{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:08:24Z","timestamp":1790813304464,"version":"4.1.0"},"reference-count":327,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001116","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","award":["TA-GT-0715-0665-LUMC"],"award-info":[{"award-number":["TA-GT-0715-0665-LUMC"]}],"id":[{"id":"10.13039\/100001116","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Netherlands Organization for Health Research and Development","award":["43200004"],"award-info":[{"award-number":["43200004"]}]},{"name":"Million Dollar Bike Ride Grant Program","award":["MDBR-19-131-CRB1"],"award-info":[{"award-number":["MDBR-19-131-CRB1"]}]},{"name":"Million Dollar Bike Ride Grant Program","award":["MDBR-20-112-CRB1"],"award-info":[{"award-number":["MDBR-20-112-CRB1"]}]},{"name":"Dutch blindness funds","award":["Uitzicht 2013-13"],"award-info":[{"award-number":["Uitzicht 2013-13"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inherited retinal dystrophies and optic neuropathies cause chronic disabling loss of visual function. The development of recombinant adeno-associated viral vectors (rAAV) gene therapies in all disease fields have been promising, but the translation to the clinic has been slow. The safety and efficacy profiles of rAAV are linked to the dose of applied vectors. DNA changes in the rAAV gene cassette affect potency, the expression pattern (cell-specificity), and the production yield. Here, we present a library of rAAV vectors and elements that provide a workflow to design novel vectors. We first performed a meta-analysis on recombinant rAAV elements in clinical trials (2007\u20132020) for ocular gene therapies. We analyzed 33 unique rAAV gene cassettes used in 57 ocular clinical trials. The rAAV gene therapy vectors used six unique capsid variants, 16 different promoters, and six unique polyadenylation sequences. Further, we compiled a list of promoters, enhancers, and other sequences used in current rAAV gene cassettes in preclinical studies. Then, we give an update on pro-viral plasmid backbones used to produce the gene therapy vectors, inverted terminal repeats, production yield, and rAAV safety considerations. Finally, we assess rAAV transgene and bioactivity assays applied to cells or organoids in vitro, explants ex vivo, and clinical studies.<\/jats:p>","DOI":"10.3390\/ijms21124197","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T03:17:32Z","timestamp":1592191052000},"page":"4197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9594-1123","authenticated-orcid":false,"given":"Thilo","family":"Buck","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center (LUMC), 2333 ZC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0099-460X","authenticated-orcid":false,"given":"Jan","family":"Wijnholds","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center (LUMC), 2333 ZC Leiden, The Netherlands"},{"name":"Netherlands Institute of Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), 1105 BA Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rodrigues, G.A., Shalaev, E., Karami, T.K., Cunningham, J., Slater, N.K.H., and Rivers, H.M. (2019). Pharmaceutical Development of AAV-Based Gene Therapy Products for the Eye. Pharm. Res., 36.","DOI":"10.1007\/s11095-018-2554-7"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/mt.2012.280","article-title":"A comprehensive review of retinal gene therapy","volume":"21","author":"Boye","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/gt.2008.170","article-title":"Tailoring the AAV vector capsid for gene therapy","volume":"16","author":"Vandenberghe","year":"2009","journal-title":"Gene Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-associated virus vector as a platform for gene therapy delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1089\/hum.2014.147","article-title":"Perspectives on Best Practices for Gene Therapy Programs","volume":"26","author":"Cheever","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.preteyeres.2012.09.001","article-title":"Clinical applications of retinal gene therapy","volume":"32","author":"Lipinski","year":"2013","journal-title":"Prog. Retin. Eye Res. Clin. Appl. Retin. Gene Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.trsl.2012.12.007","article-title":"Gene therapy for retinal disease","volume":"161","author":"McClements","year":"2013","journal-title":"Transl. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.tig.2009.02.003","article-title":"Prospects for retinal gene replacement therapy","volume":"25","author":"Smith","year":"2009","journal-title":"Trends Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/sj.gt.3302812","article-title":"Gene therapy progress and prospects: The eye","volume":"13","author":"Bainbridge","year":"2006","journal-title":"Gene Ther."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Duncan, J.L., Pierce, E.A., Laster, A.M., Daiger, S.P., Birch, D.G., Ash, J.D., Iannaccone, A., Flannery, J.G., Sahel, J.A., and Zack, D.J. (2018). Inherited retinal degenerations: Current landscape and knowledge gaps. Transl. Vis. Sci. Technol., 7.","DOI":"10.1167\/tvst.7.4.6"},{"key":"ref_11","unstructured":"Fahim, A.T., Daiger, S.P., and Weleber, R.G. (2017, January 19). Nonsyndromic Retinitis Pigmentosa Overview, Available online: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20301590."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrg2141","article-title":"Engineering targeted viral vectors for gene therapy","volume":"8","author":"Waehler","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2019.01.038","article-title":"Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae","volume":"177","author":"Ma","year":"2019","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ziccardi, L., Cordeddu, V., Gaddini, L., Matteucci, A., Parravano, M., Malchiodi-Albedi, F., and Varano, M. (2019). Gene therapy in retinal dystrophies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225722"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zallocchi, M., Binley, K., Lad, Y., Ellis, S., Widdowson, P., Iqball, S., Scripps, V., Kelleher, M., Loader, J., and Miskin, J. (2014). EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: Development of UshStat. PLoS ONE.","DOI":"10.1371\/journal.pone.0094272"},{"key":"ref_16","unstructured":"Truran, R., Buckley, R., Radcliffe, P., Miskin, J., and Mitrophanous, K. (2015). Virus Purification. (9169491B2), U.S. Patent."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1099\/0022-1317-75-2-425","article-title":"Characterization of infectious molecular clones of equine infectious anaemia virus","volume":"75","author":"Payne","year":"1994","journal-title":"J. Gen. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1038\/gt.2008.78","article-title":"Correction of the disease phenotype in the mouse model of Stargardt disease by lentiviral gene therapy","volume":"15","author":"Kong","year":"2008","journal-title":"Gene Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"V\u00e1zquez-Dom\u00ednguez, I., Garanto, A., and Collin, R.W.J. (2019). Molecular Therapies for Inherited Retinal Diseases-Current Standing, Opportunities and Challenges. Genes, 10.","DOI":"10.3390\/genes10090654"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Aschauer, D.F., Kreuz, S., and Rumpel, S. (2013). Analysis of Transduction Efficiency, Tropism and Axonal Transport of AAV Serotypes 1, 2, 5, 6, 8 and 9 in the Mouse Brain. PLoS ONE.","DOI":"10.1371\/journal.pone.0076310"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Duong, T.T., Lim, J., Vasireddy, V., Papp, T., Nguyen, H., Leo, L., Pan, J., Zhou, S., Chen, I., and Bennett, J. (2019). Comparative AAV-EGFP transgene expression using vector serotypes 1\u20139, 7M8, and 8b in human pluripotent stem cells, RPEs, and human and rat cortical neurons. Stem Cells Int., 2019.","DOI":"10.1155\/2019\/7281912"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.ymthe.2019.08.013","article-title":"Long-term Structural Outcomes of Late-stage RPE65 Gene Therapy","volume":"28","author":"Gardiner","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1128\/JVI.77.6.3495-3504.2003","article-title":"Genetic Fate of Recombinant Adeno-Associated Virus Vector Genomes in Muscle","volume":"77","author":"Schnepp","year":"2003","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14009","DOI":"10.1038\/mtm.2014.9","article-title":"Specific tools for targeting and expression in M\u00fcller glial cells","volume":"1","author":"Pellissier","year":"2014","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1038\/mt.2009.184","article-title":"Molecular evolution of adeno-associated virus for enhanced glial gene delivery","volume":"17","author":"Koerber","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pleticha, J., Heilmann, L.F., Evans, C.H., Asokan, A., Samulski, R.J., and Beutler, A.S. (2014). Preclinical toxicity evaluation of AAV for pain: Evidence from human AAV studies and from the pharmacology of analgesic drugs. Mol. Pain, 10.","DOI":"10.1186\/1744-8069-10-54"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Calcedo, R., and Wilson, J.M. (2013). Humoral Immune Response to AAV. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00341"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1093\/hmg\/ddp133","article-title":"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","volume":"18","author":"Tan","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1177\/014107680609900417","article-title":"Genetics of inherited retinal disease","volume":"99","author":"Francis","year":"2006","journal-title":"J. R. Soc. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1172\/JCI42258","article-title":"Lighting a candle in the dark: Advances in genetics and gene therapy of recessive retinal dystrophies","volume":"120","author":"Black","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_31","unstructured":"Daiger, S., Sullivan, L., and Bowne, S. (2020, June 11). RetNet. Available online: https:\/\/sph.uth.edu\/retnet\/sum-dis.htm#A-genes."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1001\/archopht.1982.01030030287011","article-title":"Bardet-Biedl Syndrome and Related Disorders","volume":"100","author":"Schachat","year":"1982","journal-title":"Arch. Ophthalmol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3109\/09286586.2012.737890","article-title":"Relative frequencies of inherited retinal dystrophies and optic neuropathies in Southern France: Assessment of 21-year data management","volume":"20","author":"Bocquet","year":"2013","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_34","unstructured":"Lei, B., Zhang, K., Yue, Y., Ghosh, A., and Duan, D. (2010). Retinal Degenerative Diseases, Spring."