{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T08:02:28Z","timestamp":1792828948863,"version":"4.5.0"},"reference-count":38,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,9,10]],"date-time":"2014-09-10T00:00:00Z","timestamp":1410307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000262","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000262","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes & Diseases"],"published-print":{"date-parts":[[2014,12]]},"DOI":"10.1016\/j.gendis.2014.09.002","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T00:26:09Z","timestamp":1410827169000},"page":"227-237","source":"Crossref","is-referenced-by-count":13,"title":["Highly efficient retinal gene delivery with helper-dependent adenoviral vectors"],"prefix":"10.1016","volume":"1","author":[{"given":"Simon","family":"Lam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huibi","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongqi","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"39","key":"10.1016\/j.gendis.2014.09.002_bib1","doi-asserted-by":"crossref","first-page":"15112","DOI":"10.1073\/pnas.0807027105","article-title":"Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics","volume":"105","author":"Cideciyan","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"issue":"10","key":"10.1016\/j.gendis.2014.09.002_bib2","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1089\/hum.2008.107","article-title":"Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial","volume":"19","author":"Hauswirth","year":"2008","journal-title":"Hum Gene Ther"},{"issue":"21","key":"10.1016\/j.gendis.2014.09.002_bib3","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1056\/NEJMoa0802315","article-title":"Safety and efficacy of gene transfer for Leber's congenital amaurosis","volume":"358","author":"Maguire","year":"2008","journal-title":"N Engl J Med"},{"issue":"9701","key":"10.1016\/j.gendis.2014.09.002_bib4","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/S0140-6736(09)61836-5","article-title":"Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial","volume":"374","author":"Maguire","year":"2009","journal-title":"Lancet"},{"issue":"3","key":"10.1016\/j.gendis.2014.09.002_bib5","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/mt.2009.277","article-title":"Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration","volume":"18","author":"Simonelli","year":"2010","journal-title":"Mol Ther"},{"issue":"120","key":"10.1016\/j.gendis.2014.09.002_bib6","doi-asserted-by":"crossref","first-page":"120ra115","DOI":"10.1126\/scitranslmed.3002865","article-title":"AAV2 gene therapy readministration in three adults with congenital blindness","volume":"4","author":"Bennett","year":"2012","journal-title":"Sci Transl Med"},{"issue":"5","key":"10.1016\/j.gendis.2014.09.002_bib7","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1172\/JCI34316","article-title":"Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice","volume":"118","author":"Allocca","year":"2008","journal-title":"J Clin Invest"},{"issue":"1","key":"10.1016\/j.gendis.2014.09.002_bib8","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/mt.2009.256","article-title":"Evidence for the failure of adeno-associated virus serotype 5 to package a viral genome > or = 8.2\u00a0kb","volume":"18","author":"Lai","year":"2009","journal-title":"Mol Ther"},{"issue":"1","key":"10.1016\/j.gendis.2014.09.002_bib9","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/mt.2009.280","article-title":"Little vector, big gene transduction: fragmented genome reassembly of adeno-associated virus","volume":"18","author":"Hirsch","year":"2010","journal-title":"Mol Ther"},{"issue":"1","key":"10.1016\/j.gendis.2014.09.002_bib10","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/mt.2009.255","article-title":"Effect of genome size on AAV vector packaging","volume":"18","author":"Wu","year":"2010","journal-title":"Mol Ther"},{"issue":"19","key":"10.1016\/j.gendis.2014.09.002_bib11","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"},{"issue":"4","key":"10.1016\/j.gendis.2014.09.002_bib12","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/mt.2014.3","article-title":"Uncovering and dissecting the genotoxicity of self-inactivating lentiviral vectors in\u00a0vivo","volume":"22","author":"Cesana","year":"2014","journal-title":"Mol Ther"},{"issue":"6414","key":"10.1016\/j.gendis.2014.09.002_bib13","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/361724a0","article-title":"Retinal age pigments generated by self-assembling lysosomotropic detergents","volume":"361","author":"Eldred","year":"1993","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.gendis.2014.09.002_bib14","first-page":"737","article-title":"Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin","volume":"40","author":"Holz","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"7","key":"10.1016\/j.gendis.2014.09.002_bib15","first-page":"1981","article-title":"The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells","volume":"41","author":"Sparrow","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"5","key":"10.1016\/j.gendis.2014.09.002_bib16","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.exer.2005.01.007","article-title":"RPE lipofuscin and its role in retinal pathobiology","volume":"80","author":"Sparrow","year":"2005","journal-title":"Exp Eye Res"},{"issue":"24","key":"10.1016\/j.gendis.2014.09.002_bib17","doi-asserted-by":"crossref","first-page":"13565","DOI":"10.1073\/pnas.93.24.13565","article-title":"A helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal","volume":"93","author":"Parks","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5 Pt 1","key":"10.1016\/j.gendis.2014.09.002_bib18","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S1525-0016(03)00059-5","article-title":"Reduced inflammation and improved airway expression using helper-dependent adenoviral vectors with a K18 promoter","volume":"7","author":"Toietta","year":"2003","journal-title":"Mol