Adeno-Associated Virus Mediated Gene Therapy for Retinal Degenerative Diseases

Methods in Molecular Biology

Volumn 807, Issue , 2011, Pages 179-218

  Stieger, Knut ^a   Cronin, Therese ^b   Bennett, Jean ^b   Rolling, Fabienne ^c  

^a JUSTUS LIEBIG UNIVERSITY   (Germany)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITÉ DE NANTES   (France)

Author keywords

AAV; AAV serotypes; Animal models; Gene therapy; Inherited retinal diseases; Retina; RPE65 clinical trial

Indexed keywords

ADENO ASSOCIATED VIRUS; ANIMAL; ARTICLE; GENE THERAPY; GENE VECTOR; GENETICS; HUMAN; METHODOLOGY; RETINA MACULA DEGENERATION;

ANIMALS; DEPENDOVIRUS; GENE THERAPY; GENETIC VECTORS; HUMANS; MACULAR DEGENERATION;

EID: 83455219474     PISSN: 10643745     EISSN: 19406029     Source Type: Book Series    
DOI: 10.1007/978-1-61779-370-7_8     Document Type: Chapter

References (156)

1. Chung, D. C., Lee, V., and Maguire, A. M. (2009) Recent advances in ocular gene therapy Curr. Opin. Ophthalmol 20, 377–381.
2. Smith, A. J., Bainbridge, J. W., and Ali, R. R. (2009) Prospects for retinal gene replacement therapy Trends Genet. 25, 156–165.
3. Surace, E. M. and Auricchio, A. (2008) Versatility of AAV vectors for retinal gene transfer Vision Res. 48, 353–359.
4. Anand, V., Chirmule, N., Fersh, M., Maguire, A. M., and Bennett, J. (2000) Additional transduction events after subretinal readministration of recombinant adeno-associated virus Hum Gene Ther 11, 449–457.
5. Barker, S. E., Broderick, C. A., Robbie, S. J., Duran, Y., Natkunarajah, M., Buch, P., Balaggan, K. S., MacLaren, R. E., Bainbridge, J. W., Smith, A. J., and Ali, R. R. (2009) Subretinal delivery of adeno-associated virus serotype 2 results in minimal immune responses that allow repeat vector administration in immunocompetent mice J. Gene Med. 11, 486–497.
6. Bennett, J., Maguire, A. M., Cideciyan, A. V., Schnell, M., Glover, E., Anand, V., Aleman, T. S., Chirmule, N., Gupta, A. R., Huang, Y., Gao, G. P., Nyberg, W. C., Tazelaar, J., Hughes, J., Wilson, J. M., and Jacobson, S. G. (1999) Stable transgene expression in rod photoreceptors after recombinant adeno-associated virus-mediated gene transfer to monkey retina Proc. Natl. Acad. Sci. U. S. A 96, 9920–9925.
7. Moosajee, M., Tulloch, M., Baron, R. A., Gregory-Evans, C. Y., Pereira-Leal, J. B., and Seabra, M. C. (2009) Single choroideremia gene in nonmammalian vertebrates explains early embryonic lethality of the zebrafish model of choroideremia Invest Ophthalmol Vis. Sci. 50, 3009–3016.
8. Jang, Y. P., Matsuda, H., Itagaki, Y., Nakanishi, K., and Sparrow, J. R. (2005) Characterization of peroxy-A2E and furan-A2E photooxida-tion products and detection in human and mouse retinal pigment epithelial cell lipofus-cin J. Biol. Chem. 280, 39732–39739.
9. Hagstrom, S. A., Duyao, M., North, M. A., and Li, T. (1999) Retinal degeneration in tulp1−/− mice: vesicular accumulation in the interphotoreceptor matrix Invest Ophthalmol Vis. Sci. 40, 2795–2802.
10. Tam, B. M. and Moritz, O. L. (2006) Characterization of rhodopsin P23H-induced retinal degeneration in a Xenopus laevis model of retinitis pigmentosa Invest Ophthalmol Vis. Sci. 47, 3234–3241.
11. Weber, B. H., Schrewe, H., Molday, L. L., Gehrig, A., White, K. L., Seeliger, M. W., Jaissle, G. B., Friedburg, C., Tamm, E., and Molday, R. S. (2002) Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure Proc. Natl. Acad. Sci. U. S. A 99, 6222–6227.
12. Keeler, C. (1927) Rodless retina, an ophthalmic mutation in the house mouse, Mus musculus, Jour Exp Zool 46, 355–407.
13. Fadool, J. M. and Dowling, J. E. (2008) Zebrafish: a model system for the study of eye genetics Prog. Retin. Eye Res. 27, 89–110.
14. Hong, C. C. (2009) Large-scale small-molecule screen using zebrafish embryos Methods Mol. Biol. 486, 43–55.
15. Bennett, J., Anand, V., Acland, G. M., and Maguire, A. M. (2000) Cross-species comparison of in vivo reporter gene expression after recombinant adeno-associated virus-mediated retinal transduction Methods Enzymol. 316, 777–789.
16. 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., and Bennett, J. (2001) Gene therapy restores vision in a canine model of childhood blindness Nat Genet 28, 92–5.
17. Acland, G. M., Aguirre, G. D., Bennett, J., Aleman, T. S., Cideciyan, A. V., Bennicelli, J., Dejneka, N. S., Pearce-Kelling, S. E., Maguire, A. M., Palczewski, K., Hauswirth, W. W., and Jacobson, S. G. (2005) Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness Mol Ther 12, 1072–82.
18. 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., and Bennett, J. (2008) Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer Mol. Ther 16, 458–465.
19. Le Meur, G., Stieger, K., Smith, A. J., Weber, M., Deschamps, J. Y., Nivard, D., Mendes-Madeira, A., Provost, N., Pereon, Y., Cherel, Y., Ali, R. R., Hamel, C., Moullier, P., and Rolling, F. (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.
20. Narfstrom, K., Katz, M. L., Bragadottir, R., Seeliger, M., Boulanger, A., Redmond, T. M., Caro, L., Lai, C. M., and Rakoczy, P. E. (2003) Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog Invest Ophthalmol Vis Sci 44, 1663–72.