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1056\/NEJMoa0802268","article-title":"Effect of gene therapy on visual function in Leber\u2019s congenital amaurosis","volume":"358","author":"Bainbridge","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/gt.2016.66","article-title":"Development of an optimized AAV2\/5 gene therapy vector for Leber congenital amaurosis owing to defects in RPE65","volume":"23","author":"Georgiadis","year":"2016","journal-title":"Gene Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1073\/pnas.79.6.2077","article-title":"Cloning of adeno-associated virus into pBR322: Rescue of intact virus from the recombinant plasmid in human cells","volume":"79","author":"Samulski","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0378-1119(83)90217-2","article-title":"Cloning of infectious adeno-associated virus genomes in bacterial plasmids","volume":"23","author":"Laughlin","year":"1983","journal-title":"Gene"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rakoczy, E.P. (2015). Gene Therapy for Leber\u2019s Congenital Amaurosis Due to RPE65 Mutations. Gene- and Cell-Based Treatment Strategies for the Eye, Springer.","DOI":"10.1007\/978-3-662-45188-5"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.ebiom.2016.07.002","article-title":"Long-term outcomes of gene therapy for the treatment of Leber\u2019s hereditary optic neuropathy","volume":"10","author":"Yang","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ymthe.2018.11.003","article-title":"Preclinical Evaluation of ADVM-022, a Novel Gene Therapy Approach to Treating Wet Age-Related Macular Degeneration","volume":"27","author":"Grishanin","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1089\/humc.2015.164","article-title":"Safety and Biodistribution Evaluation in Cynomolgus Macaques of rAAV2tYF-PR1.7-hCNGB3, a Recombinant AAV Vector for Treatment of Achromatopsia","volume":"27","author":"Ye","year":"2016","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1089\/humc.2018.168","article-title":"Toxicology and pharmacology of an AAV vector expressing codon-optimized RPGR in RPGR-deficient Rd9 mice","volume":"29","author":"Song","year":"2018","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rumachik, N.G., Malaker, S.A., Poweleit, N., Maynard, L.H., Adams, C.M., Leib, R.D., Cirolia, G., Thomas, D., Stamnes, S., and Holt, K. (2019). Methods Matter\u2014Standard Production Platforms For Recombinant AAV Can Produce Chemically And Functionally Distinct Vectors. bioRxiv, 640169.","DOI":"10.1101\/640169"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1146\/annurev.biochem.72.121801.161520","article-title":"The RNA Polymerase II Core Promoter","volume":"72","author":"Smale","year":"2003","journal-title":"Annu. Rev. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chanda, D., Hensel, J.A., Higgs, J.T., Grover, R., Kaza, N., and Ponnazhagan, S. (2017). Effects of cellular methylation on transgene expression and site-specific integration of adeno-associated virus. Genes, 8.","DOI":"10.3390\/genes8090232"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1172\/JCI68205","article-title":"CpG-depleted adeno-associated virus vectors evade immune detection","volume":"123","author":"Faust","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Even, D.Y., Kedmi, A., Basch-Barzilay, S., Ideses, D., Tikotzki, R., Shir-Shapira, H., Shefi, O., and Juven-Gershon, T. (2016). Engineered promoters for potent transient overexpression. PLoS ONE.","DOI":"10.1371\/journal.pone.0148918"},{"key":"ref_49","unstructured":"Hartl, D., Sch\u00fcbeler, D., Roska, B., Krebs, A., and J\u00fcttner, J. (2017). Synp161, a Promoter for the Specific Expression of Genes in Rod Photoreceptors. (WO2017093935A1)."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/s41593-019-0431-2","article-title":"Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates and humans","volume":"22","author":"Szabo","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1089\/104303401300042500","article-title":"CMV-beta-actin promoter directs higher expression from an adeno-associated viral vector in the liver than the cytomegalovirus or elongation factor 1 alpha promoter and results in therapeutic levels of human factor X in mice","volume":"12","author":"Xu","year":"2001","journal-title":"Hum. Gene Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1038\/sj.gt.3302028","article-title":"Simian lentiviral vector-mediated retinal gene transfer of pigment epithelium-derived factor protects retinal degeneration and electrical defect in Royal College of Surgeons rats","volume":"10","author":"Miyazaki","year":"2003","journal-title":"Gene Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/jgm.1421","article-title":"Cytokine stimulation and the choice of promoter are critical factors for the efficient transduction of mouse T cells with HIV-1 vectors","volume":"12","author":"Gilham","year":"2010","journal-title":"J. Gene Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1089\/hum.2010.245","article-title":"Optimizing promoters for recombinant adeno-associated virus-mediated gene expression in the peripheral and central nervous system using self-complementary vectors","volume":"22","author":"Gray","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1182\/blood-2004-09-3496","article-title":"Phenotypic correction and long-term expression of factor VIII in hemophilic mice by immunotolerization and nonviral gene transfer using the Sleeping Beauty transposon system","volume":"105","author":"Ohlfest","year":"2005","journal-title":"Blood"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0006-8993(95)01488-8","article-title":"Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector","volume":"713","author":"McCown","year":"1996","journal-title":"Brain Res."},{"key":"ref_57","first-page":"49","article-title":"Viral expression cassette elements to enhance transgene target specificity and expression in gene therapy","volume":"19","author":"Powell","year":"2015","journal-title":"Discov. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1006\/exnr.1997.6736","article-title":"Neuron-specific transduction in the rat septohippocampal or nigrostriatal pathway by recombinant adeno-associated virus vectors","volume":"150","author":"Klein","year":"1998","journal-title":"Exp. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Farjo, R., Skaggs, J., Quiambao, A.B., Cooper, M.J., and Naash, M.I. (2006). Efficient non-viral ocular gene transfer with compacted DNA nanoparticles. PLoS ONE.","DOI":"10.1371\/journal.pone.0000038"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1093\/hmg\/ddv062","article-title":"Gene therapy into photoreceptors and M\u00fcller glial cells restores retinal structure and function in CRB1 retinitis pigmentosa mouse models","volume":"24","author":"Pellissier","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1016\/j.ophtha.2018.04.001","article-title":"Clustered Regularly Interspaced Short Palindromic Repeats-Based Genome Surgery for the Treatment of Autosomal Dominant Retinitis Pigmentosa","volume":"125","author":"Tsai","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.stemcr.2019.03.002","article-title":"Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and M\u00fcller Glia Are Targets of AAV5","volume":"12","author":"Quinn","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0378-1119(91)90434-D","article-title":"Efficient selection for high-expression transfectants with a novel eukaryotic vector","volume":"108","author":"Niwa","year":"1991","journal-title":"Gene"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1038\/sj.gt.3302133","article-title":"Rapid and highly efficient transduction by double-stranded adeno-associated virus vectors in vitro and in vivo","volume":"10","author":"Wang","year":"2003","journal-title":"Gene Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1006\/excr.1998.4175","article-title":"SHORT NOTE A Composite CMV-IE Enhancer\/\u03b2-Actin Promoter Is Ubiquitously Expressed in Mouse Cutaneous Epithelium","volume":"244","author":"Sawicki","year":"1998","journal-title":"Exp. Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7739","DOI":"10.1167\/iovs.14-15388","article-title":"LHON gene therapy vector prevents visual loss and optic neuropathy induced by G11778A mutant mitochondrial DNA: Biodistribution and toxicology profile","volume":"55","author":"Koilkonda","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1073\/pnas.91.6.2076","article-title":"Convection-enhanced delivery of macromolecules in the brain","volume":"91","author":"Bobo","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Rastegar, M., Hotta, A., Pasceri, P., Makarem, M., Cheung, A.Y.L., Elliott, S., Park, K.J., Adachi, M., Jones, F.S., and Clarke, I.D. (2009). MECP2 isoform-specific vectors with regulated expression for Rett syndrome gene therapy. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006810"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/gt.2008.134","article-title":"A small regulatory element from chromosome 19 enhances liver-specific gene expression","volume":"16","author":"Li","year":"2009","journal-title":"Gene Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1038\/sj.gt.3301561","article-title":"Increased persistence of lung gene expression using plasmids containing the ubiquitin C or elongation factor 1alpha promoter","volume":"8","author":"Gill","year":"2001","journal-title":"Gene Ther."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Lu, Y., Krishnan, A., Brommer, B., Tian, X., Meer, M., Vera, D.L., Wang, C., Zeng, Q., Yu, D., and Bonkowski, M.S. (2019). Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming. bioRxiv, 710210.","DOI":"10.1101\/710210"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"283","DOI":"10.2144\/000112243","article-title":"Translational efficiency of EMCV IRES in bicistronic vectors is dependent upon IRES sequence and gene location","volume":"41","author":"Bochkov","year":"2006","journal-title":"Biotechniques"},{"key":"ref_73","first-page":"299","article-title":"Effect of intercistronic length on internal ribosome entry site (IRES) efficiency in bicistronic mRNA","volume":"8","author":"Attal","year":"1999","journal-title":"Gene Expr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ncrna.2018.11.005","article-title":"Modifying inter-cistronic sequence significantly enhances IRES dependent second gene expression in bicistronic vector: Construction of optimised cassette for gene therapy of familial hypercholesterolemia","volume":"4","author":"Abduljaleel","year":"2019","journal-title":"Non-Coding RNA Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/gt.2013.71","article-title":"A compact dual promoter adeno-associated viral vector for efficient delivery of two genes to dorsal root ganglion neurons","volume":"21","author":"Fagoe","year":"2014","journal-title":"Gene Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1248\/bpb.b14-00771","article-title":"Challenges in retinal circuit regeneration: Linking neuronal connectivity to circuit function","volume":"38","author":"Osakada","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.neuron.2016.09.021","article-title":"A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons","volume":"92","author":"Tervo","year":"2016","journal-title":"Neuron"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41592-019-0435-6","article-title":"High-performance calcium sensors for imaging activity in neuronal populations and microcompartments","volume":"16","author":"Dana","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"6091","DOI":"10.1167\/iovs.17-22634","article-title":"AAV2-mediated transduction of the mouse retina after optic nerve injury","volume":"58","author":"Nickells","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-3-030-27378-1_12","article-title":"RNA-Based Therapeutic Strategies for Inherited Retinal Dystrophies","volume":"1185","author":"Garanto","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1167\/iovs.11-8484","article-title":"Long-term rescue of rat retinal ganglion cells and visual function by AAV-mediated BDNF expression after acute elevation of intraocular pressure","volume":"53","author":"Ren","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"16078","DOI":"10.1038\/mtm.2016.78","article-title":"Significant changes in endogenous retinal gene expression assessed 1 year after a single intraocular injection of AAV-CNTF or AAV-BDNF","volume":"3","author":"LeVaillant","year":"2016","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_83","first-page":"3622","article-title":"Retinal degeneration is slowed in transgenic rats by AAV-mediated delivery of FGF-2","volume":"41","author":"Lau","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1038\/sj.gt.3302791","article-title":"AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells","volume":"13","author":"Leaver","year":"2006","journal-title":"Gene Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/mt.2011.62","article-title":"AAV mediated GDNF secretion from retinal glia slows down retinal degeneration in a rat model of retinitis pigmentosa","volume":"19","author":"Dalkara","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1089\/hum.2017.069","article-title":"Design of a Novel Gene Therapy Construct to Achieve Sustained Brain-Derived Neurotrophic Factor Signaling in Neurons","volume":"29","author":"Osborne","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.omtn.2019.01.012","article-title":"Suppression of Choroidal Neovascularization by AAV-Based Dual-Acting Antiangiogenic Gene Therapy","volume":"16","author":"Askou","year":"2019","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nature04791","article-title":"Fatality in mice due to oversaturation of cellular microRNA\/short hairpin RNA pathways","volume":"441","author":"Grimm","year":"2006","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.1167\/iovs.08-3189","article-title":"Rlbp1 promoter drives robust M\u00fcller glial GFP expression in transgenic mice","volume":"50","author":"Clark","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Hanlon, K.S., Chadderton, N., Palfi, A., Fernandez, A.B., Humphries, P., Kenna, P.F., Millington-Ward, S., and Farrar, G.J. (2017). A novel retinal ganglion cell promoter for utility in AAV vectors. Front. Neurosci., 11.","DOI":"10.3389\/fnins.2017.00521"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3954","DOI":"10.1167\/iovs.07-0257","article-title":"AAV-mediated expression targeting of rod and cone photoreceptors with a human rhodopsin kinase promoter","volume":"48","author":"Khani","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"9597","DOI":"10.1128\/JVI.79.15.9597-9607.2005","article-title":"Two Sp1\/Sp3 Binding Sites in the Major Immediate-Early Proximal Enhancer of Human Cytomegalovirus Have a Significant Role in Viral Replication","volume":"79","author":"Isomura","year":"2005","journal-title":"J. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0092-8674(83)90210-6","article-title":"The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter","volume":"35","author":"Dynan","year":"1983","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1126\/science.3529394","article-title":"Purification and biochemical characterization of the promoter-specific transcription factor, Sp1","volume":"234","author":"Briggs","year":"1986","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1242\/jcs.113.14.2619","article-title":"CD44 expression and regulation during mammary gland development and function","volume":"113","author":"Hebbard","year":"2000","journal-title":"J. Cell Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1007\/s11064-004-6881-1","article-title":"Expression Specificity of GFAP Transgenes","volume":"29","author":"Su","year":"2004","journal-title":"Neurochem. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"8562","DOI":"10.1167\/iovs.10-6835","article-title":"Hypoxia-regulated retinal glial cell-specific promoter for potential gene therapy in disease","volume":"52","author":"Prentice","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"7748","DOI":"10.1523\/JNEUROSCI.0397-08.2008","article-title":"A core paired-type and POU homeodomain-containing transcription factor program drives retinal bipolar cell gene expression","volume":"28","author":"Kim","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Aartsen, W.M., van Cleef, K.W.R.R., Pellissier, L.P., Hoek, R.M., Vos, R.M., Blits, B., Ehlert, E.M.E.E., Balaggan, K.S., Ali, R.R., and Verhaagen, J. (2010). GFAP-driven GFP expression in activated mouse M\u00fcller glial cells aligning retinal blood vessels following intravitreal injection of AAV2\/6 vectors. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012387"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1172\/JCI35977","article-title":"Antioxidant or neurotrophic factor treatment preserves function in a mouse model of neovascularization-associated oxidative stress","volume":"119","author":"Dorrell","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_101","unstructured":"Choi, V., Bigelow, C.E., Dryja, T.P., and Police, S.R. (2013). Viral Vectors for the Treatment of Retinal Dystrophy. (9163259B2), U.S. Patent."},{"key":"ref_102","first-page":"471","article-title":"Robust hypoxia-selective regulation of a retinal pigment epithelium-specific adeno-associated virus vector","volume":"14","author":"Dougherty","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1096\/fasebj.14.2.368","article-title":"Role of activating protein-1 and high mobility group-I(Y) protein in the induction of CD44 gene expression by interleukin-1\u03b2 in vascular smooth muscle cells","volume":"14","author":"Foster","year":"2000","journal-title":"Faseb J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.neulet.2004.12.072","article-title":"Rhodopsin promoter-EGFP fusion transgene expression in photoreceptor neurons of retina and pineal complex in mice","volume":"379","author":"Ichsan","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"11372","DOI":"10.1128\/JVI.01327-07","article-title":"Novel adeno-associated virus serotypes efficiently transduce murine photoreceptors","volume":"81","author":"Allocca","year":"2007","journal-title":"J. Virol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/gt.2008.32","article-title":"Targeting gene expression to cones with human cone opsin promoters in recombinant AAV","volume":"15","author":"Alexander","year":"2008","journal-title":"Gene Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1017\/S095252380001258X","article-title":"A 221-bp fragment of the mouse opsin promoter directs expression specifically to the rod photoreceptors of transgenic mice","volume":"14","author":"Quiambao","year":"1997","journal-title":"Vis. Neurosci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4076","DOI":"10.1167\/iovs.03-0197","article-title":"A Short, Highly Active Photoreceptor-Specific Enhancer\/Promoter Region Upstream of the Human Rhodopsin Kinase Gene","volume":"44","author":"Young","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/gt.2009.104","article-title":"Gene therapy with a promoter targeting both rods and cones rescues retinal degeneration caused by AIPL1 mutations","volume":"17","author":"Sun","year":"2010","journal-title":"Gene Ther."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/j.ymthe.2017.05.004","article-title":"Optimization of Retinal Gene Therapy for X-Linked Retinitis Pigmentosa Due to RPGR Mutations","volume":"25","author":"Beltran","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Pang, J., Deng, W.-T., Dai, X., Lei, B., Everhart, D., Umino, Y., Li, J., Zhang, K., Mao, S., and Boye, S.L. (2012). AAV-mediated cone rescue in a naturally occurring mouse model of CNGA3-achromatopsia. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035250"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1167\/iovs.05-1670","article-title":"Human blue-opsin promoter preferentially targets reporter gene expression to rat s-cone photoreceptors","volume":"47","author":"Glushakova","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1038\/mt.2010.149","article-title":"Restoration of cone vision in the CNGA3-\/- mouse model of congenital complete lack of cone photoreceptor function","volume":"18","author":"Michalakis","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_114","first-page":"1","article-title":"Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa","volume":"106","author":"Beltran","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/978-1-4614-3209-8_87","article-title":"Cone specific promoter for use in gene therapy of retinal degenerative diseases","volume":"801","author":"Dyka","year":"2014","journal-title":"Adv Exp Med Biol"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1001\/jamaophthalmol.2020.1032","article-title":"Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia: A Nonrandomized Controlled Trial [published online ahead of print, 30 April 2020]","volume":"138","author":"Fischer","year":"2020","journal-title":"JAMA Ophthalmol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1167\/iovs.04-0663","article-title":"Deciphering the contribution of known cis-elements in the mouse cone arrestin gene to its cone-specific expression","volume":"45","author":"Pickrell","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.visres.2007.07.026","article-title":"Cone-specific expression using a human red opsin promoter in recombinant AAV","volume":"48","author":"Li","year":"2008","journal-title":"Vis. Res."