Gene therapy of inherited retinopathies: A long and successful road from viral vectors to patients

Human Gene Therapy

Volumn 23, Issue 8, 2012, Pages 796-807

  Colella, Pasqualina ^a   Auricchio, Alberto ^a,b  

^a TELETHON INSTITUTE OF GENETICS AND MEDICINE TIGEM   (Italy)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOVIRUS VECTOR; LENTIVIRUS VECTOR;

GENE EXPRESSION; HUMAN; LEBER CONGENITAL AMAUROSIS; MONOGENIC DISORDER; MUTAGENESIS; PHOTORECEPTOR; PIGMENT EPITHELIUM; RETINOPATHY; REVIEW; VISION;

ANIMALS; DEPENDOVIRUS; EYE PROTEINS; GENETIC THERAPY; GENETIC VECTORS; HUMANS; LEBER CONGENITAL AMAUROSIS; PHOTORECEPTOR CELLS; RETINAL DISEASES; RETINAL PIGMENT EPITHELIUM;

EID: 84865263487     PISSN: 10430342     EISSN: 15577422     Source Type: Journal    
DOI: 10.1089/hum.2012.123     Document Type: Review

References (164)

1. Acland, G.M., Aguirre, G.D., Ray, J., et al. (2001). Gene therapy restores vision in a canine model of childhood blindness. Nat. Genet. 28, 92-95.
2. Akimoto, M., Miyatake, S., Kogishi, J., et al. (1999). Adenovirally expressed basic fibroblast growth factor rescues photoreceptor cells in RCS rats. Invest. Ophthalmol. Vis. Sci. 40, 273-279.
3. -/- mice and humans with Leber congenital amaurosis. Invest. Oph-thalmol. Vis. Sci. 45, 1259-1271.
4. Alexander, J.J., Umino, Y., Everhart, D., et al. (2007). Restoration of cone vision in a mouse model of achromatopsia. Nat. Med. 13, 685-687.
5. Ali, R.R., Sarra, G.M., Stephens, C., et al. (2000). Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Nat. Genet. 25, 306-310.
6. Allocca, M., Mussolino, C., Garcia-Hoyos, M., et al. (2007). Novel adeno-associated virus serotypes efficiently transduce murine photoreceptors. J. Virol. 81, 11372-11380.
7. Allocca, M., Doria, M., Petrillo, M., et al. (2008). Serotype-de-pendent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice. J. Clin. Invest. 118, 1955-1964.
8. Allocca, M., Manfredi, A., Iodice, C., et al. (2011). AAV-mediated gene replacement either alone or in combination with physical and pharmacological agents results in partial and transient protection from photoreceptor degeneration associated with bPDE deficiency. Invest. Ophthalmol. Vis. Sci. 52, 5713-5719.
9. Anand, V., Duffy, B., Yang, Z., et al. (2002). A deviant immune response to viral proteins and transgene product is generated on subretinal administration of adenovirus and adeno-asso-ciated virus. Mol. Ther. 5, 125-132.
10. Andrieu-Soler, C., Bejjani, R.A., De Bizemont, T., et al. (2006). Ocular gene therapy: a review of nonviral strategies. Mol. Vis. 12, 1334-1347.
11. Annear, M.J., Bartoe, J.T., Barker, S.E., et al. (2011). Gene therapy in the second eye of RPE65-deficient dogs improves retinal function. Gene Ther. 18, 53-61.
12. Ashtari, M., Cyckowski, L.L., Monroe, J.F., et al. (2011). The human visual cortex responds to gene therapy-mediated recovery of retinal function. J. Clin. Invest. 121, 2160-2168.
13. Auricchio, A. (2003). Pseudotyped AAV vectors for constitutive and regulated gene expression in the eye. Vision Res. 43, 913-918.
14. Auricchio, A. (2011). Fighting blindness with adeno-associated virus serotype 8. Hum. Gene Ther. 22, 1169-1170.
15. Auricchio, A., Kobinger, G., Anand, V., et al. (2001). Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model. Hum. Mol. Genet. 10, 3075-3081.
16. Baehr, W., and Frederick, J.M. (2009). Naturally occurring animal models with outer retina phenotypes. Vision Res. 49, 2636-2652.
17. Bainbridge, J.W., Stephens, C., Parsley, K., et al. (2001). In vivo gene transfer to the mouse eye using an HIV-based lentiviral vector; efficient long-term transduction of corneal endothe-lium and retinal pigment epithelium. Gene Ther. 8, 1665-1668.