21. Narfstrom, K., Katz, M. L., Ford, M., Redmond, T. M., Rakoczy, E., and Bragadottir, R. (2003) In vivo gene therapy in young and adult RPE65−/− dogs produces long-term visual improvement J Hered 94, 31–7.
22. Jacobson, S. G., Boye, S. L., Aleman, T. S., Conlon, T. J., Zeiss, C. J., Roman, A. J., Cideciyan, A. V., Schwartz, S. B., Komaromy, A. M., Doobrajh, M., Cheung, A. Y., Sumaroka, A., Pearce-Kelling, S. E., Aguirre, G. D., Kaushal, S., Maguire, A. M., Flotte, T. R., and Hauswirth, W. W. (2006) Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis Hum Gene Ther 17, 845–58.
23. Bainbridge, J. W., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., Petersen-Jones, S., Bhattacharya, S. S., Thrasher, A. J., Fitzke, F. W., Carter, B. J., Rubin, G. S., Moore, A. T., and Ali, R. R. (2008) Effect of gene therapy on visual function in Leber’s congenital amaurosis N. Engl. J. Med. 358, 2231–2239.
24. Cideciyan, A. V., Aleman, T. S., Boye, S. L., Schwartz, S. B., Kaushal, S., Roman, A. J., Pang, J. J., Sumaroka, A., Windsor, E. A., Wilson, J. M., Flotte, T. R., Fishman, G. A., Heon, E., Stone, E. M., Byrne, B. J., Jacobson, S. G., and Hauswirth, W. W. (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.
25. Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Jr., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., Rossi, S., Lyubarsky, A., Arruda, V. R., Konkle, B., Stone, E., Sun, J., Jacobs, J., Dell’osso, L., Hertle, R., Ma, J. X., Redmond, T. M., Zhu, X., Hauck, B., Zelenaia, O., Shindler, K. S., Maguire, M. G., Wright, J. F., Volpe, N. J., McDonnell, J. W., Auricchio, A., High, K. A., and Bennett, J. (2008) Safety and efficacy of gene transfer for Leber’s congenital amaurosis N. Engl. J. Med. 358, 2240–2248.
26. Hartong, D. T., Berson, E. L., and Dryja, T. P. (2006) Retinitis pigmentosa, Lancet 368, 1795–809.
27. Hamel, C. P. (2007) Cone rod dystrophies Orphanet. J. Rare. Dis. 2, 7.
28. Michaelides, M., Hardcastle, A. J., Hunt, D. M., and Moore, A. T. (2006) Progressive cone and cone-rod dystrophies: phenotypes and underlying molecular genetic basis Surv Ophthalmol 51, 232–58.
29. Cremers, F. P., van de Pol, D. J., van, D. M., den Hollander, A. I., van Haren, F. J., Knoers, N. V., Tijmes, N., Bergen, A. A., Rohrschneider, K., Blankenagel, A., Pinckers, A. J., Deutman, A. F., and Hoyng, C. B. (1998) Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt’s disease gene ABCR Hum Mol. Genet. 7, 355–362.
30. Wissinger, B., Gamer, D., Jagle, H., Giorda, R., Marx, T., Mayer, S., Tippmann, S., Broghammer, M., Jurklies, B., Rosenberg, T., Jacobson, S. G., Sener, E. C., Tatlipinar, S., Hoyng, C. B., Castellan, C., Bitoun, P., Andreasson, S., Rudolph, G., Kellner, U., Lorenz, B., Wolff, G., Verellen-Dumoulin, C., Schwartz, M., Cremers, F. P., pfelstedt-Sylla, E., Zrenner, E., Salati, R., Sharpe, L. T., and Kohl, S. (2001) CNGA3 mutations in hereditary cone photoreceptor disorders Am. J. Hum Genet. 69, 722–737.
31. Hameed, A., Abid, A., Aziz, A., Ismail, M., Mehdi, S. Q., and Khaliq, S. (2003) Evidence of RPGRIP1 gene mutations associated with recessive cone-rod dystrophy J. Med. Genet. 40, 616–619.
32. Freund, C. L., Gregory-Evans, C. Y., Furukawa, T., Papaioannou, M., Looser, J., Ploder, L., Bellingham, J., Ng, D., Herbrick, J. A., Duncan, A., Scherer, S. W., Tsui, L. C., Loutradis-Anagnostou, A., Jacobson, S. G., Cepko, C. L., Bhattacharya, S. S., and McInnes, R. R. (1997) Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor Cell 91, 543–553.
33. Kelsell, R. E., Gregory-Evans, K., Payne, A. M., Perrault, I., Kaplan, J., Yang, R. B., Garbers, D. L., Bird, A. C., Moore, A. T., and Hunt, D. M. (1998) Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy Hum Mol. Genet. 7, 1179–1184.
34. Sohocki, M. M., Perrault, I., Leroy, B. P., Payne, A. M., Dharmaraj, S., Bhattacharya, S. S., Kaplan, J., Maumenee, I. H., Koenekoop, R., Meire, F. M., Birch, D. G., Heckenlively, J. R., and Daiger, S. P. (2000) Prevalence of AIPL1 mutations in inherited retinal degenerative disease Mol. Genet. Metab 70, 142–150.
35. Demirci, F. Y., Rigatti, B. W., Wen, G., Radak, A. L., Mah, T. S., Baic, C. L., Traboulsi, E. I., Alitalo, T., Ramser, J., and Gorin, M. B. (2002) X-linked cone-rod dystrophy (locus COD1): identification of mutations in RPGR exon ORF15 Am. J. Hum Genet. 70, 1049–1053.
36. Koenekoop, R. K. (2004) An overview of Leber congenital amaurosis: a model to understand human retinal development Surv Ophthalmol 49, 379–98.
37. Lorenz, B., Gyurus, P., Preising, M., Bremser, D., Gu, S., Andrassi, M., Gerth, C., and Gal, A. (2000) Early-onset severe rod-cone dystrophy in young children with RPE65 mutations Invest Ophthalmol Vis Sci 41, 2735–42.