},{"key":"ref_119","first-page":"3426","article-title":"ARVO Annual Meeting Poster A197 Development and efficacy assessment of AAV2\/8-hG1.7p.coCNGA3, a CNGA3 gene therapy vector","volume":"60","author":"Georgiadis","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_120","unstructured":"Rizzi, M., Ali, R., Smith, A., and Nishiguchi, K. (2018). Gene Therapy to Improve Vision. (20180030477A1), U.S. Patent."},{"key":"ref_121","unstructured":"Forbes, A. (2018). United States Securities and Exchange Commission (SEC) Form S-1 Registration Statement MeiraGTx Holdings plc, United States Securities and Exchange Commission."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Watanabe, S., Sanuki, R., Ueno, S., Koyasu, T., Hasegawa, T., and Furukawa, T. (2013). Tropisms of AAV for Subretinal Delivery to the Neonatal Mouse Retina and Its Application for In Vivo Rescue of Developmental Photoreceptor Disorders. PLoS ONE.","DOI":"10.1371\/journal.pone.0054146"},{"key":"ref_123","unstructured":"Horsager, A., Smith, A., and Matteo, B.C. (2012). Modulation Neural Pathways. (WO 2012\/051599 A2)."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/gt.2016.42","article-title":"AAV-mediated transduction and targeting of retinal bipolar cells with improved mGluR6 promoters in rodents and primates","volume":"23","author":"Lu","year":"2016","journal-title":"Gene Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1006\/mthe.2002.0588","article-title":"Adenoviral-mediated, high-level, cell-specific transgene expression: A SYN1-WPRE cassette mediates increased transgene expression with no loss of neuron specificity","volume":"5","author":"Glover","year":"2002","journal-title":"Mol. Ther."},{"key":"ref_126","unstructured":"Dalkara, D., Picaud, S., Desrosiers, M., Sahel, J.-A., Duebel, J., Bemelmans, A., and Roska, B. (2018). Promoters and uses thereof. (20180355354A1), U.S. Patent."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1089\/hum.2018.118","article-title":"New MiniPromoter Ple345 (NEFL) drives strong and specific expression in retinal ganglion cells of mouse and primate retina","volume":"30","author":"Simpson","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_128","unstructured":"Ali, R.R., Bainbridge, J.W.B., and Smith, A.J. (2010). Devices and Methods for Delivering Polynucleotides into Retinal Cells of the Macula and Fovea. (20100081707A1), U.S. Patent."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ymthe.2017.11.019","article-title":"Triple Vectors Expand AAV Transfer Capacity in the Retina","volume":"26","author":"Maddalena","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_130","unstructured":"J\u00fcttner, J., Krol, J., and Roska, B. (2016). Synpiii, a Promoter for the Specific Expression of Genes in Retinal Pigment Epithelium. (WO2019106035A1)."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/jgm.860","article-title":"Stable RNA interference: Comparison of U6 and H1 promoters in endothelial cells and in mouse brain","volume":"8","author":"Koponen","year":"2006","journal-title":"J. Gene Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1080\/21541264.2017.1322170","article-title":"Mutation of nucleotides around the +1 position of type 3 polymerase III promoters: The effect on transcriptional activity and start site usage","volume":"8","author":"Gao","year":"2017","journal-title":"Transcription"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1089\/hum.2005.16.1404","article-title":"Hybrid cytomegalovirus enhancer-h1 promoter-based plasmid and baculovirus vectors mediate effective RNA interference","volume":"16","author":"Ong","year":"2005","journal-title":"Hum. Gene Ther."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1038\/mtna.2012.24","article-title":"The Cellular Processing Capacity Limits the Amounts of Chimeric U7 snRNA Available for Antisense Delivery","volume":"1","author":"Eckenfelder","year":"2012","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/sj.mt.6300027","article-title":"Design of tissue-specific regulatory cassettes for high-level rAAV-mediated expression in skeletal and cardiac muscle","volume":"15","author":"Salva","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"11488","DOI":"10.1073\/pnas.210319397","article-title":"Ribozyme rescue of photoreceptor cells in P23H transgenic rats: Long-term survival and late-stage therapy","volume":"97","author":"LaVail","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Xu, L., Zhao, L., Gao, Y., Xu, J., and Han, R. (2017). Empower multiplex cell and tissue-specific CRISPR-mediated gene manipulation with self-cleaving ribozymes and tRNA. Nucleic Acids Res., 45.","DOI":"10.1093\/nar\/gkw1048"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.omtn.2016.12.006","article-title":"Inclusion of the Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances AAV2-Driven Transduction of Mouse and Human Retina","volume":"6","author":"Barnard","year":"2017","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1756-6606-7-17","article-title":"Optimization of AAV expression cassettes to improve packaging capacity and transgene expression iChoi J-H, Yu N-K, Baek G-C, Bakes J, Seo D, Nam HJ, Baek SH, Lim C-S, Lee Y-S, Kaang B-K. 2014. Optimization of AAV expression cassettes to improve packaging","volume":"7","author":"Choi","year":"2014","journal-title":"Mol. Brain"},{"key":"ref_140","unstructured":"Michalakis, S., Biel, M., Seeliger, M., and Schoen, C. (2017). Gene Therapy for the Treatment of a Retinal Degeneration Disease. (20180353620A1), U.S. Patent."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1006\/mthe.2000.0190","article-title":"Lentiviral vectors for enhanced gene expression in human hematopoietic cells","volume":"2","author":"Ramezani","year":"2000","journal-title":"Mol. Ther."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1089\/hum.2006.17.1036","article-title":"Synthetic intron improves transduction efficiency of trans-splicing adeno-associated viral vectors","volume":"17","author":"Lai","year":"2006","journal-title":"Hum. Gene Ther."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/sj.mt.6300355","article-title":"Optimization of self-complementary AAV vectors for liver-directed expression results in sustained correction of hemophilia B at low vector dose","volume":"16","author":"Wu","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1089\/hum.2016.140","article-title":"A 5\u2032 noncoding exon containing engineered intron enhances transgene expression from recombinant AAV vectors in vivo","volume":"28","author":"Lu","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Karali, M., Manfredi, A., Puppo, A., Marrocco, E., Gargiulo, A., Allocca, M., de Corte, M., Rossi, S., Giunti, M., and Bacci, M.L. (2011). MicroRNA-Restricted transgene expression in the retina. PLoS ONE.","DOI":"10.1371\/journal.pone.0022166"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"4144","DOI":"10.1182\/blood-2007-03-078493","article-title":"A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice","volume":"110","author":"Brown","year":"2007","journal-title":"Blood"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.ymthe.2017.03.028","article-title":"Short DNA Hairpins Compromise Recombinant Adeno-Associated Virus Genome Homogeneity","volume":"25","author":"Xie","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"R3","DOI":"10.1093\/hmg\/ddz148","article-title":"Next-generation AAV vectors\u2014Do not judge a virus (only) by its cover","volume":"28","author":"Domenger","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_149","first-page":"575","article-title":"Optimization of plasmid vectors for high-level expression in lung epithelial cells","volume":"8","author":"Yew","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"5085","DOI":"10.1128\/JVI.72.6.5085-5092.1998","article-title":"Woodchuck hepatitis virus contains a tripartite posttranscriptional regulatory element","volume":"72","author":"Donello","year":"1998","journal-title":"J. Virol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1016\/S1525-0016(16)32967-7","article-title":"158. Cryptic ATG Removal from Synthetic Introns Increase the Therapeutic Efficacy of AAV Vector Mediated Gene Transfer","volume":"24","author":"Ronzitti","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"15022","DOI":"10.1038\/mtm.2015.22","article-title":"AAV-mediated RLBP1 gene therapy improves the rate of dark adaptation in Rlbp1 knockout mice","volume":"2","author":"Choi","year":"2015","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_153","unstructured":"Beltran, W.A., Aguirre, G.D., Jacobson, S.G., Cideciyan, A.V., Lewin, A.S., Boye, S.L., Hauswirth, W.W., and Deng, W.-T. (2017). AAV-Mediated Gene Therapy for RPGR X-Linked Retinal Degeneration. (9770491B2), U.S. Patent."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1111\/jcmm.13504","article-title":"SV40 intron, a potent strong intron element that effectively increases transgene expression in transfected Chinese hamster ovary cells","volume":"22","author":"Xu","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/S0140-6736(13)62117-0","article-title":"Retinal gene therapy in patients with choroideremia: Initial fi ndings from a phase 1\/2 clinical trial","volume":"383","author":"MacLaren","year":"2014","journal-title":"Lancet"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1001\/archophthalmol.2011.298","article-title":"Gene therapy for leber congenital amaurosis caused by RPE65 mutations: Safety and efficacy in 15 children and adults followed up to 3 years","volume":"130","author":"Jacobson","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ajo.2018.09.012","article-title":"Choroideremia Gene Therapy Phase 2 Clinical Trial: 24-Month Results","volume":"197","author":"Lam","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"5276","DOI":"10.1074\/jbc.270.10.5276","article-title":"Role of intron I in expression of the human factor IX gene","volume":"270","author":"Kurachi","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Lee, S.R., Li, L.H., Park, H.J., Park, J.H., Lee, K.Y., Kim, M.K., Shin, B.A., and Choi, S.Y. (2011). High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice. PLoS ONE.","DOI":"10.1371\/journal.pone.0018556"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0378-1119(97)00412-5","article-title":"A novel dicistronic AAV vector using a short IRES segment derived from hepatitis C virus genome","volume":"200","author":"Urabe","year":"1997","journal-title":"Gene"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1002\/j.1460-2075.1993.tb05909.x","article-title":"Poly(A) signals and transcriptional pause sites combine to prevent interference between RNA polymerase II promoters","volume":"12","author":"Eggermont","year":"1993","journal-title":"Embo J."