gene Ther Clin Dev. 2016;27(1):37–48.
   PubMed Web of Science ®Google Scholar
• Song C, Dufour VL, Cideciyan AV, et al. Dose range finding studies with two RPGR transgenes in a canine model of X-linked retinitis pigmentosa treated with subretinal gene therapy. Hum Gene Ther. 2020;31(13–14):743–755.
   PubMed Web of Science ®Google Scholar
• Boye SE, Alexander JJ, Boye SL, et al. The human rhodopsin kinase promoter in an AAV5 vector confers rod- and cone-specific expression in the primate retina. Hum Gene Ther. 2012;23(10):1101–1115.
   PubMed Web of Science ®Google Scholar
• Global cell and gene therapy market to reach $11.96 billion by 2025. Bloomberg, UK: Markets Insider. 2019
   Google Scholar