Subretinal delivery of adeno-associated virus serotype 2 results in minimal immune responses that allow repeat vector administration in immunocompetent mice
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Background: Adeno‐associated virus serotype 2 (AAV2) vectors show considerable promise for ocular gene transfer. However, one potential barrier to efficacious long‐term therapy is the development of immune responses against the vector or transgene product. Methods: We evaluated cellular and humoural responses in mice following both single and repeated subretinal administration of AAV2, and examined their effects on RPE65 and green fluorescent protein transgene expression. Results: Following subretinal administration of vector, splenocytes and T‐cells from draining lymph nodes showed minimal activation following stimulation by co‐culture with AAV2. Neutralizing antibodies (NAbs) were not detected in the ocular fluids of any mice receiving AAV2 or in the serum of mice receiving a lower dose. NAbs were present in the serum of a proportion of mice receiving a higher dose of the vector. Furthermore, no differences in immunoglobulin titre in serum or ocular fluids against RPE65 protein or AAV2 capsid between treated and control mice were detected. Histological examination showed no evidence of retinal toxicity or leukocyte infiltration compared to uninjected eyes. Repeat administration of low‐dose AAV.hRPE65.hRPE65 to both eyes of RPE65−/− mice resulted in transgene expression and functional rescue, but re‐administration of high‐dose AAV2 resulted in boosted NAb titres and variable transgene expression in the second injected eye. Conclusions: These data, which were obtained in mice, suggest that, following subretinal injection, immune responses to AAV2 are dose‐dependent. Low‐dose AAV2 is well tolerated in the eye, with minimal immune responses, and transgene expression after repeat administration of vector is achievable. Higher doses lead to the expression of NAbs that reduce the efficacy of repeated vector administration. Copyright © 2009 John Wiley & Sons, Ltd.
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Innate and adaptive immune responses are dose-dependent after intravitreal and subretinal injections in preclinical and clinical trials.
“Innate and adaptive immune responses are dose-dependent after IVT (Cukras et al., 2018) and subretinal injections in preclinical (Barker et al., 2009) and clinical trials (Le Meur et al., 2018).”
From AAV2 and AAV9 tropism and transgene expression in the mouse eye and major tissues after intravitreal and subretinal delivery (2023) · cites this paper as Barker et al., 2009
A higher vector dose can elicit immune responses.
“However, a higher vector dose can elicit immune responses (Barker et al., 2009; Cukras et al., 2018).”
From AAV2 and AAV9 tropism and transgene expression in the mouse eye and major tissues after intravitreal and subretinal delivery (2023) · cites this paper as Barker et al., 2009
Higher doses lead to the expression of neutralizing antibodies that reduce the efficacy of repeated vector administration.
“Indeed, higher doses lead to the expression of neutralizing antibodies that reduce the efficacy of repeated vector administration (58).”
