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Here, we characterized an induced pluripotent stem cell (iPSC)\u2010derived disease model derived from a patient with non\u2010syndromic <jats:italic>CLN3<\/jats:italic>\u2010associated retinopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patient\u2010iPSC, carrying the 1\u00a0kb\u2010deletion and c.175G&gt;A variants in <jats:italic>CLN3<\/jats:italic>, coisogenic iPSC, in which the c.175G&gt;A variant was corrected, and control iPSC were differentiated into neural retinal organoids (NRO) and cardiomyocytes. <jats:italic>CLN3<\/jats:italic> transcripts were analyzed by Sanger sequencing. Gene expression was characterized by qPCR and western blotting. NRO were characterized by immunostaining and electron microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Novel <jats:italic>CLN3<\/jats:italic> transcripts were detected in adult human retina and control\u2010NRO. The major transcript detected in patient\u2010NRO displayed skipping of exons 2 and 4\u20139. Accumulation of subunit\u2010C of mitochondrial ATPase (SCMAS) protein was demonstrated in patient\u2010derived cells. Photoreceptor progenitor cells in patient\u2010NRO displayed accumulation of peroxisomes and vacuolization of inner segments. Correction of the c.175G&gt;A variant restored <jats:italic>CLN3<\/jats:italic> mRNA and protein expression and prevented SCMAS and inner segment vacuolization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate the expression of novel <jats:italic>CLN3<\/jats:italic> transcripts in human retinal tissues. The c.175G&gt;A variant alters splicing of the <jats:italic>CLN3<\/jats:italic> pre\u2010mRNA, leading to features consistent with CLN3 deficiency, which were prevented by gene correction.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1601","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T20:42:10Z","timestamp":1611693730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Gene correction of the <i>CLN3<\/i> c.175G&gt;A variant in patient\u2010derived induced pluripotent stem cells prevents pathological changes in retinal organoids"],"prefix":"10.1002","volume":"9","author":[{"given":"Xiao","family":"Zhang","sequence":"first","affiliation":[{"name":"Centre for Ophthalmology and Visual Science The University of Western Australia Perth WA Australia"},{"name":"Ocular Tissue Engineering Laboratory Lions Eye Institute Perth WA 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