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Volume 34 #3

Contents

  1. Variability of the pattern VEP parameters in children without visual impairment and questions of preclinical diagnostics
  2. Three tactics for gene therapy of two congenital retinal diseases. Review
  3. Discrimination of rippled spectra with different ripple densities
  4. Method of iterative tomography reconstruction of cropped sinograms
  5. ANALYSIS OF A STOPPING METHOD FOR TEXT RECOGNITION IN VIDEO STREAM USING AN EXTENDED RESULT MODEL WITH PER-CHARACTER ALTERNATIVES
  6. Recognition of projectively transformed planar figures. XIV. New methods for projectively-invariant description of ovals, using an H-polar curve and dual points
  7. Radial distortion correction for camera submerged under water

Three tactics for gene therapy of two congenital retinal diseases. Review

© 2020 E. M. Maximova, P. V. Maximov

Institute for Information Transmission Problems of the Russian Academy of Sciences 127051 Moscow, Bolshoy Karetny per., 19, Russia

Received 02 Mar 2020

Data on the genetic causes of two congenital retinal diseases – LCA2 and LCA10 (childhood progressive blindness) and modern methods for their treatment are presented. The cause of LCA2 is an interruption of the visual cycle due to a defect in the RPE65 gene, which expresses in retinal pigment epithelium (RPE). “Augmentation gene therapy” – vector delivery of normal RPE65 gene by subretinal administration – has been developed and successfully applied for LCA2 treatment. LCA10 is a ciliopathy caused by a mutation of the CEP290 gene, expressed at the base of the connecting cilium of photoreceptor. For treatment, “antisense” therapy is used that eliminates the intron mutation (“sense” but defective) in the pre-mature mRNA molecule during the synthesis of the CEP290 protein. The “BRILLIANCE” project – the first trial of the genome editing using CRISPR/Cas9 technology direct in the LCA10 patient’s body, announced in Nature for 2020, is mentioned.

Key words: retinal pigment epithelium, RPE65, CEP290, LCA2, LCA10, gene therapy, cilium, genome editing, CRISPR/Cas9, sepofarsen

DOI: 10.31857/S0235009220030051

Cite: Maximova E. M., Maximov P. V. Tri taktiki gennoi terapii dvukh vrozhdennykh zabolevanii setchatki. obzor [Three tactics for gene therapy of two congenital retinal diseases. review]. Sensornye sistemy [Sensory systems]. 2020. V. 34(3). P. 188-200 (in Russian). doi: 10.31857/S0235009220030051

References:

  • Vinnikov Ya.A. Tsitologicheskie i molekulyarnye osnovy retseptsii [Cytological and molecular basis of reception]. L.: Nauka Publ, 1971. 298 p. (in Russian).
  • Zavarzin A.A. Osnovy chastnoi tsitologii i sravnitel’noi gistologii mnogokletochnykh zhivotnykh [Fundamentals of private cytology and comparative histology of multicellular animals]. L.: Nauka Publ. 1976. 411 p. (in Russian).
  • Kalamkarov G.R., Ostrovsky M.A. Molekulyarnye mekhanizmy zritel’noi retseptsii [Molecular mechanisms of visual reception]. M.: Nauka Publ. 2002. 279 p. (in Russian).
  • Maximova E.M. Poslednie dostizheniya v oblasti vosstanovleniya zreniya pri setchatochnoi nedostatochnosti u mlekopitayushchikh [Recent advances in restoration of the visual function at retinal deficiencies in mammals]. Sensornye sistemy [Sensory systems]. 2010. V. 24 (3). P. 188–197. (in Russian).
  • Abramowicz A., Gos M. Splicing mutations in human genetic disorders: examples, detection, and confirmation. J Appl Genetics. 2019. V. 60 (2). P. 231. https://doi.org/10.1007/s13353-019-00493-z
  • Acland G.M., Aguirre G.D., Ray J., Zhang Q., Aleman T.S., Cideciyan A.V., Pearce-Kelling S.E., Anand V., Zeng Y., Maguire A.M., Jacobson S.G., Hauswirth W.W., Bennett J. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet. 2001. V. 28 (1). P. 92–95. https://doi.org/10.1038/ng0501-92
  • Aguirre G., Baldwin V., Pearce-Kelling S., Narfstrom K., Ray K., Acland G. Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect. Mol Vis. 1998. V. 4 (23). P. 1–7.
  • Aguirre G., Baldwin V., Pearce-Kelling S., N*arfstrom K., Ray K., Acland G. Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect. Mol Vis. 1998. V. 4 (23). P. 1–7.
  • Bainbridge J., Ali R. Gene therapy for inherited childhood blindness shows promise. Expert Rev. Ophthalmol. 2008a. 3 (4). P. 357–359. https://doi.org/10.1586/17469899.3.4.357
  • Bainbridge J.W., Mehat M.S., Sundaram V. Long-term effect of gene therapy on Leber’s congenital amaurosis. N. Engl. J. Med. 2015. V. 372 (20). P. 1887–1897. https://doi.org/10.1056/NEJMoa1414221
  • Bainbridge J.W., Smith A.J., Barker S.S., Robbie S., Henderson R., Balaggan K., Viswanathan A., Holder G.E., Stockman A., Tyler N., Peterson-Jones S., Battacharya S.S., Thrasher A.J., Fitzke F.W., Carter B.J., Rubin G.S., Moore A.T., Ali R.R. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N. Engl. J. Med. 2008b. V. 358 (21). P. 2231–2239. https://doi.org/10.1056/NEJMoa0802268
  • Bemelmans A.-P., Kostic C., Crippa S.V., Hauswirth W.W., Lem J., Munier F.L., Seeliger M.W, Wenzel A., Arsenijevic Y. Lentiviral Gene Transfer of Rpe65 Rescues Survival and Function of Cones in a Mouse Model of Leber Congenital Amaurosis. PLoS Med. 2006. V. 3 (10). P. 1892–1903. https://doi.org/10.1371/journal.pmed.0030347
  • Bennett J. Taking Stock of Retinal Gene Therapy: Looking Back and Moving Forward. Mol. Ther. 2017. V. 25 (5). P. 1076–1094. https://doi.org/10.1016/j.ymthe.2017.03.008
  • Bennett J., Wellman J., Marshall K.A., McCague S., Ashtari M., DiStefano-Pappas J., Elci O.U., Chung D.C., Sun J., Wright J.F., Cross D.R., Aravand P., Cyckowski L.L., Bennicelli J.L., Mingozzi F., Auricchio A., Pierce E.A., Ruggiero J., Leroy B.P., Simonelli F., High K.A., Maguire A.M. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutatons: a follow-on phase 1 trial. Lancet. 2016. V. 388 (10045). P. 661–672. https://doi.org/(16)30371-3 https://doi.org/10.1016/S0140-6736
  • Bennicelli J., Wright J.F., Koma*romy A., Jacobs J.B., Hauck B., Zelenaia O., Mingozzi F., Hui D., Chung D., Rex T.S., Wei Z., Qu G., Zhou S., Zeiss C., Arruda V.R., Acland G.M., Dell’Osso L.F., High K.A., Maguire A.M., Bennett J. Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer. Mol Ther. 2008. V. 16 (3). P. 458–465. https://doi.org/10.1038/sj.mt.6300389