From Subretinal therapy: technological solutions to surgical and immunological challenges (2022) · cites this paper as [58]
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Progress and problems with the use of viral vectors for gene therapy
Thomas, C. E., Ehrhardt, A., & Kay, M. A. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1066 · Cited by 2,501 · see citing works
Manno, C. S., Pierce, G. F., Arruda, V. R., Glader, B., Ragni, M., Rasko, J. J. E., Ozelo, M. C., Hoots, K., Blatt, P., Konkle, B., et al. (2006) · Nature Medicine · doi:10.1038/nm1358 · Cited by 2,163 · see citing works
Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802315 · Cited by 2,145 · see citing works
Effect of gene therapy on visual function in Leber’s congenital amaurosis
Bainbridge, J. W. B., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802268 · Cited by 1,924 · see citing works
Self-citationAdeno-associated Virus Serotypes: Vector Toolkit for Human Gene Therapy
Wu, Z., Asokan, A., & Samulski, R. J. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.05.009 · Cited by 921 · see citing works
Ocular immune privilege: therapeutic opportunities from an experiment of nature
Streilein, J. W. (2003) · Nature Reviews Immunology · doi:10.1038/nri1224 · Cited by 807 · see citing works
Cd8(+) T-Cell Responses to Adeno-Associated Virus Capsid in Humans
Mingozzi, F., Maus, M. V., Hui, D. J., Sabatino, D. E., Murphy, S. L., Rasko, J. E. J., Ragni, M. V., Manno, C. S., Sommer, J., Jiang, H., et al. (2007) · Nature Medicine · doi:10.1038/nm1549 · Cited by 748 · see citing works
CD69 is an immunoregulatory molecule induced following activation
Sancho, D., Gómez, M., & Sánchez‐Madrid, F. (2005) · Trends in Immunology · doi:10.1016/j.it.2004.12.006 · Cited by 472 · see citing works
The CD69 receptor: a multipurpose cell-surface trigger for hematopoietic cells
Testi, R., D’Ambrosio, D., Maria, R. D., & Santoni, A. (1994) · Immunology Today · doi:10.1016/0167-5699(94)90193-7 · Cited by 451 · see citing works
Jiang, H., Couto, L. B., Patarroyo-White, S., Liu, T., Nagy, D., Vargas, J. A., Zhou, S., Scallan, C. D., Sommer, J., Vijay, S., et al. (2006) · Blood · doi:10.1182/blood-2006-04-017913 · Cited by 330 · see citing works
Both integrated and differential regulation of components of the IL-2/IL-2 receptor system
Kim, H., Imbert, J., & Leonard, W. J. (2006) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2006.07.003 · Cited by 325 · see citing works
Immune Responses to AAV in Clinical Trials
Mingozzi, F., & A. High, K. (2011) · Current Gene Therapy · doi:10.2174/156652311796150354 · Cited by 324 · see citing works
Moss, R. B., Milla, C. E., Colombo, J. L., Accurso, F. J., Zeitlin, P. L., Clancy, J. P., Spencer, L. T., Pilewski, J. M., Waltz, D. A., Dorkin, H. L., et al. (2007) · Human Gene Therapy · doi:10.1089/hum.2007.022 · Cited by 276 · see citing works
Bennicelli, J., Wright, J. F., Komaromy, A., Jacobs, J. B., Hauck, B., Zelenaia, O., Mingozzi, F., Hui, D., Chung, D., Rex, T. S., et al. (2008) · Molecular Therapy · doi:10.1038/sj.mt.6300389 · Cited by 267 · see citing works
Immune responses to AAV in a phase I study for Canavan disease
McPhee, S. W. J., Janson, C. G., Li, C., Samulski, R. J., Camp, A. S., Francis, J., Shera, D., Lioutermann, L., Feely, M., Freese, A., et al. (2006) · The Journal of Gene Medicine · doi:10.1002/jgm.885 · Cited by 241 · see citing works
Immune Responses to AAV in Clinical Trials
Mingozzi, F., & High, K. A. (2007) · Current Gene Therapy · doi:10.2174/156652307782151425 · Cited by 238 · see citing works
Halbert, C. L., Miller, A. D., McNamara, S., Emerson, J., Gibson, R. L., Ramsey, B. W., & Aitken, M. L. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.440 · Cited by 227 · see citing works
