{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:46:20Z","timestamp":1777923980366,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Nucleic Acid Therapeutics"],"published-print":{"date-parts":[[2024,6,1]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic toggle=\"yes\">ABCA4<\/jats:italic>\n                    gene, involved in Stargardt disease, has a high percentage of splice-altering pathogenic variants, some of which cause complex RNA defects. Although antisense oligonucleotides (AONs) have shown promising results in splicing modulation, they have not yet been used to target complex splicing defects. Here, we performed AON-based rescue studies on\n                    <jats:italic toggle=\"yes\">ABCA4<\/jats:italic>\n                    complex splicing defects. Intron 13 variants c.1938-724A&gt;G, c.1938-621G&gt;A, c.1938-619A&gt;G, and c.1938-514A&gt;G all lead to the inclusion of different pseudo-exons (PEs) with and without an upstream PE (PE1). Intron 44 variant c.6148-84A&gt;T results in multiple PE inclusions and\/or exon skipping events. Five novel AONs were designed to target these defects. AON efficacy was assessed by\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    splice assays using midigenes containing the variants of interest. All screened complex splicing defects were effectively rescued by the AONs. Although varying levels of efficacy were observed between AONs targeting the same PEs, for all variants at least one AON restored splicing to levels comparable or better than wildtype. In conclusion, AONs are a promising approach to target complex splicing defects in\n                    <jats:italic toggle=\"yes\">ABCA4<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1089\/nat.2024.0008","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T05:19:05Z","timestamp":1716787145000},"page":"125-133","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Antisense Oligonucleotide-Based Rescue of Complex Intronic Splicing Defects in\n                    <i>ABCA4<\/i>"],"prefix":"10.1177","volume":"34","author":[{"given":"Zelia","family":"Corradi","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebekkah J.","family":"Hitti-Malin","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura A.","family":"de Rooij","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5721-1560","authenticated-orcid":false,"given":"Alejandro","family":"Garanto","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands."},{"name":"Department of Pediatrics, Amalia Children\u2019s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob W. J.","family":"Collin","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frans P. M.","family":"Cremers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0805"},{"key":"e_1_3_5_3_2","first-page":"453","article-title":"Stargardt\u2019s disease and fundus flavimaculatus: Evaluation of morphologic progression and intrafamilial co-existence","volume":"84","author":"Aaberg TM","year":"1986","unstructured":"Aaberg TM. Stargardt\u2019s disease and fundus flavimaculatus: Evaluation of morphologic progression and intrafamilial co-existence. Trans Am Ophthalmol Soc, 1986; 84:453\u2013487.","journal-title":"Trans Am Ophthalmol Soc"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0397-236"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(00)00756-X"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.15.10303"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1802519115"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1927"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2009.02.004"},{"key":"e_1_3_5_10_2","article-title":"Compendium of clinical variant classification for 2,247 unique ABCA4 variants to improve genetic medicine access for Stargardt disease","author":"Cornelis SS","year":"2023","unstructured":"Cornelis SS, , Bauwens M, , Haer-Wigman L, et al. 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In vitro and in\u00a0vivo rescue of aberrant splicing in CEP290-associated LCA by antisense oligonucleotide delivery. 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