38. Lorenz, B., Wabbels, B., Wegscheider, E., Hamel, C. P., Drexler, W., and Preising, M. N. (2004) Lack of fundus autofluorescence to 488 nanometers from childhood on in patients with early-onset severe retinal dystrophy associated with mutations in RPE65 Ophthalmology 111, 1585–1594.
39. den Hollander, A. I., Roepman, R., Koenekoop, R. K., and Cremers, F. P. (2008) Leber congenital amaurosis: genes, proteins and disease mechanisms Prog. Retin. Eye Res. 27, 391–419.
40. Gerth, C., ndrassi-Darida, M., Bock, M., Preising, M. N., Weber, B. H., and Lorenz, B. (2002) Phenotypes of 16 Stargardt macular dystrophy/fundus flavimaculatus patients with known ABCA4 mutations and evaluation of genotype-phenotype correlation Graefes Arch Clin Exp Ophthalmol 240, 628–638.
41. Lorenz, B. and Preising, M. N. (2005) Age matters – thoughts on a grading system for ABCA4 mutations Graefes Arch. Clin. Exp. Ophthalmol. 243, 87–89.
42. Martinez-Mir, A., Paloma, E., Allikmets, R., Ayuso, C., del, R. T., Dean, M., Vilageliu, L., Gonzalez-Duarte, R., and Balcells, S. (1998) Retinitis pigmentosa caused by a homozygous mutation in the Stargardt disease gene ABCR Nat. Genet. 18, 11–12.
43. Kohl, S. (2009) (Genetic causes of hereditary cone and cone-rod dystrophies) Ophthalmologe 106, 109–115.
44. Kohl, S., Marx, T., Giddings, I., Jagle, H., Jacobson, S. G., pfelstedt-Sylla, E., Zrenner, E., Sharpe, L. T., and Wissinger, B. (1998) Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel Nat. Genet. 19, 257–259.
45. Kohl, S., Baumann, B., Broghammer, M., Jagle, H., Sieving, P., Kellner, U., Spegal, R., Anastasi, M., Zrenner, E., Sharpe, L. T., and Wissinger, B. (2000) Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21 Hum Mol. Genet. 9, 2107–2116.
46. Kohl, S., Baumann, B., Rosenberg, T., Kellner, U., Lorenz, B., Vadala, M., Jacobson, S. G., and Wissinger, B. (2002) Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia Am. J. Hum Genet. 71, 422–425.
47. Sikkink, S. K., Biswas, S., Parry, N. R., Stanga, P. E., and Trump, D. (2007) X-linked retinoschisis: an update J. Med. Genet. 44, 225–232.
48. Khan, N. W., Jamison, J. A., Kemp, J. A., and Sieving, P. A. (2001) Analysis of photoreceptor function and inner retinal activity in juvenile X-linked retinoschisis Vision Res. 41, 3931–3942.
49. Sauer, C. G., Gehrig, A., Warneke-Wittstock, R., Marquardt, A., Ewing, C. C., Gibson, A., Lorenz, B., Jurklies, B., and Weber, B. H. (1997) Positional cloning of the gene associated with X-linked juvenile retinoschisis Nat. Genet. 17, 164–170.
50. Rosenberg, T. and Schwartz, M. (1998) X-linked ocular albinism: prevalence and mutations – a national study Eur. J. Hum Genet. 6, 570–577.
51. Ray, K., Chaki, M., and Sengupta, M. (2007) Tyrosinase and ocular diseases: some novel thoughts on the molecular basis of oculocutaneous albinism type 1 Prog. Retin. Eye Res. 26, 323–358.
52. King, R. A., Pietsch, J., Fryer, J. P., Savage, S., Brott, M. J., Russell-Eggitt, I., Summers, C. G., and Oetting, W. S. (2003) Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype Hum Genet. 113, 502–513.
53. Bennett, J., Duan, D., Engelhardt, J. F., and Maguire, A. M. (1997) Real-time, noninvasive in vivo assessment of adeno-associated virus-mediated retinal transduction Invest Ophthalmol Vis Sci 38, 2857–63.
54. Dudus, L., Anand, V., Acland, G. M., Chen, S. J., Wilson, J. M., Fisher, K. J., Maguire, A. M., and Bennett, J. (1999) Persistent transgene product in retina, optic nerve and brain after intraocular injection of rAAV Vision Res 39, 2545–53.
55. Lebherz, C., Maguire, A., Tang, W., Bennett, J., and Wilson, J. M. (2008) Novel AAV serotypes for improved ocular gene transfer J. Gene Med. 10, 375–382.
56. Guy, J., Qi, X., Muzyczka, N., and Hauswirth, W. W. (1999) Reporter expression persists 1 year after adeno-associated virus-mediated gene transfer to the optic nerve Arch Ophthalmol 117, 929–37.
57. Ali, R. R., Reichel, M. B., Thrasher, A. J., Levinsky, R. J., Kinnon, C., Kanuga, N., Hunt, D. M., and Bhattacharya, S. S. (1996) Gene transfer into the mouse retina mediated by an adeno-associated viral vector Hum Mol Genet 5, 591–4.
58. Allocca, M., Mussolino, C., Garcia-Hoyos, M., Sanges, D., Iodice, C., Petrillo, M., Vandenberghe, L. H., Wilson, J. M., Marigo, V., Surace, E. M., and Auricchio, A. (2007) Novel adeno-associated virus serotypes efficiently transduce murine photoreceptors J Virol 81, 11372–80.
59. Weber, M., Rabinowitz, J., Provost, N., Conrath, H., Folliot, S., Briot, D., Cherel, Y., Chenuaud, P., Samulski, J., Moullier, P., and Rolling, F. (2003) Recombinant adeno-associated virus serotype 4 mediates unique and exclusive long-term transduction of retinal pigmented epithelium in rat, dog, and nonhuman primate after subretinal delivery Mol Ther 7, 774–81.