Cao, O., Dobrzynski, E., Wang, L., Nayak, S., Mingle, B., Terhorst, C., & Herzog, R. W. (2007) · Blood · doi:10.1182/blood-2007-02-073304 · Cited by 220 · see citing works
Wang, Z., Kuhr, C. S., Allen, J. M., Blankinship, M. J., Gregorevic, P., Chamberlain, J. S., Tapscott, S. J., & Storb, R. F. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300161 · Cited by 218 · see citing works
Immune Responses to Adeno-Associated Virus Vectors
Zaiss, A. K., & Muruve, D. A. (2005) · Current Gene Therapy · doi:10.2174/1566523054065039 · Cited by 214 · see citing works
Heparin binding directs activation of T cells against adeno-associated virus serotype 2 capsid
Vandenberghe, L. H., Wang, L., Somanathan, S., Zhi, Y., Figueredo, J., Calcedo, R., Sanmiguel, J., Desai, R. A., Chen, C. S., Johnston, J., et al. (2006) · Nature Medicine · doi:10.1038/nm1445 · Cited by 208 · see citing works
Novel AAV serotypes for improved ocular gene transfer
Lebherz, C., Maguire, A. M., Tang, W., Bennett, J., & Wilson, J. M. (2008) · The Journal of Gene Medicine · doi:10.1002/jgm.1126 · Cited by 207 · see citing works
Pang, J., Chang, B., Hawes, N. L., Hurd, R. E., Davisson, M. T., Li, J., Noorwez, S. M., Malhotra, R., McDowell, J. H., Kaushal, S., et al. (2005) · PubMed · Cited by 206 · see citing works
Rivière, C., Danos, O., & Douar, A. M. (2006) · Gene Therapy · doi:10.1038/sj.gt.3302766 · Cited by 192 · see citing works
Recent developments in adeno‐associated virus vector technology
Büning, H., Perabò, L., Coutelle, O., Quadt‐Humme, S., & Hallek, M. J. (2008) · The Journal of Gene Medicine · doi:10.1002/jgm.1205 · Cited by 189 · see citing works
Interleukin 2 receptor gene expression in normal human T lymphocytes.
Leonard, W. J., Krönke, M., Peffer, N. J., Depper, J. M., & Greene, W. C. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.18.6281 · Cited by 164 · see citing works
Schmidt, M., Voutetakis, A., Afione, S. A., Zheng, C., Mandikian, D., & Chiorini, J. A. (2007) · Journal of Virology · doi:10.1128/jvi.02012-07 · Cited by 162 · see citing works
ROLE OF FAS-FAS LIGAND INTERACTIONS IN THE IMMUNOREJECTION OF ALLOGENEIC MOUSE CORNEAL TRANSPLANTS1
Yamagami, S., Kawashima, H., Tsuru, T., Yamagami, H., Kayagaki, N., Yagita∥, H., Okumura, K., & Gregerson, D. S. (1997) · Transplantation · doi:10.1097/00007890-199710270-00004 · Cited by 142 · see citing works
Perabò, L., Goldnau, D., White, K., Endell, J., Bouças, J., Humme, S., Work, L. M., Janicki, H., Hallek, M. J., Baker, A. H., et al. (2006) · Journal of Virology · doi:10.1128/jvi.00076-06 · Cited by 135 · see citing works
Immune response following intraocular delivery of recombinant viral vectors
Bennett, J. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302030 · Cited by 133 · see citing works
Kjellström, S., Bush, R. A., Zeng, Y., Takada, Y., & Sieving, P. A. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0203 · Cited by 126 · see citing works
Wang, Z., Allen, J. M., Riddell, S. R., Gregorevic, P., Storb, R. F., Tapscott, S. J., Chamberlain, J. S., & Kuhr, C. S. (2007) · Human Gene Therapy · doi:10.1089/hum.2006.093 · Cited by 124 · see citing works
AAV-mediated gene therapy for retinal disorders: from mouse to man
Buch, P. K., Bainbridge, J. W., & Ali, R. R. (2008) · Gene Therapy · doi:10.1038/gt.2008.66 · Cited by 122 · see citing works
Self-citationYuasa, K., Yoshimura, M., Urasawa, N., Ohshima, S., Howell, J. M., Nakamura, A., Hijikata, T., Miyagoe‐Suzuki, Y., & Takeda, S. (2007) · Gene Therapy · doi:10.1038/sj.gt.3302984 · Cited by 107 · see citing works
Wang, Z., Allen, J. M., Riddell, S. R., Gregorevic, P., Storb, R. F., Tapscott, S. J., Chamberlain, J. S., & Kuhr, C. S. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.ft-273 · Cited by 107 · see citing works
Human retinal pigment epithelial cell-induced apoptosis in activated T cells.