  • Betleja E., Cole D.G. Ciliary Trafficking: CEP290 Guards a Gated Community. Curr. Biol. 2010. V. 20 (21). P. R928–R931. https://doi.org/10.1016/j.cub.2010.09.058
  • Burnight E.R., Wiley L.A., Drack A.V., Braun T.A., Anfinson K.R., Kaalberg E.E., Halder J.A., Affatigato L.M., Mullins R.F., Stone E.M., Tucker B.A. CEP290 gene transfer rescues Leber congenital amaurosis cellular phenotype. Gene. Ther. 2014. V. 21 (7). P. 662–672. https://doi.org/10.1038/gt.2014.39
  • Cideciyan A.V. Leber Congenital Amaurosis due to RPE65 Mutations and its Treatment with Gene Therapy. Prog. Retin. Eye. Res. 2010. V. 29 (5). P. 398–427. https://doi.org/10.1016/j.preteyeres.2010.04.002
  • Cideciyan A.V., Hauswirth W.W., Aleman T.S., et al. Vision 1 year after gene therapy for Leber’s congenital amaurosis. N. Engl. J. Med. 2009. V. 361 (7). P.725–727. https://doi.org/10.1056/NEJMc0903652
  • Cideciyan A.V., Jacobson S.G., Beltran W.A., Sumaroka A., Swider M., Iwabe S., Roman A.J., Olivares M.B., Schwartz S.B., Komáromy A.M., Hauswirth W.W., Aguirre G.D. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc. Natl. Acad. Sci. U S A. 2013. V. 110 (6). P. E517–E525. https://doi.org/10.1073/pnas.1218933110
  • Coppieters F., Lefever S., Leroy B.P., de Baere E.B. CEP290, a gene with many faces: mutation overview and presentation of CEP290base. Hum. Mutat. 2010. V. 31 (10). P. 1097–1108. https://doi.org/10.1002/humu.21337
  • Ding J.-D., Salinas R.Y., Arshavsky V.Y. Discs of mammalian rod photoreceptors form through the membrane evagination mechanism. J. Cell. Biol. 2015. V. 211 (3). P. 495–502. https://doi.org/10.1083/jcb.201508093
  • Drivas T.G., Bennett J. CEP290 and the Primary Cilium. Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. New York. Springer, 2014. P. 519–525. https://doi.org/10.1007/978-1-4614-3209-8_66
  • Du Q.-S., Cui J., C.-jie Zhang, He K.Visualization analysis of CRISPR/Cas9 gene editing technology studies. J. Zhejiang. Univ. Sci. B. 2016. V.17 (10). P. 798–806. https://doi.org/10.1631/jzus.B1601985
  • Duijkers L., van den Born I., Neidhardt J., Bax N.M., Pierrache L.H.M., Klevering B.J., Collin R.W.J., Garanto A. Antisense Oligonucleotide-Based Splicing Correction in Individuals with Leber Congenital Amaurosis due to Compound Heterozygosity for the c.2991+1655A>G Mutation in CEP290. Int. J. Mol. Sci. 2018. V. 19 (3). P. 753–760. https://doi.org/10.3390/ijms19030753
  • Dulla K., Aguila M., Lane A., Jovanovic K., Parfitt D.A., Schulkens I., Chan H.L., Schmidt I., Beumer W., Vorthoren L., Collin R.W.J., Garanto A., Duijkers L., Brugulat- Panes A., Semo M., Vugler A.A., Biasutto P., Adamson P., Cheetham M.E. Splice-Modulating Oligonucleotide QR-110 (sepofarsen) Restores CEP290mRNA and Functionin Human c.2991+1655A>G LCA10 Models. Mol. Ther. Nucleic. Acids. 2018. V. 12. P. 730–740. https://doi.org/10.1016/j.omtn.2018.07.010
  • Doudna J.A., Charpentier E. The new frontier of genome engineering with CRISPR-Cas9. Review. Science. 2014. V. 346, Issue 6213, 1258096. https://doi.org/10.1126/science.1258096
  • Gu S.M., Thompson D.A., Srikumari C.R., Lorenz B., Finckh U., Nicoletti A., Murthy K.R., Rathmann M., Kumaramanickavel G., Denton M.J., Gal A. Mutations in RPE65 cause autosomal recessive childhoodonset severe retinal dystrophy. Nat. Genet. 1997. V. 17 (2). P. 194–197. https://doi.org/10.1038/ng1097-194
  • Hastie E., Samulski R.J. Adeno-associated virus at 50: a golden anniversary of discovery, research, and gene therapy success–a personal perspective. Hum. Gene. Ther. 2015. V. 26 (5). P. 257–265. https://doi.org/10.1089/hum.2015.025