60. Dorrell, M. I., Aguilar, E., Jacobson, R., Yanes, O., Gariano, R., Heckenlively, J., Banin, E., Ramirez, G. A., Gasmi, M., Bird, A., Siuzdak, G., and Friedlander, M. (2009) Antioxidant or neurotrophic factor treatment preserves function in a mouse model of neo-vascularization-associated oxidative stress J. Clin Invest. 119,611-623
61. Folliot, S., Briot, D., Conrath, H., Provost, N., Cherel, Y., Moullier, P., and Rolling, F. (2003) Sustained tetracycline-regulated transgene expression in vivo in rat retinal ganglion cells using a single type 2 adeno-associated viral vector J Gene Med 5, 493–501.
62. Liang, F. Q., Aleman, T. S., Dejneka, N. S., Dudus, L., Fisher, K. J., Maguire, A. M., Jacobson, S. G., and Bennett, J. (2001) Long-term protection of retinal structure but not function using RAAV.CNTF in animal models of retinitis pigmentosa Mol Ther 4, 461–72.
63. Ciulla, T. A. and Rosenfeld, P. J. (2009) Antivascular endothelial growth factor therapy for neovascular ocular diseases other than age-related macular degeneration Curr. Opin. Ophthalmol 20, 166–174.
64. Ciulla, T. A. and Rosenfeld, P. J. (2009) Antivascular endothelial growth factor therapy for neovascular age-related macular degeneration Curr. Opin. Ophthalmol 20, 158–165.
65. Klimczak, R. R., Koerber, J. T., Dalkara, D., Flannery, J. G., and Schaffer, D. V. (2009) A novel adeno-associated viral variant for efficient and selective intravitreal transduction of rat Muller cells PLoS. One. 4, e7467.
66. Dalkara, D., Kolstad, K. D., Caporale, N., Visel, M., Klimczak, R. R., Schaffer, D. V., and Flannery, J. G. (2009) Inner limiting membrane barriers to AAV-mediated retinal transduction from the vitreous Mol. Ther 17, 2096–2102.
67. Park, T. K., Wu, Z., Kjellstrom, S., Zeng, Y., Bush, R. A., Sieving, P. A., and Colosi, P. (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.
68. Ali, R. R., Reichel, M. B., De Alwis, M., Kanuga, N., Kinnon, C., Levinsky, R. J., Hunt, D. M., Bhattacharya, S. S., and Thrasher, A. J. (1998) Adeno-associated virus gene transfer to mouse retina Hum Gene Ther 9, 81–6.
69. Auricchio, A., Kobinger, G., Anand, V., Hildinger, M., O’Connor, E., Maguire, A. M., Wilson, J. M., and Bennett, J. (2001) Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model Hum Mol Genet 10, 3075–81.
70. Yang, G. S., Schmidt, M., Yan, Z., Lindbloom, J. D., Harding, T. C., Donahue, B. A., Engelhardt, J. F., Kotin, R., and Davidson, B. L. (2002) Virus-mediated transduction of murine retina with adeno-associated virus: effects of viral capsid and genome size J Virol 76, 7651–60.
71. Natkunarajah, M., Trittibach, P., McIntosh, J., Duran, Y., Barker, S. E., Smith, A. J., Nathwani, A. C., and Ali, R. R. (2007) Assessment of ocular transduction using single-stranded and self-complementary recombinant adeno-associated virus serotype 2/8 Gene Ther 15,463-467
72. Lei, B., Zhang, K., Yue, Y., Ghosh, A., and Duan, D. (2009) Adeno-associated virus serotype-9 efficiently transduces the retinal outer plexiform layer Mol. Vis. 15, 1374–1382.
73. Koerber, J. T., Klimczak, R., Jang, J. H., Dalkara, D., Flannery, J. G., and Schaffer, D. V. (2009) Molecular evolution of adeno-associated virus for enhanced glial gene delivery Mol. Ther 17, 2088–2095.
74. Bello, A., Tran, K., Chand, A., Doria, M., Allocca, M., Hildinger, M., Beniac, D., Kranendonk, C., Auricchio, A., and Kobinger, G. P. (2009) Isolation and evaluation of novel adeno-associated virus sequences from porcine tissues Gene Ther 16, 1320–1328.
75. Rabinowitz, J. E., Rolling, F., Li, C., Conrath, H., Xiao, W., Xiao, X., and Samulski, R. J. (2002) Cross-packaging of a single adeno-associated virus (AAV) type 2 vector genome into multiple AAV serotypes enables transduction with broad specificity J Virol 76, 791–801.
76. Stieger, K., Colle, M. A., Dubreil, L., Mendes-Madeira, A., Weber, M., Le, M. G., Deschamps, J. Y., Provost, N., Nivard, D., Cherel, Y., Moullier, P., and Rolling, F. (2008) Subretinal delivery of recombinant AAV serotype 8 vector in dogs results in gene transfer to neurons in the brain Mol. Ther. 16, 916–923.
77. Li, H. L., Zheng, X. Z., Wang, H. P., Li, F., Wu, Y., and Du, L. F. (2009) Ultrasound-targeted microbubble destruction enhances AAV-mediated gene transfection in human RPE cells in vitro and rat retina in vivo Gene Ther 16, 1146–1153.
78. Bainbridge, J. W., Mistry, A., Schlichtenbrede, F. C., Smith, A., Broderick, C., De Alwis, M., Georgiadis, A., Taylor, P. M., Squires, M., Sethi, C., Charteris, D., Thrasher, A. J., Sargan, D., and Ali, R. R. (2003) Stable rAAV-mediated transduction of rod and cone photoreceptors in the canine retina Gene Ther 10, 1336–44.
79. Lotery, A. J., Yang, G. S., Mullins, R. F., Russell, S. R., Schmidt, M., Stone, E. M., Lindbloom, J. D., Chiorini, J. A., Kotin, R. M., and Davidson, B. L. (2003) Adeno-associated virus type 5: transduction efficiency and cell-type specificity in the primate retina Hum Gene Ther 14, 1663–71.
80. Petersen-Jones, S. M., Bartoe, J. T., Fischer, A. J., Scott, M., Boye, S. L., Chiodo, V., and Hauswirth, W. W. (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.