Jørgensen, A. K., Wiencke, A. K., la Cour, M., Kæstel, C. G., Madsen, H. O., Hamann, S., Lui, G. M., Scherfig, E., Prause, J. U., Svejgaard, A., et al. (1998) · PubMed · Cited by 105 · see citing works
Blankinship, M. J., Gregorevic, P., & Chamberlain, J. S. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.11.001 · Cited by 91 · see citing works
Sonoda, K., Sakamoto, T., Qiao, H., Hisatomi, T., Oshima, T., Tsutsumi‐Miyahara, C., Exley, M., Balk, S. P., Taniguchi, M., & Ishibashi, T. (2005) · Immunology · doi:10.1111/j.1365-2567.2005.02239.x · Cited by 87 · see citing works
Schlichtenbrede, F. C., da Cruz, L., Stephens, C., Smith, A. J., Georgiadis, A., Thrasher, A. J., Bainbridge, J. W., Seeliger, M. W., & Ali, R. R. (2003) · The Journal of Gene Medicine · doi:10.1002/jgm.401 · Cited by 79 · see citing works
Self-citationDetermination of Specific CD4 and CD8 T Cell Epitopes after AAV2- and AAV8-hF.IX Gene Therapy
Chen, J., Wu, Q., Yang, P., Hsu, H., & Mountz, J. D. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.10.006 · Cited by 76 · see citing works
Petry, H., Brooks, A. R., Orme, A. E., Wang, P., Liu, P., Xie, J., Kretschmer, P. J., Qian, H. S., Hermiston, T. W., & Harkins, R. N. (2007) · Gene Therapy · doi:10.1038/sj.gt.3303037 · Cited by 60 · see citing works
Visualization of antigen-specific T cell activation and cytokine expression in vivo
Rogers, W. O., Weaver, C. T., Kraus, L. A., Li, J., Li, L., & Bucy, R. P. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.2.649 · Cited by 50 · see citing works
Rapid development of genotypic resistance to lamivudine when combined with zidovudine in pregnancy
Clarke, J. R., Braganza, R., Mirza, A., Stainsby, C. M., Ait‐Khaled, M., Wright, A., Lyall, H., Parker, D., McClure, M. O., Weber, J. N., et al. (1999) · Journal of Medical Virology · doi:10.1002/(sici)1096-9071(199911)59:3 · Cited by 44 · see citing works
Petry, H., Orme, A. E., Liu, P., Bauzone, M., Gibson, H. M., Qian, H. S., Rubanyi, G. M., & Harkins, R. N. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.08.1088 · Cited by 43 · see citing works
McTiernan, C. F., Mathier, M. A., Zhu, X., Xiao, X., Klein, E., Swan, C. H., Mehdi, H., Gibson, G., Trichel, A. M., Glorioso, J. C., et al. (2007) · Gene Therapy · doi:10.1038/sj.gt.3303020 · Cited by 40 · see citing works
AAV-Mediated Gene Transfer for Treatment of Hemophilia
Wang, L., & Herzog, R. W. (2005) · Current Gene Therapy · doi:10.2174/1566523054065048 · Cited by 36 · see citing works
Camelo, S., Kezic, J. M., & McMenamin, P. G. (2005) · Clinical and Experimental Ophthalmology · doi:10.1111/j.1442-9071.2005.01044.x · Cited by 28 · see citing works
Sequence and structure of the mouse gene for RPE65.
