{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:23:02Z","timestamp":1787682182674,"version":"build-2784847793"},"reference-count":47,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"Netherlands Organisation for Health Research and Development","doi-asserted-by":"publisher","award":["90715614"],"award-info":[{"award-number":["90715614"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"publisher","award":["917.164.455"],"award-info":[{"award-number":["917.164.455"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch Rare Disease Foundation (ZZF)","award":["Exon skipping for EB"],"award-info":[{"award-number":["Exon skipping for EB"]}]},{"name":"Dutch Butterfly Child Foundation (Stichting Vlinderkind)","award":["Exon skipping for EB"],"award-info":[{"award-number":["Exon skipping for EB"]}]},{"DOI":"10.13039\/501100011960","name":"Debra","doi-asserted-by":"publisher","award":["McLean13"],"award-info":[{"award-number":["McLean13"]}],"id":[{"id":"10.13039\/501100011960","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EJP RD COFUND","award":["825575"],"award-info":[{"award-number":["825575"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epidermolysis bullosa is a group of genetic skin conditions characterized by abnormal skin (and mucosal) fragility caused by pathogenic variants in various genes. The disease severity ranges from early childhood mortality in the most severe types to occasional acral blistering in the mildest types. The subtype and severity of EB is linked to the gene involved and the specific variants in that gene, which also determine its mode of inheritance. Current treatment is mainly focused on symptomatic relief such as wound care and blister prevention, because truly curative treatment options are still at the preclinical stage. Given the current level of understanding, the broad spectrum of genes and variants underlying EB makes it impossible to develop a single treatment strategy for all patients. It is likely that many different variant-specific treatment strategies will be needed to ultimately treat all patients. Antisense-oligonucleotide (ASO)-mediated exon skipping aims to counteract pathogenic sequence variants by restoring the open reading frame through the removal of the mutant exon from the pre-messenger RNA. This should lead to the restored production of the protein absent in the affected skin and, consequently, improvement of the phenotype. Several preclinical studies have demonstrated that exon skipping can restore protein production in vitro, in skin equivalents, and in skin grafts derived from EB-patient skin cells, indicating that ASO-mediated exon skipping could be a viable strategy as a topical or systemic treatment. The potential value of exon skipping for EB is supported by a study showing reduced phenotypic severity in patients who carry variants that result in natural exon skipping. In this article, we review the substantial progress made on exon skipping for EB in the past 15 years and highlight the opportunities and current challenges of this RNA-based therapy approach. In addition, we present a prioritization strategy for the development of exon skipping based on genomic information of all EB-involved genes.<\/jats:p>","DOI":"10.3390\/ijms222212222","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T08:10:22Z","timestamp":1636704622000},"page":"12222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Therapeutic Prospects of Exon Skipping for Epidermolysis Bullosa"],"prefix":"10.3390","volume":"22","author":[{"given":"Franciscus","family":"Vermeer","sequence":"first","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Bremer","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, The Netherlands"},{"name":"University of Groningen, University Medical Center Groningen, Department of Dermatology, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sietsma","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, The Netherlands"},{"name":"University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen","family":"Sandilands","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Hickerson","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"Bolling","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Dermatology, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pasmooij","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Dermatology, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henny","family":"Lemmink","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morris","family":"Swertz","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, The Netherlands"},{"name":"University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nine","family":"Knoers","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"van der Velde","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, The Netherlands"},{"name":"University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3734-753X","authenticated-orcid":false,"given":"Peter","family":"van den Akker","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, The Netherlands"},{"name":"Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.jaad.2014.01.903","article-title":"Inherited epidermolysis bullosa: Updated recommendations on diagnosis and classification","volume":"70","author":"Fine","year":"2014","journal-title":"J. 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