{"doi":"10.1016/j.stemcr.2020.12.018","title":"Gene Therapy of Dominant CRX-Leber Congenital Amaurosis using Patient Stem Cell-Derived Retinal Organoids","abstract":"Mutations in the photoreceptor transcription factor gene cone-rod homeobox (CRX) lead to distinct retinopathy phenotypes, including early-onset vision impairment in dominant Leber congenital amaurosis (LCA). Using induced pluripotent stem cells (iPSCs) from a patient with CRX-I138fs48 mutation, we established an in vitro model of CRX-LCA in retinal organoids that showed defective photoreceptor maturation by histology and gene profiling, with diminished expression of visual opsins. Adeno-associated virus (AAV)-mediated CRX gene augmentation therapy partially restored photoreceptor phenotype and expression of phototransduction-related genes as determined by single-cell RNA-sequencing. Retinal organoids derived from iPSCs of a second dominant CRX-LCA patient carrying K88N mutation revealed the loss of opsin expression as a common phenotype, which was alleviated by AAV-mediated augmentation of CRX. Our studies provide a proof-of-concept for developing gene therapy of dominant CRX-LCA and other CRX retinopathies.","journal":"Stem Cell Reports","year":2021,"id":148709,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":120,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":632674,"name":"Zepeng Qu","orcid":"0000-0003-1208-0557","position":1,"is_corresponding":false},{"id":325251,"name":"James L. Gentry","orcid":"0000-0002-7737-7987","position":2,"is_corresponding":false},{"id":633622,"name":"Benjamin R. Fadl","orcid":null,"position":3,"is_corresponding":false},{"id":327341,"name":"Linn Gieser","orcid":null,"position":4,"is_corresponding":false},{"id":633623,"name":"Suja Hiriyanna","orcid":null,"position":5,"is_corresponding":false},{"id":301400,"name":"Zachary Batz","orcid":"0000-0002-4483-2402","position":6,"is_corresponding":false},{"id":632675,"name":"Mugdha D. Samant","orcid":"0000-0002-7387-6869","position":7,"is_corresponding":false},{"id":632676,"name":"A. Samanta","orcid":"0009-0006-9615-606X","position":8,"is_corresponding":false},{"id":243358,"name":"Colin J. Chu","orcid":"0000-0003-2088-8310","position":9,"is_corresponding":false},{"id":393182,"name":"Laura Campello","orcid":"0000-0002-0869-1315","position":10,"is_corresponding":false},{"id":330902,"name":"Brian P. Brooks","orcid":"0000-0002-1916-7551","position":11,"is_corresponding":false},{"id":337427,"name":"Zhijian Wu","orcid":"0000-0002-7189-3358","position":12,"is_corresponding":false},{"id":54657,"name":"Anand Swaroop","orcid":"0000-0002-1975-1141","position":13,"is_corresponding":false},{"id":261412,"name":"Kamil Kruczek","orcid":null,"position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:42:46.224799Z","pmid":"33513359","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}