18. Bainbridge, J.W., Smith, A.J., Barker, S.S., et al. (2008). Effect of gene therapy on visual function in Leber's congenital amau-rosis. N. Engl. J. Med. 358, 2231-2239.
19. Balaggan, K.S., and Ali, R.R. (2012). Ocular gene delivery using lentiviral vectors. Gene Ther. 19, 145-153.
20. Balaggan, K.S., Binley, K., Esapa, M., et al. (2006). Stable and efficient intraocular gene transfer using pseudotyped EIAV lentiviral vectors. J. Gene Med. 8, 275-285.
21. Balaggan, K.S., Duran, Y., Georgiadis, A., et al. (2012). Absence of ocular malignant transformation after sub-retinal delivery of rAAV2/2 or integrating lentiviral vectors in p53-deficient mice. Gene Ther. 19, 182-188.
22. Batten, M.L., Imanishi, Y., Tu, D.C., et al. (2005). Pharmacological and rAAV gene therapy rescue of visual functions in a blind mouse model of Leber congenital amaurosis. PLoS Med. 2, e333.
23. Bemelmans, A.P., Bonnel, S., Houhou, L., et al. (2005). Retinal cell type expression specificity of HIV-1-derived gene transfer vectors upon subretinal injection in the adult rat: influence of pseudotyping and promoter. J. Gene Med. 7, 1367-1374.
24. Bemelmans, A.P., Kostic, C., Crippa, S.V., et al. (2006). Lentiviral gene transfer of RPE65 rescues survival and function of cones in a mouse model of Leber congenital amaurosis. PLoS Med. 3, e347.
25. Bennett, J. (2003). Immune response following intraocular delivery of recombinant viral vectors. Gene Ther. 10, 977-982.
26. Bennett, J., Wilson, J., Sun, D., et al. (1994). Adenovirus vector-mediated in vivo gene transfer into adult murine retina. Invest. Ophthalmol. Vis. Sci. 35, 2535-2542.
27. Bennett, J., Tanabe, T., Sun, D., et al. (1996). Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy. Nat. Med. 2, 649-654.
28. Bennett, J., Zeng, Y., Bajwa, R., et al. (1998). Adenovirus-medi-ated delivery of rhodopsin-promoted bcl-2 results in a delay in photoreceptor cell death in the rd/rd mouse. Gene Ther. 5, 1156-1164.
29. Bennett, J., Ashtari, M., Wellman, J., et al. (2012). AAV2 gene therapy readministration in three adults with congenital blindness. Sci. Transl. Med. 4, 120ra15.
30. Berger, W., Kloeckener-Gruissem, B., and Neidhardt, J. (2010). The molecular basis of human retinal and vitreoretinal diseases. Prog. Retin. Eye Res. 29, 335-375.
31. Bok, D., Yasumura, D., Matthes, M.T., et al. (2002). Effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds/peripherin mutation. Exp. Eye Res. 74, 719-735.
32. Boye, S.E., Boye, S.L., Pang, J., et al. (2010). Functional and behavioral restoration of vision by gene therapy in the guanylate cyclase-1 (GC1) knockout mouse. PLoS One 5, e11306.
33. Boye, S.L., Conlon, T., Erger, K., et al. (2011). Long-term preservation of cone photoreceptors and restoration of cone function by gene therapy in the guanylate cyclase-1 knockout (GC1KO) mouse. Invest. Ophthalmol. Vis. Sci. 52, 7098-7108.
34. Brines, M., and Cerami, A. (2005). Emerging biological roles for erythropoietin in the nervous system. Nat. Rev. Neurosci. 6, 484-494.
35. Busskamp, V., Picaud, S., Sahel, J.A., et al. (2012). Optogenetic therapy for retinitis pigmentosa. Gene Ther. 19, 169-175.
36. Cai, X., Conley, S., and Naash, M. (2008). Nanoparticle applications in ocular gene therapy. Vision Res. 48, 319-324.
37. Calame, M., Cachafeiro, M., Philippe, S., et al. (2011). Retinal degeneration progression changes lentiviral vector cell targeting in the retina. PLoS One 6, e23782.
38. Carvalho, L.S., Xu, J., Pearson, R.A., et al. (2011). Long-term and age-dependent restoration of visual function in a mouse model of CNGB3-associated achromatopsia following gene therapy. Hum. Mol. Genet. 20, 3161-3175.
