{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T05:39:21Z","timestamp":1778305161580,"version":"3.51.4"},"reference-count":70,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["NE2118\/2-1"],"award-info":[{"award-number":["NE2118\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Efficacy and safety considerations constitute essential steps during development of in vivo gene therapies. Herein, we evaluated efficacy and safety of splice factor-based treatments to correct mutation-induced splice defects in an Opa1 mutant mouse line. We applied adeno-associated viruses to the retina. The viruses transduced retinal cells with an engineered U1 snRNA splice factor designed to correct the Opa1 splice defect. We found the treatment to be efficient in increasing wild-type Opa1 transcripts. Correspondingly, Opa1 protein levels increased significantly in treated eyes. Measurements of retinal morphology and function did not reveal therapy-related side-effects supporting the short-term safety of the treatment. Alterations of potential off-target genes were not detected. Our data suggest that treatments of splice defects applying engineered U1 snRNAs represent a promising in vivo therapeutic approach. The therapy increased wild-type Opa1 transcripts and protein levels without detectable morphological, functional or genetic side-effects in the mouse eye. The U1 snRNA-based therapy can be tailored to specific disease gene mutations, hence, raising the possibility of a wider applicability of this promising technology towards treatment of different inherited retinal diseases.<\/jats:p>","DOI":"10.3390\/cells12060955","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T06:56:48Z","timestamp":1679381808000},"page":"955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["In Vivo Efficacy and Safety Evaluations of Therapeutic Splicing Correction Using U1 snRNA in the Mouse Retina"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6793-3070","authenticated-orcid":false,"given":"Sebastian","family":"Swirski","sequence":"first","affiliation":[{"name":"Human Genetics, Department of Human Medicine, Faculty of Medicine and Health Sciences, University of Oldenburg, Carl-von-Ossietzky-Stra\u00dfe 9-11, 26129 Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"May","sequence":"additional","affiliation":[{"name":"Human Genetics, Department of Human Medicine, Faculty of Medicine and Health Sciences, University of Oldenburg, Carl-von-Ossietzky-Stra\u00dfe 9-11, 26129 Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malte","family":"Ahlers","sequence":"additional","affiliation":[{"name":"Visual Neuroscience, Department of Neuroscience, Faculty of Medicine and Health Sciences, University of Oldenburg, Carl-von-Ossietzky-Stra\u00dfe 9-11, 26129 Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8964-5953","authenticated-orcid":false,"given":"Bernd","family":"Wissinger","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Elfriede-Aulhorn-Stra\u00dfe 7, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Greschner","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Elfriede-Aulhorn-Stra\u00dfe 7, 72076 T\u00fcbingen, Germany"},{"name":"Research Center Neurosensory Science, University of Oldenburg, Carl-von-Ossietzky-Stra\u00dfe 9-11, 26129 Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5842-4824","authenticated-orcid":false,"given":"Christoph","family":"J\u00fcschke","sequence":"additional","affiliation":[{"name":"Human Genetics, Department of Human Medicine, Faculty of Medicine and Health Sciences, University of Oldenburg, Carl-von-Ossietzky-Stra\u00dfe 9-11, 26129 Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9205-8394","authenticated-orcid":false,"given":"John","family":"Neidhardt","sequence":"additional","affiliation":[{"name":"Human Genetics, Department of Human Medicine, Faculty of Medicine and Health Sciences, University of Oldenburg, Carl-von-Ossietzky-Stra\u00dfe 9-11, 26129 Oldenburg, Germany"},{"name":"Research Center Neurosensory Science, University of Oldenburg, Carl-von-Ossietzky-Stra\u00dfe 9-11, 26129 Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1261\/rna.876308","article-title":"Splicing regulation: From a parts list of regulatory elements to an integrated splicing code","volume":"14","author":"Wang","year":"2008","journal-title":"RNA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a003707","DOI":"10.1101\/cshperspect.a003707","article-title":"Spliceosome structure and function","volume":"3","author":"Will","year":"2011","journal-title":"Cold Spring Harb. 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