Boulanger, A., Liu, S., Si, Y., & Redmond, T. M. (2001) · PubMed · Cited by 11 · see citing works
High-Titer Stocks of Adeno-Associated Virus from Replicating Amplicons and Herpes Vectors
Mistry, A., de Alwis, M., Feudner, E., Ali, R. R., & Thrasher, A. J. (2003) · Humana Press eBooks · doi:10.1385/1-59259-141-8:445 · Cited by 8 · see citing works
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Bucher, K., Rodríguez-Bocanegra, E., Dauletbekov, D., & Fischer, M. D. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100915 · Cited by 242 · see citing works
Clinical Characteristics and Current Therapies for Inherited Retinal DegenerationsPreprint
Sahel, J., Marazova, K., & Audo, I. S. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a017111 · Cited by 234 · see citing works
Wang, L., Calcedo, R., Bell, P., Lin, J., Grant, R. L., Siegel, D. L., & Wilson, J. M. (2011) · Human Gene Therapy · doi:10.1089/hum.2011.031 · Cited by 212 · see citing works
Early and late stage gene therapy interventions for inherited retinal degenerations
Botto, C., Rucli, M., Tekinsoy, M. D., Pulman, J., Sahel, J.-A., & Dalkara, D. (2022) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100975 · Cited by 190 · see citing works
Subretinal injection: a review on the novel route of therapeutic delivery for vitreoretinal diseases
Peng, Y., Tang, L., & Zhou, Y. (2017) · Ophthalmic Research · doi:10.1159/000479157 · Cited by 175 · see citing works
Amado, D., Mingozzi, F., Hui, D., Bennicelli, J. L., Wei, Z., Chen, Y., Bote, E., Grant, R. L., Golden, J. A., Narfstrom, K., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000659 · Cited by 140 · see citing works
Novel adeno-associated viral vectors for retinal gene therapy.
Vandenberghe, L. H., & Auricchio, A. (2012) · Gene Therapy · doi:10.1038/gt.2011.151 · Cited by 131 · see citing works
Boye, S. E., Alexander, J. J., Boye, S. L., Witherspoon, C. D., Sandefer, K. J., Conlon, T. J., Erger, K., Sun, J., Ryals, R., Chiodo, V. A., et al. (2012) · Human Gene Therapy · doi:10.1089/hum.2012.125 · Cited by 117 · see citing works
Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons
Tang, J. B., Wu, Y. F., Cao, Y., Chuan-hao, C., Zhou, Y. L., Avanessian, B. K., Shimada, M., Wang, X. T., & Liu, P. Y. (2016) · Scientific Reports · doi:10.1038/srep20643 · Cited by 100 · see citing works
Evading the immune response upon in vivo gene therapy with viral vectors.
Sack, B. K., & Herzog, R. W. (2009) · PubMed · Cited by 89 · see citing works
Adeno-associated Virus as a Mammalian DNA Vector
Salganik, M., Hirsch, M. L., & Samulski, R. J. (2015) · Microbiology Spectrum · doi:10.1128/microbiolspec.mdna3-0052-2014 · Cited by 88 · see citing works
Koirala, A., Makkia, R. S., Conley, S. M., Cooper, M. J., & Naash, M. I. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt013 · Cited by 75 · see citing works
Gene therapy in the second eye of RPE65-deficient dogs improves retinal function
Annear, M. J., Bartoe, J. T., Barker, S. E., Smith, A. J., Curran, P. G., Bainbridge, J. W., Ali, R. R., & Petersen‐Jones, S. M. (2010) · Gene Therapy · doi:10.1038/gt.2010.111 · Cited by 74 · see citing works
Self-citationGene supplementation therapy for recessive forms of inherited retinal dystrophies
Smith, A. J., Bainbridge, J. W., & Ali, R. R. (2011) · Gene Therapy · doi:10.1038/gt.2011.161 · Cited by 58 · see citing works
Self-citationHost immune responses after suprachoroidal delivery of AAV8 in nonhuman primate eyes
Chung, S. H., Mollhoff, I. N., Mishra, A., Sin, T.-N., Ngo, T., Ciulla, T., Sieving, P., Thomasy, S. M., & Yiu, G. (2021) · Human Gene Therapy · doi:10.1089/hum.2020.281 · Cited by 57 · see citing works
Subretinal therapy: technological solutions to surgical and immunological challenges