39. Cashman, S.M., McCullough, L., and Kumar-Singh, R. (2007). Improved retinal transduction in vivo and photoreceptor-spe-cific transgene expression using adenovirus vectors with modified penton base. Mol. Ther. 15, 1640-1646.
40. Chadderton, N., Millington-Ward, S., Palfi, A., et al. (2009). Improved retinal function in a mouse model of dominant retinitis pigmentosa following AAV-delivered gene therapy. Mol. Ther. 17, 593-599.
41. Chader, G.J. (2002). Animal models in research on retinal degenerations: past progress and future hope. Vision Res. 42, 393-399.
42. -/- mice. Invest. Ophthalmol. Vis. Sci. 47, 1177-1184.
43. Cideciyan, A.V. (2010). Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog. Retin. Eye Res. 29, 398-427.
44. Cideciyan, A.V., Aleman, T.S., Boye, S.L., et al. (2008). Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc. Natl. Acad. Sci. U.S.A. 105, 15112-15117.
45. Cideciyan, A.V., Hauswirth, W.W., Aleman, T.S., et al. (2009a). Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Hum. Gene Ther. 20, 999-1004.
46. Cideciyan, A.V., Hauswirth, W.W., Aleman, T.S., et al. (2009b). Vision 1 year after gene therapy for Leber's congenital am-aurosis. N. Engl. J. Med. 361, 725-727.
47. Cideciyan, A.V., Moore, A., Zrenner, E., et al. (2012). Increased vision within days of oral cis-retinoid (QLT091001) treatment in blindness due to mutations in retinal pigment epithelium-specific protein 65kDa (RPE65) or lecithin retinol acyl-transferase (LRAT). In ARVO 2012 Annual Meeting Abstracts, Retina Late-Breaking Papers Session. Fort Lauderdale, FL; May 6-10, 2012.
48. Colella, P., and Auricchio, A. (2010). AAV-Mediated Gene Supply for Treatment of Degenerative and Neovascular Retinal Diseases. Curr. Gene Ther. 10, 371-380.
49. Colella, P., Cotugno, G., and Auricchio, A. (2009). Ocular gene therapy: current progress and future prospects. Trends Mol. Med. 15, 23-31.
50. Colella, P., Iodice, C., Di Vicino, U., et al. (2011). Non-erythropoietic erythropoietin derivatives protect from light-induced and genetic photoreceptor degeneration. Hum. Mol. Genet. 20, 2251-2262.
51. Daiger, S.P., Sullivan, L.S., and Bowne S.J. (2011). RetNet. Retinal Information Network.
52. Dejneka, N.S., Surace, E.M., Aleman, T.S., et al. (2004). In utero gene therapy rescues vision in a murine model of congenital blindness. Mol. Ther. 9, 182-188.
53. den Hollander, A.I., Roepman, R., Koenekoop, R.K., et al. (2008). Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog. Retin. Eye Res. 27, 391-419.
54. Dong, B., Nakai, H., and Xiao, W. (2010). Characterization of genome integrity for oversized recombinant AAV vector. Mol. Ther. 18, 87-92.
55. Duan, D., Yue, Y., and Engelhardt, J.F. (2001). Expanding AAV packaging capacity with trans-splicing or overlapping vectors: a quantitative comparison. Mol. Ther. 4, 383-391.
56. Duisit, G., Conrath, H., Saleun, S., et al. (2002). Five recombinant simian immunodeficiency virus pseudotypes lead to exclusive transduction of retinal pigmented epithelium in rat. Mol. Ther. 6, 446-454.
57. Fagone, P., Wright, J.F., Nathwani, A.C., et al. (2012). Systemic errors in quantitative polymerase chain reaction titration of self-complementary adeno-associated viral vectors and improved alternative methods. Hum. Gene Ther. Methods 23, 1-7.
58. Fischer, M.D., Huber, G., Beck, S.C., et al. (2009). Noninvasive, in vivo assessment of mouse retinal structure using optical coherence tomography. PLoS One 4, e7507.
59. Fishman, G.A. (2010). Historical evolution in the understanding of Stargardt macular dystrophy. Ophthalmic Genet. 31, 183-189.
60. Gao, G., Vandenberghe, L.H., and Wilson, J.M. (2005). New recombinant serotypes of AAV vectors. Curr. Gene Ther. 5, 285-297.