81. Nicoletti, A., Kawase, K., and Thompson, D. A. (1998) Promoter analysis of RPE65, the gene encoding a 61-kDa retinal pigment epithelium-specific protein Invest Ophthalmol Vis Sci 39, 637–44.
82. Esumi, N., Oshima, Y., Li, Y., Campochiaro, P. A., and Zack, D. J. (2004) Analysis of the VMD2 promoter and implication of E-box binding factors in its regulation J Biol Chem 279, 19064–73.
83. Kuzmanovic, M., Dudley, V. J., and Sarthy, V. P. (2003) GFAP promoter drives Muller cell-specific expression in transgenic mice Invest Ophthalmol Vis Sci 44, 3606–13.
84. Young, J. E., Vogt, T., Gross, K. W., and Khani, S. C. (2003) A short, highly active photoreceptor-specific enhancer/promoter region upstream of the human rhodopsin kinase gene Invest Ophthalmol Vis Sci 44, 4076–85.
85. Lem, J., Applebury, M. L., Falk, J. D., Flannery, J. G., and Simon, M. I. (1991) Tissue-specific and developmental regulation of rod opsin chimeric genes in transgenic mice Neuron 6, 201–10.
86. Zack, D. J., Bennett, J., Wang, Y., Davenport, C., Klaunberg, B., Gearhart, J., and Nathans, J. (1991) Unusual topography of bovine rhodopsin promoter-lacZ fusion gene expression in transgenic mouse retinas Neuron 6, 187–99.
87. Bennett, J., Sun, D., and Kariko, K. (1995) Sequence analysis of the 5.34-kb 5 flanking region of the human rhodopsin-encoding gene Gene 167, 317–20.
88. Chen, J., Tucker, C. L., Woodford, B., Szel, A., Lem, J., Gianella-Borradori, A., Simon, M. I., and Bogenmann, E. (1994) The human blue opsin promoter directs transgene expression in short-wave cones and bipolar cells in the mouse retina Proc Natl Acad Sci U S A 91, 2611–5.
89. Alexander, J. J., Umino, Y., Everhart, D., Chang, B., Min, S. H., Li, Q., Timmers, A. M., Hawes, N. L., Pang, J. J., Barlow, R. B., and Hauswirth, W. W. (2007) Restoration of cone vision in a mouse model of achromatopsia Nat Med 13, 685–7.
90. Fei, Y. (2003) Development of the cone photoreceptor mosaic in the mouse retina revealed by fluorescent cones in transgenic mice Mol Vis 9, 31–42.
91. Komaromy, A. M., Alexander, J. J., Cooper, A. E., Chiodo, V. A., Glushakova, L. G., Acland, G. M., Hauswirth, W. W., and Aguirre, G. D. (2008) Targeting gene expression to cones with human cone opsin promoters in recombinant AAV Gene Ther. 15, 1049–1055.
92. Le Meur, G., Weber, M., Pereon, Y., Mendes-Madeira, A., Nivard, D., Deschamps, J. Y., Moullier, P., and Rolling, F. (2005) Postsurgical assessment and long-term safety of recombinant adeno-associated virus-mediated gene transfer into the retinas of dogs and primates Arch Ophthalmol 123, 500–6.
93. Hennig, A. K., Levy, B., Ogilvie, J. M., Vogler, C. A., Galvin, N., Bassnett, S., and Sands, M. S. (2003) Intravitreal gene therapy reduces lysosomal storage in specific areas of the CNS in mucopolysaccharidosis VII mice J Neurosci 23, 3302–7.
94. Griffey, M., Macauley, S. L., Ogilvie, J. M., and Sands, M. S. (2005) AAV2-mediated ocular gene therapy for infantile neuronal ceroid lipofuscinosis Mol Ther 12, 413–21.
95. Provost, N., Le Meur, G., Weber, M., Mendes-Madeira, A., Podevin, G., Cherel, Y., Colle, M. A., Deschamps, J. Y., Moullier, P., and Rolling, F. (2005) Biodistribution of rAAV vectors following intraocular administration: evidence for the presence and persistence of vector DNA in the optic nerve and in the brain Mol Ther 11, 275–83.
96. Jacobson, S. G., Acland, G. M., Aguirre, G. D., Aleman, T. S., Schwartz, S. B., Cideciyan, A. V., Zeiss, C. J., Komaromy, A. M., Kaushal, S., Roman, A. J., Windsor, E. A., Sumaroka, A., Pearce-Kelling, S. E., Conlon, T. J., Chiodo, V. A., Boye, S. L., Flotte, T. R., Maguire, A. M., Bennett, J., and Hauswirth, W. W. (2006) Safety of recombinant adeno-associated virus type 2-RPE65 vector delivered by ocular subretinal injection Mol Ther 13, 1074–84.
97. Stieger, K., Schroeder, J., Provost, N., Mendes-Madeira, A., Belbellaa, B., Le, M. G., Weber, M., Deschamps, J. Y., Lorenz, B., Moullier, P., and Rolling, F. (2009) Detection of intact rAAV particles up to 6 years after successful gene transfer in the retina of dogs and primates, Mol. Ther. 17, 516–523.
98. Jin, M., Li, S., Moghrabi, W. N., Sun, H., and Travis, G. H. (2005) Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium Cell 122, 449–59.
99. Moiseyev, G., Chen, Y., Takahashi, Y., Wu, B. X., and Ma, J. X. (2005) RPE65 is the isomerohydrolase in the retinoid visual cycle Proc Natl Acad Sci U S A 102, 12413–8.
100. Aguirre, G. D., Baldwin, V., Pearce-Kelling, S., Narfstrom, K., Ray, K., and Acland, G. M. (1998) Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect Mol Vis 4, 23.
101. Veske, A., Nilsson, S. E., Narfstrom, K., and Gal, A. (1999) Retinal dystrophy of Swedish briard/briard-beagle dogs is due to a 4-bp deletion in RPE65 Genomics 57, 57–61.