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1182\/blood-2008-04-152686","article-title":"Stroma-dependent apoptosis in clonal hematopoietic precursors correlates with expression of PYCARD","volume":"113","author":"Mhyre","year":"2009","journal-title":"Blood"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1089\/hum.2014.041","article-title":"Establishment of a novel cell line for the enhanced production of recombinant adeno-associated virus vectors for gene therapy","volume":"25","author":"Satkunanathan","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"ref_164","unstructured":"VectorBuilder Inc. (2020, June 11). Vectorbuilder.com\/Learning-Center\/Vector-Component\/Promoter. Available online: https:\/\/en.vectorbuilder.com\/learning-center\/vector-component\/linker.html."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1007\/s00253-012-4403-7","article-title":"Improving the safety of viral DNA vaccines: Development of vectors containing both 5\u2032 and 3\u2032 homologous regulatory sequences from non-viral origin","volume":"97","author":"Encinas","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.plasmid.2005.11.005","article-title":"Evaluation of a novel short polyadenylation signal as an alternative to the SV40 polyadenylation signal","volume":"56","author":"McFarland","year":"2006","journal-title":"Plasmid"},{"key":"ref_167","first-page":"298620","article-title":"Rational design of a compact CRISPR-Cas9 activator for AAV-mediated delivery","volume":"9","author":"Vora","year":"2018","journal-title":"bioRxiv"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1089\/hum.2007.165","article-title":"An internal polyadenylation signal substantially increases expression levels of lentivirus-delivered transgenes but has the potential to reduce viral titer in a promoter-dependent manner","volume":"19","author":"Hager","year":"2008","journal-title":"Hum. Gene Ther."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/sj.mt.6300152","article-title":"Improving transcriptional termination of self-inactivating gamma-retroviral and lentiviral vectors","volume":"15","author":"Schambach","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1073\/pnas.0409845102","article-title":"A shortened adeno-associated virus expression cassette for CFTR gene transfer to cystic fibrosis airway epithelia","volume":"102","author":"Ostedgaard","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_171","unstructured":"Kumar-Singh, R., Leaderer, D., and Cashman, S. (2019). Compositions, Kits and Methods for Treatment of Complement-Related Disorders. (20170209535A1), U.S. Patent."},{"key":"ref_172","first-page":"2104","article-title":"Identification of sequences in the herpes simplex virus thymidine kinase gene required for efficient processing and polyadenylation","volume":"5","author":"Cole","year":"1985","journal-title":"Mol. Cell. Biol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/978-3-030-27378-1_13","article-title":"A Comparison of Inducible Gene Expression Platforms: Implications for Recombinant Adeno-Associated Virus (rAAV) Vector-Mediated Ocular Gene Therapy","volume":"Volume 1185","author":"Grimm","year":"2019","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/j.1432-1033.1986.tb10077.x","article-title":"Structure and regulation of the sheep metallothionein-Ia gene","volume":"160","author":"Peterson","year":"1986","journal-title":"Eur. J. Biochem."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"9428","DOI":"10.1128\/JVI.72.12.9428-9435.1998","article-title":"Mouse mammary tumor virus sequences responsible for activating cellular oncogenes","volume":"72","author":"Grimm","year":"1998","journal-title":"J. Virol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1146\/annurev.ge.19.120185.001233","article-title":"Steroid Receptor Regulated Transcription of Specific Genes and Gene Networks","volume":"19","author":"Yamamoto","year":"1985","journal-title":"Annu. Rev. Genet."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ab.2011.06.008","article-title":"Fluorescence-based evaluation of shRNA efficacy","volume":"417","author":"Naughton","year":"2011","journal-title":"Anal. Biochem."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/s41467-020-14491-x","article-title":"High-throughput identification of synthetic riboswitches by barcode-free amplicon-sequencing in human cells","volume":"11","author":"Strobel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Reid, C.A., Nettesheim, E.R., Connor, T.B., and Lipinski, D.M. (2018). Development of an inducible anti-VEGF rAAV gene therapy strategy for the treatment of wet AMD. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-29726-7"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1006\/abio.1996.0187","article-title":"T7 vectors with modified T7lac promoter for expression of proteins in Escherichia coli","volume":"236","author":"Rikkonen","year":"1996","journal-title":"Anal. Biochem."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Cenik, C., Chua, H.N., Zhang, H., Tarnawsky, S.P., Akef, A., Derti, A., Tasan, M., Moore, M.J., Palazzo, A.F., and Roth, F.P. (2011). Genome analysis reveals interplay between 5\u2032UTR introns and nuclear mRNA export for secretory and mitochondrial genes. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1001366"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.molcel.2017.07.002","article-title":"Introns Protect Eukaryotic Genomes from Transcription-Associated Genetic Instability","volume":"67","author":"Bonnet","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1016\/j.ymthe.2018.07.011","article-title":"Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy","volume":"26","author":"Duan","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/343180a0","article-title":"Very mild muscular dystrophy associated with the deletion of 46% of dystrophin","volume":"343","author":"England","year":"1990","journal-title":"Nature"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1038\/s41591-019-0604-2","article-title":"Surrogate gene therapy for muscular dystrophy","volume":"25","author":"Davies","year":"2019","journal-title":"Nat. Med."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1089\/hum.2017.049","article-title":"Gene Therapy Using a miniCEP290 Fragment Delays Photoreceptor Degeneration in a Mouse Model of Leber Congenital Amaurosis","volume":"29","author":"Zhang","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_187","unstructured":"Kremer, J.M.J., Keunen, J.E.E., and van Wijk, H.A.R. (2018). Gene therapy using miniUSH2A genes improves visual function in a zebrafish ush2a knock-out model. Towards gene therapy for USH2A-associated retinitis pigmentosa. ~Fishing for answers~ [Doctoral Thesis], Radboud University Nijmegen."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1038\/s41591-019-0594-0","article-title":"Non-immunogenic utrophin gene therapy for the treatment of muscular dystrophy animal models","volume":"25","author":"Song","year":"2019","journal-title":"Nat. Med."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1093\/hmg\/ddl194","article-title":"Pals1\/Mpp5 is required for correct localization of Crb1 at the subapical region in polarized M\u00fcller glia cells","volume":"15","author":"Aartsen","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/hmg\/dds398","article-title":"Loss of CRB2 in the mouse retina mimics human retinitis pigmentosa due to mutations in the CRB1 gene","volume":"22","author":"Alves","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Alves, C.H., Boon, N., Mulder, A.A., Koster, A.J., Jost, C.R., and Wijnholds, J. (2019). CRB2 Loss in Rod Photoreceptors Is Associated with Progressive Loss of Retinal Contrast Sensitivity. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174069"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1523\/JNEUROSCI.3496-06.2007","article-title":"A single amino acid substitution (Cys249Trp) in Crb1 causes retinal degeneration and deregulates expression of pituitary tumor transforming gene Pttg1","volume":"27","author":"Meuleman","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Alves, C.H., Bossers, K., Vos, R.M., Essing, A.H.W., Swagemakers, S., van der Spek, P.J., Verhaagen, J., and Wijnholds, J. (2013). Microarray and morphological analysis of early postnatal CRB2 mutant retinas on a pure C57BL\/6J genetic background. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082532"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"3384","DOI":"10.1093\/hmg\/ddu048","article-title":"Targeted ablation of Crb2 in photoreceptor cells induces retinitis pigmentosa","volume":"23","author":"Alves","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1093\/hmg\/ddy194","article-title":"CRB2 in immature photoreceptors determines the superior-inferior symmetry of the developing retina to maintain retinal structure and function","volume":"27","author":"Quinn","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1002\/glia.20561","article-title":"Crb1 is a determinant of retinal apical M\u00fcller glia cell features","volume":"55","author":"Sanz","year":"2007","journal-title":"Glia"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"4169","DOI":"10.1242\/jcs.01301","article-title":"Crumbs homologue 1 is required for maintenance of photoreceptor cell polarization and adhesion during light exposure","volume":"117","author":"Kantardzhieva","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Pellissier, L.P., Alves, C.H., Quinn, P.M., Vos, R.M., Tanimoto, N., Lundvig, D.M.S., Dudok, J.J., Hooibrink, B., Richard, F., and Beck, S.C. (2013). Targeted ablation of CRB1 and CRB2 in retinal progenitor cells mimics Leber congenital amaurosis. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003976"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1093\/hmg\/ddu089","article-title":"CRB2 acts as a modifying factor of CRB1-related retinal dystrophies in mice","volume":"23","author":"Pellissier","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/hmg\/ddy337","article-title":"Loss of CRB2 in M\u00fcller glial cells modifies a CRB1-associated retinitis pigmentosa phenotype into a Leber congenital amaurosis phenotype","volume":"28","author":"Quinn","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1167\/iovs.04-1417","article-title":"MPP5 recruits MPP4 to the CRB1 complex in photoreceptors","volume":"46","author":"Kantardzhieva","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.ophtha.2017.01.047","article-title":"Genotypic and Phenotypic Characteristics of CRB1-Associated Retinal Dystrophies: A Long-Term Follow-up Study","volume":"124","author":"Talib","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_203","first-page":"80","article-title":"The pathway from genes to gene therapy in glaucoma: A review of possibilities for using genes as glaucoma drugs","volume":"6","year":"2017","journal-title":"Asia-Pacific J. Ophthalmol."},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Kong, D.H., Kim, M.R., Jang, J.H., Na, H.J., and Lee, S. (2017). A review of anti-angiogenic targets for monoclonal antibody cancer therapy. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081786"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/gt.2008.115","article-title":"Novel anti-VEGF chimeric molecules delivered by AAV vectors for inhibition of retinal neovascularization","volume":"16","author":"Pechan","year":"2009","journal-title":"Gene Ther."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S0140-6736(17)30979-0","article-title":"Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: A phase 1, open-label trial","volume":"390","author":"Heier","year":"2017","journal-title":"Lancet"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1089\/hum.2013.079","article-title":"Suppression of neovascularization of donor corneas by transduction with equine infectious anemia virus-based lentiviral vectors expressing endostatin and angiostatin","volume":"25","author":"Parker","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"ref_208","unstructured":"Buchberger, A. (2016). The Therapeutic Utility of Factor I in the Treatment of Complement Dependent Pathophysiological Processes. [Ph.D. Thesis, University of Leicester]."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.ymthe.2017.12.002","article-title":"AAV8-antiVEGFfab Ocular Gene Transfer for Neovascular Age-Related Macular Degeneration","volume":"26","author":"Liu","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Cashman, S.M., Ramo, K., and Kumar-Singh, R. (2011). A non membrane-targeted human soluble CD59 attenuates choroidal neovascularization in a model of age related macular degeneration. PLoS ONE.","DOI":"10.1371\/journal.pone.0019078"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.exer.2009.12.006","article-title":"Channelrhodopsin-2 gene transduced into retinal ganglion cells restores functional vision in genetically blind rats","volume":"90","author":"Tomita","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"S106","DOI":"10.1016\/S1525-0016(16)33077-5","article-title":"268. Optogenetic Engineering of Retinal Ganglion Cells with AAV2.7m8-ChrimsonR-tdTomato (GS030-DP) Is Well Tolerated and Induces Functional Responses to Light in Non-Human Primates","volume":"24","author":"Douar","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Lundstrom, K. (2018). Viral Vectors in Gene Therapy. Diseases, 6.","DOI":"10.3390\/diseases6020042"},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Trapani, I. (2019). Adeno-Associated Viral Vectors as a Tool for Large Gene Delivery to the Retina. Genes, 10.","DOI":"10.3390\/genes10040287"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"6811","DOI":"10.1093\/hmg\/ddv386","article-title":"Improved dual AAV vectors with reduced expression of truncated proteins are safe and effective in the retina of a mouse model of Stargardt disease","volume":"24","author":"Trapani","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1089\/hum.2018.156","article-title":"An AAV Dual Vector Strategy Ameliorates the Stargardt Phenotype in Adult Abca4-\/- Mice","volume":"30","author":"McClements","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Kumar, N., Stanford, W., de Solis, C., Abraham, N.D., Dao, T.M.J., Thaseen, S., Sairavi, A., Gonzalez, C.U., and Ploski, J.E. (2018). The development of an AAV-based CRISPR SaCas9 genome editing system that can be delivered to neurons in vivo and regulated via doxycycline and Cre-recombinase. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00413"},{"key":"ref_218","doi-asserted-by":"crossref","unstructured":"Hanlon, K.S., Kleinstiver, B.P., Garcia, S.P., Zaborowski, M.P., Volak, A., Spirig, S.E., Muller, A., Sousa, A.A., Tsai, S.Q., and Bengtsson, N.E. (2019). High levels of AAV vector integration into CRISPR-induced DNA breaks. Nat. Commun., 10.","DOI":"10.1038\/s41467-019-12449-2"},{"key":"ref_219","doi-asserted-by":"crossref","unstructured":"Yu, W., Mookherjee, S., Chaitankar, V., Hiriyanna, S., Kim, J.W., Brooks, M., Ataeijannati, Y., Sun, X., Dong, L., and Li, T. (2017). Nrl knockdown by AAV-delivered CRISPR\/Cas9 prevents retinal degeneration in mice. Nat. Commun., 8.","DOI":"10.1038\/ncomms14716"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/cr.2017.57","article-title":"Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors","volume":"27","author":"Zhu","year":"2017","journal-title":"Cell Res."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"14500","DOI":"10.1038\/ncomms14500","article-title":"In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni","volume":"8","author":"Kim","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ymthe.2018.10.009","article-title":"Long-Term Effects of In Vivo Genome Editing in the Mouse Retina Using Campylobacter jejuni Cas9 Expressed via Adeno-Associated Virus","volume":"27","author":"Jo","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/nmeth.2600","article-title":"RNA-guided gene activation by CRISPR-Cas9-based transcription factors","volume":"10","author":"Kocak","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nature14136","article-title":"Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex","volume":"517","author":"Konermann","year":"2015","journal-title":"Nature"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"e260","DOI":"10.1038\/mtna.2015.32","article-title":"Advanced characterization of DNA molecules in rAAV vector preparations by single-stranded virus next-generation sequencing","volume":"4","author":"Lecomte","year":"2015","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/sj.mt.6300389","article-title":"Reversal of Blindness in Animal Models of Leber Congenital Amaurosis Using Optimized AAV2-mediated Gene Transfer","volume":"16","author":"Bennicelli","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3390\/pathogens4020157","article-title":"Antibiotic-free selection in biotherapeutics: Now and forever","volume":"4","author":"Mignon","year":"2015","journal-title":"Pathogens"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1038\/nbt.1708","article-title":"A robust system for production of minicircle DNA vectors","volume":"28","author":"Kay","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"e355","DOI":"10.1038\/mtna.2016.60","article-title":"DNA Minicircle Technology Improves Purity of Adeno-associated Viral Vector Preparations","volume":"5","author":"Schmeer","year":"2016","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0014-5793(96)01149-0","article-title":"Role of terminal repeat GAGC trimer, the major Rep78 binding site, in adeno-associated virus DNA replication","volume":"397","author":"Bishop","year":"1996","journal-title":"Febs Lett."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1128\/jvi.70.3.1542-1553.1996","article-title":"Sequence requirements for binding of Rep68 to the adeno-associated virus terminal repeats","volume":"70","author":"Ryan","year":"1996","journal-title":"J. Virol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/sj.mt.6300397","article-title":"Adeno-associated virus of a single-polarity DNA genome is capable of transduction in vivo","volume":"16","author":"Zhou","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1128\/jvi.70.3.1668-1677.1996","article-title":"Rescue and replication of adeno-associated virus type 2 as well as vector DNA sequences from recombinant plasmids containing deletions in the viral inverted terminal repeats: Selective encapsidation of viral genomes in progeny virions","volume":"70","author":"Wang","year":"1996","journal-title":"J. Virol."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1128\/jvi.71.4.3077-3082.1997","article-title":"Adeno-associated virus type 2 DNA replication in vivo: Mutation analyses of the D sequence in viral inverted terminal repeats","volume":"71","author":"Wang","year":"1997","journal-title":"J. Virol."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1089\/hum.2020.018","article-title":"AAV D-sequence-mediated suppression of expression of a human major histocompatibility class II gene: Implications in the development of AAV vectors for modulating humoral immune response","volume":"31","author":"Kwon","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0092-8674(83)90342-2","article-title":"Rescue of adeno-associated virus from recombinant plasmids: Gene correction within the terminal repeats of AAV","volume":"33","author":"Samulski","year":"1983","journal-title":"Cell"},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Tian, W., Liu, C., Lian, Z., Dong, X., and Wu, X. (2017). Deletion of the B-B\u2019 and C-C\u2019 regions of inverted terminal repeats reduces rAAV productivity but increases transgene expression. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-04054-4"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/1743-422X-7-218","article-title":"Substitution of adeno-associated virus Rep protein binding and nicking sites with human chromosome 19 sequences","volume":"7","author":"McAlister","year":"2010","journal-title":"Virol. J."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/0006-291X(76)90845-7","article-title":"Random location and absence of movement of the nucleosomes on SV 40 nucleoprotein complex isolated from infected cells","volume":"73","author":"Pignatti","year":"1976","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.ymthe.2005.11.010","article-title":"A histone deacetylase inhibitor enhances recombinant adeno-associated virus-mediated gene expression in tumor cells","volume":"13","author":"Okada","year":"2006","journal-title":"Mol. Ther."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/0092-8674(77)90159-3","article-title":"Preferential association of newly synthesized histones with replicating SV40 DNA","volume":"12","author":"Chestier","year":"1977","journal-title":"Cell"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"11276","DOI":"10.1073\/pnas.1503607112","article-title":"Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction","volume":"112","author":"Mano","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ymthe.2004.09.022","article-title":"Biodistribution of rAAV vectors following intraocular administration: Evidence for the presence and persistence of vector DNA in the optic nerve and in the brain","volume":"11","author":"Provost","year":"2005","journal-title":"Mol. Ther."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/ng1380","article-title":"Adeno-associated virus vectors integrate at chromosome breakage sites","volume":"36","author":"Miller","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"6969","DOI":"10.1128\/JVI.75.15.6969-6976.2001","article-title":"Extrachromosomal recombinant adeno-associated virus vector genomes are primarily responsible for stable liver transduction in vivo","volume":"75","author":"Nakai","year":"2001","journal-title":"J. Virol."