{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:50:03Z","timestamp":1792097403410,"version":"4.4.0"},"reference-count":107,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:00:00Z","timestamp":1619395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye\u2019s accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.<\/jats:p>","DOI":"10.3390\/ijms22094534","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T02:31:43Z","timestamp":1619490703000},"page":"4534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials"],"prefix":"10.3390","volume":"22","author":[{"given":"Wei","family":"Chiu","sequence":"first","affiliation":[{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7906-1612","authenticated-orcid":false,"given":"Ting-Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7964-9993","authenticated-orcid":false,"given":"Yun-Chia","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8516-743X","authenticated-orcid":false,"given":"Henkie","family":"Isahwan-Ahmad Mulyadi Lai","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen-Che","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliaksandr A.","family":"Yarmishyn","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiuan-Chen","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kao-Jung","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Bai","family":"Chou","sequence":"additional","affiliation":[{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2354-2999","authenticated-orcid":false,"given":"Chih-Chien","family":"Hsu","sequence":"additional","affiliation":[{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai-Chi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1528-9252","authenticated-orcid":false,"given":"Yueh","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University, Taipei 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