102. Pang, J. J., Chang, B., Hawes, N. L., Hurd, R. E., Davisson, M. T., Li, J., Noorwez, S. M., Malhotra, R., McDowell, J. H., Kaushal, S., Hauswirth, W. W., Nusinowitz, S., Thompson, D. A., and Heckenlively, J. R. (2005) Retinal degeneration 12 (rd12): a new, spontaneously arising mouse model for human Leber congenital amaurosis (LCA) Mol Vis 11, 152–62.
103. Lai, C. M., Yu, M. J., Brankov, M., Barnett, N. L., Zhou, X., Redmond, T. M., Narfstrom, K., and Rakoczy, P. E. (2004) Recombinant adeno-associated virus type 2-mediated gene delivery into the Rpe65−/− knockout mouse eye results in limited rescue Genet Vaccines Ther 2, 3–7.
104. 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., and Hauswirth, W. W. (2006) Gene therapy restores vision-dependent behavior as well as retinal structure and function in a mouse model of RPE65 Leber congenital amaurosis Mol Ther 13, 565–72.
105. Dejneka, N. S., Surace, E. M., Aleman, T. S., Cideciyan, A. V., Lyubarsky, A., Savchenko, A., Redmond, T. M., Tang, W., Wei, Z., Rex, T. S., Glover, E., Maguire, A. M., Pugh, E. N., Jr., Jacobson, S. G., and Bennett, J. (2004) In utero gene therapy rescues vision in a murine model of congenital blindness Mol. Ther. 9, 182–188.
106. Narfstrom, K., Vaegan, Katz, M., Bragadottir, R., Rakoczy, E. P., and Seeliger, M. (2005) Assessment of structure and function over a 3-year period after gene transfer in RPE65−/− dogs Doc Ophthalmol 111, 39–48.
107. Batten, M. L., Imanishi, Y., Maeda, T., Tu, D. C., Moise, A. R., Bronson, D., Possin, D., Van Gelder, R. N., Baehr, W., and Palczewski, K. (2004) Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver J Biol Chem 279, 10422–32.
108. Batten, M. L., Imanishi, Y., Tu, D. C., Doan, T., Zhu, L., Pang, J., Glushakova, L., Moise, A. R., Baehr, W., Van Gelder, R. N., Hauswirth, W. W., Rieke, F., and Palczewski, K. (2005) Pharmacological and rAAV gene therapy rescue of visual functions in a blind mouse model of Leber congenital amaurosis PLoS Med 2, e333.
109. Incerti, B., Cortese, K., Pizzigoni, A., Surace, E. M., Varani, S., Coppola, M., Jeffery, G., Seeliger, M., Jaissle, G., Bennett, D. C., Marigo, V., Schiaffino, M. V., Tacchetti, C., and Ballabio, A. (2000) Oa1 knock-out: new insights on the pathogenesis of ocular albinism type 1 Hum Mol Genet 9, 2781–8.
110. Surace, E. M., Domenici, L., Cortese, K., Cotugno, G., Di Vicino, U., Venturi, C., Cellerino, A., Marigo, V., Tacchetti, C., Ballabio, A., and Auricchio, A. (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, 652–8.
111. Gargiulo, A., Bonetti, C., Montefusco, S., Neglia, S., Di, V. U., Marrocco, E., Corte, M. D., Domenici, L., Auricchio, A., and Surace, E. M. (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.
112. Smith, A. J., Schlichtenbrede, F. C., Tschernutter, M., Bainbridge, J. W., Thrasher, A. J., and Ali, R. R. (2003) AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa Mol. Ther. 8, 188–195.
113. Jomary, C., Vincent, K. A., Grist, J., Neal, M. J., and Jones, S. E. (1997) Rescue of photoreceptor function by AAV-mediated gene transfer in a mouse model of inherited retinal degeneration Gene Ther 4, 683–90.
114. Chang, B., Hawes, N. L., Pardue, M. T., German, A. M., Hurd, R. E., Davisson, M. T., Nusinowitz, S., Rengarajan, K., Boyd, A. P., Sidney, S. S., Phillips, M. J., Stewart, R. E., Chaudhury, R., Nickerson, J. M., Heckenlively, J. R., and Boatright, J. H. (2007) Two mouse retinal degenerations caused by missense mutations in the beta-subunit of rod cGMP phosphodiesterase gene Vision Res. 47, 624–633.
115. Pang, J. J., Boye, S. L., Kumar, A., Dinculescu, A., Deng, W., Li, J., Li, Q., Rani, A., Foster, T. C., Chang, B., Hawes, N. L., Boatright, J. H., and Hauswirth, W. W. (2008) AAV-mediated gene therapy for retinal degeneration in the rd10 mouse containing a recessive PDEbeta mutation Invest Ophthalmol. Vis. Sci. 49, 4278–4283.
116. Chang, B., Dacey, M. S., Hawes, N. L., Hitchcock, P. F., Milam, A. H., Atmaca-Sonmez, P., Nusinowitz, S., and Heckenlively, J. R. (2006) Cone photoreceptor function loss-3, a novel mouse model of achromatopsia due to a mutation in Gnat2 Invest Ophthalmol Vis Sci 47, 5017–21.
117. Seddon, J. M., Hampson, E. C., Smith, R. I., and Hughes, I. P. (2006) Genetic heterogeneity of day blindness in Alaskan Malamutes Anim Genet. 37, 407–410.
118. Komaromy, A. M., Alexander, J. J., Chiodo, V., Garcia, M. M., Tanaka, J. C., Craft, C. M., Acland, G. M., Hauswirth, W. W., and Aguirre, G. D. (2008) Longterm rescue of cone function in a canine model of achromatopsia by AAV mediated gene therapy ARVO presentation (Association of Research in Vision and Ophthalmology, 2008 annual meeting) April 28th, Fort Lauderdale
119. Haire, S. E., Pang, J., Boye, S. L., Sokal, I., Craft, C. M., Palczewski, K., Hauswirth, W. W., and Semple-Rowland, S. L. (2006) Light-driven cone arrestin translocation in cones of postnatal guanylate cyclase-1 knockout mouse retina treated with AAV-GC1 Invest Ophthalmol Vis Sci 47, 3745–53.