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.omtm.2017.11.007","article-title":"Emerging Issues in AAV-Mediated In Vivo Gene Therapy","volume":"8","author":"Colella","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/ng1179","article-title":"AAV serotype 2 vectors preferentially integrate into active genes in mice","volume":"34","author":"Nakai","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_248","unstructured":"Ceiler, J., Afzal, S., Leuchs, B., Fronza, R., Lulay, C., B\u00fcning, H., Schmidt, M., and Gil-Farina, I. (2017, January 10). Wild-Type and Recombinant AAV Integration in Human Cardiomyocytes: Focus on Mitochondrial Genome. Proceedings of the AAV Vector Biology, Available online: https:\/\/www.researchgate.net\/publication\/316699961_Wild-Type_and_Recombinant_AAV_Integration_in_Human_Cardiomyocytes_Focus_on_Mitochondrial_Genome."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1038\/mt.2016.52","article-title":"Recombinant AAV Integration Is Not Associated with Hepatic Genotoxicity in Nonhuman Primates and Patients","volume":"24","author":"Fronza","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41591-018-0327-9","article-title":"Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10","volume":"25","author":"Maeder","year":"2019","journal-title":"Nat. Med."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1038\/mt.2012.157","article-title":"AAV vectors containing rDNA homology display increased chromosomal integration and transgene persistence","volume":"20","author":"Wang","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/gt.2014.109","article-title":"Adeno-associated virus inverted terminal repeats stimulate gene editing","volume":"22","author":"Hirsch","year":"2015","journal-title":"Gene Ther."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"16049","DOI":"10.1038\/mtm.2016.49","article-title":"A translationally optimized AAV-UGT1A1 vector drives safe and long-lasting correction of Crigler-Najjar syndrome","volume":"3","author":"Ronzitti","year":"2016","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/sj.gt.3301514","article-title":"Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis","volume":"8","author":"McCarty","year":"2001","journal-title":"Gene Ther."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1038\/mt.2008.171","article-title":"Self-complementary AAV vectors; advances and applications","volume":"16","author":"McCarty","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1001\/archophthalmol.2010.135","article-title":"Induction of rapid and highly efficient expression of the human ND4 complex I subunit in the mouse visual system by self-complementary adeno-associated virus","volume":"128","author":"Koilkonda","year":"2010","journal-title":"Arch. Ophthalmol."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1167\/iovs.06-1306","article-title":"Ocular gene transfer with self-complementary AAV vectors","volume":"48","author":"Yokoi","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/978-1-61779-095-9_11","article-title":"Vector characterization methods for quality control testing of recombinant adeno-associated viruses","volume":"737","author":"Wright","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.omtm.2018.07.004","article-title":"Accurate Titration of Infectious AAV Particles Requires Measurement of Biologically Active Vector Genomes and Suitable Controls","volume":"10","author":"Bouzelha","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_260","first-page":"1","article-title":"Poster C0048 ARVO: Potency Assay for AAV Vector Encoding Retinal Pigment Epithelial 65 Protein","volume":"57","author":"Couto","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.omtm.2018.03.009","article-title":"The Biological Activity of AAV Vectors for Choroideremia Gene Therapy Can Be Measured by In Vitro Prenylation of RAB6A","volume":"9","author":"Barnard","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_262","doi-asserted-by":"crossref","unstructured":"Wang, L., Xiao, R., Andres-Mateos, E., and Vandenberghe, L.H. (2017). Single stranded adeno-associated virus achieves efficient gene transfer to anterior segment in the mouse eye. PLoS ONE.","DOI":"10.1371\/journal.pone.0182473"},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/jgm.886","article-title":"Mechanisms of AAV transduction in glaucoma-associated human trabecular meshwork cells","volume":"8","author":"Xue","year":"2006","journal-title":"J. Gene Med."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/1743-422X-10-74","article-title":"A survey of ex vivo\/in vitro transduction efficiency of mammalian primary cells and cell lines with Nine natural adeno-associated virus (AAV1-9) and one engineered adeno-associated virus serotype","volume":"10","author":"Ellis","year":"2013","journal-title":"Virol. J."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1089\/hum.2018.027","article-title":"Assessment of AAV Vector Tropisms for Mouse and Human Pluripotent Stem Cell-Derived RPE and Photoreceptor Cells","volume":"29","author":"Goh","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_266","doi-asserted-by":"crossref","unstructured":"Sayyad, Z., Sirohi, K., Radha, V., and Swarup, G. (2017). 661W is a retinal ganglion precursor-like cell line in which glaucoma-associated optineurin mutants induce cell death selectively. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-17241-0"},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1167\/iovs.03-1114","article-title":"Expression of cone-photoreceptor-specific antigens in a cell line derived from retinal tumors in transgenic mice","volume":"45","author":"Tan","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_268","first-page":"1090","article-title":"Quantifying transduction efficiencies of unmodified and tyrosine capsid mutant AAV vectors in vitro using two ocular cell lines","volume":"17","author":"Ryals","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.omtm.2019.03.004","article-title":"CRISPR Activation Enhances In Vitro Potency of AAV Vectors Driven by Tissue-Specific Promoters","volume":"13","author":"McDougald","year":"2019","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_270","unstructured":"Drivas, T.G., and Bennett, J. (2015). Compositions and Methods for Treatment of Disorders Related to CEP290. (10301366B2), U.S. Patent."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1091\/mbc.e17-01-0051","article-title":"Practical method for targeted disruption of ciliarelated genes by using CRISPR\/Cas9-mediated, homology-independent knock-in system","volume":"28","author":"Katoh","year":"2017","journal-title":"Mol. Biol. Cell"},{"key":"ref_272","doi-asserted-by":"crossref","unstructured":"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 M\u00fcller cells. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007467"},{"key":"ref_273","first-page":"1","article-title":"The Appropriate Marker for Astrocytes: Comparing the Distribution and Expression of Three Astrocytic Markers in Different Mouse Cerebral Regions","volume":"2019","author":"Zhang","year":"2019","journal-title":"Biomed Res. Int."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2015.06.003","article-title":"Glia-neuron interactions in the mammalian retina","volume":"51","author":"Vecino","year":"2016","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1634\/stemcells.2006-0724","article-title":"MIO-M1 Cells and Similar M\u00fcller Glial Cell Lines Derived from Adult Human Retina Exhibit Neural Stem Cell Characteristics","volume":"25","author":"Lawrence","year":"2007","journal-title":"Stem Cells"},{"key":"ref_276","first-page":"864","article-title":"In vitro characterization of a spontaneously immortalized human M\u00fcller cell line (MIO-M1)","volume":"43","author":"Limb","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_277","unstructured":"Koch, P., de Greef, S., Chtarto, A., Kemp, T., Bockstae, O., Velu, T., Caspers, L., and Tenenbaum, L. (2004). ARVO abstract: In vitro comparison of AAV\u2013mediated eGFP gene transfer on M\u00fcller cells and ARPE cells. Investig. Ophthalmol. Vis. Sci., 45."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/stem.1037","article-title":"Efficient stage-specific differentiation of human pluripotent stem cells toward retinal photoreceptor cells","volume":"30","author":"Mellough","year":"2012","journal-title":"Stem Cells"},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"14011","DOI":"10.1038\/mtm.2014.11","article-title":"Proof of concept for AAV2\/5-mediated gene therapy in iPSC-derived retinal pigment epithelium of a choroideremia patient","volume":"1","author":"Cereso","year":"2014","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.scr.2018.01.009","article-title":"Use of induced pluripotent stem cell models to probe the pathogenesis of Choroideremia and to develop a potential treatment","volume":"27","author":"Duong","year":"2018","journal-title":"Stem Cell Res."},{"key":"ref_281","doi-asserted-by":"crossref","unstructured":"Brydon, E.M., Bronstein, R., Buskin, A., Lako, M., Pierce, E.A., and Fernandez-Godino, R. (2019). AAV-mediated gene augmentation therapy restores critical functions in mutant iPSC-derived PRPF31+\/- cells. bioRxiv, 729160.","DOI":"10.1101\/729160"},{"key":"ref_282","unstructured":"Wright, J.F., and Sumaroka, M. (2019). Rab Escort Protein Potency Assay. (201662418637P), U.S. Patent."},{"key":"ref_283","doi-asserted-by":"crossref","unstructured":"Garita-Hernandez, M., Guibbal, L., Toualbi, L., Routet, F., Chaffiol, A., Winckler, C., Harinquet, M., Robert, C., Fouquet, S., and Bellow, S. (2018). Optogenetic light sensors in human retinal organoids. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00789"},{"key":"ref_284","doi-asserted-by":"crossref","unstructured":"Garita-Hernandez, M., Routet, F., Guibbal, L., Khabou, H., Toualbi, L., Riancho, L., Reichman, S., Duebel, J., Sahel, J.A., and Goureau, O. (2020). AAV-mediated gene delivery to 3D retinal organoids derived from human induced pluripotent stem cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030994"},{"key":"ref_285","doi-asserted-by":"crossref","unstructured":"Dudek, A.M., Pillay, S., Puschnik, A.S., Nagamine, C.M., Cheng, F., Qiu, J., Carette, J.E., and Vandenberghe, L.H. (2018). An Alternate Route for Adeno-associated Virus (AAV) Entry Independent of AAV Receptor. J. Virol., 92.","DOI":"10.1128\/JVI.02213-17"},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"44735","DOI":"10.18632\/oncotarget.8203","article-title":"Molecular and clinical significance of fibroblast growth factor 2 (FGF2\/bFGF) in malignancies of solid and hematological cancers for personalized therapies","volume":"7","author":"Akl","year":"2016","journal-title":"Oncotarget"},{"key":"ref_287","unstructured":"(2020, June 11). ThermoScientific Growth Factors in HyClone Cell Culture Serum. Available online: https:\/\/static.thermoscientific.com\/images\/D22225~.pdf."