  • Hauswirth W.W., Aleman T.S., Kaushal S., Cideciyan A.V., Schwartz S.B., Wang L, Conlon T.J., Boye S.L., Flotte T.R., Byrne B.J., Jacobson S.G. Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum. Gene. Ther. 2008. V. 19 (10). P. 979–990. https://doi.org/10.1089/hum.2008.107
  • Havens M.A., Hastings M.L. Splice-switching antisense oligonucleotides as therapeutic drugs. Nucleic. Acids. Res. 2016. V. 44 (14). P. 6549–6563. https://doi.org/10.1093/nar/gkw533
  • Hollander A.I., Black A., Bennett J., Cremers F.P. Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies. J. Clin. Invest. 2010. V. 120 (9). P. 3042–3053. https://doi.org/10.1172/JCI42258
  • Hussain R.M., Tran K.D., Maguire A.M., Berrocal A.M. Subretinal Injection of Voretigene Neparvovec-rzyl in a Patient With RPE65-Associated Leber’s Congenital Amaurosis. Ophthalmic Surg Lasers Imaging Retina. 2019. V. 50 (10). P. 661–663. https://doi.org/10.3928/23258160-20191009-01
  • Insinna C., Besharse J.C. Intraflagellar Transport and the Sensory Outer Segment of Vertebrate Photoreceptors. Dev Dyn. 2008. V. 237 (8). P. 1982–1992. https://doi.org/10.1002/dvdy.21554
  • Insinna C., Humby M., Sedmak T., Wolfrum U., Besharse J.C. Different Roles For KIF17 and Kinesin II In Photoreceptor Development and Maintenance. Dev Dyn. 2009. V. 238 (9). P. 2211–2222. https://doi.org/10.1002/dvdy.21956
  • Jacobson S.G., Cideciyan A.V., Aleman T.S., Sumaroka A., Windsor E.A.M., Schwartz S.B., Heon E., Stone E.M. Photoreceptor Layer Topography in Children with Leber Congenital Amaurosis Caused by RPE65 Mutations. Invest. Ophthalmol. Vis. Sci. 2008. V. 49 (10). P. 4573–4577. https://doi.org/10.1167/iovs.08-2121
  • Jacobson S.G., Cideciyan A.V., Ratnakaram R., Heon E., Schwartz S.B., Roman A.J., Peden M.C., Aleman T.S., Boye S.L., Sumaroka A., Conlon T.J., Calcedo R., Pang J.-J., Erger K.E., Olivares M.B., Mullins C.L., Swider M., Kaushal S., Feuer W.J., Iannaccone A., Fishman G.A., Stone E.M., Byrne B.J., Hauswirth W.W. 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. V. 130 (1). P. 9–24. https://doi.org/10.1001/archophthalmol.2011.298
  • Jinek M., Chylinski K., Fonfara I., Hauer M., Doudna J.A., Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012. V. 17. 337 (6096). P. 816–821. https://doi.org/10.1126/science.1225829
  • Le Meur G., Lebranchu P., Billaud F., Adjali O., Schmitt S., Bézieau S., Péréon Y., Valabregue R., Ivan C., Darmon C., Moullier P., Rolling F., Weber M. Safety and Long-Term Efficacy of AAV4 Gene Therapy in Patients with RPE65 Leber Congenital Amaurosis. Mol Ther. 2018. V. 26 (1). P. 256–268. https://doi.org/10.1016/j.ymthe.2017.09.014
  • Leber T. Uber retinitis pigmentosa und angeborene amaurose. von Graefe’s archives. Ophthalmology. 1869. V. 15. P. 1–25.
  • Ledford H. CRISPR treatment inserted directly into the body for first time. Nature. 2020. V. 579 (7798). P. 185–190. https://doi.org/10.1038/d41586-020-00655-8
  • Li L., Xiao X., Li S., Jia X., Wang P., Guo X., Jiao X., Zhang Q., Hejtmancik J. F. Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis. PLoS ONE. 2011. V. 6 (5). https://doi.org/10.1371/journal.pone.0019458
  • Li Y., Wang H., Peng J., Gibbs R.A., Lewis R.A., et al. Mutation survey of known LCA genes and loci in the Saudi Arabian population. Invest. Ophthalmol. Vis. Sci. 2009. V. 50 (3). P. 1336–1343. https://doi.org/10.1167/iovs.08-2589
  • Liu J., Bu J. A Gene Scan Study of RPE65 in Chinese Patients with Leber Congenital Amaurosis. Chin. Med. J. (Engl). 2017. V. 130 (22). P. 2709–2712. https://doi.org/10.4103/0366-6999.218007
  • Long H., Huang K. Transport of Ciliary Membrane Proteins. Front. Cell. Dev. Biol. 2020. V. 7. P. 381–390. https://doi.org/10.3389/fcell.2019.00381
  • Lorenz B., Gyurus P., Preising M., Bremser D., Gu S., Andrassi M., Gerth C., Gal A. Early-onset severe rodcone dystrophy in young children with RPE65 mutations. Invest. Ophthalmol. Vis. Sci. 2000. V. 41 (9). P. 2735–2742.