61. Gao, G.P., Alvira, M.R., Wang, L., et al. (2002). Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc. Natl. Acad. Sci. U.S.A. 99, 11854-11859.
62. Gargiulo, A., Bonetti, C., Montefusco, S., et al. (2009). AAV-mediated tyrosinase gene transfer restores melanogenesis and retinal function in a model of oculo-cutaneous albinism type I (OCA1). Mol. Ther. 17, 1347-1354.
63. Ghosh, A., Yue, Y., Lai, Y., et al. (2008). A hybrid vector system expands adeno-associated viral vector packaging capacity in a transgene-independent manner. Mol. Ther. 16, 124-130.
64. Gorbatyuk, M., Justilien, V., Liu, J., et al. (2007a). Suppression of mouse rhodopsin expression in vivo by AAV mediated siRNA delivery. Vision Res. 47, 1202-1208.
65. Gorbatyuk, M., Justilien, V., Liu, J., et al. (2007b). Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme. Exp. Eye Res. 84, 44-52.
66. Gorbatyuk, M.S., Pang, J.J., Thomas, J., Jr., et al. (2005). Knockdown of wild-type mouse rhodopsin using an AAV vectored ribozyme as part of an RNA replacement approach. Mol. Vis. 11, 648-656.
67. Grieger, J.C., and Samulski, R.J. (2005). Packaging capacity of adeno-associated virus serotypes: impact of larger genomes on infectivity and postentry steps. J. Virol. 79, 9933-9944.
68. Grimm, C., Hermann, D.M., Bogdanova, A. et al. (2005). Neuroprotection by hypoxic preconditioning: HIF-1 and erythropoietin protect from retinal degeneration. Semin. Cell Dev. Biol. 16, 531-538.
69. Gruter, O., Kostic, C., Crippa, S.V., et al. (2005). Lentiviral vector-mediated gene transfer in adult mouse photoreceptors is impaired by the presence of a physical barrier. Gene Ther. 12, 942-947.
70. Hartong, D.T., Berson, E.L., and Dryja, T.P. (2006). Retinitis pigmentosa. Lancet 368, 1795-1809.
71. Hashimoto, T., Gibbs, D., Lillo, C., et al. (2007). Lentiviral gene replacement therapy of retinas in a mouse model for Usher syndrome type 1B. Gene Ther. 14, 584-594.
72. Hauswirth, W.W., Aleman, T.S., Kaushal, S., et al. (2008). 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. 19, 979-990.
73. Hirsch, M.L., Agbandje-McKenna, M., and Samulski, R.J. (2010). Little vector, big gene transduction: fragmented genome reassembly of adeno-associated virus. Mol. Ther. 18, 6-8.
74. Jacobson, S.G., Aleman, T.S., Cideciyan, A.V., et al. (2005). Identifying photoreceptors in blind eyes caused by RPE65 mutations: prerequisite for human gene therapy success. Proc. Natl. Acad. Sci. U.S.A. 102, 6177-6182.
75. Jacobson, S.G., Cideciyan, A.V., Aleman, T.S., et al. (2008). Photoreceptor layer topography in children with Leber congenital amaurosis caused by RPE65 mutations. Invest. Oph-thalmol. Vis. Sci. 49, 4573-4577.
76. Jacobson, S.G., Cideciyan, A.V., Ratnakaram, R., et al. (2012). 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. 130, 9-24.
77. Jomary, C., Vincent, K.A., Grist, J., et al. (1997). Rescue of pho-toreceptor function by AAV-mediated gene transfer in a mouse model of inherited retinal degeneration. Gene Ther. 4, 683-690.
78. Kachi, S., Binley, K., Yokoi, K., et al. (2009). Equine infectious anemia viral vector-mediated codelivery of endostatin and angiostatin driven by retinal pigmented epithelium-specific VMD2 promoter inhibits choroidal neovascularization. Hum. Gene Ther. 20, 31-39.
79. Kochanek, S. (1999). High-capacity adenoviral vectors for gene transfer and somatic gene therapy. Hum. Gene Ther. 10, 2451-2459.
80. Kolstad, K.D., Dalkara, D., Guerin, K., et al. (2010). Changes in adeno-associated virus-mediated gene delivery in retinal degeneration. Hum. Gene Ther. 21, 571-578.