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/4758","article-title":"Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2","volume":"5","author":"Qing","year":"1999","journal-title":"Nat. Med."},{"key":"ref_289","doi-asserted-by":"crossref","unstructured":"Capowski, E.E., Samimi, K., Mayerl, S.J., Phillips, M.J., Pinilla, I., Howden, S.E., Saha, J., Jansen, A.D., Edwards, K.L., and Jager, L.D. (2019). Reproducibility and staging of 3D human retinal organoids across multiple pluripotent stem cell lines. Development, 146.","DOI":"10.1242\/dev.171686"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/sctm.18-0267","article-title":"Systematic Comparison of Retinal Organoid Differentiation from Human Pluripotent Stem Cells Reveals Stage Specific, Cell Line, and Methodological Differences","volume":"8","author":"Mellough","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.addr.2018.05.005","article-title":"Stem cell-based retina models","volume":"140","author":"Achberger","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1089\/hum.2017.179","article-title":"Assessment of Adeno-Associated Virus Serotype Tropism in Human Retinal Explants","volume":"29","author":"Wiley","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_293","doi-asserted-by":"crossref","unstructured":"Khabou, H., Garita-Hernandez, M., Chaffiol, A., Reichman, S., Jaillard, C., Brazhnikova, E., Bertin, S., Forster, V., Desrosiers, M., and Winckler, C. (2018). Noninvasive gene delivery to foveal cones for vision restoration. Jci Insight, 3.","DOI":"10.1172\/jci.insight.96029"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/gt.2017.85","article-title":"Tropism of engineered and evolved recombinant AAV serotypes in the rd1 mouse and ex vivo primate retina","volume":"24","author":"Hickey","year":"2017","journal-title":"Gene Ther."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/978-1-4939-7522-8_20","article-title":"AAV serotype testing on cultured human donor retinal explants","volume":"Volume 1715","author":"Boon","year":"2018","journal-title":"Methods in Molecular Biology"},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"6429","DOI":"10.1167\/iovs.17-22281","article-title":"Improvement of photoreceptor targeting via intravitreal delivery in mouse and human retina using combinatory rAAV2 capsid mutant vectors","volume":"58","author":"Reid","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_297","first-page":"4093","article-title":"Potency assay for AAV-gene vectors in human iPSCs-derived retinas and donor retinas | IOVS | ARVO Journals","volume":"58","author":"Buck","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"E9391","DOI":"10.1073\/pnas.1808903115","article-title":"Developmental stage-specific proliferation and retinoblastoma genesis in RB-deficient human but not mouse cone precursors","volume":"115","author":"Singh","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1089\/hum.2017.020","article-title":"Rod Outer Segment Development Influences AAV-Mediated Photoreceptor Transduction After Subretinal Injection","volume":"28","author":"Petit","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"7957","DOI":"10.1128\/JVI.77.14.7957-7963.2003","article-title":"Delivery of Adeno-Associated Virus Vectors to the Fetal Retina: Impact of Viral Capsid Proteins on Retinal Neuronal Progenitor Transduction","volume":"77","author":"Surace","year":"2003","journal-title":"J. Virol."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/978-3-319-17121-0_67","article-title":"Distinct Expression Patterns of AAV8 Vectors with Broadly Active Promoters from Subretinal Injections of Neonatal Mouse Eyes at Two Different Ages","volume":"854","author":"Xiong","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_302","first-page":"71","article-title":"Topographic variations in the rabbit and primate internal limiting membrane. | IOVS | ARVO Journals","volume":"2","author":"Matsumoto","year":"1984","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1089\/hum.2019.144","article-title":"Ocular Inflammatory Response to Intravitreal Injection of Adeno-Associated Virus Vector: Relative Contribution of Genome and Capsid","volume":"31","author":"Timmers","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1038\/mt.2009.181","article-title":"Inner limiting membrane barriers to aav-mediated retinal transduction from the vitreous","volume":"17","author":"Dalkara","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.omtm.2017.12.002","article-title":"Efficacy and Safety of Glycosidic Enzymes for Improved Gene Delivery to the Retina following Intravitreal Injection in Mice","volume":"9","author":"Milosavljevic","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.omtm.2018.12.006","article-title":"Trans-ocular Electric Current In Vivo Enhances AAV-Mediated Retinal Gene Transduction after Intravitreal Vector Administration","volume":"13","author":"Song","year":"2019","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41434-019-0100-9","article-title":"Retina transduction by rAAV2 after intravitreal injection: Comparison between mouse and rat","volume":"26","author":"Dias","year":"2019","journal-title":"Gene Ther."},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1089\/hum.2009.194","article-title":"Changes in adeno-associated virus-mediated gene delivery in retinal degeneration","volume":"21","author":"Kolstad","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_309","doi-asserted-by":"crossref","unstructured":"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., and MacLaren, R.E. (2013). Assessment of Tropism and Effectiveness of New Primate-Derived Hybrid Recombinant AAV Serotypes in the Mouse and Primate Retina. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060361"},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41434-019-0094-3","article-title":"AAVrh-10 transduces outer retinal cells in rodents and rabbits following intravitreal administration","volume":"26","author":"Zeng","year":"2019","journal-title":"Gene Ther."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.exer.2010.08.011","article-title":"Transduction of the inner mouse retina using AAVrh8 and AAVrh10 via intravitreal injection","volume":"91","author":"Giove","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1038\/mt.2012.144","article-title":"Terminal differentiation of cardiac and skeletal myocytes induces permissivity to AAV transduction by relieving inhibition imposed by DNA damage response proteins","volume":"20","author":"Lovric","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.3389\/fphys.2018.01008","article-title":"Autophagy dysfunction and oxidative stress, two related mechanisms implicated in retinitis pigmentosa","volume":"9","author":"Moreno","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_314","doi-asserted-by":"crossref","unstructured":"Blasiak, J., Piechota, M., Pawlowska, E., Szatkowska, M., Sikora, E., and Kaarniranta, K. (2017). Cellular senescence in age-related macular degeneration: Can autophagy and DNA damage response play a role?. Oxid. Med. Cell. Longev., 2017.","DOI":"10.1155\/2017\/5293258"},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/nrc2440","article-title":"Living on a break: Cellular senescence as a DNA-damage response","volume":"8","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1089\/104303403322542301","article-title":"Adeno-Associated Virus Type 5: Transduction Efficiency and Cell-Type Specificity in the Primate Retina","volume":"14","author":"Lotery","year":"2003","journal-title":"Hum. Gene Ther."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"S184","DOI":"10.1016\/S1525-0016(16)43391-5","article-title":"561. Evaluation of AAV Vectors Based on Serotypes 1,2 and 5 in Non-Human Primate Muscle, Liver and Retina","volume":"5","author":"Gao","year":"2002","journal-title":"Mol. Ther."},{"key":"ref_318","doi-asserted-by":"crossref","unstructured":"Vandenberghe, L.H., Bell, P., Maguire, A.M., Xiao, R., Hopkins, T.B., Grant, R., Bennett, J., and Wilson, J.M. (2013). AAV9 targets cone photoreceptors in the nonhuman primate retina. PLoS ONE, 8.","DOI":"10.1371\/annotation\/64b90996-4634-4c63-b737-634397b0b445"},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1089\/hum.2016.111","article-title":"Evaluation of Dose and Safety of AAV7m8 and AAV8BP2 in the Non-Human Primate Retina","volume":"28","author":"Ramachandran","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1089\/hum.2017.154","article-title":"Synthetic Adeno-Associated Viral Vector Efficiently Targets Mouse and Nonhuman Primate Retina in Vivo","volume":"29","author":"Carvalho","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1089\/hum.2012.125","article-title":"The Human Rhodopsin Kinase Promoter in an AAV5 Vector Confers Rod- and Cone-Specific Expression in the Primate Retina","volume":"23","author":"Boye","year":"2012","journal-title":"Hum. Gene Ther."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1167\/iovs.10-6250","article-title":"Intravitreal injection of AAV2 transduces macaque inner retina","volume":"52","author":"Yin","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.ymthe.2016.10.008","article-title":"Improved Intravitreal AAV-Mediated Inner Retinal Gene Transduction after Surgical Internal Limiting Membrane Peeling in Cynomolgus Monkeys","volume":"25","author":"Takahashi","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.1073\/pnas.1821000116","article-title":"AAV cis-regulatory sequences are correlated with ocular toxicity","volume":"116","author":"Xiong","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jneumeth.2017.04.007","article-title":"Light and the laboratory mouse","volume":"300","author":"Peirson","year":"2018","journal-title":"J. Neurosci. Methods"},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1089\/hum.2018.144","article-title":"Dosage Thresholds and Influence of Transgene Cassette in Adeno-Associated Virus-Related Toxicity","volume":"29","author":"Khabou","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nrg2988","article-title":"Therapeutic in vivo gene transfer for genetic disease using AAV: Progress and challenges","volume":"12","author":"Mingozzi","year":"2011","journal-title":"Nat. Rev. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/12\/4197\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:38:17Z","timestamp":1760175497000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/12\/4197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,12]]},"references-count":327,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["ijms21124197"],"URL":"https:\/\/doi.org\/10.3390\/ijms21124197","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,12]]}}}