Ladha, R., Caspers, L. E., Willermain, F., & de Smet, M. D. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.846782 · Cited by 54 · see citing works
Charbel Issa, P., De Silva, S. R., Lipinski, D. M., Singh, M. S., Mouravlev, A., You, Q., Barnard, A. R., Hankins, M. W., During, M. J., & MacLaren, R. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060361 · Cited by 53 · see citing works
Self-citationKoirala, A., Conley, S. M., Makkia, R., Liu, Z., Cooper, M. J., Sparrow, J. R., & Naash, M. I. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.08.299 · Cited by 47 · see citing works
Gene Therapy Restores Mfrp and Corrects Axial Eye Length
Velez, G., Tsang, S. H., Tsai, Y.-T., Hsu, C., Gore, A. M., Abdelhakim, A. H., Mahajan, M., Silverman, R. H., Sparrow, J. R., Bassuk, A. G., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-16275-8 · Cited by 45 · see citing works
Gene therapy for Leber congenital amaurosis: advances and future directions
Hufnagel, R. B., Ahmed, Z. M., Corrêa, Z. M., & Sisk, R. A. (2012) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-012-2028-2 · Cited by 44 · see citing works
Han, Z., Koirala, A., Makkia, R. S., Cooper, M. J., & Naash, M. I. (2012) · Nanomedicine · doi:10.2217/nnm.11.158 · Cited by 41 · see citing works
Tian, L., Yang, P., Lei, B., Shao, J., Wang, C., Xiang, Q., Lin, W., Peng, Z., & Kijlstra, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019542 · Cited by 40 · see citing works
West, E. L., Pearson, R. A., Durán, Y., Gonzalez-Cordero, A., MacLaren, R. E., Smith, A. J., Sowden, J. C., & Ali, R. R. (2012) · Cell Transplantation · doi:10.3727/096368911x623871 · Cited by 39 · see citing works
Self-citationShao, J., Tian, L., Lei, B., Lin, W., Yang, Y., Kijlstra, A., & Yang, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037773 · Cited by 36 · see citing works
Adeno-Associated Virus Mediated Gene Therapy for Retinal Degenerative Diseases
Stieger, K., Cronin, T., Bennett, J., & Rolling, F. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-370-7_8 · Cited by 35 · see citing works
Mary, B., Maurya, S., Kumar, M., Bammidi, S., Kumar, V. S., & Jayandharan, G. R. (2019) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.9b00959 · Cited by 33 · see citing works
Chronic Dicer1 deficiency promotes atrophic and neovascular outer retinal pathologies in mice
Wright, C. B., Uehara, H., Kim, Y., Yasuma, T. R., Yasuma, R., Hirahara, S., Makin, R. D., Apicella, I., Pereira, F., Nagasaka, Y., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1909761117 · Cited by 34 · see citing works
Teo, K. Y. C., Lee, S. Y., Barathi, A. V., Tun, S. B. B., Tan, L., & Constable, I. J. (2018) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.18-24333 · Cited by 33 · see citing works
Black, A. D., Vasireddy, V., Chung, D., Maguire, A., Gaddameedi, R., Tolmachova, T., Seabra, M., & Bennett, J. (2014) · Journal of Gene Medicine · doi:10.1002/jgm.2768 · Cited by 32 · see citing works
Wiley, L. A., Burnight, E. R., Drack, A. V., Banach, B. B., Ochoa, D., Cranston, C. M., Madumba, R. A., East, J. S., Mullins, R. F., Stone, E. M., et al. (2016) · Human Gene Therapy · doi:10.1089/hum.2016.049 · Cited by 32 · see citing works
Hutt, J. A., Assaf, B. T., Bolon, B. N., Cavagnaro, J. A., Galbreath, E. J., Grubor, B., Kattenhorn, L. M., Romeike, A., & Whiteley, L. O. (2021) · Toxicologic Pathology · doi:10.1177/01926233211041962 · Cited by 27 · see citing works
McCrudden, C. M., McBride, J. W., McCaffrey, J., Ali, A., Dunne, N., Kett, V. L., Coulter, J. A., Robson, T., & McCarthy, H. O. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2016.12.010 · Cited by 24 · see citing works
Marginal integrity of self- and total-etching adhesives in two different application protocols.
