{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T08:02:23Z","timestamp":1792828943810,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010321","name":"Dutch blindness funds","doi-asserted-by":"publisher","award":["Uitzicht 2019-19"],"award-info":[{"award-number":["Uitzicht 2019-19"]}],"id":[{"id":"10.13039\/501100010321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010321","name":"Dutch blindness funds","doi-asserted-by":"publisher","award":["Uitzicht 2017-3"],"award-info":[{"award-number":["Uitzicht 2017-3"]}],"id":[{"id":"10.13039\/501100010321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Viral vector delivery of gene therapy represents a promising approach for the treatment of numerous retinal diseases. Adeno-associated viral vectors (AAV) constitute the primary gene delivery platform; however, their limited cargo capacity restricts the delivery of several clinically relevant retinal genes. In this study, we explore the feasibility of employing high-capacity adenoviral vectors (HC-AdVs) as alternative delivery vehicles, which, with a capacity of up to 36 kb, can potentially accommodate all known retinal gene coding sequences. We utilized HC-AdVs based on the classical adenoviral type 5 (AdV5) and on a fiber-modified AdV5.F50 version, both engineered to deliver a 29.6 kb vector genome encoding a fluorescent reporter construct. The tropism of these HC-AdVs was evaluated in an induced pluripotent stem cell (iPSC)-derived human retinal organoid model. Both vector types demonstrated robust transduction efficiency, with sustained transgene expression observed for up to 110 days post-transduction. Moreover, we found efficient transduction of photoreceptors and M\u00fcller glial cells, without evidence of reactive gliosis or loss of photoreceptor cell nuclei. However, an increase in the thickness of the photoreceptor outer nuclear layer was observed at 110 days post-transduction, suggesting potential unfavorable effects on M\u00fcller glial or photoreceptor cells associated with HC-AdV transduction and\/or long-term reporter overexpression. These findings suggest that while HC-AdVs show promise for large retinal gene delivery, further investigations are required to assess their long-term safety and efficacy.<\/jats:p>","DOI":"10.3390\/ijms26010055","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T19:29:52Z","timestamp":1735154992000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Conventional and Tropism-Modified High-Capacity Adenoviral Vectors Exhibit Similar Transduction Profiles in Human iPSC-Derived Retinal Organoids"],"prefix":"10.3390","volume":"26","author":[{"given":"Andrew","family":"McDonald","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0180-5671","authenticated-orcid":false,"given":"Carmen","family":"Gallego","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Andriessen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Orlov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel A. F. V.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Einthovenweg 20, 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), Albinusdreef 2, 2333 ZA Leiden, The Netherlands"},{"name":"Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103610","DOI":"10.1016\/j.drudis.2023.103610","article-title":"Treatment to cure: Advancing AAV gene therapy manufacture","volume":"28","author":"Young","year":"2023","journal-title":"Drug Discov. 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