  • Maguire A.M., High K.A., Auricchio A., Wright J.F., Pierce E.A., Testa F. Age-dependent effects of RPE65 gene therapy for Leber’s congenital amaurosis:a phase 1 dose-escalation trial. Lancet. 2009. V. 374. P. 1597–1605. https://doi.org/10.1016/S0140-6736
  • Maguire A.M., Simonelli F., Pierce E.A., et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N. Engl. J. Med. 2008. V. 358 (21). P. 2240–2248. https://doi.org/10.1056/NEJMoa0802315
  • Marszalek J.R., Liu X., Roberts E.A., Marth J.D., Williams D.S., Goldstein L.S.B. Genetic Evidence for Selective Transport of Opsin and Arrestin by Kinesin-II in Mammalian Photoreceptors. Cell. 2000. V. 102 (2). P. 175–187. https://doi.org/10.1016/S0092-8674
  • McKibbin M., Ali M., Mohamed M.D., Booth A.P., Bishop F. Genotype-phenotype correlation for leber congenital amaurosis in Northern Pakistan. Arch. Ophthalmol. 2010. V. 128 (1). P. 107–113. https://doi.org/10.1001/archophthalmol.2010.309
  • Narfström K., Wrigstad A., Nilsson S.E. The Briard dog: a new animal model of congenital stationary night blindness. Br. J. Ophthalmol. 1989. V.73 (9). P.750–756. https://doi.org/10.1136/bjo.73.9.750
  • Nathans J. Determinants of visual pigment absorbance: identification of the retinylidene Schiff’s base counterion in bovine rhodopsin. Biochemistry. 1990. V. 29 (41). P. 9746–9752. https://doi.org/10.1021/bi00493a034
  • Pang J.J., Chang B., Kumar A., Nusinowitz S., Noorwez S.M., Li J., Rani A., Foster T.C., Chiodo V.A., Doyle T., Li H., Malhotra R., Teusner J.T., McDowell J.H., Min S.H., Li Q., Kaushal S., Hauswirth W.W. Gene Therapy Restores Vision-Dependent Behavior as Well as Retinal Structure and Function in a Mouse Model of RPE65 Leber Congenital Amaurosis. Mol. Ther. 2006. V. 13 (3). P. 565–572. https://doi.org/10.1016/j.ymthe.2005.09.001
  • Pazour G.J., Baker S.A., Deane J.A., Cole D.G., Dickert B.L., Rosenbaum J.L., Witman G.B., Besharse J.C. The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. J. Cell. Biol. 2002. V. 157 (1). P. 103–113. https://doi.org/10.1083/jcb.200107108
  • Peng Y., Tang L., Zhou Y. Subretinal Injection: A Review on the Novel Route of Therapeutic Delivery for Vitreoretinal Diseases. Ophthalmic. Res. 2017. V. 58 (4). P. 217–226. https://doi.org/10.1159/000479157
  • Pennesi M.E., Weleber R.G., Yang P., Whitebirch C., Thean B., Flotte T.R., Humphries M., Chegarnov E., Beasley K.N., Stout J.T., Chulay J.D. Results at 5 years after gene therapy for RPE65-deficient retinal dystrophy. Hum. Gene. Ther. 2018. V. 29 (12). P. 1428–1437. https://doi.org/10.1089/hum.2018.014
  • Petersen-Jones S.M., Komáromy A.M. Dog Models for Blinding Inherited Retinal Dystrophies. Hum. Gene. Ther. Clin Dev. 2015. V. 26 (1). P. 15–26. https://doi.org/10.1089/humc.2014.155
  • Pollack A. Orphan Drug Law Spurs Debate. The New York Times. 1990.
  • Prevo B., Scholey J.M., Peterman E.J.G. Intraflagellar Transport: Mechanisms of Motor Action, Cooperation and Cargo Delivery. FEBS J. 2017. V. 284 (18). P. 2905–2931. https://doi.org/10.1111/febs.14068
  • Redmond T.M., Poliakov E., Yu S., Tsai J.Y., Lu Z., Gentleman S. Mutation of key residues of RPE65 abolishes its enzymatic role as isomerohydrolase in the visual cycle. Proc. Natl. Acad. Sci. U S A. 2005. V. 102 (38). P. 13658–13663. https://doi.org/10.1073/pnas.0504167102
  • Redmond T.M., Yu S., Lee E., Bok D., Hamasaki D., Chen N., Goletz. P., Ma J.X., Crouch R.K., Pfeifer K. Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle. Nat. Genet. 1998. V. 20 (4). P. 344–351. https://doi.org/10.1038/3813
  • Redmond T.M. and Hamel C.P. Genetic analysis of RPE65: from human disease to mouse model. Methods. Enzymol. 2000. V. 316. P. 705–724. https://doi.org/10.1016/s0076-6879