Ernsta, C.-P., Kötter, T., Victor, A., Canbek, K., Brandenbusch, M., & Willershausen, B. (2004) · PubMed · Cited by 24 · see citing works
Koponen, S., Kokki, E., Tamminen, T., & Ylä-Herttuala, S. (2023) · Frontiers in Drug Delivery · doi:10.3389/fddev.2023.1148795 · Cited by 21 · see citing works
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Elsayed, M. E. A. A., Taylor, L. J., Josan, A. S., Fischer, M. D., & MacLaren, R. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241814354 · Cited by 14 · see citing works
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Chu, C. J., Barker, S. E., Dick, A. D., & Ali, R. R. (2012) · Ocular Immunology and Inflammation · doi:10.3109/09273948.2012.726392 · Cited by 14 · see citing works
Self-citationBalaggan, K. S., Durán, Y., Georgiadis, A., Thaung, C., Barker, S. E., Buch, P. K., MacNeil, A., Robbie, S. J., Bainbridge, J. W., Smith, A. J., et al. (2011) · Gene Therapy · doi:10.1038/gt.2011.194 · Cited by 14 · see citing works
Self-citationImmune mechanisms of intraocular inflammation
Schewitz‐Bowers, L. P., Lee, R., & Dick, A. D. (2010) · Expert Review of Ophthalmology · doi:10.1586/eop.09.68 · Cited by 13 · see citing works
Petersen‐Jones, S. M., Annear, M. J., Bartoe, J. T., Mowat, F. M., Barker, S. E., Smith, A. J., Bainbridge, J. W., & Ali, R. R. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0631-0_24 · Cited by 13 · see citing works
Self-citationShyam, R., Ogando, D. G., Kim, E. T., Murugan, S., Choi, M., & Bonanno, J. A. (2021) · Ophthalmology Science · doi:10.1016/j.xops.2021.100084 · Cited by 11 · see citing works
Grigsby, D., Klingeborn, M., Kelly, U., Chew, L. A., Asokan, A., Devlin, G. W., Smith, S. M. R., Keyes, L. R., Timmers, A. M., Scaria, A., et al. (2023) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.64.10.25 · Cited by 8 · see citing works
Understanding Gene Therapy in Acute Respiratory Distress Syndrome
Zhang, X., Zhang, W., Qiu, Y., Ju, M., Tu, G.-W., & Luo, Z. (2019) · Current Gene Therapy · doi:10.2174/1566523219666190702154817 · Cited by 9 · see citing works
Benefits of gene therapy for both eyes
MacLaren, R. E. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30783-8 · Cited by 6 · see citing works
Self-citationRNA gene editing in the eye and beyond: The neglected tool of the gene editing armatorium?