120. Tan, M. H., Smith, A. J., Pawlyk, B., Xu, X., Liu, X., Bainbridge, J. B., Basche, M., McIntosh, J., Tran, H. V., Nathwani, A., Li, T., and Ali, R. R. (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.
121. Sun, X., Pawlyk, B., Xu, X., Liu, X., Bulgakov, O. V., Adamian, M., Sandberg, M. A., Khani, S. C., Tan, M. H., Smith, A. J., Ali, R. R., and Li, T. (2011) Gene therapy with a promoter targeting both rods and cones rescues retinal degeneration caused by AIPL1 mutations Gene Ther 17, 117–131.
122. Weng, J., Mata, N. L., Azarian, S. M., Tzekov, R. T., Birch, D. G., and Travis, G. H. (1999) Insights into the function of Rim protein in photoreceptors and etiology of Stargardt’s disease from the phenotype in abcr knockout mice Cell 98, 13–23.
123. Radu, R. A., Mata, N. L., Bagla, A., and Travis, G. H. (2004) Light exposure stimulates formation of A2E oxiranes in a mouse model of Stargardt’s macular degeneration Proc. Natl. Acad. Sci. U. S. A 101, 5928–5933.
124. Allocca, M., Doria, M., Petrillo, M., Colella, P., Garcia-Hoyos, M., Gibbs, D., Kim, S. R., Maguire, A., Rex, T. S., Di, V. U., Cutillo, L., Sparrow, J. R., Williams, D. S., Bennett, J., and Auricchio, A. (2008) Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice J. Clin. Invest 118, 1955–1964.
125. Pawlyk, B. S., Smith, A. J., Buch, P. K., Adamian, M., Hong, D. H., Sandberg, M. A., Ali, R. R., and Li, T. (2005) Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP Invest Ophthalmol Vis Sci 46, 3039–45.
126. Ali, R. R., Sarra, G. M., Stephens, C., Alwis, M. D., Bainbridge, J. W., Munro, P. M., Fauser, S., Reichel, M. B., Kinnon, C., Hunt, D. M., Bhattacharya, S. S., and Thrasher, A. J. (2000) Restoration of photoreceptor ultra-structure and function in retinal degeneration slow mice by gene therapy Nat Genet 25, 306–10.
127. Schlichtenbrede, F. C., da, C. L., Stephens, C., Smith, A. J., Georgiadis, A., Thrasher, A. J., Bainbridge, J. W., Seeliger, M. W., and Ali, R. R. (2003) Long-term evaluation of retinal function in Prph2Rd2/Rd2 mice following AAV-mediated gene replacement therapy J. Gene Med. 5, 757–764.
128. Sarra, G. M., Stephens, C., De, A. M., Bainbridge, J. W., Smith, A. J., Thrasher, A. J., and Ali, R. R. (2001) Gene replacement therapy in the retinal degeneration slow (rds) mouse: the effect on retinal degeneration following partial transduction of the retina Hum. Mol. Genet. 10, 2353–2361.
129. Schlichtenbrede, F. C., Smith, A. J., Bainbridge, J. W., Thrasher, A. J., Salt, T. E., and Ali, R. R. (2004) Improvement of neuronal visual responses in the superior collicu-lus in Prph2(Rd2/Rd2) mice following gene therapy Mol Cell Neurosci 25, 103–10.
130. Gehrig, A. E., Warneke-Wittstock, R., Sauer, C. G., and Weber, B. H. (1999) Isolation and characterization of the murine X-linked juvenile retinoschisis (Rs1h) gene Mamm. Genome 10, 303–307.
131. Zeng, Y., Takada, Y., Kjellstrom, S., Hiriyanna, K., Tanikawa, A., Wawrousek, E., Smaoui, N., Caruso, R., Bush, R. A., and Sieving, P. A. (2004) RS-1 Gene Delivery to an Adult Rs1h Knockout Mouse Model Restores ERG b-Wave with Reversal of the Electronegative Waveform of X-Linked Retinoschisis Invest Ophthalmol Vis Sci 45, 3279–85.
132. Kjellstrom, S., Bush, R. A., Zeng, Y., Takada, Y., and Sieving, P. A. (2007) Retinoschisin gene therapy and natural history in the Rs1h-KO mouse: long-term rescue from retinal degeneration Invest Ophthalmol Vis Sci 48, 3837–45.
133. Takada, Y., Vijayasarathy, C., Zeng, Y., Kjellstrom, S., Bush, R. A., and Sieving, P. A. (2008) Synaptic pathology in retinoschisis knockout (Rs1-/y) mouse retina and modification by rAAV-Rs1 gene delivery Invest Ophthalmol Vis. Sci. 49, 3677–3686.
134. Min, S. H., Molday, L. L., Seeliger, M. W., Dinculescu, A., Timmers, A. M., Janssen, A., Tonagel, F., Tanimoto, N., Weber, B. H., Molday, R. S., and Hauswirth, W. W. (2005) Prolonged recovery of retinal structure/func-tion after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis Mol Ther 12, 644–51.
135. Janssen, A., Min, S. H., Molday, L. L., Tanimoto, N., Seeliger, M. W., Hauswirth, W. W., Molday, R. S., and Weber, B. H. (2008) Effect of late-stage therapy on disease progression in AAV-mediated rescue of photoreceptor cells in the retinoschisin-deficient mouse Mol. Ther 16, 1010–1017.
136. Dryja, T. P., Hahn, L. B., Cowley, G. S., McGee, T. L., and Berson, E. L. (1991) Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa Proc Natl Acad Sci U S A 88, 9370–4.
137. Kennan, A., Aherne, A., Palfi, A., Humphries, M., McKee, A., Stitt, A., Simpson, D. A., Demtroder, K., Orntoft, T., Ayuso, C., Kenna, P. F., Farrar, G. J., and Humphries, P. (2002) Identification of an IMPDH1 mutation in autosomal dominant retinitis pigmentosa (RP10) revealed following comparative microarray analysis of transcripts derived from retinas of wild-type and Rho(−/−) mice Hum Mol. Genet. 11, 547–557.
138. Lewin, A. S. and Hauswirth, W. W. (2001) Ribozyme gene therapy: applications for molecular medicine Trends Mol Med 7, 221–8.