81. Komaromy, A.M., Alexander, J.J., Rowlan, J.S., et al. (2010). Gene therapy rescues cone function in congenital achromatopsia. Hum. Mol. Genet. 19, 2581-2593.
82. Kong, F., Li, W., Li, X., et al. (2010). Self-complementary AAV5 vector facilitates quicker transgene expression in photorecep-tor and retinal pigment epithelial cells of normal mouse. Exp. Eye Res. 90, 546-554.
83. Kong, J., Kim, S.R., Binley, K., et al. (2008). Correction of the disease phenotype in the mouse model of Stargardt disease by lentiviral gene therapy. Gene Ther. 15, 1311-1320.
84. Kreppel, F., Luther, T.T., Semkova, I., et al. (2002). Long-term transgene expression in the RPE after gene transfer with a high-capacity adenoviral vector. Invest. Ophthalmol. Vis. Sci. 43, 1965-1970.
85. Ku, C.A., Chiodo, V.A., Boye, S.L., et al. (2011). Gene therapy using self-complementary Y733F capsid mutant AAV2/8 restores vision in a model of early onset Leber congenital am-aurosis. Hum. Mol. Genet. 20, 4569-4581.
86. Kumar-Singh, R. (2008). Barriers for retinal gene therapy: separating fact from fiction. Vision Res. 48, 1671-1680.
87. Kumar-Singh, R., and Farber, D.B. (1998). Encapsidated adeno-virus mini-chromosome-mediated delivery of genes to the retina: application to the rescue of photoreceptor degeneration. Hum. Mol. Genet. 7, 1893-1900.
88. Lai, Y., Yue, Y., and Duan, D. (2010). Evidence for the failure of adeno-associated virus serotype 5 to package a viral genome ‡ 8.2 kb. Mol. Ther. 18, 75-79.
89. LaVail, M.M., Yasumura, D., Matthes, M.T., et al. (2000). Ribo-zyme rescue of photoreceptor cells in P23H transgenic rats: long-term survival and late-stage therapy. Proc. Natl. Acad. Sci. U.S.A. 97, 11488-11493.
90. Le Meur, G., Stieger, K., Smith, A.J., et al. (2007). Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium. Gene Ther. 14, 292-303.
91. Leist, M., Ghezzi, P., Grasso, G., et al. (2004). Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 305, 239-242.
92. Lewin, A.S., Drenser, K.A., Hauswirth, W.W., et al. (1998). Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa. Nat. Med. 4, 967-971.
93. Li, T., Adamian, M., Roof, D.J., et al. (1994). In vivo transfer of a reporter gene to the retina mediated by an adenoviral vector. Invest. Ophthalmol. Vis. Sci. 35, 2543-2549.
94. Liang, F.Q., Anand, V., Maguire, A.M., and Bennett, J. (2000). Intraocular delivery of recombinant virus. In Vision Research Protocols. P.E. Rakoczy, ed. (Humana Press Inc., Totowa, NJ) pp.125-139.
95. Lin, C.T., Gould, D.J., Petersen-Jonest, S.M., and Sargan, D.R. (2002). Canine inherited retinal degenerations: update on molecular genetic research and its clinical application. J. Small Anim. Pract. 43, 426-432.
96. Lotery, A.J., Yang, G.S., Mullins, R.F., et al. (2003). Adeno-associated virus type 5: transduction efficiency and celltype specificity in the primate retina. Hum. Gene Ther. 14, 1663-1671.
97. Maguire, A.M., Simonelli, F., Pierce, E.A., et al. (2008). Safety and efficacy of gene transfer for Leber's congenital amaurosis. N. Engl. J. Med. 358, 2240-2248.
98. Maguire, A.M., High, K.A., Auricchio, A., et al. (2009). Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial. Lancet 374, 1597-1605.
99. Mancuso, K., Hauswirth, W.W., Li, Q., et al. (2009). Gene therapy for red-green colour blindness in adult primates. Nature 461, 784-787.
100. Mao, H., James, T., Jr., Schwein, A., et al. (2011). AAV delivery of wild-type rhodopsin preserves retinal function in a mouse model of autosomal dominant retinitis pigmentosa. Hum. Gene Ther. 22, 567-575.
101. Mao, H., Gorbatyuk, M.S., Rossmiller, B., et al. (2012). Long-term rescue of retinal structure and function by rhodopsin RNA replacement with a single adeno-associated viral vector in P23H RHO transgenic mice. Hum. Gene Ther. 23, 356-366.