Ther"},{"issue":"2","key":"10.1016\/j.gendis.2014.09.002_bib19","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"},{"issue":"3","key":"10.1016\/j.gendis.2014.09.002_bib20","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1073\/pnas.97.3.1002","article-title":"Optimization of the helper-dependent adenovirus system for production and potency in\u00a0vivo","volume":"97","author":"Sandig","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.gendis.2014.09.002_bib21","first-page":"371","article-title":"Preparation of helper-dependent adenoviral vectors","volume":"69","author":"Ng","year":"2002","journal-title":"Methods Mol Med"},{"issue":"5","key":"10.1016\/j.gendis.2014.09.002_bib22","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.ymthe.2003.08.014","article-title":"Improved system for helper-dependent adenoviral vector production","volume":"8","author":"Palmer","year":"2003","journal-title":"Mol Ther"},{"key":"10.1016\/j.gendis.2014.09.002_bib23","first-page":"131","article-title":"Subretinal injections in rodent eyes: effects on electrophysiology and histology of rat retina","volume":"7","author":"Timmers","year":"2001","journal-title":"Mol Vis"},{"issue":"5","key":"10.1016\/j.gendis.2014.09.002_bib24","first-page":"2535","article-title":"Adenovirus vector-mediated in\u00a0vivo gene transfer into adult murine retina","volume":"35","author":"Bennett","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"6","key":"10.1016\/j.gendis.2014.09.002_bib25","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/gt.2011.6","article-title":"Adenovirus-mediated delivery of CD46 attenuates the alternative complement pathway on RPE: implications for age-related macular degeneration","volume":"18","author":"Sweigard","year":"2011","journal-title":"Gene Ther"},{"issue":"1","key":"10.1016\/j.gendis.2014.09.002_bib26","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1080\/02713680701799408","article-title":"Distinctive gene transduction efficiencies of commonly used viral vectors in the retina","volume":"33","author":"Zhang","year":"2008","journal-title":"Curr Eye Res"},{"issue":"29","key":"10.1016\/j.gendis.2014.09.002_bib27","doi-asserted-by":"crossref","first-page":"7158","DOI":"10.1016\/j.biomaterials.2013.06.002","article-title":"A review of therapeutic prospects of non-viral gene therapy in the retinal pigment epithelium","volume":"34","author":"Koirala","year":"2013","journal-title":"Biomaterials"},{"issue":"3","key":"10.1016\/j.gendis.2014.09.002_bib28","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"},{"issue":"5","key":"10.1016\/j.gendis.2014.09.002_bib29","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1017\/S0952523800175029","article-title":"Rod and cone visual cycle consequences of a null mutation in the 11-cis-retinol dehydrogenase gene in man","volume":"17","author":"Cideciyan","year":"2000","journal-title":"Vis Neurosci"},{"issue":"7","key":"10.1016\/j.gendis.2014.09.002_bib30","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1056\/NEJMc0903652","article-title":"Vision 1 year after gene therapy for Leber's congenital amaurosis","volume":"361","author":"Cideciyan","year":"2009","journal-title":"N Engl J Med"},{"issue":"11","key":"10.1016\/j.gendis.2014.09.002_bib31","doi-asserted-by":"crossref","first-page":"e333","DOI":"10.1371\/journal.pmed.0020333","article-title":"Pharmacological and rAAV gene therapy rescue of visual functions in a blind mouse model of Leber congenital amaurosis","volume":"2","author":"Batten","year":"2005","journal-title":"PLoS Med"},{"issue":"8","key":"10.1016\/j.gendis.2014.09.002_bib32","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/sj.gt.3302460","article-title":"Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy","volume":"12","author":"Tschernutter","year":"2005","journal-title":"Gene Ther"},{"issue":"22","key":"10.1016\/j.gendis.2014.09.002_bib33","doi-asserted-by":"crossref","first-page":"12584","DOI":"10.1073\/pnas.221364198","article-title":"Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk","volume":"98","author":"Vollrath","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"issue":"2","key":"10.1016\/j.gendis.2014.09.002_bib34","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S1525-0016(03)00144-8","article-title":"AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa","volume":"8","author":"Smith","year":"2003","journal-title":"Mol Ther"},{"issue":"4","key":"10.1016\/j.gendis.2014.09.002_bib35","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1167\/iovs.11-8831","article-title":"Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal preservation in RCS rats","volume":"53","author":"Deng","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.gendis.2014.09.002_bib36","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/ncomms1391","article-title":"Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells","volume":"2","author":"Lutschg","year":"2011","journal-title":"Nat Commun"},{"issue":"4","key":"10.1016\/j.gendis.2014.09.002_bib37","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.exer.2008.01.004","article-title":"Pharmacological disruption of the outer limiting membrane leads to increased retinal integration of transplanted photoreceptor precursors","volume":"86","author":"West","year":"2008","journal-title":"Exp Eye Res"},{"issue":"2","key":"10.1016\/j.gendis.2014.09.002_bib38","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1167\/iovs.09-3884","article-title":"Identification of barriers to retinal engraftment of transplanted stem cells","volume":"51","author":"Johnson","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"}],"container-title":["Genes & Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352304214000191?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352304214000191?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,9,29]],"date-time":"2018-09-29T16:30:28Z","timestamp":1538238628000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352304214000191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,12]]}},"alternative-id":["S2352304214000191"],"URL":"https:\/\/doi.org\/10.1016\/j.gendis.2014.09.002","relation":{},"ISSN":["2352-3042"],"issn-type":[{"value":"2352-3042","type":"print"}],"subject":[],"published":{"date-parts":[[2014,12]]}}}