1. На главную
  2. Электронные версии
  3. Сенсорные системы
  4. T. 34, № 3, 2020

Сенсорные системы, 2020, T. 34, № 3, стр. 188-200

Три тактики генной терапии двух врожденных заболеваний сетчатки. Обзор

Е. М. Максимова 1, *, П. В. Максимов 1

1 Федеральное государственное бюджетное учреждение науки Институт проблем передачи информации им. А.А. Харкевича РАН
127051 Москва, Большой Каретный пер., 19, Россия

* E-mail: maximova@iitp.ru

Поступила в редакцию 02.03.2020
После доработки 06.04.2020
Принята к публикации 27.04.2020

Аннотация

Приведены литературные данные о генетических причинах двух врожденных заболеваний сетчатки – LCA2 и LCA10 (детская прогрессирующая слепота) и о современных способах их лечения. Причиной LCA2 является разрыв зрительного цикла из-за дефекта гена RPE65, экспрессирующегося в клетках пигментного эпителия сетчатки (RPE). Для лечения разработана и применяется усиливающая генная терапия (augmentation therapy): векторное субретинальное введение нормального гена RPE65. LCA10 – цилиопатия, вызванная мутацией гена CEP290, экспрессирующегося в основании связывающей реснички (CC) фоторецептора. Для лечения применяется “антисмысловая” терапия, устраняющая интронную (дефектную) мутацию в молекуле пре-мРНК в процессе синтеза белка CEP290. Рассказано о проекте “BRILLIANCE” – первом испытании прямого редактирования генома методом CRISPR/Cas9 прямо в теле пациента LCA10, анонсированном в номере Nature за 2020 г.

Ключевые слова: сетчатка, пигментный эпителий, RPE65, CEP290, LCA2, LCA10, генная терапия, цилия, редактирование генома, CRISPR/Cas9, сепофарсен

DOI: 10.31857/S0235009220030051

Список литературы

  1. Винников Я.А. Цитологические и молекулярные основы рецепции. Л.: Наука, 1971. 298 с.

  2. Заварзин A.A. Основы частной цитологии и сравнительной гистологии многоклеточных животных. Л.: Наука, 1976. 411 с.

  3. Каламкаров Г.Р., Островский М.А. Молекулярные механизмы зрительной рецепции. М.: Наука, 2002. 279 с.

  4. Максимова Е.М. Последние достижения в области восстановления зрения при сетчаточной недостаточности у млекопитающих. Сенсорные системы. 2010. Т. 24. № 3. С. 188–197.

  5. 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

  6. 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

  7. 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.

  8. Aronson J.K. Rare diseases and orphan drugs. Br J Clin Pharmacol. 2006. V. 61 (3). P. 243–245. https://doi.org/10.1111/j.1365-2125.2006.02617.x

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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)30371-3https://doi.org/10.1016/S0140-6736

  15. Bennicelli J., Wright J.F., Komaromy 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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 childhood-onset severe retinal dystrophy. Nat. Genet. 1997. V. 17 (2). P. 194–197. https://doi.org/10.1038/ng1097-194

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

  37. 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

  38. 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

  39. 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

  40. Leber T. Uber retinitis pigmentosa und angeborene amaurose. von Graefe’s archives. Ophthalmology. 1869. V. 15. P. 1–25.

  41. 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

  42. 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

  43. 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

  44. 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

  45. 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

  46. Lorenz B., Gyurus P., Preising M., Bremser D., Gu S., Andrassi M., Gerth C., Gal A. Early-onset severe rod-cone dystrophy in young children with RPE65 mutations. Invest. Ophthalmol. Vis. Sci. 2000. V. 41 (9). P. 2735–2742.

  47. 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

  48. 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

  49. 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

  50. 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

  51. 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

  52. 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

  53. 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

  54. 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

  55. 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

  56. 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

  57. 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

  58. Pollack A. Orphan Drug Law Spurs Debate. The New York Times. 1990.

  59. 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

  60. 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

  61. 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

  62. 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

  63. Rosenbaum J.L., Witman G.B. Intraflagellar transport. Nat. Rev. Mol. Cell. Biol. 2002. V. 3 (11). P. 813–825.

  64. 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

  65. 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

  66. 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

  67. 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.

  68. 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

  69. 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

  70. 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

  71. 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.

  72. 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

  73. 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

  74. 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

  75. 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

  76. 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

  77. 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

  78. 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

  79. 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

Дополнительные материалы отсутствуют.

Инструменты

следующая статья выпуска предыдущая статья выпуска содержание выпуска

Сенсорные системы

Архивы выпусков Информация о журнале Отправить рукопись в журнал