102. McCarty, D.M. (2008). Self-complementary AAV vectors; advances and applications. Mol. Ther. 16, 1648-1656.
103. Metzker, M.L. (2010). Sequencing technologies-the next generation. Nat. Rev. Genet. 11, 31-46.
104. Michaelides, M., Hunt, D.M., and Moore, A.T. (2004). The cone dysfunction syndromes. Br. J. Ophthalmol. 88, 291-297.
105. -/- mouse model of congenital complete lack of cone photoreceptor function. Mol. Ther. 18, 2057-2063.
106. Mieziewska, K. (1996). The interphotoreceptor matrix, a space in sight. Microsc. Res. Tech. 35, 463-471.
107. Mihelec, M., Pearson, R.A., Robbie, S.J., et al. (2011). Long-term preservation of cones and improvement in visual function following gene therapy in a mouse model of Leber congenital amaurosis caused by guanylate cyclase-1 deficiency. Hum. Gene Ther. 22, 1179-1190.
108. Millan, J.M., Aller, E., Jaijo, T., et al. (2011). An update on the genetics of Usher syndrome. J. Ophthalmol. 2011, 417217.
109. Millington-Ward, S., Chadderton, N., O'Reilly, M., et al. (2011). Suppression and replacement gene therapy for autosomal dominant disease in a murine model of dominant retinitis pigmentosa. Mol. Ther. 19, 642-649.
110. Miyoshi, H., Takahashi, M., Gage, F.H., et al. (1997). Stable and efficient gene transfer into the retina using an HIV-based lentiviral vector. Proc. Natl. Acad. Sci. U.S.A. 94, 10319-10323.
111. Monnier, L., Lhériteau, E., Weber, M., et al. (2012). AAV-mediated gene therapy restores retinal function and vision in the PDE6b-deficient dog. In ARVO 2012 Annual Meeting Abstracts, Gene Therapy and Delivery I Session. Fort Lauderdale, FL; May 6-10, 2012.
112. Mussolino, C., Della Corte, M., Rossi, S., et al. (2011a). AAV-mediated photoreceptor transduction of the pig cone-enriched retina. Gene Ther. 18, 637-645.
113. Mussolino, C., Sanges, D., Marrocco, E., et al. (2011b). Zinc-finger-based transcriptional repression of rhodopsin in a model of dominant retinitis pigmentosa. EMBO Mol. Med. 3, 118-128.
114. Narfstrom, K., Katz, M.L., Bragadottir, R., et al. (2003). Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog. Invest. Ophthalmol. Vis. Sci. 44, 1663-1672.
115. Natkunarajah, M., Trittibach, P., McIntosh, J. et al. (2008). Assessment of ocular transduction using single-stranded and self-complementary recombinant adeno-associated virus serotype 2/8. Gene Ther. 15, 463-467.
116. Nicoud, M., Kong, J., Iqball, S., et al. (2007). Development of photoreceptor-specific promoters and their utility to investigate EIAV lentiviral vector mediated gene transfer to photo-receptors. J. Gene Med. 9, 1015-1023.
117. O'Reilly, M., Palfi, A., Chadderton, N., et al. (2007). RNA interference-mediated suppression and replacement of human rhodopsin in vivo. Am. J. Hum. Genet. 81, 127-135.
118. O'Reilly, M., Millington-Ward, S., Palfi, A., et al. (2008). A transgenic mouse model for gene therapy of rhodopsin-linked retinitis pigmentosa. Vision Res. 48, 386-391.
119. Pang, J., Cheng, M., Haire, S.E., et al. (2006). Efficiency of lenti-viral transduction during development in normal and rd mice. Mol. Vis. 12, 756-767.
120. Pang, J.J., Dai, X., Boye, S.E., et al. (2011). Long-term retinal function and structure rescue using capsid mutant AAV8 vector in the rd10 mouse, a model of recessive retinitis pig-mentosa. Mol. Ther. 19, 234-242.
121. Pang, J.J., Deng, W.T., Dai, X., et al. (2012). AAV-mediated cone rescue in a naturally occurring mouse model of CNGA3-achromatopsia. PLoS One 7, e35250.
122. Park, T.K., Wu, Z., Kjellstrom, S., et al. (2009). Intravitreal delivery of AAV8 retinoschisin results in cell type-specific gene expression and retinal rescue in the Rs1-KO mouse. Gene Ther. 16, 916-926.