  • Rosenbaum J.L., Witman G.B. Intraflagellar transport. Nat. Rev. Mol. Cell. Biol. 2002. V. 3 (11). P. 813–825.
  • Salinas R.Y., Pearring J.N., Ding J.-D., Spencer W.J., Hao Y., Arshavsky V.Y. Photoreceptor discs form through peripherin-dependent suppression of ciliary ectosome release. JCB. 2017. V. 216 (5). P. 1489–1499. https://doi.org/10.1083/jcb.201608081
  • Sanagala R., Moola A.K., Bollipo Diana R.K. A review on advanced methods in plant gene targeting. J. Genet. Eng. Biotechnol. 2017. V. 15 (2). P. 317–321. https://doi.org/10.1016/j.jgeb.2017.07.004
  • Satir P., Pedersen L.B., Christensen S.T. The primary cilium at a glance. J. Cell. Sci. 2010. V. 123 (Pt 4). P. 499–503. https://doi.org/10.1242/jcs.050377
  • Seong M.W., Kim S.Y., Yu Y.S., Hwang J.M., Kim J.Y. Molecular characterization of Leber congenital amaurosis in Koreans. Mol. Vis. 2008. V. 14. P. 1429–1436.
  • Sheck L., Davies W.I.L., Moradi P., Robson A.G., Kumaran N., Liasis A.C., Webster A.R., Moore A.T., Michaelides M. Leber Congenital Amaurosis Associated with Mutations in CEP290, Clinical Phenotype, and Natural History in Preparation for Trials of Novel Therapies. Ophthalmology. 2018. V. 125 (6). P. 894–903. https://doi.org/10.1016/j.ophtha.2017.12.013
  • Simonelli F., Maguire A.M., Testa F., Pierce E.A., Mingozzi F., Bennicelli J.L., Rossi S., Marshall K., Banfi S., Surace E.M., Sun J., Redmond T.M., Zhu X., Shindler K.S., Ying G.S., Ziviello C., Acerra C., Wright J.F., McDonell J.W., High K.A., Bennett J., Auricchio A. Gene therapy for Leber’s congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol. Ther. 2010. V. 18 (3). P. 643–650. https://doi.org/10.1038/mt.2009.277
  • Siva K., Covello G., Denti M.A. Exon-skipping antisense oligonucleotides to correct missplicing in neurogenetic diseases. Nucleic. Acid. Ther. 2014. V. 24 (1). P. 69–86. https://doi.org/10.1089/nat.2013.0461
  • Sundaresan P., Vijayalakshmi P., Thompson S., Ko A.C., Fingert J.H., et al. Mutations that are a common cause of Leber congenital amaurosis in northern America are rare in southern India. Mol. Vis. 2009. V.15. P. 1781–1787.
  • Takkar B., Bansal P., Venkatesh P. Leber’s Congenital Amaurosis and Gene Therapy. Indian. J. Pediatr. 2018. V. 85 (3). P. 237–242. https://doi.org/10.1007/s12098-017-2394-1
  • Veske A., Nilsson S., Narfström K., Gal A. Retinal dystrophy of Swedish Briard/Briard-Beagle dogs is due to a 4-bp deletion in RPE65. Genomics. 1999. V. 57 (1). P. 57–61. https://doi.org/10.1006/geno.1999.5754
  • Wang X., Yu C., Tzekov R.T., Zhu Y., Li1 W. The effect of human gene therapy for RPE65-associated Leber’s congenital amaurosis on visual function: a systematic review and meta-analysis. Orphanet. J. Rare. Dis. 2020. V. 15 (1). P. 49–55. https://doi.org/10.1186/s13023-020-1304-1
  • Warrington K.H. Jr, Herzog R.W. Treatment of human disease by adeno-associated viral gene transfer. Hum. Genet. 2006. V. 119 (6). P. 571–603. https://doi.org/10.1007/s00439-006-0165-6
  • Weleber R.G., Pennesi M.E., David J.W., Kaushal Sh., Erker L.R., Jensen L., McBride M.T., Flotte T.R., Humphries M., Calcedo R., Hauswirth, W.W., Chulay J.D., Stout J.T. Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy. Ophthalmology. 2016. V. 123 (7). P. 1606–1620. https://doi.org/10.1016/j.ophtha.2016.03.003
  • Wheway G., Parry D.A., Johnson C.A. The role of primary cilia in the development and disease of the retina. Organogenesis. 2014. V. 10 (1). P. 69–85. https://doi.org/10.4161/org.26710
  • Wolf G. Function of the Protein RPE65 in the Visual Cycle. Nutr. Rev. 2005. V. 63 (3). P. 97–100. https://doi.org/10.1111/j.1753-4887.2005.tb00127.x
  • Young R.W. The renewal of photoreceptor cell outer segments. J. Cell. Biol. 1967. V. 33 (1). P. 61–72. https://doi.org/10.1083/jcb.33.1.61