Han, R. C., & MacLaren, R. E. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.009 · Cited by 5 · see citing works
Self-citationTropism of the Novel AAVBR1 Capsid Following Subretinal Delivery
Carroll, L. S., Uehara, H., Zhang, X., & Ambati, B. K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147738 · Cited by 4 · see citing works
Adeno-associated virus neutralising antibodies in type 1 diabetes mellitus
Andrzejewski, S., Murali, A., Ramlogan‐Steel, C. A., Edwards, K. P., Efron, N., Steel, J. C., & Layton, C. J. (2019) · Gene Therapy · doi:10.1038/s41434-019-0076-5 · Cited by 4 · see citing works
Adeno-associated Virus as a Mammalian DNA Vector
Salganik, M., Hirsch, M. L., & Samulski, R. J. (2015) · ASM Press eBooks · doi:10.1128/9781555819217.ch37 · Cited by 4 · see citing works
Translational benefits of gene therapy to date
McMenamin, M. M. (2011) · Clinical Oncology and Cancer Research · doi:10.1007/s11805-011-0551-2 · Cited by 3 · see citing works
Advances in technical methods and applications of subretinal injections in experimental animals
Song, C., Ji, Y., Wang, Y., & Yang, W. (2025) · Frontiers in Veterinary Science · doi:10.3389/fvets.2025.1574519 · Cited by 2 · see citing works
AAV-mediated transduction of songbird retina
Seth, P. K., Heyers, D., Satish, B., Mendoza, E., Haase, K., Borowsky, L., Musielak, I., Koch, K., Feederle, R., Scharff, C., et al. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1549585 · Cited by 1 · see citing works
Stimulation of AAV Gene Editing via DSB Repair
Mitchell, A. M., Moser, R. J., Samulski, R. J., & Hirsch, M. L. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-3509-3_8 · Cited by 1 · see citing works
Liu, J., Copland, D. A., Clare, A. J., Gorski, M., Richards, B. T., Scott, L. M., Theodoropoulou, S., Greferath, U., Cox, K. H. M., Bell, O. H., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.27.559733 · Cited by 1 · see citing works
Induction of Immunological Tolerance to Transgene Products
Sack, B. K., Markusic, D. M., & Herzog, R. W. (2012) · Springer eBooks · doi:10.1007/978-1-4614-5480-9_15
Mitchell, A. M. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/f5kg-n202
Advanced Combinatorial Radioimmunogenetic Therapy for Cancer
Hanjabam, J. S. (2017) · Insights in Biomedicine · doi:10.21767/2572-5610.10033
Assaf, B. T., Harper, C. G., & Phillips, J. A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-821047-5.00034-8
Modulation of the intraocular immune environment by viral gene transfer in mouse models of uveitis
Chu, C. J. (2015) · UCL Discovery (University College London)
Development of safe and efficient aav vectors for retinal gene therapy
Khabou, H. (2018) · theses.fr (ABES) · doi:10.70675/aa896663z9772z4d87z9bd1z247af1f0e3f1
- Authors
- Barker, S. E., Broderick, C. A., Robbie, S. J., Duran, Y., Natkunarajah, M., Buch, P., Balaggan, K. S., MacLaren, R. E., Bainbridge, J. W. B., Smith, A. J., & Ali, R. R.
- Affiliations
- University College London (GB)
- Corresponding author
- Barker, Susie E.
- ORCID
- Venue
- The Journal of Gene Medicine
- Publisher
- Wiley
- Published
- 2009-04
- Volume
- 11
- Issue
- 6
- Pages
- 486-497
- ISSN
- 1099-498X (ISSN-L)
- 1521-2254
- PMC
- PMC2841821
- OpenAlex
- W2017708248
- Cited by
- 59
- References
- 49
- Citations by year
- 2025: 2 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 7
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Gene Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
- National Institute for Health and Care Research (NF-SI-0508-10130)
- Moorfields Eye Hospital NHS Foundation Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- AAV2, subretinal gene therapy, neutralizing antibodies, RPE65, retinal degeneration, immunocompetent mice, retinal toxicity
- MeSH terms
- Retinoid Isomerohydrolase, Dependovirus, Animals, Carrier Proteins, Cell Line, Electroretinography, Eye, Eye Proteins, Female, Genetic Vectors, Immunocompetence, Injections, Mice, Inbred C57BL, Mice, Transgenic, Neutralization Tests, Genetic Therapy, cis-trans-Isomerases, Mice
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