123. Pauwels, K., Gijsbers, R., Toelen, J., et al. (2009). State-of-the-art lentiviral vectors for research use: risk assessment and bio-safety recommendations. Curr. Gene Ther. 9, 459-474.
124. Pawlyk, B.S., Smith, A.J., Buch, P.K., et al. (2005). Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP. Invest. Ophthalmol. Vis. Sci. 46, 3039-3045.
125. Perabo, L., Huber, A., Marsch, S., et al. (2008). Artificial evolution with adeno-associated viral libraries. Comb. Chem. High Throughput Screen 11, 118-126.
126. Petersen-Jones, S.M., Bartoe, J.T., Fischer, A.J., et al. (2009). AAV retinal transduction in a large animal model species: comparison of a self-complementary AAV2/5 with a single-stranded AAV2/5 vector. Mol. Vis. 15, 1835-1842.
127. Petrs-Silva, H., Dinculescu, A., Li, Q., et al. (2009). High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors. Mol. Ther. 17, 463-471.
128. Petrs-Silva, H., Dinculescu, A., Li, Q., et al. (2011). Novel properties of tyrosine-mutant AAV2 vectors in the mouse retina. Mol. Ther. 19, 293-301.
129. Reich, S.J., Auricchio, A., Hildinger, M., et al. (2003). Efficient trans-splicing in the retina expands the utility of adeno-associated virus as a vector for gene therapy. Hum. Gene Ther. 14, 37-44.
130. Reichel, M.B., Ali, R.R., Thrasher, A.J., et al. (1998). Immune responses limit adenovirally mediated gene expression in the adult mouse eye. Gene Ther. 5, 1038-1046.
131. Schlichtenbrede, F.C., da Cruz, L., Stephens, C., et al. (2003a). Long-term evaluation of retinal function in Prph2Rd2/Rd2 mice following AAV-mediated gene replacement therapy. J. Gene Med. 5, 757-764.
132. Schlichtenbrede, F.C., MacNeil, A., Bainbridge, J.W., et al. (2003b). Intraocular gene delivery of ciliary neurotrophic factor results in significant loss of retinal function in normal mice and in the Prph2Rd2/Rd2 model of retinal degeneration. Gene Ther. 10, 523-527.
133. Sieving, P.A., Caruso, R.C., Tao, W., et al. (2006). Ciliary neu-rotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proc. Natl. Acad. Sci. U.S.A. 103, 3896-3901.
134. Simonelli, F., Maguire, A.M., Testa, F., et al. (2010). Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol. Ther. 18, 643-650.
135. Smith, A.J., Schlichtenbrede, F.C., Tschernutter, M., et al. (2003). AAV-mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa. Mol. Ther. 8, 188-195.
136. Smith, A.J., Bainbridge, J.W., and Ali, R.R. (2009). Prospects for retinal gene replacement therapy. Trends Genet. 25, 156-165.
137. Sullivan, T., Kodali, K., and Rex, T.S. (2011). Systemic gene delivery protects the photoreceptors in the retinal degeneration slow mouse. Neurochem. Res. 36, 613-618.
138. Sun, X., Pawlyk, B., Xu, X., et al. (2010). Gene therapy with a promoter targeting both rods and cones rescues retinal degeneration caused by AIPL1 mutations. Gene Ther. 17, 117-131.
139. Surace, E.M., and Auricchio, A. (2008). Versatility of AAV vectors for retinal gene transfer. Vision Res. 48, 353-359.
140. Surace, E.M., Domenici, L., Cortese, K., et al. (2005). Amelioration of both functional and morphological abnormalities in the retina of a mouse model of ocular albinism following AAV-mediated gene transfer. Mol. Ther. 12, 652-658.
141. Sweigard, J.H., Cashman, S.M., and Kumar-Singh, R. (2010). Adenovirus vectors targeting distinct cell types in the retina. Invest. Ophthalmol. Vis. Sci. 51, 2219-2228.
142. Takahashi, M., Miyoshi, H., Verma, I.M., et al. (1999). Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. J. Virol. 73, 7812-7816.
143. Tan, M.H., Smith, A.J., Pawlyk, B., et al. (2009). Gene therapy for retinitis pigmentosa and Leber congenital amaurosis caused by defects in AIPL1: effective rescue of mouse models of partial and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors. Hum. Mol. Genet. 18, 2099-2114.