139. Lewin, A. S., Drenser, K. A., Hauswirth, W. W., Nishikawa, S., Yasumura, D., Flannery, J. G., and LaVail, M. M. (1998) Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa Nat Med 4, 967–71.
140. LaVail, M. M., Yasumura, D., Matthes, M. T., Drenser, K. A., Flannery, J. G., Lewin, A. S., and Hauswirth, W. W. (2000) Ribozyme rescue of photoreceptor cells in P23H transgenic rats: long-term survival and late-stage therapy Proc Natl Acad Sci U S A 97, 11488–93.
141. Gorbatyuk, M. S., Pang, J. J., Thomas, J., Jr., Hauswirth, W. W., and Lewin, A. S. (2005) Knockdown of wild-type mouse rhodopsin using an AAV vectored ribozyme as part of an RNA replacement approach Mol Vis 11, 648–56.
142. Gorbatyuk, M., Justilien, V., Liu, J., Hauswirth, W. W., and Lewin, A. S. (2007) Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme Exp Eye Res 84, 44–52.
143. Tessitore, A., Parisi, F., Denti, M. A., Allocca, M., Di Vicino, U., Domenici, L., Bozzoni, I., and Auricchio, A. (2006) Preferential silencing of a common dominant rhodopsin mutation does not inhibit retinal degeneration in a transgenic model Mol Ther 14, 692–9.
144. Gorbatyuk, M., Justilien, V., Liu, J., Hauswirth, W. W., and Lewin, A. S. (2007) Suppression of mouse rhodopsin expression in vivo by AAV mediated siRNA delivery Vision Res 47, 1202–8.
145. O’Reilly, M., Palfi, A., Chadderton, N., Millington-Ward, S., Ader, M., Cronin, T., Tuohy, T., Auricchio, A., Hildinger, M., Tivnan, A., McNally, N., Humphries, M. M., Kiang, A. S., Humphries, P., Kenna, P. F., and Farrar, G. J. (2007) RNA interference-mediated suppression and replacement of human rhodopsin in vivo Am J Hum Genet 81, 127–35.
146. Chadderton, N., Millington-Ward, S., Palfi, A., O’Reilly, M., Tuohy, G., Humphries, M. M., Li, T., Humphries, P., Kenna, P. F., and Farrar, G. J. (2009) Improved retinal function in a mouse model of dominant retinitis pigmentosa following AAV-delivered gene therapy Mol. Ther 17, 593–599.
147. Palczewski, K. (2006) G protein-coupled receptor rhodopsin Annu. Rev. Biochem. 75, 743–767.
148. O’Reilly, M., Millington-Ward, S., Palfi, A., Chadderton, N., Cronin, T., McNally, N., Humphries, M. M., Humphries, P., Kenna, P. F., and Farrar, G. J. (2007) A transgenic mouse model for gene therapy of rhodopsin-linked Retinitis Pigmentosa Vision Res 48, 386–391.
149. Palfi, A., Millington-Ward, S., Chadderton, N., O’Reilly, M., Goldmann, T., Humphries, M. M., Wolfrum, U., Humphries, P., Kenna, P. F., and Farrar, G. J. (2011) AAV-Mediated Rhodopsin Replacement Provides Therapeutic Benefit in Mice with a Targeted Disruption of the Rhodopsin Gene Hum Gene Ther 21, 311–323.
150. Tam, L. C., Kiang, A. S., Kennan, A., Kenna, P. F., Chadderton, N., Ader, M., Palfi, A., Aherne, A., Ayuso, C., Campbell, M., Reynolds, A., McKee, A., Humphries, M. M., Farrar, G. J., and Humphries, P. (2008) Therapeutic benefit derived from RNAi-mediated ablation of IMPDH1 transcripts in a murine model of autosomal dominant retinitis pigmentosa (RP10) Hum. Mol. Genet. 17, 2084–2100.
151. Jacobson, S. G., Aleman, T. S., Cideciyan, A. V., Sumaroka, A., Schwartz, S. B., Windsor, E. A., Traboulsi, E. I., Heon, E., Pittler, S. J., Milam, A. H., Maguire, A. M., Palczewski, K., Stone, E. M., and Bennett, J. (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.
152. Maguire, A. M., High, K. A., Auricchio, A., Wright, J. F., Pierce, E. A., Testa, F., Mingozzi, F., Bennicelli, J. L., Ying, G. S., Rossi, S., Fulton, A., Marshall, K. A., Banfi, S., Chung, D. C., Morgan, J. I., Hauck, B., Zelenaia, O., Zhu, X., Raffini, L., Coppieters, F., De, B. E., Shindler, K. S., Volpe, N. J., Surace, E. M., Acerra, C., Lyubarsky, A., Redmond, T. M., Stone, E., Sun, J., McDonnell, J. W., Leroy, B. P., Simonelli, F., and Bennett, J. (2009) Age-dependent effects of RPE65 gene therapy for Leber’s congenital amaurosis: a phase 1 dose-escalation trial Lancet 374, 1597–1605.
153. Cideciyan, A. V., Hauswirth, W. W., Aleman, T. S., Kaushal, S., Schwartz, S. B., Boye, S. L., Windsor, E. A., Conlon, T. J., Sumaroka, A., Pang, J. J., Roman, A. J., Byrne, B. J., and Jacobson, S. G. (2009) Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year Hum Gene Ther 20, 999–1004.
154. Cideciyan, A. V., Hauswirth, W. W., Aleman, T. S., Kaushal, S., Schwartz, S. B., Boye, S. L., Windsor, E. A., Conlon, T. J., Sumaroka, A., Roman, A. J., Byrne, B. J., and Jacobson, S. G. (2009) Vision 1 year after gene therapy for Leber’s congenital amaurosis N. Engl. J. Med. 361, 725–727.
155. 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., McDonnell, J. W., High, K. A., Bennett, J., and Auricchio, A. (2010) Gene Therapy for Leber’s Congenital Amaurosis is Safe and Effective Through 1.5 Years After Vector Administration Mol. Ther 18, 643–650.
156. 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., and Jacobson, S. G. (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.