{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:51:36Z","timestamp":1793173896879,"version":"4.5.0"},"reference-count":37,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"N\/A","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,22]]},"abstract":"<jats:p>\n                    Patient-specific induced pluripotent stem cell\u2013derived (iPSC-derived) cell lines allow for therapies to be tailored to individual patients, increasing therapeutic precision and efficiency. Bietti crystalline dystrophy (BCD) is a rare blinding disease estimated to affect about 67,000 individuals worldwide. Here, we used iPSC-derived retinal pigment epithelium (iRPE) cells from patients with BCD to evaluate adeno-associated virus\u2013mediated (AAV-mediated) gene augmentation therapy strategies. We found that BCD iRPE cells were vulnerable to blue light\u2013induced oxidative stress and that cellular phenotype can be quantified using 3 robust biomarkers: reactive oxygen species (ROS), 4-hydroxy 2-nonenal (4-HNE) levels, and cell death rate. Additionally, we demonstrated that AAV-mediated gene therapy can significantly reduce light-induced cell death in BCD iRPE cells. This is the first proof-of-concept study to our knowledge to show that AAV-\n                    <jats:italic>CYP4V2<\/jats:italic>\n                    gene therapy can be used to treat light-induced RPE damage in BCD. Furthermore, we observed significant variability in cellular phenotypes among iRPE from patients with BCD of divergent mutations, which outlined genotype-phenotype correlations in BCD patient\u2013specific cell disease models. Our results reveal that patient-specific iRPE cells retained personalized responses to AAV-mediated gene therapy. Therefore, this approach can advance BCD therapy and set a precedent for precision medicine in other diseases, emphasizing the necessity for personalization in healthcare to accommodate individual diversity.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.177231","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T10:23:32Z","timestamp":1726136612000},"source":"Crossref","is-referenced-by-count":11,"title":["Evaluating precision medicine approaches for gene therapy in patient-specific cellular models of Bietti crystalline dystrophy"],"prefix":"10.1172","volume":"9","author":[{"given":"Yao","family":"Li","sequence":"first","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Yang","sequence":"additional","affiliation":[{"name":"Reflection Biotechnologies, New Territories, Hong Kong."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0530-1713","authenticated-orcid":true,"given":"Yong-Shi","family":"Li","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Wei","family":"Hsu","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8959-7074","authenticated-orcid":true,"given":"Laura A.","family":"Jenny","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Kong","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merry Z.C.","family":"Ruan","sequence":"additional","affiliation":[{"name":"Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet R.","family":"Sparrow","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9082-2427","authenticated-orcid":true,"given":"Stephen H.","family":"Tsang","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Columbia University, New York, New York, USA."},{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA."},{"name":"Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA."},{"name":"Columbia Stem Cell Initiative, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/17469899.2018.1475232"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.013"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-54892-7"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.04.006"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061396"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1086\/383228"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2013.11.042"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S185744"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.12.2.27"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.07.024"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1717338115"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-12210-8"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232113108"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-13717"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac181"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-022-02557-6"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.184"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.04.112"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2016-309696"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1124\/mi.11.2.10"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1124\/mol.112.080085"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800170-JLR200"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.138"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2117553119"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2004"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/aos.13768"},{"key":"B27","first-page":"1141","article-title":"Disease-associated mutations in CNGB3 produce gain of function alterations in cone cyclic nucleotide-gated channels","volume":"11","author":"Bright","year":"2005","journal-title":"Mol Vis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197001082820205"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.1975.tb06025.x"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-008-0985-8"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010351630856"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/7651_2015_225"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.100"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29914"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.07.002"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.33"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.281"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/177231\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:41:37Z","timestamp":1779136897000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/177231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,22]]},"references-count":37,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,7,18]]},"published-print":{"date-parts":[[2024,8,22]]}},"alternative-id":["10.1172\/jci.insight.177231"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.177231","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,22]]},"article-number":"e177231"}}