144. Tessitore, A., Parisi, F., Denti, M.A., et al. (2006). Preferential silencing of a common dominant rhodopsin mutation does not inhibit retinal degeneration in a transgenic model. Mol. Ther. 14, 692-699.
145. Testa, F., Surace, E.M., Rossi, S., et al. (2011). Evaluation of Italian patients with Leber congenital amaurosis due to AIPL1 mutations highlights the potential applicability of gene therapy. Invest. Ophthalmol. Vis. Sci. 52, 5618-5624.
146. Thiadens, A.A., Somervuo, V., van den Born, L.I., et al. (2010). Progressive loss of cones in achromatopsia: an imaging study using spectral-domain optical coherence tomography. Invest. Ophthalmol. Vis. Sci. 51, 5952-5957.
147. Thomas, M.G., Kumar, A., Kohl, S., et al. (2011). High-resolution in vivo imaging in achromatopsia. Ophthalmology 118, 882-887.
148. Tschernutter, M., Schlichtenbrede, F.C., Howe, S., et al. (2005). Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy. Gene Ther. 12, 694-701.
149. van Velthoven, M.E., Faber, D.J., Verbraak, F.D., et al. (2007). Recent developments in optical coherence tomography for imaging the retina. Prog. Retin. Eye Res. 26, 57-77.
150. Vandenberghe, L.H., and Auricchio, A. (2012). Novel adeno-associated viral vectors for retinal gene therapy. Gene Ther. 19, 162-168.
151. Vandenberghe, L.H., Bell, P., Maguire, A.M., et al. (2011). Dosage thresholds for AAV2 and AAV8 photoreceptor gene therapy in monkey. Sci. Transl. Med. 3, 88ra54.
152. Vollrath, D., Feng, W., Duncan, J.L., et al. (2001). Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk. Proc. Natl. Acad. Sci. U.S.A. 98, 12584-12589.
153. Von Seggern, D.J., Aguilar, E., Kinder, K., et al. (2003). In vivo transduction of photoreceptors or ciliary body by intravitreal injection of pseudotyped adenoviral vectors. Mol. Ther. 7, 27-34.
154. Wadsworth, S. (2012). Gene transfer to the inner retina. In ARVO 2012 Annual Meeting Abstracts, Ocular Gene Therapy Session. Fort Lauderdale, FL; May 6-10, 2012.
155. Wen, R., Song, Y., Kjellstrom, S., et al. (2006). Regulation of rod phototransduction machinery by ciliary neurotrophic factor. J. Neurosci. 26, 13523-13530.
156. Weymouth, A.E., and Vingrys, A.J. (2008). Rodent electroreti-nography: methods for extraction and interpretation of rod and cone responses. Prog. Retin. Eye Res. 27, 1-44.
157. Williams, M.L., Coleman, J.E., Haire, S.E., et al. (2006). Lentiviral expression ofretinal guanylate cyclase-1 (RetGC1) restores vision in an avian model of childhood blindness. PLoS Med. 3, e201.
158. Wright, A.F., Chakarova, C.F., Abd El-Aziz, M.M., et al. (2010). Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait. Nat. Rev. Genet. 11, 273-284.
159. Wu, Z., Yang, H., and Colosi, P. (2010). Effect of genome size on AAV vector packaging. Mol. Ther. 18, 80-86.
160. Yanez-Munoz, R.J., Balaggan, K.S., MacNeil, A., et al. (2006). Effective gene therapy with nonintegrating lentiviral vectors. Nat. Med. 12, 348-353.
161. Yin, L., Greenberg, K., Hunter, J.J., et al. (2011). Intravitreal injection of AAV2 transduces macaque inner retina. Invest. Ophthalmol. Vis. Sci. 52, 2775-2783.
162. Yokoi, K., Kachi, S., Zhang, H.S., et al. (2007). Ocular gene transfer with self-complementary AAV vectors. Invest. Oph-thalmol. Vis. Sci. 48, 3324-3328.
163. Zhong, L., Li, B., Jayandharan, G., et al. (2008a). Tyrosine- phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression. Virology 381, 194-202.
164. Zhong, L., Li, B., Mah, C.S., et al. (2008b). Next generation of adeno-associated virus 2 vectors: point mutations in tyrosines lead to high-efficiency transduction at lower doses. Proc. Natl. Acad. Sci. U.S.A. 105, 7827-7832.